A New Way To Teach

Cite this article as:
Team DFTB. A New Way To Teach, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28420

At DFTB we are very excited to be able to present the DFTB Modules – a set of free, open access teaching modules which are mapped to the UK and Australasian Paediatric Emergency curriculum that you can pick up and run in your own organisation.

This is a project that has been developed by our DFTB Fellows at the Royal London Hospital – Rebecca Paxton, Helena Winstanley, Chris Odedun, and Michelle Alisio. The DFTB Modules would not have been possible without our wonderful community of writers and contributors from around the world who have spent time crafting and reviewing the modules over the past year.

We’ve prioritized flexibility in creating the modules with cases and discussions with both basic and advanced trainees in mind. This way you can adapt them to your learners and existing resources. The first 15 modules have been released and we have another 30 in the pipeline. These will be published over the next few months. We would love to get your feedback or comments at fellows@dontforgetthebubbles.com

Why did we create the project?

The DFTB mission is about taking a “World recognized leadership role in making meaning of information in paediatric medicine, for clinicians“. Our principles are structured around being collaborative, pioneering, community-focused, and evidence-based.

Opportunities for teaching and learning across the curriculum in paediatrics, particularly in paediatric emergency, are variable between hospitals often due to access to useful resources. Whilst there are many fantastic educators in hospitals, many fill clinical roles. This means that their time to prepare for teaching is limited. For trainees, who often rotate from hospital to hospital, having access to structured resources and an opportunity for case-based discussion of a wide range of topics will help strengthen their learning.

By collaborating, as a group of medical professionals across the world, in writing these modules – we are working together as an international community to support thoughtful, evidence-based sessions.

Access the DFTB Modules here

Safeguarding Module

Cite this article as:
Team DFTB. Safeguarding Module, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27747
TopicSafeguarding
AuthorVictoria Currie
DurationUp to 2 hours
Equipment requiredNone
  • Basics (10 mins)
  • Main session: (2 x 15 minute) case discussions covering the key points and evidence
  • Advanced session: (2 x 20 minutes) case discussions covering grey areas, diagnostic dilemmas; advanced management and escalation
  • Quiz (10 mins)
  • Infographic sharing (5 mins): 5 take-home learning points

We also recommend printing/sharing a copy of your local guideline.

The Child Protection Companion. Last published December 2017. Available on RCPCH website and Paediatric Care Online

RCPCH: Child Protection Evidence (evidence based resources for clinicians to help inform child protection procedures)

Child Protection Processes: PaediatricFOAMed

DFTB: Skeletal Survey in NAI

St Emlyns: Child Protection

https://www.aliem.com/pem-pearls-child-abuse-case-1/

Safeguarding children is everyone’s responsibility. Abuse of children can come in many forms; physical, sexual and emotional abuse, and neglect.

Children can present in various ways- this teaching tool aims to discuss the terminology surrounding safeguarding, the investigations that are required and processes that occur when a child presents with suspected maltreatment.

Cruelty to children and young people is a criminal offence, and child abuse and neglect can have serious adverse health and social consequences for children and young people.

These include:

Bruising is the most common injury sustained by children who have been physically abused. Paediatricians must have the skills to differentiate abusive bruises from those that arise from everyday activity or unintentional injury

  • Young children who are referred to the paediatric child protection team with suspected physical abuse (PA) frequently have bruises. It is unclear whether there is any difference between the pattern of bruises when PA is confirmed and when PA is excluded.
  • Bruising is the commonest injury seen in physical abuse.
  • The odds of a bruise on the buttocks or genitalia, cheeks, neck, trunk, head, front of thighs, upper arms were significantly greater in children with PA than in children with PA-excluded.
  • Petechiae, linear or bruises with distinct pattern, bruises in clusters, additional injuries or a child known to social services for previous child abuse concerns were significantly more likely in PA.

All professionals working with children have a duty to safeguard their wellbeing. So, if anybody identifies safeguarding concerns, they should raise it with their local Child Protection services.

6-month-old child (Lisa) on a child protection plan presents to ED with coryzal symptoms and fever of 37.8oC. On examination it is felt that Lisa has a viral illness however after exposing her she is  noted to have multiple bruises on their back of differing colors and sizes.

Lisa had been left with her grandmother and grandfather over the weekend as her mother had spent the weekend with her new partner.

What is your next course of action? 

Why are the bruises on this child’s back concerning?

What bruising patterns are more concerning in children presenting to the ED? 

What questions do you need to incorporate into a paediatric history when you are concerned about safeguarding issues? 

ABCDE assessment of Lisa

Two issues here are the viral illness but the concerning multiple bruises. Assessment and examination to determine the viral symptoms and if further medical treatment is needed. Assessment of pain and suitable analgesia if required.

Detailed history with specific questions relating to safeguarding issues. (see below)

On examination you notice that Lisa is mildly coryzal. You note that the clothes Lisa is wearing seem inadequate. It’s a cold day and Lisa  has arrived solely in a baby grow. There is no respiratory distress and the child is cardiovascularly stable. Lisa is alert and active with normal power and tone and a level anterior fontanelle. 

On exposing Lisa you notice multiple bruises. There are some bruises on her back, with further bruises behind Lisa’s ears (they are round and look like fingertip marks). These bruises concern you. You also notice the nappy is sodden and does not look like it has been changed in a while. The car seat Lisa has arrived in is really dirty with crumbs in it. 

You think about the toddler you have just seen prior to reviewing Lisa who was a 3 year old boy that had fallen over with a minor head injury but you had noted multiple bruises on his shin and you now question if you should have been worried by these bruises. 

Children, especially toddlers can often have accidents in the home or at school that can result in bruising. In the ED there are often bruises noted that are not worrying to us as clinicians based on the site of bruise and the child’s developmental age. Bruising in children is common and often not a cause for concern. A polite inquisitive style including asking the child how they attained the injury can often give a plausible and valid reason for the injury. 

Bruises are unusual in babies 6 months or less who are unable to move or crawl. When children become more mobile bruising becomes more common. These bruises are usually <1 cm in diameter, often over the forehead, bony part of the cheek or jaw, or shins. An active baby in the first 18 months might have two or perhaps three of this type of bruise at the same time. 

In older children most accidental bruises are on bony prominences and are often associated with a graze. In children 18m to 3 years facial and forehead bruises are common, however in older children this is less common. In older children bruises of the hands, feet, lower legs- in particular shins are common. Lower back bruises can be seen on  older children but should be a cause for concern in children under the age of three. 

Non-accidental bruises are more likely to be around the mouth and adjacent cheek, neck, eye-socket, ear, chest, abdomen, upper arms, buttocks and upper legs. All these areas are relatively protected.

Concerning bruising patterns (According to NICE guideline 89 Child maltreatment: when to expect child maltreatment <18s)

Suspect child maltreatment if a child or young person has bruising in the shape of a hand, ligature, stick, teeth mark, grip or implement. 

Suspect child maltreatment if there is bruising or petechiae (tiny red or purple spots) that are not caused by a medical condition (for example, a causative coagulation disorder) and if the explanation for the bruising is unsuitable.

 Examples include:  

  • bruising in a child who is not independently mobile  
  • multiple bruises or bruises in clusters  
  • bruises of a similar shape and size  
  • bruises on any non-bony part of the body or face including the eyes, ears and buttocks and back 
  • bruises on the neck that look like attempted strangulation 
  •  bruises on the ankles and wrists that look like ligature marks or holding/restraint marks

Now you have examined Lisa and are happy that the fever is only being caused by a coryzal illness. You prescribe some paracetamol and go on to take a more extensive history from her mother.

Do you need to extend the history- is there any explanation parents can give for the bruising? If there is a mechanism given does it fit the child’s developmental age? Do you need to take a developmental history?

If there is a period of time as in this case when Lisa was left with grandparents, do you need to extend the history to asking other family members about the injury- including siblings who may be too scared of the consequences if they are to admit there was an accident with their brother/ sister? Can this be done over the phone or could you speak to them in person? 

In ALL children presenting to the ED (irrespective of their presenting complaint) it should be commonplace to ask about:

  • The family set up
  • What adults do the children spend time with
  • Who lives in the same household as the child? 
  • Who has parental responsibility? 
  • Do the family have a social worker?
  • Or have they been previously known to social care? 

Important points to be elicited in the context of physical abuse include:

What the injuries are and how they presented
Timing of injuries and preceding events
The explanations given for the injuries and who gave them
Any discrepancy evident in the account
Action taken by parents or carers after the injury was discovered
Previous injuries
Explanation consistent or not with the developmental level of the child.

 Lisa’s mother had noticed some bruising after picking up Lisa from her grandparents yesterday. She was worried about it but did not come immediately to hospital. Lisa’s mother is unsure if her parents may have done this to Lisa. She wants Lisa to be OK but is worried that Lisa will be taken from her. 

Mo is a 3-month-old boy. He has presented to the ED due to family concerns that he is not moving his left leg. Parents are concerned that it looks a bit swollen. 

Mo is normally fit and well. He was born at term by NVD. He lives with his Mother, Father and extended family.

On examination: Mo has normal observations. He has a normal respiratory, cardiovascular, abdominal and neurological examination. On further examination you notice that Mo is reluctant to move his left leg – there looks to be some swelling over the femur. He cries when you examine it. 

You ask more questions- establishing that Mo’s Dad has been away for the last few days at work and Mo has predominantly been with his Mum. Mo has a social worker who was allocated as Mum had disclosed depression and had not wanted to continue with the pregnancy but due to pressure from the extended family had continued with the pregnancy. 

Mo is not yet mobile or rolling. There is no history to suggest how this might have happened. You can’t find any other evidence of injury on examination. You do notice on examination that Mo’s pram has old food in it, his clothes appear dirty. When you are examining him you notice that his nappy is very full and he has some evidence of nappy rash. 

What can some of the more subtle signs be that can alert you to child protection issues?

How do you move forward now? 

You wonder if Mo’s Mum and Dad will agree to all of this and what will happen if they don’t? 

It is important especially when working in a fast paced ED to recognise the more subtle signs of neglect might highlight a cause for concern and a discussion with a Senior colleague. 

Some of these signs may be

  • Child looking unkempt- soiled clothes, pram, dirty fingernails
  • Large full wet nappy (that looks like its been on for a while) the child may have nappy rash- that might suggest nappy has been on for long periods of time
  • Child who is mobile who has been brought out without shoes- an adult wouldn’t come out without shoes on- so why should we expect a child who is walking to do the same?
  • Child not dressed appropriately e.g. in cold weather no coat
  • Poor dental hygiene or dental caries- that would suggest lack of teeth brushing

These signs alone may be the product of a stressed parent who is worried about their child and quickly wants to get to the Emergency Department (a parent rushing out without a coat, or before changing a child who has just spilled food all over themself). However a few of these signs along with a parents behaviour, an unusual injury or a general feeling about the family- may be signs of neglect or even physical abuse. It is important to discuss this with a Senior colleague. 

These signs should be documented in the notes and even if they are the only concerns you have a discussion with social care or with a Health visitor (after discussion with a Senior colleague) can be a good way of sharing information and highlighting the more subtle signs. 

Always discuss the more subtle signs of neglect with a senior colleague.

You decide to give Mo some analgesia and request some X-rays.  X-ray of the left femur shows a mid shaft spiral fracture of the left femur.

The first step is to make sure that Mo has been given adequate analgesia. If required discuss with Trauma and Orthopaedics regarding management of the fracture. 

This is a concerning injury- Mo is non mobile and no history for the injury has been given. 

In house actions

  • Discuss with a Senior colleague in your department – make sure that your Registrar/ Consultant has been informed and knows there are safeguarding concerns
  • Discuss with your local in house safeguarding team (usually present during working hours). There should be a local safeguarding team available usually through your hospital switchboard or intranet. This team should be able to give you advice and tell you the local processes in your hospital/ local area. 
  • Have a read of the local guidelines for the hospital you are working in this may give you an idea of for example who this child should be admitted under if there are acute concerns in ED and the child is not able to be discharged. 

You speak to your consultant in ED who points you in the direction of the hospital intranet page for safeguarding. You speak to the Lead Safeguarding nurse, Brian. He tells you that you need to discuss the matter with the Child Protection Services  . Brian asks you to discuss the matter with both the General Paediatric team and the Trauma and Orthopaedic team once the initial process has been started by the local safeguarding team. Mo needs admission for management of the fracture along with a child protection examination and further investigations.

  • Some children who already have a known Social worker – the social worker can be contacted directly (usually if they present in hours). If they are not available or it is out of hours you may need to speak to the duty or on call Child Protection Services social worker.
  • How you refer to your local Children’s Protection services differs internationally and from region to region. Please ensure you are familiar with the local policy in your area.
  • All services will have a 24 hour accessible referral system, usually by phone in the first instance and then often followed by a written referral by secure email or via on-line web-portal

You wonder – what information should you be expected to provide when you make the referral to the Local Children’s Protection services. ED is really busy- there are lots of patients waiting to be seen- can somebody else complete this referral? 

It’s much easier if you know this before making the call!

  • Name, date of birth and address of the child, parents , siblings and any other household members
  • If the family lives between different households- e.g parents are separated- addresses of all places the child spends time
  • School/ Nursery/ GP name and address
  • Concerns that have lead you to refer the child on this occasion 
  • Have there been any previous concerns that you know about? Previously known to Social Care? Name and number of social worker/ family support worker?
  • Where the child is now and how can they contact you- This is really important if you are going off shift/ the child is moving to a different place from the ED for admission. 
  • They may also like to know if there are any other children in the household who may at present be at risk. 

It is everyone’s responsibility to safeguard children. However the form can be completed by medical or nursing staff. Some trusts will insist that before a child is admitted to a ward this form should be completed ( you know the story so it may be that you are the best person to do this). 

It needs to be clearly handed over to staff if the referral has not been done and why- along with any communication that has already taken place with Social Care. 

After you have made the referral to Social Care they are able to tell you that Mo’s known social worker is actually on duty. Mo’s mother has been very low in mood and the social worker had been having regular contact as they had been concerned she was not coping. The social worker and a member of the police are en route to the hospital to talk to Mo’s parents. There are no other children at home. You inform then Mo is being admitted to the T and O ward- under joint care with General Paediatrics team- who are preparing to perform a full child protection medical examination and further investigations. 

The legislation on holding a child against their parent’s wishes differs internationally.

In most countries the police force are the appropriate first responders to contact when you are concerned that a child may be at risk of harm if they are removed from a place of safety (e.g. hospital). 

In general police powers to hold a child in a place of safety do not override the parent or guardian’s rights to consent (or to refuse consent) to medical investigation/treatment and in most countries a court order is required to override the parent/guardian’s wishes.

You have just seen Eric, a 7 year old boy who, with his siblings, have an allocated social worker. He presented with a two day history of fever and not drinking. On examination you believe he has findings consistent with bacterial tonsillitis. You want to discharge him on oral antibiotics. During your clerking Mum mentions that they have a Social Worker who mum gives you the name and number of. 

Mum has attended during schooltime with all of the children – you notice three of them should be in school. You need to inform the Social Worker about the attendance to ED.

How does a child come to be placed on a ‘Child in need’ or ‘Child Protection plan’?  

Child Protection Processes: The Lowdown (PaediatricFOAMed)

 Each time a referral is made to the Local Child Safeguarding team the team receiving the referral will decide on one of 4 potential outcomes:

1. No further action is required

2. The case is suitable for Early Help (see Chapter 1 in ‘Working Together to Safeguard Children’)

3. An assessment of the family is carried out leading to the child becoming a Child in Need (CIN) under Section 17 of the Children Act 1989

4. The child has sustained or is at risk of significant harm and Child Protection proceedings must be started under Section 47 of the Children Act 1989

Once the referral has been made you should chase the outcome and if you don’t agree challenge it.

Section 47: Local authority should coordinate an investigation where a child has been subject to or at risk of harm. The aim of the meeting is to decide if any action is required to safeguard the child.

If the  threshold has been met for a Section 47 meeting- then a ‘strategy’ meeting should be arranged.  Meeting between social care, police and medical team. A decision will be made if it should be a ‘single’ or ‘joint agency’ between social care and police. 

The role of the Doctor in the strategy meeting is to consider the need for and timing of a medical examination.

The Aim of the Child Protection Plan is to- 

  • Ensure the child is safe and prevent them from suffering further harm
  • Promote the child’s health, welfare and development (this is where we can contribute most to the discussion!)
  • Support the family to protect and promote the child’s welfare, provided this is in the child’s best interests.

The document should specify timescales and allocate professionals to lead on each point of the plan. Crucially, a review conference should be held at regular intervals – first review is at 3 months then at 6 monthly intervals. If all the points of the CP Plan have been achieved, and the child is no longer considered to be at risk of harm, the CP plan can be discontinued. However, if not, or if the child has been on a CP plan for approaching 2 years, a legal planning meeting is held to decide if care proceedings should be started. This may result in the child being taken into care, becoming ‘Looked After’.

You want to inform Social Care about the fact that Eric attended the ED and that his siblings were not in school- it is nearly midnight and you wonder how you can do this – as you are due to be on two weeks of annual leave after today? 

Children attend emergency departments at all times of the day. Often they may be a child who is known to Social care who you need to inform of their attendance but there is nothing that is acutely concerning about the presentation. Some hospitals will have automatic alerts that come up when you see a child who is on a child protection plan. Often the alert says ‘ please inform the social worker of every attendance’. This can be hard when you are seeing the child out of hours. 

Check with your hospital what the system is- sometimes it is enough to document in the notes and there may be a fallback mechanism for a team to contact Social care within working hours. 

There is always an option of calling the out of hours Local Children’s Protections Services to inform them of the attendance and any further information. You are unlikely to get through to the child’s own social worker however you can leave information in a secure way.

You leave a message with the Local Authority Children’s safeguarding team. Who are able to look at the case noted and inform you that the family’s social worker is due to go and visit the following day- so they will leave a note for her of the information you have given. 

Liah is an 8 year old girl who you had seen on your previous shift in ED- she had presented with multiple bruises. You were concerned at the time that she had ITP. You had seen her and sent bloods off before you left – however you handed her over to a colleague as her bloods were not back when you left. You find out when you are back on shift that her results were normal. Liah was admitted under the General Paediatrics team. She is undergoing investigations for suspected non-accidental injury.

What are the investigations that should be performed in a child with suspected non-accidental injury? 

What investigations need to be performed when concerned about child protection? (The Child Protection Manual: RCPCH)

  • Full blood count
  • Coagulation studies (basic and extended)
  • Liver function tests
  • Amylase
  • Bone chemistry and vitamin D/parathyroid hormone
  • Urine and blood toxicology (if appropriate depending on history)
  • Skeletal survey with follow up films
  • Bone scan (done in certain situations)
  • Computed tomography (CT) head scan
  • Magnetic resonance imaging (MRI) brain and spinal cord
  • Ophthalmology examination

You hear from the Medical Team that Liah’s parents initially refused these investigations along with an examination of Liah specifically to look for injuries (Child Protection Medical examination). 

  • Do not be judgemental. You don’t know what happened
  • Speak to the parents in a neutral tone, calmly and kindly
  • Use open body language
  • Explain that you would like to go through the history with them again even though you know they have already been through it with a number of doctors
  • Explain to the parents that the child is the most important thing for you, your role is to find out what has happened and so you are obliged to refer to the Local Children’s Protection Services
  • Many parents will become upset and angry. That’s why it’s important to have another health professional with you. Many, on the other hand, will surprise you if you explain the situation well, by behaving very reasonably
  • Call security if you feel the situation may escalate or if you feel that you and other health professional staff are at risk of harm

If the situation becomes too confrontational and the parents insist on taking the child out of the hospital, you cannot restrain them. Advise them that you will be calling the police

Communication is key in cases of suspected non accidental injury. Open and honest conversation with the family about the need for investigations to check for any underlying conditions that may have caused the bruising. Early open and honest conversation with the family regarding the need for involvement with the Local Children’s Protection Services care social team.

Consent must be gained from parents before investigation or examination.

 You can get consent or authorization from:

  •  a child or young person who has the maturity and understanding to make the decision,
  • a person with parental responsibility if the child or young person does not have the capacity to give consent (it is usually enough to have consent from one person with parental responsibility)
  • the courts – for example, the family courts or the High Court.

When consent is not given

If the child refuses- explore their ideas, concerns and expectations. If they understand and are competent then their decision must be respected- even if it means that forensic evidence is inadequate.

Sometimes a child or young person may refuse consent because they are afraid of the person who is abusing them, or because they are under pressure to refuse. If you suspect this, you should consider the risk of harm to the child or young person and discuss your concerns with your named or designated professional or lead clinician or, if they are not available, an experienced colleague.

If a child or young person refuses, or their parents refuse, to give their consent to a child protection examination that you believe is necessary, and you believe that the child or young person is at immediate risk of harm, you should contact the police and Local Children’s Protection Services, which may take emergency action to protect them.

The medical team informed you that they did eventually get consent for the investigations along with the Child Protection Medical Examination.

(Paediatric FOAM Child protection documentation – where do we start?)

This an extensive history and examination that focuses on history from both the child and parents.  

Try not to use medical jargon- remember there are going to be non-medical professionals reading the report.

 The documentation is usually made up of- 

1.     Medical proforma- most trusts will have their own version. It can act as a prompt to remind you of what questions to ask. Remember to use the child’s own words as much as possible. Consent must be gained, and ideally written consent is best

2.     Growth chart- good practice to document the height and weight especially if there are child protection concerns. For example, neglect may present as a child that is failing to thrive. (available on RCPCH website https://www.rcpch.ac.uk/resources/growth-charts )

3.     Medical Photography- this is an extremely useful resource. Consent again must be gained. This is useful for example in a child with bruising which may change over time. Generally, this requires written consent and needs to be done via the hospital’s medical illustration department. This isn’t always available out of hours- in some hospitals A and E may have a camera that can be used for this purpose (not appropriate to use a phone camera!).

4.     Body mapping- Essential way of documenting examination findings. Dr Gayle Hann (Consultant Paediatrician, North Middlesex Hospital) and Dr Caroline Fertleman (Consultant Paediatrician, Whittington Hospital) have recently published new, more detailed body maps in different age groups to help paediatrician’s make better documentation. These can be found here:

https://www.londonpaediatrics.co.uk/resources

Body mapping can be overwhelming especially if there are lots of areas to draw. Have a colleague with you- draw it as you examine the child. It is useful to examine with a tape measure handy so you can measure the areas. Draw the injury as close to what you can see as possible use terminology like (graze, cut, scar, linear, colour). It makes it easier to number the marks- so it is easier to describe them in your written report- which always must accompany any body map.

Liah disclosed during the child protection examination that she had for the last few months been hit by her older brother. Social care are now involved and with support and her brother no longer being allowed to visit Liah was eventually discharged home with her mother and father. 

 Blood tests have been performed for Zain a 4 month old child who you have seen in ED  He has unexplained bruising- your consultant asks you to request further investigations before the child goes to the ward- what are they?

A: No further investigations required if bloods are normal

B: Ophthalmology review, x-ray or areas that are bruised, CT head

C: Skeletal survey, ophthalmology review, CT/MRI head

The correct answer is C.

What does a ‘Section 47’ mean?

A: This refers to children who have a Police protection order in place- police have the right to remove them to a place of safety for 72 hours- parents still have consent

B: Local authority should coordinate an investigation where a child has been subject to or at risk of harm. The aim of the meeting is to decide if any action is required to safeguard the child.

C: Child is under a child protection plan and should therefore be raised to the Local Authority Children’s care social team

The correct answer is B.

You are asked by your consultant to organize some photographs of a child who has presented with bruising- it is a Sunday and medical illustration is not open- what should you do?

A: With consent from parent use the consultant’s phone

B: Get the parent to take photos on their phone and then get them to send them to your secure work account

C: Try to get the designated camera from another area in the hospital (A&E) if this is not available then do not take the photos and organize for them to be done as soon as medical illustration is available.

The correct answer is C.

NICE Guideline: NG 76 Child Abuse and Neglect Published October 2017.

NICE Guideline: NG 89 Child maltreatment: when to suspect maltreatment in under 18’s. Published 22nd July 2009. Last updated 09th October 2017.

https://www.nice.org.uk/guidance/cg89

https://www.paediatricfoam.com/2018/02/child-protection-documentation-where-do-we-even-start/

https://www.paediatricfoam.com/2018/10/child-protection/

Kemp AM, Maguire SA, Nuttall D, et alBruising in children who are assessed for suspected physical abuseArchives of Disease in Childhood 2014;99:108-113.

Maguire S. Which injuries may indicate child abuse? Archives of disease in childhood – Education & practice edition, 6 December 2010, Vol.95(6), p.170

https://www.gmc-uk.org/ethical-guidance/ethical-guidance-for-doctors/protecting-children-and-young-people/child-protection-examinations

https://pcouk.org/chapter.aspx?sectionid=112958400&bookid=1674

The Child Protection Companion. Last published December 2017. Available on RCPCH website and Paediatric Care Online.

https://www.rcpch.ac.uk/resources/growth-charts

https://www.londonpaediatrics.co.uk/resources



Please download our Facilitator and Learner guides

Common Rashes Module

Cite this article as:
Aoife Fox. Common Rashes Module, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27731
TopicCommon rashes
AuthorAoife Fox
DurationUp to 2 hours
Equipment requiredNone
  • Basics (10 mins)
  • Main session: (2 x 15 minute) case discussions covering the key points and evidence
  • Advanced session: (2 x 20 minutes) case discussions covering grey areas, diagnostic dilemmas; advanced management and escalation
  • Game
    Quiz (10 mins)
  • Infographic sharing (5 mins): 5 take home learning points

We also recommend printing/sharing a copy of your local guideline.

Definitions/rash description:

  • Macule: a flat area of colour change <1 cm in size (e.g., viral exanthem [such as measles and rubella], morbilliform drug eruption).
  • Patch: a large macule >1 cm in size (e.g., viral exanthem [such as measles and rubella], morbilliform drug eruption).
  • Papule: a raised area <1 cm in size (e.g., wart).
  • Nodule: a larger papule, >1 cm in size (e.g. nodular prurigo). 
  • Plaque: a flat-topped raised area (a cross between a nodule and a patch; e.g., psoriasis).
  • Vesicle: a small fluid-filled lesion (blister) <0.5 cm in size (e.g. varicella, eczema herpeticum).
  • Bulla: a larger vesicle >0.5 cm (e.g. bullous impetigo).
  • Pustule: a pus-filled lesion (e.g. folliculitis).
  • Wheal: a transient raised papule or plaque caused by dermal oedema (e.g. urticaria)
  • Scale: flakes of stratum corneum (e.g. eczema, psoriasis).
  • Crust: dried serum, blood, or purulent exudate on the skin surface (e.g. impetigo).
  • Erosion: loss of epidermis, heals without scarring (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis).
  • Ulcer: loss of epidermis and dermis, heals with scarring (e.g. venous ulcer, pyoderma gangrenosum).
  • Excoriation: loss of epidermis following trauma such as scratching (e.g. pruritus).
  • Fissure: a split in the skin (e.g. angular cheilitis, palmoplantar keratoderma).
  • Lichenification: thickening of the skin with accentuation of skin markings (e.g. chronic eczema, lichen simplex chronicus).
  • Purpura: an area of colour change (red or purple) due to bleeding into the skin; does not blanch on pressure (e.g. vasculitis, disseminated intravascular coagulation).
  • Petechia: a pin-point purpuric lesion (e.g.,vasculitis, disseminated intravascular coagulation).
  • Ecchymosis: a larger area of purpura (e.g. vasculitis, disseminated intravascular coagulation).
Some important points to note in history:
  • Where did the rash start?
  • Sequence of the rash?
  • Type of rash?
  • Time of onset and duration?
  • Involvement of palms and soles?
  • Involvement of mucous membranes?
  • Involvement of conjunctiva?
  • Desquamating?
  • Systemic involvement?
  • Associated symptoms – fever/cough/conjunctivitis/runny nose/sore throat/strawberry tongue/itchiness/pain/weakness/headache/lymphadenopathy/swollen extremities/nausea/vomiting/diarrhoea? 
  • Exposures – immunizations/pets/foreign travel/bites (insects/ticks)/recent injury to skin/sexual history/sick contacts?

Common childhood rashes

The terminology for all but fifth disease is not used anymore, however, should anyone be curious here they are:

Also known as..What causes it?When?What rash?Where is the rash?FeverAssociated findings
First diseaseMeaslesParamyxovirusWinter – spring Erythematous, confluent, maculopapularBegins at the hairline spreads inferiorlyHigh feverKoplik spots, cough, coryza and conjunctivitis, Forchheimer spots
Second diseaseScarlet feverStreptococcus pyogenesAutumn – spring Generalised erythema with a sandpaper textureBegins on the face and upper part of trunk and spreads inferiorlyHigh feverPastia lines, Forchheimer spots, strawberry tongue, exudative pharyngitis, abdominal pain, rheumatic fever, circumoral pallor
Third diseaseRubellaRubivirusLate winter – spring Rose-pink, maculopapularSpreads inferiorlySlightly high feverLymphadenopathy, arthralgias, Forchheimer spots
Fourth diseaseThe existence of “fourth disease” is controversial. It was described as a generalised maculopapular rash and desquamation. This exanthema may be staphylococcal scalded skin syndrome
Fifth diseaseSlapped cheekParvovirus B19Winter and spring“Slapped cheek” appearance, lacy reticular rashErythematous cheeks, reticular extremities Slightly high feverRash, waxes and wanes over weeks, arthritis, aplastic crisis
Sixth diseaseRoseola Human herpesvirus 6 and 7SpringRose-pink, maculopapularNeck and trunk High feverLymphadenopathy, febrile seizures, Nagayama spots
Others of note..ChickenpoxHerpes zoster virusLater winter and early springVesicles on erythematous base, crustsBegins on face and trunk and spreads centripetallyHigh feverPruritus
Hand-foot-and-mouthCoxsackie A virusLate summer or early winterElliptical vesicles on an erythematous base, oral vesicle, erosionsMouth, hands and feetHigh feverVesicles on the hands, feet and in the mouth

Forchheimer spots: rose coloured spots on the soft palate that may coalesce into a red blush and extend over the fauces

Koplik spots: clustered white lesions on the buccal mucosa. They are pathognomonic for measles.

Pastia lines: where pink or red lines formed of confluent petechiae are found in the skin creases.

Nagayama spots: erythematous papules on the mucosa of the soft palate and the base of the uvula. You may see these present on the fourth day in two thirds of patients with roseola.

(based on case from RCEM Learning RCEM Learning – Common Childhood Exanthems)

Mark is a 3-year-old boy brought to the ED by his mother with a rash, temperatures and decreased oral intake. His older brother has a similar rash and illness and mum reports that there was an outbreak of chickenpox in the older brother’s school. 

On exam you note a quiet child with a diffuse vesicular rash. On palpation he has generalised lymphadenopathy.

What are the differentials of chicken pox in this case?

What is the incubation period of chicken pox? How long will Mark be infective?

What investigations are necessary?

How would you manage this illness? What treatment would you give?

What patients would you give anti-VZV immunoglobulin to?

Mark’s mum tell you that she has a 2-week old baby at home – what will you do?

What complications of chickenpox can occur?

Mum tells you that the children’s childminder is pregnant what advice do you give?

Discussion point – Do you use NSAIDs?

(Diffuse) disseminated gonococcaemia

(Local) hand, foot and mouth (coxsackievirus)

(Local) herpes zoster

Staphylococcal bacteraemia

DFTB – Exclusion period for infections

The incubation period for chicken pox is usually 10-21 days. The infectivity period starts when symptoms first appear and lasts until all the lesions have crusted over. This is usually around 5-6 days after the onset of the illness, with most crusts disappearing by 20 days.

Chicken pox is a very common illness and the vast majority of cases can be managed symptomatically at home. Prolonged fever >4 days should prompt the suspicion of complications of varicella such as secondary bacterial sepsis. Under these circumstances, patients should be examined carefully with appropriate blood test work up and a chest x-ray, depending on their clinical presentation.

Oral acyclovir has been shown to reduce the effects of chicken pox, for example the number of lesions and duration of fever, if used within 24 hours of the onset of rash in immunocompetent children. Oral acyclovir has not been shown to reduce the incidence of varicella zoster virus pneumonia or other complications when compared to placebo. Cochrane results do not support the widespread use of acyclovir in immunocompetent children.

Pediatric EM Morsels – Chicken Pox

It is used for high risk patients including, immunocompromised children, newborns with maternal Varicella that develops 5 days before to 2 days after delivery, premature babies and hospitalized infants.

Paediatrics Open – Management of varicella in neonates and infants

Asymptomatic newborn in contact with VZV from any infected subject

The mother is proved seropositive:
Very low risk of disease in the baby.
No treatment should be provided.

Observance of the baby at home and encourage parents to come back if any clinical sign or symptom appears in the 2 weeks after contact.

The mother is proved seronegative or refuses testing:
Treat the baby with acyclovir PO 80 mg/kg/day divided into four doses to start 7 days after infective contact and administer during 7 days.

Careful surveillance of the baby during the risk period. Indication and duration of hospitalisation (with airborne and contact precautions) should be discussed in each case depending on child clinical status, parental compliance and social setting. If any doubt, hospitalisation with optimal medical surveillance are warranted during the risk period.

Pneumonia

Bacteraemia

Encephalitis

Bacterial superinfection of skin

Problems may arise where there is a failure to recognise the complications of secondary streptococcal or staphylococcal infections or to appropriately manage high-risk groups. A prolonged fever for more than 4 days in a child with chicken pox, for example, should prompt the suspicion of secondary bacterial complications.

A range of complications including pneumonia, bacteraemia and encephalitis are increasingly being recognised. Neurological complications may occur without a preceding rash.

The incidence of congenital varicella syndrome is low if maternal infection occurs before 20 weeks of gestation. Congenital varicella syndrome is associated with shortened limbs, skin scarring, cataracts and growth retardation.

RCOG – Chickenpox in Pregnancy

The childminder should contact her own GP. She should avoid contact with children until establishing her risk of contracting VZV. 

DFTB – Varicella and NSAIDs

There is a long history of anecdotal evidence associating invasive group A Strep (GAS) complications, or severe skin and soft tissue infections (SSTIs) with exposure to NSAIDs. 

There are currently 5 papers, ranging from 1997 to 2008 which try to answer this question. Almost all the studies used a case-control method to try and answer this question. Where they took a group of children who had varicella and the outcome of interest (invasive GAS infection, severe SSTI), and compared them to a group of children who had varicella and did not get these outcomes, seeing which groups were more likely to have had ibuprofen.

The studies are pretty heterogeneous, so unsurprisingly the results varied. These studies all found an association, but they generally all suffer from the same big problem, which is confounding by indication. It might not be that ibuprofen causes complications, but rather bad varicella needs ibuprofen, and is also more likely to get complications anyway. As the famous saying goes, “Correlation does not equal causation”. The absolute risk increase of GAS complications or SSTIs is 0.00016% in the worst case scenario. 

NICE advises against giving ibuprofen due to the uncertainty but you must risk assess the clinical scenario yourself. 

(Based on a case from the American Academy of dermatology – American Academy of Dermatology – Viral exanthems)

Caleb is a 9-year-old boy who presents for evaluation of fever and rash. His mother noted a fever of 40 °C two days ago. He appeared well and was eating and playing normally, so his mother was not alarmed. After the fever resolved, Caleb developed red rash that progressed rapidly over the past 24 hours.

What is the most likely diagnosis?

What are the differentials?

What is the cause of roseola?

Who gets it?

How is it spread?

What are the signs and symptoms of roseola?

How is it diagnosed?

What is the treatment?

What are the complications from roseola?

Roseola

Measles

Rubella

Erythema infectiosum (fifth disease)

It is caused most commonly by human herpesvirus 6 (HHV-6) and less commonly by human herpesvirus 7 (HHV-7).

Children aged 6 months – 4 years are most typically affected. Most children (86%) will have had roseola by the age of 1 year. It is rarely seen in adults and infection is thought to confer lifelong immunity.

It is spread person-to-person via the saliva of asymptomatic family members. The incubation period is 9-10 days.

It results in an acute febrile illness lasting between 3 and 7 days, which is then followed by the characteristic rash of roseola in around 20% of infected children. 

The prodrome to the rash is a high fever (39-40 °C), palpebral oedema, cervical lymphadenopathy and mild upper respiratory symptoms. The child appears well. As the fever subsites the exanthem appear. This consists of a pink macules and papules surrounded by white halos. It begins on the trunk and spreads to the neck and proximal extremities. Nagayama spots may occur on the soft palate and uvula. The rash is non-itchy, painless and does not blister.

Diagnosis is usually based solely on the characteristic history and physical exam. 

Roseola is usually benign and self-limiting. Rest, maintaining fluid intake and paracetamol for fever is all that is usually required. Treatment may be necessary for atypical cases with complications and immunosuppressed patients. 

Complications are rare in most children.  The most common complication is febrile convulsion that occurs in 5-15% of children.

Acute encephalitis, hepatitis, myocarditis, haemophagocytic syndrome and infectious mononucleosis-like illness occur very rarely. 

Reactivation of HHV-6 with drug exposure can lead to drug-induced hypersensitivity syndrome, which results in fever, rash, pneumonia, hepatitis, bone marrow suppression and encephalitis. 

Simple Febrile Convulsions generally occur in children aged from 6 months to 5 years. They are common affecting 1 in every 20 children. The most common causes are viral URTIs, ear infections, bacterial tonsillitis and UTIs. 

They are generalised seizures, which last less than 15 minutes and occur only once during 24 hours. 

The recurrence risk depends on child’s age at presentation: 1 year old: 50% recurrence;

2 year old: 30% recurrence

Where there are no neurodevelopmental problems and no family history of epilepsy, the subsequent risk of epilepsy is 1% (equivalent to the population risk).

A 5-year-old girl, Emma, attends the ED with after being unwell for the last 3 days. It initially started out with fever, headache and a sore throat. She then developed a rash 24 hours ago. Her parents report that the rash started on her abdomen and spread to the neck and arms and legs and it feels rough to touch. 

On exam she has a sandpaper type rash on her trunk and limbs which is more pronounced in flexures. 

What is the most likely diagnosis?

What other symptoms might Emma have?

What is it caused by?

What are the differential diagnoses?

How is the diagnosis confirmed? What investigations will you do?

What is the treatment? Why do you treat?

Discussion point – Evidence for antibiotic therapy 

What are the possible complications? How can you categorise them?

What advice do you give to Emma’s parents in order to prevent transmission of Scarlet fever?

Is there anything else you need to do?

Scarlet fever 

The symptoms of Scarlet fever start with fever (over 38.3°C), sore throat and general fatigue/headache/nausea. 12-48 hours later a rash appears on the abdomen and spreads to neck and extremities. 

Characteristic features of the rash are a rough texture (like sandpaper) and worse in the skin folds e.g. groin, axilla, neck folds (Pastia’s lines). 

Other symptoms include white coating on tongue which then peels and leaves a ‘strawberry tongue’; flushed red face with perioral pallor and cervical lymphadenopathy. Most symptoms resolve within a week. After the symptoms have resolved it is common to get peeling on the fingers and toes. 

In Emma’s case the other symptoms that you would look for are – cervical lymphadenopathy, white tongue or strawberry tongue and a flushed face with peri-oral pallor. 

Scarlet fever is caused by the bacterium Streptococcus pyogenes (also known as group A streptococcus, or GAS). It can be found on the skin or in the throat, where it is usually unproblematic in asymptomatic carriers – 20% of children are colonized. 

However, certain virulent forms of S. pyogenes carry genes that code for streptococcal superantigens, including pyrogenic exotoxins, which can cause non-invasive infections such as scarlet fever. The typical rash is caused by the exotoxin.

They include measles, glandular fever, slapped cheek infections, other viral pathogens, Kawasaki disease, staphylococcal toxic shock syndrome, and allergic reactions.

The diagnosis is clinical. A throat swab is not routinely recommended, although during specific outbreaks Public Health England might advise this.

Streptococcal antibody tests are used to confirm previous group A streptococcal infection. They may be of value in patients with suspected acute renal failure, acute glomerulonephritis or rheumatic fever.  

Antistreptolysin O (ASO) test is the most commonly available streptococcal antibody test. ASO titres peaks 2-4 weeks after an acute infection and returns to normal over the next 6-12 months. Streptolysin O is produced by almost all strains of S. pyogenes (group A streptococci) and many group C and group G beta-haemolytic streptococci. 

Anti-deoxyribonuclease B (anti-DNase B (ADB)) titres rise after both pharyngeal and skin infections. DNase B is produced by group A streptococci and is therefore more specific than the ASO antibody test.

General guidance for patients may include advice on rest, drinking plenty of fluids, good hygiene measures to minimise the risk of cross-infection, and the use of paracetamol to reduce discomfort and high temperature.

Overall, the evidence base for the management of scarlet fever is limited, and there is a need for more evidence of the benefits and harms of antibiotics.

Public Health England, NICE and the Department of Health in Western Australia recommend treating people with scarlet fever with antibiotics regardless of severity of illness to speed recovery, to reduce the length of time the infection is contagious, and to reduce the risk of complications.

Recommended antibiotic therapy is Penicillin V QDS x 10/7 or azithromycin OD x 5/7 if penicillin allergic. 

Complications of Scarlet Fever are much the same as complications of strep tonsillitis. They are divided into suppurative, and nonsuppurative.

Suppurative complications occur due to the infection spreading and include otitis media; mastoiditis; sinusitis; peritonsillar abscess; meningitis; endocarditis; retropharyngeal abscess; and invasive group A strep (IGAS).

Non-suppurative complications occur later and occur mainly in untreated patients. They are rheumatic fever and post-strep glomerulonephritis.

IGAS is not common in children, but those at increased risk are children with co-morbidities, immunocompromised children, and those with co-existing chickenpox.

(DFTB – Exclusion period for infections)

Children should be excluded from school until they have had 24 hours of antibiotics.

Check if you need to contact the public health authorities – scarlet fever is a notifiable disease in many jurisdictions e.g. England, Wales, Northern Ireland and Western Australia. 

(Based on Life in the Fast Lane case – LITFL – Kawasaki Disease)

Alex, a 4 year-old boy has been brought to the emergency department by his worried parents. He has had fevers for the past 6 days. They are concerned because he is not getting better despite repeated visits to a number of doctors. Each time they were told he had a viral illness.

On examination you note the presence of bilateral conjunctivitis, and erythematous rash on his torso and limbs, a 4 cm tender left-sided cervical lymph node and a diffusely red pharynx.

What is the most likely diagnosis?

How is the diagnosis made?

Who gets this condition?

What are the important differential diagnosis?

What investigations should be performed?

What complications may occur?

What specific treatment is required?

Discussion point – Incomplete Kawasaki Disease: Another child, Sarah, attends the ED with 6 days of fever. On exam you find a strawberry tongue and cervical lymphadenopathy >1.5cm. No other signs of Kawasaki disease are present. What might you consider?

Discussion point – Is there a roll for steroids in Kawasaki disease?

Kawasaki disease, also known as Mucocutaneous Lymph Node Syndrome, this vasculitic disorder was first described by Dr. Tomisaku Kawaski in 1967. It is of uncertain etiology, but may be a post-infectious condition.

The diagnosis is made on the basis of the following clinical criteria (A + B):

A.Fever ≥5 days
B.At least 4 of the 5 following physical examination findings:
1.Bilateral, nonexudative bulbar conjunctival injectionbilateral scleral injection with peri-limbic sparing
2.Oropharyngeal mucous membrane changespharyngeal erythema, red/cracked lips, and a strawberry tongue
3.Cervical lymphadenopathywith at least one node >1.5 cm in diameter
4.Peripheral extremity changesacute phase: diffuse erythema and swelling of the hands and feetconvalescent phase: periungual desquamation (weeks 2 to 3)The diffuse palmar erythema seen in KD is in contrast to the discrete macular lesions of various viral illnesses (e.g., measles) that can sometimes be seen on the palms and soles.
5.A polymorphous generalized rashNon-vesicular and non-bullousThere is no specific rash that is pathognomonic for KD

The manifestations may appear sequentially rather than concurrently. Atypical cases may not meet all the criteria but may still have the same risks of cardiac complications. These 

‘incomplete’ cases occur more often in infants less than 6 months-old — further investigations (see Q5) should be performed if fever of 5 days and 2 or 3 of the other criteria are present.

Kawasaki disease may occur in any child of any age, and even adults in some cases. However, it is more common in:

  • children aged < 5 years
  • child of Asian descent
  • males (RR 1.5)

Diagnosis may be difficult as Kawasaki disease may mimic a number of other conditions:

  • Viral exanthemas including measles
  • Streptococcal disease (e.g. scarlet fever, toxic shock syndrome)
  • Staphylococcal disease (e.g. scalded skin syndrome, toxic shock syndrome)
  • Bilateral cervical lymphadenitis
  • Leptospirosis and rickettsial diseases
  • Stevens-Johnson syndrome and Toxic Epidermal Necrolysis
  • Drug reactions including mercury hypersensitivity reaction
  • Juvenile Chronic Arthritis

Echocardiography —
this is the most important investigation to assess for cardiac complications.
If no abnormalities on presentation the study should be repeated in 4-6 weeks.

Laboratory tests
Rule out other causes:
— ASOT, AntiDNAse B, throat swabs, blood cultures
Non-specific findings seen in Kawasaki disease include:
— FBC: normochromic anaemia and leucocytosis; thrombocytosis (in the 2nd week)
— LFT changes and hypoalbuminemia
— increased CRP and ESR
— Sterile pyuria of ≥10 WBCs per high-power field

Cardiac complications:

  • Carditis during the febrile phase
    — myocarditis with ST-T changes (25%), pericardial effusions (20-40%), valvular dysfunction (1-2%) and cardiac failure (~5%)
  • Coronary vessel abnormalities (occur in 20% of cases if untreated and <5% if treated; peaks at 2-4 weeks)
    — aneurysm formation may lead to fatalities from thrombosis, rupture or ischemia-related dysrhythmia (usually within 6 weeks of onset, but may occur many years later.

Kawasaki disease is a vasculitis that can potentially affect almost any organ, it is commonly associated with:

  • arthritis
  • keratitis and uveitis
  • diarrhoea, vomiting and gallbladder disease
  • coryza and cough

IV immunoglobulin and aspirin

IV immunoglobulin

  • 2g/kg IV over 10 hours
  • ideally start within 10 days of the onset of the illness
  • a second dose may be given if fevers persist

Aspirin

  • 3-5 mg/kg PO daily for 6-8 weeks
    (when laboratory parameters have fully normalised)
  • some advise higher doses of aspirin until the patient is afebrile or 48-72 hours, but others argue this offers no benefit in addition to treatment with IV immunoglobulin.

Despite these therapies 2-4% of cases still go on to develop coronary artery abnormalities. Corticosteroids may be considered in refractory cases, although there is little evidence supporting their use.

Another child, Sarah, attends the ED with 6 days of fever. On exam you find a strawberry tongue and cervical lymphadenopathy >1.5cm. No other signs of Kawasaki disease are present. What might you consider?

Incomplete Kawasaki disease

DFTB – Kawasaki Disease

Very easily missed
Makes up 15-20% of all cases
Patients with incomplete KD, particularly those <6 months of age and older children, may experience significant delays in diagnosis and these children are at high risk of developing coronary artery abnormalities.

Consider KD if:

  • Infants <6 months old with prolonged fever and irritability
  • Infants with prolonged fever and unexplained aseptic meningitis
  • Infants or children with prolonged fever and unexplained or culture-negative shock
  • Infants or children with prolonged fever and cervical lymphadenitis unresponsive to antibiotic therapy
  • Infants or children with prolonged fever and retropharyngeal oroparapharyngeal phlegmon unresponsive to antibiotic therapy

Fever and pyuria in an infant or young child may be diagnosed as a urinary tract infection, with subsequent development of rash, red eyes, and red lips attributed to an antibiotic reaction. Irritability and a culture-negative pleocytosis of the cerebrospinal fluid in an infant with prolonged fever suggestive of aseptic meningitis (or if antibiotics have been given, partially treated meningitis) may cause a diagnosis of KD to be overlooked. Cervical lymphadenitis as the primary clinical manifestation can be misdiagnosed as having bacterial adenitis. Gastrointestinal symptoms are considered for surgical causes, other physical findings of KD can be overlooked.

Toxin-mediated illnesses, such as group A streptococcus infections (e.g. toxic shock syndrome and scarlet fever) can also present with fever, rash, mucous membrane involvement and abnormal extremity findings. Desquamation in Kawasaki disease tends to affect the hands and feet as it does in scarlet fever and toxic shock syndrome; however, in Kawasaki disease, it usually begins in the periungual region. In scarlet fever, the desquamation tends to be diffuse and flaking, whereas in Kawasaki disease it tends to be sheet-like.

BMJ – Kawasaki disease

Children with measles and Kawasaki disease tend to be very irritable and inconsolable. It can be difficult securing the diagnosis of Kawasaki disease as the clinical features may appear sequentially rather than at the same time. In Kawasaki disease there may be presence of erythema and induration at the BCG immunisation site as there is cross reactivity between the heat-shock protein and the T-cells of patients with Kawasaki disease. 

The temperature in measles may exceed 40°C but tends to fall after day 5 of the illness. Koplik spots are not seen in Kawasaki disease and the morbilliform rash of measles begins from the ears and hairline and starts to fade by day 4; after day 7 brownish staining may be seen due to capillary haemorrhage. Desquamation in severely affected cases of measles can occur but is not seen in the hands and feet. In measles, clinical improvement typically begins within 2 days of appearance of the rash.

This table can help distinguish between differentials:

(Cochrane – Using steroids to treat Kawasaki disease)

A Cochrane review published January 2017 concluded “steroids appear to reduce the risk of heart problems after Kawasaki disease without causing any important side effects. They also reduce the length of symptoms (fever and rash), length of hospital stay, and blood markers associated with being unwell. Certain groups, including those based in Asia, those with higher risk scores, and those receiving longer steroid treatment, may have greater benefit from steroid use, especially with decreasing rates of heart problems, but more tests are needed to answer these questions”.

What disease is associated with dermatitis herpetiformis?

A: Herpes

B: Coeliac disease

C: Atopic dermatitis

D: Melanoma

The correct answer is B.

In coeliac disease, there are IgA antibodies against gluten that cross-react with reticulin fibres that anchor the basement membrane to the dermis. Thus, IgA is deposited at the tips of dermal papillae, presenting as grouped pruritic vesicles, papules or bullae. Usually found on elbows.

What is the most common causative agent of erythema multiforme?

A: Penicillin and sulphonamides

B: Systemic lupus erythematosus

C: HSV infection

D: Malignancy

The correct answer is C.

HSV is the most common etiologic agent of EM, which presents as a targetoid rash and bullae. All the other options are also associated with the disorder, but less commonly.

What disorder is characterised by an initial ‘herald patch’ which is then followed by scaly erythematous plaques usually in a ‘Christmas tree’ distribution?

A:    Pityriasis rosea

B:    Herpes

C:    Varicella zoster virus

D:   Erysipelas

The correct answer is A.

Pityriasis rosea classically presents with a salmon coloured solitary patch ‘herald patch’ which enlarges over a few days followed by generalised bilateral and symmetric macules with collarette scale. Pruritus is sometimes present. It itself resolves within 6 – 8 weeks.

What is the infective agent implicated in acne? 

A: Staphylococcus aureus

B: Streptococcus pyogenes

C: Staphylococcus epidermidis

D: Propionibacterium acnes

The correct answer is D.

Propionibacterium acnes infection produces lipases resulting in inflammation and breakdown of sebum, leading to pustule formation.

Which of the following statements about the treatment of measles is correct?

A: No specific antiviral therapy is recommend for immunocompetent patients 

B: Prevention of spread of measles depends on prompt immunization of people at risk of exposure or people already exposed who cannot provide documentation of measles immunity

C: Recommend supportive care with antipyretics, fluids and rest

D: All of the above

The correct answer is D.



Please download our Facilitator and Learner guides

Seizures Module

Cite this article as:
Peter Tormey. Seizures Module, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27858
TopicSeizures
AuthorPeter Tormey
DurationUp to 2 hours
Equipment requiredNone

Basics (10 mins)

Main session: (2 x 15 minute) case discussions covering the key points and evidence

Advanced session: (2 x 20 minutes) case discussions covering grey areas, diagnostic dilemmas; advanced management and escalation

Quiz (10 mins)

Infographic sharing (5 mins): 5 take home learning points

We also recommend sharing a copy of your local guideline.

Unprovoked seizures are common in children with around 8% having a seizure by 15 years of age

  • Most seizures are brief, self-limiting and generally cease within 5 minutes
  • Convulsive status epilepticus is the most common paediatric neurological emergency worldwide and the 2nd most common reason for PICU admission in the UK.
  • A seizure is the clinical expression of abnormal, excessive, synchronous discharges of neurons residing primarily in the cerebral cortex

Was the seizure a primary event or secondary to something else?

Seizures can be due to an underlying epilepsy or can be acute symptomatic seizures due to:

  • Hyponatraemia
  • Hypoglycaemia
  • Hypocalcaemia
  • High fever
  • Toxin exposure
  • Intracranial bleeding
  • Meningitis

Was this really a seizure or should I consider other differentials?

Tonic clonic activity and incontinence are not specific for seizures so always consider differential diagnoses.

  • Differential diagnosis of a seizure:
    • Vasovagal syncope
    • Blue breath holding spell
    • Reflex anoxic seizure
    • Arrhythmia
    • Non-epileptic paroxysmal event

Seek out clues in the history:

A sudden fright or minor trauma followed by the child turning pale and seizing is suggestive of a reflex anoxic event secondary to a vagal reflex. Hypoxia can induce a short tonic-clonic event that looks like a generalized tonic-clonic seizure but the child will recover quickly.

A history of a temper tantrum crescendo-ing into the child holding their breath, turning blue and then seizing might make you think of a breath holding attack. Again, this child will recover quickly.

Standing in a hot, stuffy room, feeling lightheaded with some visual changes and echoey hearing sounds vasovagal. Compare this to a child who describes palpitations or is exercising before the event; this child could have had an arrhythmia.

A 7-year-old boy called Simon is brought to the ED by his parents. At approximately 7am they were awoken by noises coming from his room. They ran in and noticed that the left side of his face was jerking and he was drooling and making gurgling sounds. He wasn’t responding to them.

The movements stopped after 2 minutes. He was drowsy for a few minutes after and had difficulty talking and expressing himself for 15-20minutes after. They also noticed there was a slight drooping on one side of his mouth for 15-20 minutes.

He has now fully recovered and is bright and alert in ED with GCS 15/15 and a normal neurological exam.

What are some of the key elements of Simon’s past medical history that you must ascertain?

How would you classify his seizure? 

Are there clues in the history as to what specific seizure disorder he may have?

Would you perform any investigations at this point?

Does he need to be admitted? Does he need treatment? What follow up will you arrange?

Any history of hypoxic injury at birth?

Did he have any delay in meeting his developmental milestones?

How does his school performance compare to that of his peers?

Is there any history of similar events? Or unusual behaviours or word-finding difficulties on waking from sleep?

The key here is to determine if Simon is an otherwise well child or if there are details in his medical history, such as developmental delay, that may make him more prone to developing epilepsy

It is also important to determine if he perhaps has had more subtle seizures in the past that may have been missed

This is an opportunity to look at the International League Against Epilepsy infographic.

Simon has had a focal motor seizure with impaired awareness.

Specific seizure disorder: Simon’s seizure would be most in keeping with a clinical diagnosis of benign childhood epilepsy with centrotemporal spikes (BCETS) also known as benign rolandic epilepsy.

BCETS usually presents in early school age children with normal development. The most common seizure type is a focal motor seizure involving the face. There may or may not be impaired awareness. They can also be associated with facial numbness, hypersalivation, drooling, dysphasia and speech arrest. Motor activity in the upper, but not lower, limbs is common.  They may also progress to a generalized tonic-clonic seizure. Approximately 75% of seizures occur at night or on awakening and, therefore, can be easily missed. Patients may have a post-ictal paresis, often of one side of the face which can be concerning for a cerebrovascular accident. 


A blood glucose should be checked. 

Electrolytes are often checked with a first seizure but their utility decreases with patient age and degree of recovery. 5

As this history is strongly in keeping with a diagnosis of BCETS, an EEG is not strictly necessary to confirm the diagnosis, however, your local guideline for first seizure management should be followed.

There is no indication for neuroimaging at present.

Patients generally do not need to be admitted after a first seizure with no red flags:

  • Seizure related to head injury
  • Developmental delay or regression
  • Headache prior to seizure   
  • Bleeding disorder or on anticoagulant medication
  • Drug or alcohol use
  • Focal neurological signs or incomplete recovery
  • Seizure >5 minutes
  • Social concerns e.g. parental coping mechanisms or concerns over parental ability to recognize and seek medical attention if another seizure were to occur

Patients with an uncomplicated first seizure generally do not need to be commenced on treatment. BCETS in particular generally has a benign course and rarely requires treatment. 

All children who have a first seizure episode should be referred for paediatric follow up. This may be General Paediatric or Paediatric Neurology follow up and local referral pathways should be consulted. 

The International League Against Epilepsy have a useful infographic for managing a first seizure:

https://www.ilae.org/patient-care/first-seizure

For more information on managing a 1st afebrile seizure see: 

https://dontforgetthebubbles.com/first-afebrile-seizure/

Emily is a 4-year-old girl brought to ED with episodes of disturbed sleep for the last 3 weeks. This is her 4th visit to ED. She was previously diagnosed with “night terrors” and reassured. Her mum is concerned because the episodes are now occurring each night, having previously been 1-2 per week.

Her mum has videos of the episodes, which she shows you. The events usually occur shortly after going asleep. In the videos Emily wakes from sleep, looks terrified and stares straight ahead. The episodes go on for 2-3minutes. She usually vomits or retches towards the end of the episode. She goes back to sleep after. She is well during the day.

What could be going on here?

What interesting details in the history might lead you towards a specific diagnosis?

What could help differentiate between epileptic and non-epileptic events in this case?

What is the prognosis for these patients?

These episodes sound unusual and their frequency and severity seems more pronounced that what could be put down to normal variance in sleep pattern and arousal. Emily’s symptoms are not likely to be simple night terrors.

Seizures commonly occur in sleep and as a result can be missed or present subtly or without characteristic features.

There are several features in the history that would suggest Panayiotopoulous Syndrome (PS). 

PS is a focal epilepsy that occurs in children aged 1-14 years with a mean age of 5 years. The seizures are usually nocturnal

It is thought PS accounts for 6% of children with epilepsy.

There is a strong association with vomiting (70-85%) of patients. Visual symptoms are also closely related, given the seizures originate in the occipital lobe. Autonomic features can also be seen: pallor, tachycardia, miosis, coughing and hypersalivation.

They may also have head or eye deviation and focal or generalized clonic activity.

The diagnosis of PS is often delayed due to misdiagnosis with other causes of vomiting and autonomic manifestatons e.g encephalitis, migraine, syncope or gastroenteritis.

PS could easily be clinically misdiagnosed as night terrors. Night terrors are dramatic awakenings that usually happen during the first few hours of sleep. They share several characteristics with PS but there are also some subtle differences highlighted in the table below:

Clinical FeaturePSNight Terrors
Usual duration 5-10min++
Occur during the first few hours of sleep++
Autonomic Symptoms e.g tachycardia, tachypnea, sweating+++
Impaired awareness++
Child looks scared++
Starring+++
Running or walking around during episode++
Screaming++
Vomiting++
Thrashing of arms and legs++

Table 1. Clinical characteristics of PS and night terrors

It is not unreasonable to clinically diagnose night terrors if they present with characteristic events, more in keeping with night terrors than PS. However, if there are unusual features, such as vomiting, or exaggerated autonomic symptoms, or in a child who represents, then an alternative diagnosis should be considered. 

An inter-ictal EEG will usually be diagnostic in PS with occipital spikes, which are enhanced in sleep, the characteristic feature. In a child with unusual events occurring in sleep and a normal EEG, a video telemetry EEG may be useful to try and capture and characterise the events and outrule seizures as a possibility.

PS usually has a benign course with spontaneous remission commonly occurring within 2-3 years of onset. 

Seizures are generally infrequent but oxcarbazepine may be required to reduce seizure frequency.

Emma is a 3-year-old girl with a background of refractory epilepsy and developmental delay. Her current medications include levetiracetam, sodium valproate, clobazam and lamotrigine.

She is PEG fed but has been vomiting up her feeds for the last 2 days and mum is unsure if her medications have been staying down.

She normally has up to 20 short seizures per day at home, but this has been increasing in the last 2 days.

You get a pre-alert from the ambulance service: Emma has been having a generalised tonic clonic seizure for 15 minutes. Her mum gave her buccal midazolam at 5 minutes, but it has not had any effect.

The ambulance crew ask you can they repeat the dose of buccal midazolam?

Emma arrives in resus with the seizure ongoing. What is your management plan?

Emma has had two doses of benzodiazepines. What would be your next line agent? Who else should you be calling at this stage?

You decide to suggest 2 papers, the ConSEPT and EcLiPSE papers for your department’s next journal club and to discuss what effect they will have on your department’s practice. One issue you foresee is that a lot of the patients you see are already on maintenance levetiracetam.

Does this preclude children on maintenance levetiracetam from receiving IV levetiracetam in status epilepticus, as is the case with the use of phenytoin in patients who take it as maintenance treatment?

Emma’s seizure terminated with the second line agent and she was admitted under neurology for IV fluids and ongoing management of her seizures until she could tolerate her medications by PEG again. In this case her status epilepticus was likely due to her vomiting up her medications.

Had Emma’s seizure not stopped after the loading dose of phenytoin, what would your next steps be?

There is a risk of respiratory depression with any benzodiazepine. 

A Cochrane review9 in 2018 found that 25/346 (7.2%) patients treated with buccal midazolam experienced respiratory depression. There was no statistically significant difference in risk of respiratory depression between buccal midazolam and other benzodiazepines, administered via various routes. 

The drug information leaflet or Summary of Product Characteristics (SPC) for Buccolam® and Epistatus® recommend that only a single dose be administered at home by a caregiver and that additional doses should only be administered after seeking medical advice and, preferably, under medical supervision.

In this case, it would be reasonable to advise a second dose of buccal midazolam, presuming the paramedics had the necessary equipment and skillset to manage any respiratory depression that may occur. 

Factors that may influence your decision are: the ETA of the ambulance and if the child has a history of respiratory depression with benzodiazepines.

She should be managed as per the APLS guideline (please note this is the Australian APLS guideline and has been updated to include the use of levetiracetam as a second line agent. This has not yet been included in the UK APLS guideline, see discussion below):

At this point you should be informing PICU about the patient and your PEM consultant if you haven’t done so already.

The CONCEPT and ECLIPSE trials were published concurrently in May 2019.

These two studies looked at whether levetiracetam is non-inferior to phenytoin as a second line treatment in the management of convulsive status epilepticus in children.

This question was posed as phenytoin is linked to many adverse events including liver damage, Steven-Johnson syndrome, extravasation and reports of death due to dosing errors. As a result, and because of its biopharmacology, it is a resource-intensive drug to make up in an emergency.

Levetiracetam can be given over 5 minutes (phenytoin takes 20 minutes to infuse), is more compatible with IV fluids, has less drug interactions, and has a lower risk of adverse events.

The infographic below provides a nice summary:

You can find a more detailed summary at: https://dontforgetthebubbles.com/consept-eclipse-status-epilepticus/

It’s important to note that the primary outcomes of the two studies were different:

ConSEPT – The primary outcome was seizure cessation 5 minutes after the drug infusion and where possible the seizure cessation was verified independently via a video recording to reduce observer bias between the two groups.

EcLiPSE – In a key difference to the ConSEPT study the primary outcome was time “from randomisation to cessation of all visible signs of convulsive activity, defined as cessation of all continuous rhythmic clonic activity, as judged by the treating clinician”. As per the inclusion criteria this a very real world pragmatic approach.

The two studies concluded:

ConSEPT – Levetiracetam is not superior to phenytoin as a second line agent for convulsive status epilepticus

EcLiPSE – There is no significant difference between phenytoin and levetiracetam in the second-line treatment of paediatric convulsive status epilepticus for any outcome, including time to seizure cessation

Here is a section of the commentary from the post:

“While there were differences between the study designs, the primary outcome measure of timing being the largest, the fact that both studies found no difference probably means head-to-head there is little difference.

The nature of the statistical analysis means that both groups rightly point out that in their cohorts levetiracetam wasn’t superior in outcomes to phenytoin. A future pooled analysis could still demonstrate a difference, but it seems unlikely that a critical difference will be seen (especially for the safety element).

Given the wealth of evidence on the side effects of phenytoin it is surprising the incident rates were relatively low. Whether in study conditions more care was taken with drawing up and delivering the drug or that previous safety reviews were heterogenous in their inclusion criteria is difficult to know. However, the time to draw up phenytoin, and the background concerns on its potential harm, will lead some to suggest that the switch to levetiracetam is a logical one, regardless of its effectiveness against phenytoin.

The challenge faced by many units is a capacity for PICU beds. Because phenytoin is given over 20 minutes there is time to prepare for airway/anaesthetic intervention if it is unsuccessful in terminating the seizure. The use of levetiracetam may cause some to wonder if they should then try phenytoin either as a stop gap to bed availability or because the time in status now seems ‘shorter’ than normal. These are not statistical issues, these are pragmatic clinical conundrums.

The absence of a clear winner will further fuel this debate meaning it is unlikely in the immediate future we are going to see a change from the ALSG or similar organisations. However, local units may decide, in the clear absence of harm from levetiracetam, that it is a drug they should be adding into their treatment protocols.”

The EcLiPSE trial2 did not report any increase in adverse events in children who were on maintenance leveltiracetam and received a loading dose of IV levetiracetam. The ConSEPT trial excluded all patients who were on maintenance levetiracetam and phenytoin.

The use of phenytoin in status epilepticus in patients who are on maintenance phenytoin is avoided due to its potential cardiovascular side effects. As levetiracetam does not share these side effects and is generally safe and well tolerated it is reasonable to use it in children who are already on maintenance therapy. 

The EcLiPSE trial2 did not report any increase in adverse events in children who were on maintenance leveltiracetam and received a loading dose of IV levetiracetam. The ConSEPT trial excluded all patients who were on maintenance levetiracetam and phenytoin.

The use of phenytoin in status epilepticus in patients who are on maintenance phenytoin is avoided due to its potential cardiovascular side effects. As levetiracetam does not share these side effects and is generally safe and well tolerated it is reasonable to use it in children who are already on maintenance therapy. 

The current APLS guidance in the UK would be to proceed with RSI. As we have discussed above, the Australian APLS guidelines have changed, in view of the results of the ConSEPT and EcLiPSE, to include the use of an additional second line agent prior to proceeding to RSI. As reported in the ConSEPT trial, treatment with one drug and then the other reduced the failure rate by more than 50% at the expense of only an additional 10 minutes. 

For further discussions on advanced seizure management and RSI, the following podcast is recommended:

https://broomedocs.com/2019/06/paediatric-status-epilepticus-debate/

Caroline is a 13-year old girl who presents to ED with a first seizure. Her parents describe a generalised tonic clonic seizure that lasted 20 minutes.

She is an otherwise well girl who is doing well in school. The only concern in her past medical history is that she has been having frequent syncopal episodes for the last 12 months. She has been seen by her GP for this who reassured her that syncopal events were common on her age group and advised her to drink plenty of fluids and try and avoid triggers.

Her neurological exam is normal.

How would you proceed? 

Are there any investigations you could perform in the department to investigate the syncopal episodes she reports?

Is there any link between syncope or arrhythmogenic events and seizures?

Caroline is admitted for further cardiac investigations. She also has an EEG diagnostic for frontal lobe epilepsy which is linkced to ion channel abnormalities.

A blood glucose should be checked. If she has returned to her baseline and there were no red flags with regard to the seizure it would be reasonable to arrange outpatient follow up as per departmental protocol and advise her parents what to do if she should have further seizures.

An ECG and a lying-standing blood pressure should be performed.

Caroline has an ECG performed which has features consistent with Type 1 Brugada syndrome.

Seizures may be triggered by cerebral hypoperfusion due to an arrhythmic event. They can often be treated as a primary seizure and the underlying cardiac abnormality may be missed. Long QT syndrome in particular can present with seizures and almost half of affected patients are initially misdiagnosed and treated for epilepsy before the correct diagnosis is made.

Seizures can also be seen as a primary neurological abnormality, related to the cardiac abnormality. Brugada Syndrome is an autosomal dominant condition characterized by ECG alterations and a predisposition to tachyarrhythmias and sudden death. It is caused by a mutation in the genes SCNA5 and SCN1A. SCN5A codes for the alpha subunit of the voltage-gated sodium channel. As the condition is a channelopathy it can also be associated with epileptic seizures with the channelopathy affecting neuronal pathways. 

Caroline has a ECG which is consistent with features of Type 1 Brugada Syndrome.

There is coved ST segment elevation in V1 and V2 with a negative T wave. This is the only ECG abnormality that is potentially diagnostic and is often referred to as Brugada sign.

For an approach to the paediatric ECG have a look at the following DFTB post:

https://dontforgetthebubbles.com/approaching-the-paediatric-ecg/

For further reading on the specific ECG findings in Brugada Syndrome, please see:

https://litfl.com/brugada-syndrome-ecg-library/

Which symptom is more commonly seen with Panayiotopoulos syndrome than night terrors?

A: Staring

B: Terrified expression

C: Vomiting

D: Thrashing of arms and legs

E: Tachypnoea

70-85% of seizures in PS are associated with vomiting. Vomiting is not usually described in night terrors. The diagnosis of night terrors should be carefully applied to children having events disturbing their sleep that have a strong
association with vomiting.

Which of the following are side effects of phenytoin but not levetiracetam?

A: Mood disturbance

B: Cardiovascular toxicity 

C: Purple glove syndrome

D: Gingival hypertrophy

E: Stevens Johnson syndrome

The correct answers as B, C, & D

Although levetiracetam and phenytoin have several common side effects, cardiovascular toxicity, purple glove syndrome and gingival hypertrophy are more specific to phenytoin and are not generally seen with levetiracetam. Mood
disturbance is one of the most common side effects of levetiracetam. Stevens Johnson syndrome is also reported with levetiracetam.



Which of the following ECG findings are seen in Brugada syndrome:

A: Coved ST segment elevation in V1-3, >2mm

B: Prolonged PR interval

C: Negative T wave

D: Saddleback ST elevation, >2mm

E: LVH voltage criteria

The correct answers are A, C, & D

  • Brugada Type 1 has coved ST segment elevation in V1-3, >2mm, followed by a negative T wave. This is often referred to as Brugada sign.
  • Brugada Type 2 has >2mm of saddleback-shaped ST elevation
  • Brugada Type 3 can have the morphology of type 1 or 2 but with <2mm ST segment
  • elevation
  • Prolonged PR interval and LVH voltage criteria are not characteristic features of Brugada syndrome

1. Clinical Practice Guidelines : Afebrile seizures [Internet]. [cited 2020 Apr 20]. Available from: https://www.rch.org.au/clinicalguide/guideline_index/Afebrile_seizures/

2. Lyttle MD, Rainford NEA, Gamble C, Messahel S, Humphreys A, Hickey H, et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet. 2019 May 25;393(10186):2125–34

3. https://www.uptodate.com/contents/seizures-and-epilepsy-in-children-classification-etiology-and-clinical-features?search=seizures%20in%20children&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

4. https://www.ilae.org/education/infographics

5. https://dontforgetthebubbles.com/first-afebrile-seizure/

6. Michael M, Tsatsou K, Ferrie CD. Panayiotopoulos syndrome: An important childhood autonomic epilepsy to be differentiated from occipital epilepsy and acute non-epileptic disorders. Vol. 32, Brain and Development. Elsevier; 2010. p. 4–9.

7. Ferrie CD, Grünewald RA. Panayiotopoulos syndrome: A common and benign childhood epilepsy. Vol. 357, Lancet. Elsevier Limited; 2001. p. 821–3.

8. Weir E, Gibbs J, Appleton R. Panayiotopoulos syndrome and benign partial epilepsy with centro-temporal spikes: A comparative incidence study. 2018 [cited 2020 May 4]; Available from https://doi.org/10.1016/j.seizure.2018.03.002

9. Mctague A, Martland T, Appleton R. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Vol. 2018, Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd; 2018.

10. Dalziel SR, Borland ML, Furyk J, Bonisch M, Neutze J, Donath S, et al. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial. Lancet. 2019 May 25;393(10186):2135–45.

11. Sandorfi G, Clemens B, Csanadi Z. Electrical storm in the brain and in the heart: Epilepsy and Brugada syndrome. Mayo Clin Proc. 2013 Oct 1;88(10):1167–73.

12. Camacho Velásquez JL, Rivero Sanz E, Velazquez Benito A, Mauri Llerda JA. Epilepsy and Brugada syndrome. Neurol (English Ed. 2017 Jan 1;32(1):58–60.



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Wound Management Module

Cite this article as:
Orla Kelly. Wound Management Module, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27753
TopicWound management
AuthorOrla Kelly
DurationUp to 2 hours
Equipment requiredSkin glue, paper stitches (Steristrips), suture set, sutures, artificial skin or animal product for demonstration, sharps bins
  • Basics (10 mins)
  • Main session: (4 x 15 minute) case discussions covering the key points and evidence
  • Practical stations (30-60 mins)
  • Infographic sharing (5 mins): 5 take home learning points

We also recommend sharing a copy of your local guideline.

The skin is made of three layers: epidermis, dermis and subcutaneous layer. It has many functions including as a barrier to infection and regulation of homeostasis. Wounds in both paediatric and adult populations require similar assessment – haemorrhage control, assessment for underlying structural damage, infection potential and (lastly) scarring.

Highlight the importance of a full thorough examination. Wounds (particularly ones that are bleeding on presentation) have the tendency to be distracting. A full head to toe examination with a careful history taking is essential.

History

The mechanism of injury is the most important determinant of management. A crush injury to a finger will have decidely different outcomes than an incisional wound from a knife.

Crush injury: Is an xray required? A missed open fracture is unacceptable. Where did it occur? Is there potential for a foreign body?

Incisional wound: From what? Knife edge or glass? If glass, an xray is warranted. Risk of damage to underlying nerves tendons and vessels is high, consider the need to refer to local speciality surgical team.

Road rash: These must be cleaned out thoroughly to avoid tattooing. They can often cover large surface area so sedation may be required.

Puncture wound: Again, from what instrument? Is there potential for retained foreign body? Location is important, puncture wounds to the palmar surface of hand or finger runs the risk of infection, particularly flexor tenosynovitis.

Bite wounds: These require thorough washout and antibiotic cover and are not suitable for closure in the ED. Consultation with speciality surgical services is advised, often healing by secondary intention is more appropriate to avoid sealing in deep seated infection.

A 12 year old girl is brought into ED by her mum. As she was making lunch at home, the ring came off a ring-pull can, so she tried to pull open the lid of the can by grasping and pulling the sharp edges. She arrives with a blood soaked tea towel around her hand and is tearful. On examination she has wounds to her thumb, index and middle fingers of her right hand.

What structures require assessment in a wound?

How do you assess neurovascular function in hand injuries?

How do you assess the function of the flexor and extensor tendons?

A strong knowledge of anatomy is essential in the assessment of a wound; its location will indicate the possible structures that may be damaged. For example, on the face, be particularly mindful of the facial nerve, parotid gland and lacrimal ducts.

In the fingers, assessment of radial and ulnar digital nerves and arteries, superficial and deep flexors and extensor tendon is necessary and must be documented.  Don’t forget that tendons move; looking into a wound and seeing an intact tendon does not exclude a tendon injury. Wounds to hands and forearms must be carefully assessed, and if there is any possibility of damage to these structures, plastic surgery referral is recommended.

Another important factor of location is the likelihood of tension across the wound or articulation with a joint. The possiblity of an open joint means referral to orthopaedics for washout.

This is an opportunity to reference some learning from the RCEM learning soft-tissue injuries of the hand post.

The anterior interosseous nerve is a branch of the median nerve and has purely motor function. It innervates flexor pollicis longus, pronator quadratus and the radial half of the flexor digitorum profundus. The ‘OK’ sign tests it: if the O shape is pincer-shaped, rather than O shaped, with extension at the thumb IPJ and index DIPJ, it is abnormal.

The median nerve innervates the LOAF muscles (all of the thumb muscles except adductor pollicis). Although children are often asked to make a fist (the ‘rock’ of rock paper scissors), this also tests the ulnar nerve. To test for the median nerve alone, ask the child to oppose their thumb by touching it to the little finger against resistance.

The ulnar nerve innervates adductor pollicis, the lumbricals, palmar and dorsal interossei. The ‘scissors’ test (finger abduction) tests the dorsal interossei – test by abducting fingers against resistance.

Assess flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS) function, if there is a wound on the volar (palmar) surface of the hand or finger. Remember ‘P’ for point –FDP is assessed at the distal IPJ.

  • To check FDS function, hold all adjacent fingers in extension and then release the finger you want to assess. Ask the child to flex the free digit at the PIP joint, against resistance. A normal intact FDS can be flexed at the PIP joint on the unrestricted finger.
  • To examine the FDP, hold the middle phalanx in extension and ask the child to flex the DIP joint. A normal intact FDP is indicated by flexion at the DIP joint.

The extensor tendons are assessed by asking the child to extend their finger against resistance.

To test the Extensor Pollicis Longus (EPL), ask the patient to place their hand flat on a table and lift up their thumb against resistance.In young or uncooperative children, looking for normal wrist tenodesis can give clues about whether the flexor and extensor tendons are intact or not. Check out the DFTB finger injuries post for examination pearls.

A 4 year old boy is brought to the ED by his parents. He was playing with his brother in the garden when he tripped and hit his head off the curb. He did not lose consciousness and has not vomited. On examination there is a 6cm horizontal wound with jagged edges and visible contamination on his left forehead.

What techniques can you employ to ensure the child cooperates with assessment of his wound? Discuss non-pharmacological as well as pharmacological.

In order to fully clean, explore and close a wound, the patient must be comfortable.

Distraction techniques such as smart phones, books, bubbles should all be employed. If you are lucky enough to have a play specialist in your department then they should be used as soon as possible!

Topical anaesthetic such as LAT gel is wonderful for anaesthetising wounds, and the adrenaline in it blanches surrounding skin helpfully letting you know when it’s ready. If further anaesthesia is required, local anaesthetic (for example 1% lidocaine) can be used. A few tips to avoid the pain associated with injection: to inject it through the wound edges and not through surrounding intact skin, use a small needle (insulin syringe if only a small amount is needed), buffer it with bicarbonate to raise the pH, and to make sure it’s at room temperature.

If after all the armoury has been depleted, then the patient may need to be sedated, in which case a senior doctor should be involved, local guidelines followed, and consider referral for GA if appropriate.

 Have a look at the DFTB procedural sedation post or watch Deb Shellshear’s procedural sedation talk from DFTB17.

An 8 year old girl is brought to the department by her Dad. She was cycling in front of the house when she fell off her bike. She has a large area of road rash to her left forearm and left knee. It is visibly contaminated with gravel, dirt and plant material.

How will you ensure this wound is cleaned adequately?

How would your management change if the wound was deemed to be very dirty?

What closure options are available to you?

Washout

The mainstay of treatment of wounds is cleaning. Thorough washout with normal saline is recommended for all wounds. Scrubbing with a sponge or soft brush is essential for road rash to avoid tattooing and infection. For other wounds a cannula (without needle) can be fitted to the top of a 20 ml syringe and used to create a type of pressure wash. A polystyrene cup can be placed around the syringe to create a type of splash guard. All debris and underlying haematoma must be removed, if that’s not possible then formal washout in theatre is necessary.

Closure

Wounds can be closed via secondary intention (ie, with no adjuncts), glue, steristrips or sutures. Superficial dermal wounds (more scratches) and puncture or bite wounds are usually more suited to secondary intention healing.

Glue is useful for small wounds (<3cm) with clean easily opposable edges and no tension. As with all wounds, washout is necessary. When the wound is clean and not bleeding, the two edges must be gently pinched together, everting the edges, and glued in place. Be careful when pinching the wound sides together to avoid creating a valley that the glue sticks in – this will widen the scar. Aslo be careful not to glue your gloves to the patient, which is quite easy to do!

Steristrips are useful for similar wounds as glue, but can be longer. Prep the wound edges with tincture of benzoin prior to application of the steris to increase adherence. Place the strip on one side of the wound, and with a ‘pinch and pull’ motion, bring the wound edges together. Leave some space between the strips to allow fluid to escape to avoid infection. If there is a chance that little fingers or drool can get at the wound, some duoderm over the wound will leave the strips impervious.Finally, if the wound is under tension or likely to reopen due to movement, then suturing is recommended – see case 4.

A 12 year old boy is brought in by ambulance after falling off his bike while swerving to avoid a car. He was wearing a helmet and thinks he did not hit his head. He has a painful right ankle and is unable to weight bear. He has a wound to his mid anterolateral shin. It is horizontal, 4cm wide and approximately 1 cm deep. He is unable to weight bear and has pinpoint tenderness at his lateral malleolus X-ray confirms a non displaced isolated distal fibular fracture.

What size suture would you like to use?

What type: absorbable or non-absorbable?

What do you need to ensure before the child leaves the ED?

Suturing is useful for wounds that will be subject to movement and tension. Suture material can be divided into absorbable and non absorbable. The benefits to absorbable sutures is the lack of removal, however they can take time to dissolve, adding to scarring. Therefore they are useful for wounds that are not cosmetically sensitive such as the scalp and wounds under casts. In this case, there is an isolated wound that needs to be closed, and a separate distal fracture (NB not an open fracture). In this case an absorbable suture,  e.g. vicryl rapide, would be most suitable as this patient is likely to be in a cast or boot for a number of weeks.

The two types of sutures that should be demonstrated in the practice stations are deep dermal and simple interrupted. Deep sutures must be absorbable such as vicryl or monocryl, dermal sutures can be absorbable such as vicryl rapide, or non absorbable like prolene or seralon.

  • ALWAYS ascertain the tetanus status of the patient and consult local guidelines.
  • Most simple wounds don’t require antibiotic cover, but particularly contaminated ones and bites certainly do. It’s likely in those situations specialist referral is necessary.
  • Open fractures require prompt referral to orthopaedics and IV antibiotics.
  • Patients and parents must be advised about the warning signs for infection.
  • With regards to scarring – parents must be informed that everyone and every wound scars differently. The main thing is the wound stays clean, infection will certainly worsen cosmetic outcomes. Post initial healing, longitudinal steristripping for a number of weeks followed by pinpoint massage has been thought to improve scarring. The wound should be covered from ultraviolet rays for up to 18 months.

 Description and demonstration of steristrips, glue, different suture materials and equipment.

 Equipment needed:

Skin glue

Prolene, monocryl, vicryl rapide sutures

Suture kit

Sharps bin

https://geekymedics.com/simple-interrupted-suture-osce-guide/

https://dontforgetthebubbles.com/tissue-adhesive/

Demonstration and practice of local anaesthetic injection and simple interrupted sutures using either fake skin or animal skin (if using animal products, ensure hygiene standards are adhered to – yellow bin for disposal of gloves and soft waste).

Equipment needed:

Gloves

Table cover (eg incontinence sheet)

Fake skin or animal skin

Sharps bin

Hazardous waste bin if using animal products

Plastic apron if using animal products

5ml syringes

Dermal needles

Saline

Suture kits

Prolene sutures – sizes 3-0 and 4-0

https://geekymedics.com/simple-interrupted-suture-osce-guide/

This is an opportunity to cover more challenging sutures such as deep dermal sutures and 3 point sutures. It uses the same equipment as Station 2.

See Corner and deep suture videos:

https://litfl.com/own-the-wound/



Please download our Facilitator and Learner guides

Pyrexia of Unknown Origin Module

Cite this article as:
Beatrice Zanetti. Pyrexia of Unknown Origin Module, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27689
TopicPyrexia of Unknown Origin
AuthorBeatrice Zanetti
DurationUp to 2 hours
Equipment requiredNone
  • Basics (10 mins)
  • Main session: (2 x 15 minute) case discussions covering the key points and evidence
  • Advanced session: (2 x 20 minutes) case discussions covering grey areas, diagnostic dilemmas; advanced management and escalation
  • Quiz (10 mins)
  • Infographic sharing (5 mins): 5 take home learning points

We also recommend printing/sharing a copy of your local guideline.

To prepare for this session, learners could read the below case report article (20 minutes): 

Wood M, Abinun M. and Foster H., Pyrexia of unknown origin. Archives of Disease in Childhood, Education and Practice, 89 ep 63-69 (2004) 

And/or look at these useful resources from the web: 

https://pedemmorsels.com/fever-of-unknown-origin/ (5 minutes)

https://dontforgetthebubbles.com/recurrent-or-periodic-fevers-investigate-or-reassure/ (10 minutes)

https://dontforgetthebubbles.com/tuberculosis/ (5 minutes)

https://dontforgetthebubbles.com/claire-nourse-tuberculosis-at-dftb17/ (20 minutes)

https://gppaedstips.blogspot.com/search/label/Juvenile%20idiopathic%20arthritis  (10 minutes)

https://www.paediatricfoam.com/?s=kawasaki (10 minutes)

The term pyrexia of unknown origin (PUO) is used when a patient has more than 8 days with fever (temperature> 38°C) without a clinical diagnosis after exhaustive investigations have been carried out (in hospital or in primary care). 

Other more specific PUOs are:

  • nosocomial PUO
  • neutropenic PUO
  • HIV-associated PUO

These 3 have specific risk factors and will not be covered in this session. 

Fever is a sign of an underlying pathology. In PUO, pyrexia is usually the main symptom while other signs may be very subtle. Many times, the underlying disease is a common pathology that is presenting in an atypical or incomplete way.  

Here are 3 main clinical dilemmas for clinicians: 

In the paediatric population, 30% of PUO will not reach a final diagnosis. However, in those cases, PUO is often a self-limited and benign episode. 

When a definitive diagnosis is reached, the majority of causes are related to infectious diseases (38%), followed by connective tissue disorders/autoimmune pathology (13%) and malignancies (6%).

At present, there is not a generic PUO work-up since this wouldn’t be efficient. Remember that more than ¼ of cases are benign and self-limited! 

In many cases, PUO is a consequence of a late diagnosis. Clinical history taking and careful physical examination are crucial to pick up subtle signs and guide the complementary tests and imaging. New signs and symptoms, which weren’t present on initial examination, can appear later on.

In the literature, retrospective studies have shown that when imaging requests are prompted by some examination finding, they are more likely to yield a positive result. 

Here’s a table with possible differential diagnosis based on clinical findings.

Diagnosis based on common clinical findings
Rash
Maculopapular -Purpuric-Erythema Nodosum-Butterfly rashEBV, Kawasaki Disease, SOJIA, Typhoid feverCMV, Endocarditis, Leukaemias, Histiocytosis, VasculitisTB, Ulcerative colitis, Crohn’s disease, Streptococcal infectionSLE, Dermatomyositis
Adenopathies
-Infections-Connective tissue disorders-Malignancies-Other causesCMV, EBV, TB, Bartonella (Cat-scratch disease)Rheumatoid Arthritis (RA)
Lymphomas, Leukaemias, HistiocytosisSarcoidosis and Primary Immunodeficiencies
Splenomegaly
-Infections
-Connective tissue disorders-Malignancies
-Other causes
TB, Bartonella, Malaria, Visceral Leishmaniasis, Endocarditis, Brucelosis, SalmonelosisSLE, RA
Lymphomas, Leukaemias, Histiocytosis, Macrophagic Activation SyndromePrimary immunodeficiencies
Arthritis
-Infections-Connective tissue disorders-Malignancies-Other causesTB, Lyme disease, Brucella, Staphylococcal InfectionSOJIA, RA, SLE, Rheumatic fever
Leukaemias

The speed of the complementary tests will depend on the general appearance of the patient. Empirical treatment with antibiotics can blur the microbiology results resulting in a delayed diagnosis. The empirical use of steroids can mask other pathologies and again delay the diagnosis. 

For the above reasons, clinicians should reserve empirical treatment with antibiotics or steroids to the sick patient based on clinical assessment.

Causes of fever of unknown origin
Infectious: Bacterial infections: Localised: Pyelonephritis, Sinusitis, Mastoiditis, Pneumonia/pleural effusion, Osteomyelitis, Endocarditis, Intravenous catheter infectionAbscesses (intracranial, dental, intestinal, hepatic, pelvic…)
Systemic infections: Tuberculosis, Brucellosis, Bartonella (cat-scratch disease), Leptospirosis, Q fever (Coxiella), Lyme disease, Salmonellosis (Typhoid fever), Tularaemia. 
Viruses: EBV, CMV, Adenovirus, Enterovirus, HIV, Dengue
Fungal: Blastomicosis, Histoplasmosis, Coccidiomicosis
Parasites/protozoos: Malaria, Visceral Leishmaniasis, Toxoplasmosis, Visceral Larva Migrans, Tripanosomiasis
Connective Tissue DisorderKawasaki Systemic Onset of Juvenile Idiopathic Arthritis (SOJIA)Systemic Lupus ErythematousAcute Rheumatic fever
MalignanciesLeukaemia LymphomasSolid tumours (Neuroblastoma)Hemophagocytic SyndromeMyelodysplastic syndromeHistiocytosis 
Other: Drug related feversFabricated illness Inflammatory bowel diseaseCentral origin feverPeriodic feversMetabolic fevers (hyperthyroidism, dehydration)Primary immunodeficiencies

A 14-month-old girl was referred to hospital by GP due to 8 days of fever, non-tender cervical lymphadenopathies (scattered small submandibular, posterior and 1 supraclavicular lymphadenopathies) and mild cough. On examination, the patient has a good general appearance with a mildly red throat and the above described lymphadenopathies. Father is concerned as the child also had a febrile illness the previous week which was labelled as a viral infection. 

Blood tests showed raised WCC (24×109/L) with neutrophilia (18×109/L). Normal lymphocytes (6 x109/L) with a CRP of 30 mg/L. Chest x-ray showed a bilateral bronchial opacification.

The patient was admitted and started on amoxicillin and azithromycin PO. 

Despite 5 days of treatment, the patient is still spiking fevers (see chart below). Blood culture is negative. Clinically stable, cough has now disappeared. You are classifying this patient as PUO. 


What questions do you want to ask the parents? Take a detailed history. 

Why is this patient not getting better despite treatment? 

What investigations can be prompted by clinical findings?

At this point, would you escalate the antibiotic treatment?

In PUO, a detailed clinical history is the most important diagnostic tool that can guide all investigations. Instead of ordering random tests, ask more questions!

When taking the history, consider: 

  • Characteristics of the fever: when did it start, duration and intensity. Note that this child had a previous febrile illness which can be part of the same illness. 
  • Pattern of fever: there are several patterns of fever which can help with the diagnosis. If managed in an outpatient setting, ask the family to do a symptoms diary. From looking at the fever chart, the child has an intermittent fever pattern.
Type of feverCharacteristics of feverPossible causative agent
Intermittent feverSharp febrile peak which goes back to baselineBacterial infections, TB, SOJIA
Remittent feverFever peaks and elevated basal temperatureViral illness, Endocarditis, lymphomas
Sustained feverPersistent fever with minimal variationTyphoid fever, Brucellosis
Recurrent feverPeriods of fevers intercalated with afebrile periodsMalaria, Lymphomas, Borellia
Periodic feverFebrile periods are intercalated with afebrile periods with a predictable pattern of 6 monthsPeriodic fever syndromes 
  • Age of the child: PUO in young children is often caused by infections while in older children and teenagers tends to be caused by a connective tissue disorder or a malignancy.
  • Associated symptoms and signs: headaches, vomiting and diarrhoea, rash, arthralgias, myalgias, bony pain, lymphadenopathies. They can be very subtle therefore a systematic review of all systems is necessary. 
  • Systemic symptoms: fatigue, anorexia, weight loss, sweating.
  • Previous medical history: a history of many bacterial infections can be related to a primary immunodeficiency. The most common primary immunodeficiencies are: 
  1. Common variable immunodeficiency
  2. Chronic granulomatous disease

Usually the immunodeficiencies are associated with complicated infections, failure to thrive, atopic disease or autoimmune disease.

For more information: https://dontforgetthebubbles.com/ent-infections-immunodeficiency/

  • Vaccination history: patient is fully vaccinated as per UK protocol. This includes BCG due to risk factors (Parents are from a country where incidence of TB is > 40/100,000 or more). 
  • Regular medications or any exposure to new medication (think about drug- related fevers).
  • Family History: Ethnic background, consanguinity. Family is from India and there is no consanguinity. 
  • Environmental risk factors: TB contacts, area where family lives, exposure to animals, vectors (mosquitos, ticks…), food intake (unpasteurised dairy products, uncooked meat and fish), international travels (place, malaria prophylaxis and compliance of prophylaxis). 

Patient travelled to India to visit grandparents when she was 9 months old. She was exposed to some mosquito bites.  She lived in an urban area for 3 months. Parents were not aware of any TB contacts.

For international travellers, the following website provides relevant information on potential risks and outbreaks occurring on each country: https://travelhealthpro.org.uk/

When a patient has received a provisional diagnosis plus empirical treatment for at least 48 hours and there is no improvement, clinicians should use a systematic approach to understand the reasons behind the poor response to treatment. 

Here are the four main questions to be answered: 

  1. Is there a problem with the medication? 

The diagnosis is right but the problem is within the treatment. Issues with the treatment could be related to: 

-Drug resistances (MRSA, ESBL bacteria).

This website will provide a map with all antibiotic resistances over the world:  https://resistancemap.cddep.org/AntibioticResistance.php, treatments should, when possible, be guided by microbiological culture results.

-Underdosages of the antibiotics which don’t reach the effective concentration.

-Very virulent bacteria creating a toxin that requires more antibiotics (eg. Staph. aureus PVL) 

-Adherence to treatment (low compliance) 

-Malabsorption of medication (for example vomiting, diarrhoea when taking oral medications)

-The selected antibiotics are not reaching the right place of infection (bone, abscess…)

2. Are we targeting the wrong bug?

Antibiotics are mainly covering for bacteria but the actual infection can be caused by other microbes like viruses, atypical bacteria, TB, parasites and fungal infections. 

3. Is there a problem with the host? 

Consider whether the episode could be only a prolonged febrile syndrome for a common disease due to host problem.  The problem can reside in the immunity (immunodeficiencies), structural problems that can predispose to localized infections (for example a patient with previous abdominal surgery who now has an abscess) or whether the patient has a foreign body or a central catheter that can be the source of the infection.

4. The problem is not infectious: fever can be a sign of a tissue connective disorder, malignancies and other illnesses like a central origin related fever, drug related fever or a factitious illness.

This child has now had at least 12 days of fevers. It could be even longer if we consider that he had a febrile illness labelled as “viral” before this episode. 

On examination, the main clinical sign are the small cervical lymphadenopathies bilaterally with 1 small supraclavicular lymphadenopathy. This clinical finding could prompt the clinician to investigate for others cause: URTI, EBV, CMV, pneumonia, pleural effusion, TB, Bartonella, connective tissue disorders, malignancies, histiocytosis.

After 18 days of intermittent fever, cervical lymphadenopathies and some fatigue, the patient underwent a fine-needle aspiration of the supraclavicular lymphadenopathy. The histology showed a caseating granuloma and the microbiology sample showed acid fast bacilli. TB GeneXpert of the sample and culture were positive for non-resistant Mycobacterium Tuberculosis. Patient was diagnosed with tuberculous cervical lymphadenitis (extrapulmonary TB).

Probably not. Use of antibiotics can delay microbiological diagnosis since the blood cultures’ yield is decreased. If the patient has a good general appearance and fevers are well managed with PRN antipyretics, then clinician can consider withholding the antibiotics until a definitive diagnosis is reached. 

Reaching the definitive diagnosis: 
After 5 days of treatment with amoxicillin and azithromycin and no clinical improvement, basic investigations were repeated and further were added.

Bloods tests
WCC 22 x109/L with neutrophils of 18 x109/L,
Lymphocytes 4 x109/L, CRP 36 mg/L
ESR >60 mm/h
Normal renal and liver function
Blood film normal: No reactive lymphocytes, no lymphoblasts seen
Blood cultures Negative.
CMV Serology: IgM negative, IgG Negative
EBV serology: IgM negative, IgG Negative

Microbiology
Mantoux /TST (Tuberculin skin test): 10 mm induration
(Patient received BCG vaccination)
IGRA (Interferon gamma release assay): Positive
Gastric aspirate for AFB smear: negative 
Gastric aspirate for TB GeneXpert: negative

Imaging
Repeated chest XR: similar features compared to previous one, peri-bronchial shadowing.
Ultrasound of lymph-nodes: several lymph-nodes with nodal matting and surrounding soft tissue oedema. Prominent vascularity in the hilum.

After 18 days of intermittent fever, cervical lymphadenopathies and some fatigue, the patient underwent a fine-needle aspiration of the supraclavicular lymphadenopathy. The histology showed a caseating granuloma and the microbiology sample showed acid fast bacilli. TB GeneXpert of the sample and culture were positive for non-resistant Mycobacterium Tuberculosis. Patient was diagnosed with tuberculous cervical lymphadenitis (extrapulmonary TB).

  • Systemic symptoms 
  • Supraclavicular lymph-node
  • Firm and/or fixed lymph-nodes
  • CXR changes, abnormal Full blood count or increased ESR
  • Adenopathies > 1 cm in a neonate 
  • Suspicion of TB 
  • Persistent lymphadenopathies for more than 4 weeks despite antimicrobial treatment
  • Sometimes in acute lymphadenitis if a patient is not responding after 48 hours of treatment

To note, the patient had received the BCG vaccine. However, it has about 50% efficacy which implies that patients with BCG vaccination can still have tuberculosis. BCG is more effective in preventing children from developing disseminated (Miliary) TB or TB meningitis. She was probably exposed to TB and became infected while in India, subsequently developing the disease over the next few months. 

Contact tracing of family members is mandatory to identify the source case. Usually, children are not very infectious since the majority of cases tend to be paucibacillary (low bacterial load) unless they have lung cavities or extensive lung involvement. 

TB in children often presents in a non-specific way. The typical symptoms are weight loss or failure to gain weight, fever, night sweats and fatigue. When children present with pulmonary TB, this is usually confined within the intrathoracic nodes. Patients may have persistent cough and asymmetrical and persistent wheeze caused by airway compression due to enlarged tuberculous peri-hilar nodes. 

Chest XR can be helpful in the diagnosis of early primary infection by detecting intrathoracic lymph-node enlargement. However, these changes may be subtle as a strong index of suspicion is required. More information on radiological features of paediatric TB can be found on the following link: doi: 10.1101/cshperspect.a017855

Sputum and gastric aspirate mycobacterial cultures have a low diagnostic yield since most children have paucibacillary TB. Recently, diagnostic sensibility for these samples has increased due to the rollout of new molecular techniques (GeneXpert TB PCR).

TST (Mantoux test) and new immunological assays such as IGRAs detect exposure. TST is performed by injecting 0.1ml of tuberculin purified protein derivative (PPD) intradermally into the inner surface of the forearm. The skin reaction produced by the PPD should be read between 48 and 72 hours. The reaction is measured in millimetres of induration, not redness. There are different measures to define a positive result depending on patient background history (for example BCG vaccination) and there are also many causes of false positive and false negative results.For more information (https://www.cdc.gov/tb/publications/factsheets/testing/skintesting.htm).

On the other hand, IGRA is a blood test which measures the body’s immune response (interferon-gamma production) to TB antigens. Our patient had a positive Mantoux test (10 mm) but the result might have been affected by previous BCG vaccination.  However, this result, combined with a positive IGRA, demonstrated that the child had been previously exposed to TB. Unfortunately, neither of these tests can distinguish between latent infection and active disease. 

The patient was treated with Isoniazid (with Pyridoxine), Rifampicin, Ethambutol, and Pyrazinamide for 2 months and Rifampicin and isoniazid for another 4 months. Corticosteroids were not deemed necessary in this case since the lymphadenopathies were not compressing other structures. Empirical treatment of tuberculosis is usually limited to clinical cases where milliary or CNS TB are suspected, as a treatment delay in these cases will often lead to worse outcomes.

3-year-old boy with a 5-day history of fever and loss of appetite presented to the emergency department with his mother as he had been crying all night and refused to put his T-shirt on. No history of trauma reported. On examination, he looked skinny and he was crying when the right arm was moved. Bloods test showed
Hb 9 g/L
WCC 4 x109/L
Neutrophils 1.5 x109/L
Lymphocytes 2.5 x109/L
Platelets 120 x109/L.
CRP 40 mg/L.

Right arm x-ray was normal. The patient was admitted for observation. On the ward, it was noted that he was spiking fevers every night. 

After 3 days of admission, MRI of the right upper limb was performed. MRI showed possible osteomyelitis of the right distal clavicle.  He was diagnosed with acute pyogenic osteomyelitis and was started on ceftriaxone 50mg/kg IV OD. Blood cultures (taken before administration of antibiotics) were negative. Fever settled after 5 days of antibiotics. Patient was discharged home on oral antibiotics for 3 weeks.  

10 days later, the patient was reviewed in the clinic. Mother was worried since the patient had had fevers again over the last 2 days, felt fatigued and was reluctant to walk.

At this stage, what is the differential diagnosis? 

What investigations would you perform? 

What treatment would you give? If you were to suspect an autoinflammatory disease, would you give steroids? 

What is the role of PET-CT in PUO?

Infectious diseases: 

Osteomyelitis: 

Every time a patient presents with reduced range of movement due to a bony pain, osteomyelitis should be considered. In non-verbal children, it can present with irritability and inability to bear weight. It usually affects the metaphysis of the long bones (femur, tibia…). Therefore, the original diagnosis of clavicle osteomyelitis was quite rare. Now that the patient presented again with fever and a new similar problem after receiving adequate antibiotic therapy, another diagnosis should be considered. 

Septic Arthritis: 

It has a similar presentation to osteomyelitis but usually the joint is swollen, red and hot. Ultrasound of the joint can detect joint effusion which can be a sign of septic arthritis. Urgent orthopaedic referral for aspiration +- surgical washout is necessary. 

Connective tissue disorder: 

Transient synovitis: Fever and inability to bear weight can be a common presentation for transient synovitis. In this particular case, the initial diagnosis might have been wrong and the first inflammatory/infectious process could have triggered the production of antibodies causing inflammation over the joint. 

SOJIA (Systemic Onset of Juvenile Idiopathic Arthritis): Usually the joints affected by the arthritis are hot, tender and erythematous. We can suspect this pathology when there are different joints affected at different times. It is usually associated with systemic symptoms (fever and salmon pink rash, splenomegaly, serositis).

Diagnosis is made by elevated ESR, elevated ferritin, absence of antibodies, rheumatoid factor negative and exclusion of malignancy or infectious process.

CRMO (Chronic Recurrent Multifocal Osteomyelitis): this is an idiopathic inflammatory bone disorder with chronic multifocal bone pain. Sometimes systemic symptoms like fever can appear. Clavicle involvement is characteristic of this pathology.

Diagnosis is made by lesion’s biopsy: this will show an inflammatory reaction with no microbiological growth. 

Malignancies: 

Leukaemia: can present with bony pain and fatigue, lethargy and weight loss. Pancytopenia and blast can be seen in the blood film. LDH and uric acid are raised. Definitive diagnosis is reached with the bone marrow aspirate and flow cytometry.

Neuroblastoma: This is a malignancy that usually presents with abdominal mass. Sometimes mass can be found in the thoracic cavity. It appears in children below 5 years. The neuroblasts infiltrate the bone marrow. Therefore, patients can present with bony pain and pancytopenia. 

Diagnosis is reached by abdominal ultrasound and further imaging to evaluate the stage of the disease. Bone marrow aspirate is necessary along urine Vanillylmandelic Acid (VMA). 

Bone tumours (osteosarcoma /Ewing’s Sarcoma): 

Even though bone tumours are much less common than leukaemia and neuroblastoma, the presence of bony pain and prolonged fevers would prompt the diagnosis. LDH is usually elevated with raised calcium. 

X-Ray show bony abnormalities and further imaging with MRI or CT can provide more information. Sometimes biopsy of the lesion is necessary to confirm the diagnosis. 

Bone marrow is recommended in Ewing’s sarcoma. Metastasis and benign bone tumour should also be considered in the differential diagnosis.

Other: Histiocytosis:  this is a systemic illness which can affect bones. Associated symptoms are erythematous skin lesions, oral ulcers, lymphadenopathies, cough, shortness of breath, hepatosplenomegaly, malabsorption. Diagnosis is reached by seeing Langerhans cells in the biopsy of the lesion.

At this point, the patient has had a fever on and off for more than 3 weeks. A provisional diagnosis of osteomyelitis was made based on imaging findings. However, treatment is failing and the patient is now presenting with new symptoms (unable to bear weight). 

Repeated basic investigations:

Full blood count Hb 8.5 g/LWCC 1.0 x109/LLymphocytes 9.0 x109/LPlatelets 100 x109/LBlood cultureNegative
Peripheral blood film NormalUrine cultureNegative
CRP15 mg/LMantoux testNegative
ESR>40 mm/hHIV serologyNegative
Renal functionNormal rangeSickle cell testNegative
Liver function Normal range Chest XR Normal.
LDH900 U/L (240-480)
Uric Acid 12 μmol/L (High)

If after the above investigations, the clinician does not reach a diagnosis, then: 

  • Re-take a good clinical history 
  • Re-assessment of the patient
  • Withhold current medications
  • Do specific imaging (XR/Ultrasound/MRI of the new affected area)
  • Perform immunological studies: rheumatoid factor, ANA and anti-DNA antibodies, Immunoglobulins
  • Perform a bone marrow aspirate and trephine for histology, cytology and microbiology.

In this case, the diagnosis of osteomyelitis was discarded. SOJIA vs Leukaemia were the 2 main differential diagnoses.  Discussion regarding therapeutic steroid treatment for SOJIA was raised. 

Usually in PUO, steroid treatment should be avoided until malignancy is ruled out.  Steroids are used therapeutically in many oncology protocols. The use of steroids in an unconfirmed case of leukaemia can improve symptoms but it can blur the histological picture required for the diagnosis and confuse the staging process. This would lead to a delayed and potentially incorrect treatment. 

It is crucial to perform a bone marrow aspirate before steroid treatment is given, especially if there are symptoms and signs compatible with malignancies. 

In the above case, the full blood count showed mild pancytopenia which can be related to a bone marrow infiltration. The peripheral blood film was normal. Finally, the patient underwent a bone marrow biopsy and this confirmed the diagnosis of T-cell ALL. 

PET-CT is an imaging technique that localises anatomical parts with high metabolic activity, detecting hidden infections, malignancies or any inflammatory foci. 

PET-CT has proven to be useful in patients with PUO who are generally unwell, sick-looking, since early diagnosis is urgent in those patients. Otherwise, PET-CT can be used in those patients who have had extensive investigations done, have not had clinical improvement and still no diagnosis has been reached.

4-year-old boy presented with 5 days of fever, diarrhoea and vomiting and abdominal pain. No relevant past medical history. Fully vaccinated, BCG not included.

Initial blood test showed WCC 24.5 x109/L with neutrophils of 18 x109/L. CRP 139 mg/L. Hb 110 g/L and Platelets of 395 x109/L. He was admitted and started on amoxicillin, gentamicin and metronidazole. Blood cultures were negative and urine culture showed a sterile pyuria (WCC 2250 with no growth). Stool sample was negative. Abdominal ultrasound showed free fluid in the right iliac fossa. On examination, his abdomen was soft with some tenderness in lower quadrants.  He had a second ultrasound which showed findings suggestive of an appendicular mass. A repeated urine sample had 64 WBC and no growth. 

Meanwhile, fevers persisted: on day 7, he was changed to piperacillin-tazobactam and gentamicin. He underwent a laparoscopic appendicectomy on day 8. After operation, he was afebrile for more than 48 hours and antibiotics were stopped. Histological results of the appendix were normal. On day 12 of admission, the patient started again with fever and no focus on examination.

Now that the fever has restarted, and considering the previous history, what investigations would you ask? 

Would you re-start antibiotics? 

Looking at the pattern of fever below, what can you observe? 

Would an echocardiogram help in reaching the final diagnosis?

You should probably start by repeating basic investigations. Results: raised WCC with neutrophilia and thrombocytosis. Hb 101 g/L, WCC 32 x109/L with neutrophils of 24 x109/L, Platelets of 961 x109/L. He had normal renal and liver function.

Infectious diseases investigations: 

Microbiology cultures: Blood cultures were negative, even the prolonged culture for atypical bacteria. Stool sample was negative for viruses, bacteria and parasites. Urine sample became negative (previous sterile pyuria)

Toxoplasma serology:  IgG and IgM negative

CMV serology: IgM positive and IgG positive.  Second sample sent for CMV IgM negative. CMV PCR was negative. The initial positive IgM CMV was considered to be a false positive. IgM positivity in virology/microbiology assays may be non-specific, in patients with autoimmune diseases, cross-reactions.

EBV serology: IgM and IgG negative. 

Blood PCR for EBV, CMV and adenovirus negative.

Respiratory sample PCR: negative.

Lumbar puncture: LP was performed on day 14 of admission: WBC < 3/mm3. RBC <3/mm3. Viral PCR for enterovirus, parechovirus, mumps, VHS1&2 and VVZ negative. Negative culture.

Interferon Gamma Release Assay for TB negative. 

Inflammatory conditions investigations: 
Faecal calprotectin: negative. Since the patient had gastrointestinal symptoms and fever, Inflammatory Bowel Disease (IBD) should be considered as a potential differential diagnosis.

ESR: 50 mm/h.

Ferritin 222 ng/mL: important marker for inflammation. Especially high in Hemophagocytic lymphohistiocytosis /Macrophage Activation Syndrome.

Malignancies: 
Blood film: no atypical cells. Polychromasia and raised platelet count. Neutrophilia.

LDH 446 U/L (high)

Imaging
Day 12 Chest XR: normal
Day 13 Abdominal Ultrasound: normal kidneys and bladder. Normal liver, spleen, gallbladder and bile ducts. No abnormal masses or bowel wall thickening. Trace of fluid in right iliac fossa postoperatively. No fluid collection. 

The patient was clinically stable, so it was decided to wait and hold antibiotic treatment. The patient continued to have daily fevers up to 39°C. On day 14, he had one bilious vomit and became more lethargic therefore antibiotics were restarted (Piperacillin-Tazobactam and gentamicin). The following day, he underwent a Bone marrow aspirate and MRI under general anaesthesia with results as below: 

BMA: Trilineage haematopoiesis. No evidence of abnormal infiltration. No increased haemophagocytic activity. Appearances in keeping with a reactive marrow. Negative for AAFB, both microscopy and culture. 

Abdominal MRI:  There is moderate distention of the proximal small bowel with an apparent jejunal transition point due to ileus, adhesions or oedema from handling.  Some free fluid but no abdominal collections.  No retroperitoneal collection.  No bone marrow abnormality.

On day 16, he did not spike any temperatures.  After 48 hours (on day 18 of admission), he had an evening temperature of 38.5°C.

The patient had 2 episodes when he was apyrexial:

  • the first one between day 9- 11 after antibiotics were escalated (Piperacillin-Tazobactam and Gentamicin (D7)) and after surgery under general anaesthesia (D8).
  • The second afebrile period was on day 16-18 after being re-started on Piperacillin-Tazobactam and Gentamicin (D15) and after he underwent a procedure under general anaesthesia. 

In the first episode, the lack of fever was linked to a good response to antibiotics whereas in the second episode given the fact that a non-infectious condition was highly suspected as a differential diagnosis, the afebrile episode could be linked to the anaesthesia.

A very important investigation to perform in PUO is an echocardiogram to rule out infective endocarditis. In this case, there were no positive cultures or risk factors to point towards an infective endocarditis but it would be useful to rule out this disease. Echocardiography can also help to diagnose Kawasaki disease. In this particular scenario, it would be an incomplete case of KD. 

Reaching the diagnosis: 
On day 19, the patient had an echocardiogram which revealed dilated circumflex artery and an aneurysm of the left anterior descending artery. This finding confirmed the diagnosis of Incomplete Kawasaki. The ophthalmology review showed no pathological findings.  

DIAGNOSTIC CRITERIA FOR KAWASAKI DISEASE
Full case of KawasakiIncomplete case of Kawasaki
Fever (>38°C) every day for 5 days        +At least 4 of the following 5 featuresNon purulent bilateral conjunctivitisCervical lymphadenopathyPolymorphous rashLips/oral mucosa involvementFingers/toes: acute erythema and oedema of palms and soles and then peeling.
Or positive echocardiogram at any time with less than 4 features.
Fevers (>38°C) every day for 3 days+ less than 4 features but diagnosis supported by: Lack of alternative diagnosis (lack to respond to antibiotics, no other pathogen found)High inflammatory markers (high CRP, ESR, NeutrophiliaPresent of other clinical features: Irritability without CNS infectionBCG scar inflammationOther system involvement: CSF pleiocytosis, uveitis, arthritis, gastroenteritis, myocarditis, dysuria, sterile pyuria.

In our particular case: the patient had prolonged fevers with high inflammatory markers (CRP, ESR, Neutrophilia), irritability without CSF infection, sterile pyuria, low albumin, anaemia, thrombocytosis and lack of alternative diagnosis. Furthermore, he had a characteristic echocardiographic finding of Kawasaki Disease.

Patient was started on IVIG and aspirin. Steroids were included in the treatment since the patient already had evolving coronary and or peripheral aneurysm.

For more information on criteria for steroid use in Kawasaki disease, you can read: Eleftheriou D, et al.Managment of Kawasaki disease. Arch Dis Child,99,1 2013 

With regards to the antibiotics, gentamicin was stopped while Piperacillin-tazobactam was continued while evaluating response to IVIG. Piperacillin-tazobactam was stopped after 48 hours. 

Kawasaki disease is rare but early diagnosis is important to avoid cardiological sequelae. Incomplete Kawasaki can present a clinical challenge to diagnose.

You are in an Ethiopian rural hospital. A 7-year-old boy presents to clinic severely malnourished (marasmic type). Mother is complaining of daily fevers for an unknown period of time. 

Patient has cerebral palsy due to an obstructed labour resulting in hypoxic-ischaemic injury. He was in hospital for some time after delivery. He is not vaccinated. He is on phenobarbitone 100mg OD PO for seizures. 

You admit the child to the malnutrition ward and start the appropriate treatment with F-75 Milk. Part of the SAM protocol (Severe Acute Malnutrition) includes a course of at least 7 days with Amoxicillin.  On examination, the patient has a papular rash over hands and groin compatible with scabies but no other clinical findings. On the ward, he spikes a high temperature (39°C) and he is shivering. 

Available investigations at your hospital are performed:

Blood tests: 
Hb 9.1 g/LRenal function and CRP not available in this setting.
WCC 12 x109/L with neutrophils 8 x109/L and lymphocytes 4 x109/LUrine dipstick: leucocytes and nitrates positiveUrine microscopy: many white cells. No culture available.
Platelets 300 x109/LStool: negative for parasites
Blood film: No parasites seen
GGT 61 IU/LHIV antibodies negative
GOT 72 IU/LHepatitis B and C antibodies negative
Bili < 0.5  μmol/L

Based on the above clinical picture and results, what is your differential diagnosis and management? 

Patient was empirically treated but fevers persisted. Given his background of CP and the geographical area, what other infections would you consider?

What other non-infectious causes should be considered? How can you reach the diagnoses in this low-resource-setting?

This is a very challenging patient. Due to their reduced ability to communicate and cognitive impairment, these children are difficult to assess. Furthermore, this patient is malnourished which increases the risk of infections. 

The above results showed a possible UTI which is in keeping with the clinical picture (high fevers, shivering in a patient with high risk of UTI due to his cerebral palsy and poor bladder control). Antibiotics were changed from amoxicillin to amoxicillin-clavulanic to give broader cover for gram negative bacteria (E. Coli, Klebsiella…).

To note, the patient has scabies which is a very common parasitic skin infection that affects mainly the palms and soles and the groin area. If the patient has been scratching over the genital area, it could have triggered a UTI. Furthermore, there are poor hygiene conditions in the area with limited access to water.

The slightly raised GGT and GOT was correlated to the use of phenobarbitone. The hepatitis B and C were negative but the hospital did not have the test for hepatitis A. Nevertheless, the clinical symptoms were not fitting with hepatitis A. 

The patient was treated with co-amoxiclav for 7 days. He initially improved and fevers were spacing in time. However, on day 9 he started again with very high fevers and shivering. He was looking unwell during the fever episodes so he was started on ceftriaxone IV. His baseline temperature was always raised, he had abnormal movements and was irritable. Temperature persisted despite treatment

Another urine sample was requested to rule out a UTI due to a resistant bacterium, since microbiological cultures were not available in the rural hospital. The urine microscopy was negative for WCC and urine dipstick did not show any abnormalities.

Another important differential diagnosis was meningitis. Patient was irritable, had abnormal movements and a fever. The abnormal movements consisted of small twitching of the arms while crying inconsolably. There were considered either shivering or behavioural but there was a lot of discussion if those movements could represent a seizure event. Furthermore, mother was unable to describe the usual seizures that he had at home. The team subsequently realised that there was an error with the regular medications: he was prescribed 100mg of phenobarbitone but mother clarified that at home he was taking 200mg, therefore his daily phenobarbital dose was increased to 200mg OD. To note, the patient did not have any devices (VP shunt) which could increase the risk of infections. In this rural setting, clinicians were not able to perform a lumbar puncture due to lack of laboratory equipment, so the patient was started on ceftriaxone high dose empirically. 

Pneumonia can be a common cause of infection in patients with cerebral palsy since they can have drooling, unsafe swallow prompting for aspiration. Usually, pneumonia in these children can be very silent. In addition, poor nutritional status can increase the risk of severe pneumonia. Patient was not desaturating or with respiratory symptoms but a chest XR was done (in a private clinic) and no lung abnormalities were detected. Furthermore, based on local antimicrobial resistances, the antibiotics he received earlier should have been covered for the most common bacteria causing pneumonia. Gastric aspirate for GeneXpert MTB/Rif was negative. 

Dental infections with abscesses can also present with fever and no other major symptoms. The patient had poor oral hygiene plus the lack of proper tongue movement, drooling and lack of routine dental care made him more prone to these types of infections. These infections are mainly due to anaerobes which should be covered by amoxicillin-clavulanic or ceftriaxone. On examination, no suspicious dental masses were found. 

Viruses can also cause non-specific symptoms. However, they shouldn’t last for very long. He did not have any gastrointestinal symptoms or respiratory symptoms. No palpable lymph-nodes. Unfortunately, in the hospital there were no laboratory diagnoses for viruses.  Full blood count differential was never lymphocytic. 

The most common parasites in this rural area are intestinal parasites (Giardia, Entoaemabeas) and blood parasites (Malaria). Entoaemebas can present with a dysentery which can cause fever. However, our patient did not have any diarrhoea. 

This area has a moderate risk of malaria, especially during the rainy season. Patients with malaria present with very unspecific symptoms: from fever with general malaise or headache and vomiting to seizures, coma and shock. Therefore, any patient with a fever in a tropical setting should prompt investigations for malaria. The most important element in the clinical diagnosis of malaria is a high index of suspicion. 

To reach the laboratory diagnosis, parasites should be seen or detected in blood. Blood film microscopy (thin and thick blood films) is the gold standard for malaria diagnosis, identifies the Plasmodium species and also quantifies the parasitaemia. However, in low resource settings, where microscopy is not always available or reliable, rapid diagnostic tests (RDT) are used to diagnose malaria. The RDTs detect Plasmodium antigens confirming the presence of parasites in the blood but don’t provide any information regarding the species or the parasitaemia. 

Patients with malaria can be classified into severe or non-severe malaria based on clinical and laboratory findings as per the WHO 2015 Malaria Guidelines. This classification is crucial as it will guide treatment. The most important complications of malaria infection in children are cerebral malaria, severe anaemia, respiratory distress due to acidosis and hypoglycaemia. 

Severe Malaria
Clinical findingsLaboratory
-Impaired consciousness/unrousable coma (Glasgow score <11, Blantyre score <3)- More than 2 convulsions in 24 hours- Prostration- Deep breathings/respiratory distress- Shock- Bleeding – Jaundice with parasitaemia > 2% – Severe anaemia with parasitaemia- Acidosis- Hypoglycaemia- Hyperparasitaemia- Haemoglobinuria- Renal impairment

Patients with severe malaria should receive parental antimalarial treatment with Artesunate and supportive management followed by a full course of oral artemisin combination therapy (ACT). Patients with non-severe malaria can be managed with oral antimalarial medication. 

On admission, the initial blood film was negative for haemo-parasites. Repeat blood films and a Malaria RDT (rapid diagnostic test which detects Plasmodium falciparum antigens in blood after 20 minutes) were requested. Repeat Blood film revealed presence of Plasmodium falciparum trophozoites with a parasitaemia of 2%. 

So the patient was diagnosed with Severe Malaria given the suspicion of CNS involvement and started on IV Artesunate. The patient had a good clinical response with resolution of fever and completed a course of oral Artemisin combination treatment (Artemeter Lumefantrine). However, after one week, the fever reappeared. This time, it was a low-grade fever with maximum peaks at 38.5. Repeat blood tests were normal. 

Malignancies: In this case, blood film did not reveal any blasts, chest XR was normal and abdominal ultrasound did not reveal any masses. BMA was not available locally and since the patient was otherwise well, this was not considered necessary. 


Connective tissue disorders: 

SOJIA, AR are very uncommon but still a differential diagnosis of persistent fever. In this setting, no resources were available for auto-antibodies testing, therefore clinical findings are the main way of diagnosing it. Since the patient did not have any rash, arthritis… this diagnosis was not considered. 

Acute Rheumatic Fever (ARF): this condition is quite common in low resource countries due to increased risk of streptococcal tonsillitis due to poor hygiene, overcrowding, poor accessibility to health facilities, fake drugs…  Acute rheumatic fever is an illness caused by an inflammatory reaction to streptococcal infection. It causes an acute, generalised inflammatory response. This illness targets specific parts of the body including the heart, joints, brain and skin. ARF typically leaves no lasting damage to the brain, joints or skin, but can cause persisting heart damage.  Our patient did not meet the Jones’ Criteria of ARF. 

Miscellanea (other possible causes of fever): 

Central origin fever: children affected with cerebral palsy or other neurological disorders relatively often present with chronic intermittent febrile episodes persisting for months. These episodes are not related to any infections but are actually arising from an abnormal thermal regulation resulting from the brain injury.

Hyperthermia from severe dystonia: children with cerebral palsy with dystonia can present with fevers and elevated basal temperature associated with elevated creatinine phosphokinase levels. 

Drug related fever: medications can trigger fevers. Common medications used in cerebral palsy are anticholinergic drugs (e.g. hyoscine) which can provoke unwanted fevers as a side effect. In addition, withdrawal of medications can present with fever (baclofen withdrawal syndrome). 

Lastly, factitious fever is a very challenging diagnosis. Sometimes admissions to hospital and close measurement of fevers plus observation of patient and carer interaction is as important as complementary tests. 

After 2 months of intermittent fever, it finally stopped. Basal temperature was always slightly elevated. Patient was diagnosed with central origin fever.

 The majority of PUOs are caused by: 

A: Malignancy

B: Connective Tissue Disorder 

C: Infections

D: Other diagnosis

E: Unknown diagnosis

The correct answer is C.

Infectious diseases are the main cause of PUO (about 38%), especially in younger children. No diagnosis is reached in 30% of cases but these tend to be benign and self-limited. This is followed by connective tissues disorders (13%) and Other diagnosis (13%). Lastly, malignancies are very uncommon but very important to consider given the severity of the disease.

A patient admitted to your hospital has been spiking fevers every day for 12 days. No other clinical findings are present. What is your next step? 

A: Repeat basic investigations, re-take clinical history, re-examine the patient, perform a Bone marrow aspirate.

B: Repeat basic investigations, re-take clinical history, re-examine the patient and do adequate imaging depending on clinical findings.

C: Perform a PET-CT to localise the pathology.

D: Perform autoimmune studies.

E: Perform a bone marrow aspirate.

The correct answer is B.

In many PUO cases, clinical findings are very subtle and can appear days after the fever. Therefore, re-taking the clinical history and re-examining the patient carefully is key to guide the complementary tests.

A Turkish 5-year-old girl presented with high fevers, profuse night sweating for 21 days.  Clinical detailed history revealed that parents are not consanguineous. She doesn’t have any relevant past medical history. She is fully vaccinated. The whole family was in Turkey for 2 months over the summer holidays. They were living in a farm in rural Turkey where they had goats, cows and chickens. They were drinking fresh milk from the cow. Based on the history, what diagnosis would you consider? 

A: Tuberculosis 

B: Bartonella (Cat-scratch)

C: Brucellosis

D: Toxoplasmosis

E: Lyme disease

The correct answer is B.

Brucellosis is a zoonotic infection caused by ingestion of unpasteurized milk from infected animals. It is also known as the Mediterranean fever. It is caused by a bacterium called Brucella melitensis. The main symptoms are fever, profuse sweating and joint and muscle pain. 

An unaccompanied asylum seeker from Uganda has just arrived in the UK. He refers to being a 12-year-old. He has had fevers for a prolonged time. On examination, he has splenomegaly. Blood tests revealed pancytopenia. Blood film is negative for malaria. HIV and hepatitis B, C negative. He said that in his country many people have these symptoms and they call it Kala-azar. What kind of tropical infection is he referring to? 

A: Visceral Leishmaniasis 

B: Schistosomiasis. 

C: Non falciparum malaria 

D: Visceral Larva Migrans

E: Echinoccocus granulosus

The correct answer is A.

Kala-azar is the local term for Leishmaniasis. This is a parasitic disease spread by the sand-fly. Main symptoms are fever, enlargement of spleen and liver and pancytopenia. Leishmaniasis is the second-largest parasitic killer in the world after malaria. Diagnosis is made by histological finding of amastigotes on spleen aspiration/bone marrow aspiration and RK39 Antigen detection.

A roadmap for fever of unknown origin in children- Rigante, D; Esposito S., International Journal of Immunopathology and Pharmacology. Vol.26 no 2, 315-326 (2013)

Fever in Children and Fever of Unknown Origin- Rajeshwar Dayal, Dipti Agarwal, Indian Journal of Paediatrics, 83 (1): 38-43 (2016)

Pyrexia of unknown origin-Mark Wood, Mario Abinun and Helen Foster. Archives of Disease in Childhood, Education and Practice, 89 ep 63-69 (2004) 

Barbi E, Marzuillo P, Neri E, Naviglio S, Krauss BS. Fever in Children: Pearls and Pitfalls. Children (Basel). 2017;4(9):81. Published 2017 Sep 1. doi:10.3390/children4090081

Antoon J,Peritz D, Parsons M., Skinner A.,Lohr J. Etiology and resource use of fever of unknown origin in Hospitalized children. Hospital Pediatrics, 8 (3).: 135-140(2018)

For malaria: 

https://apps.who.int/iris/bitstream/handle/10665/79317/9789241548526_eng.pdf;jsessionid=AD1DDC86455A8D51D25CFEEADF7E1C75?sequence=1

Website resources: 

https://pedemmorsels.com/fever-of-unknown-origin/

https://dontforgetthebubbles.com/ent-infections-immunodeficiency/

https://dontforgetthebubbles.com/recurrent-or-periodic-fevers-investigate-or-reassure/

https://dontforgetthebubbles.com/tuberculosis/

https://dontforgetthebubbles.com/claire-nourse-tuberculosis-at-dftb17/

https://radiopaedia.org/articles/tuberculous-cervical-lymphadenitis

https://gppaedstips.blogspot.com/search/label/Juvenile%20idiopathic%20arthritis

https://www.paediatricfoam.com/?s=kawasaki

https://gppaedstips.blogspot.com/search?q=kawasaki

https://dontforgetthebubbles.com/josh-francis-rheumatic-heart-disease-at-dftb17/



Please download our Facilitator and Learner guides

The Limping Child Module

Cite this article as:
Team DFTB. The Limping Child Module, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27391
TopicThe limping child
AuthorHelena Winstanley & Michelle Alisio
DurationUp to 2 hours
Equipment requiredExamination couch (if planning to demonstrate joint examination)
  • Basics (10 mins)
  • Main session: (2 x 15 minute) case discussions covering the key points and evidence
  • Advanced session: (2 x 20 minutes) case discussions covering grey areas, diagnostic dilemmas; advanced management and escalation
  • Sim scenario (30-60 mins)
  • Quiz (10 mins)
  • Infographic sharing (5 mins): 5 take home learning points

We also recommend printing/sharing a copy of your local guideline.

Basic joint anatomy with diagrams of lower limb joints: CHW Anatomy Review

DFTB: Fever and Limp

DFTB: The child with a Limp

Short, basic introduction to the limping child and common differentials:

NHS – Limp in Children

PEM Playbook Podcast on the limping child

A 10 year old boy is brought to ED by his dad who is concerned that his son is limping and has left knee pain. He has complained of pain a few times before – especially after sports (which he dislikes) but seems to be in much more discomfort since coming home from school yesterday.

What are the differential diagnoses in this case?

How would you refine your diagnosis further?

  • The differential is broad at this stage – it includes benign self-limiting conditions such as a minor traumatic soft tissue injury through to more serious conditions such as Perthes disease and Slipped Capital Femoral Epiphysis (SCFE).
  • A detailed history should be elicited to rule out the presence of any red flag symptoms that might suggest systemic illness
    • Night pain
    • Weight loss
    • Night sweats
    • Anorexia/general malaise
  • The child requires a thorough examination including abdomen, groin and the whole of the lower limb to establish the location of the pathology – remember that hip pain can be referred to the knee.
  • X-rays including a pelvis and frog-leg lateral are essential to look for evidence of hip joint integrity.

A thorough history establishes that the child is systemically well but overweight. He has restricted movement in his left hip. You notice that he externally rotates his hip when you try to flex it. This is his x-ray:

  • The x-ray findings suggest a slipped capital femoral epiphysis on the left hand side.
  • It is a Type I Salter Harris injury affecting the growth plate of the upper femur.
  • Triggers include growth spurt (i.e. puberty), obesity and trauma.
  • Initial management involves referral to an orthopaedic specialist
    • Must be kept non-weight bearing
    • Likely to need surgery involve pinning of epiphysis
    • Will need ongoing monitoring due to risk of long term problems e.g.
      • Osteoarthritis
      • Avascular necrosis of the femoral head
      • Slipping of the contralateral side (~20% of cases)

A four year old boy is brought to ED as he is unable to weight-bear. He woke up with a slight limp this morning which has got steadily worse throughout the day and he is now unable to walk at all. He has no recent medical history of note.

Examination is unremarkable other than a moderately restricted range of movement in his right hip. Despite the fact he is systemically well and has had good doses of analgesia he remains unable to weight-bear.

What investigations (if any) would be appropriate at this stage and why?

What is the most likely diagnosis? Can this child go home today? If so, what information would you give to parents and what follow up (if any) would you arrange?

  • X-ray – mandatory to look for evidence of e.g. Perthes
  • Bloods – could be considered as he is still not weight-bearing after analgesia.  
    • He is afebrile and systemically well so will likely be normal
    • May be useful for looking for rare causes of limp e.g. initial presentation of leukaemia
  • US – depending on availability may be useful to look for a joint effusion. In transient synovitis expect to see a simple joint effusion +/- evidence of thickened and inflamed synovium.

X-ray and baseline bloods including inflammatory markers are normal.

  • Most likely to be a transient synovitis
    • Although transient synovitis is more common after a viral illness, it does still occur in children who have been otherwise well recently.
  • As long as you are reasonably confident that this child has transient synovitis it may be possible to discharge him with careful safety-netting advice.
  • If his pain gets worse or he develops a fever his parents should bring him back to ED promptly for further assessment.
  • Some form of review is almost certainly going to be advisable as he is not weight bearing. Depending on local hospital protocol this may be an ED clinic or a paediatric rapid access clinic.

You see a 3 year old child with a two day history of fever. He has woken up with a right sided limp. On examination he is febrile with large, pus covered tonsils, cervical lymphadenopathy and discomfort in the right hip – especially on internal/external rotation. You decide to do bloods and the inflammatory markers come back as raised.

What is the role of tonsillitis in this presentation?

How might you distinguish between a transient synovitis and a septic arthritis in this case?

  • Tonsillitis gives a source for the fever and the raised infection markers
  • It can also act as a source for haematogenous spread of osteomyelitis/septic arthritis
  • Staph aureus is one of the most common causes of both tonsillitis and septic arthritis/osteomyelitis

  • Children with septic arthritis are likely to be in more pain and have a more limited range of movement and are unlikely to weight -bear.
  • They may be systemically unwell.
  • Kocher’s criteria may help clarify your level of suspicion
    • A point is given for each of the four following criteria:
  • Non-weight-bearing on affected side
  • Erythrocyte sedimentation rate >40
  • Fever > 38.5°C
  • White blood cell count >12,000
ScoreLikelihood of septic arthritis
13%
240%
393%
499%
  • Ultrasound of the hip joint may reveal a complicated effusion.
  • The only certain way to know the difference is joint aspiration

A 1 year old girl with a background of sickle cell anaemia attends ED with a history of fevers up to 39°C and diarrhoea for the last two days. Two other family members also have diarrhoea. This morning she is distressed and seems to be in a lot of pain. She is not weight bearing and the family are concerned this could be her first painful crisis.

What are the concerning features in this child – what makes her a high risk patient and why?

What are your next steps in managing this child?

  • Children with sickle cell disease are functionally asplenic due to recurrent micro-infarcts of their spleens.
  • This leaves them at high risk of infection from encapsulated bacteria such as pneumococcus and salmonella.
  • Diarrhoea could leave her dehydrated and provoke a painful crisis – as the family fear.
  • A history of fever and diarrhoea however, must make the clinician suspicious of salmonella infection with the risk of haematogenous spread.
  • She is high risk for systemic bacterial infection so, given her presentation, needs assessing for features of sepsis and shock
  • Meticulous examination of her musculoskeletal system to find a focus for the pain.
  • Initial management is likely to involve fluids, antibiotics and analgesia.

Examination reveals a painful, hot left ankle with some mild swelling. The child screams in pain when you attempt to move it.  

  • Paediatricians
  • Haematologists
  • Radiologists
  • Microbiologists
  • Orthopaedic surgeons
  • Anaesthetists
  • (Critical Care – depending on how unwell she is)

A 10 year old young man, James, with profound learning difficulties presents to the Emergency Department with reduced mobility, a poor appetite and altered behaviour. His mum says he hasn’t fallen or hurt himself recently, but she thinks he is in pain and claims that “my son is not himself”. He is afebrile and systemically well. You notice that James has an abnormal gait as he walks in from the waiting room. You offer him analgesia.

What further information would you like to elicit from the history?

What is a pGALS screen? Practice a pGALS examination with your colleague.

You suspect a hip problem but you are still unsure. What are you going to do next?

Your clinical suspicion and sense of pre-test probability tailors your examination to involve a musculoskeletal and joint exam. With mum’s help, distraction techniques and imaginative play James manages through an incomplete pGALS examination. He doesn’t allow you to complete a comprehensive general examination and mum tells you the last time James had a blood test, the doctor almost got a needle-stick injury.

Despite attempts at a thorough history and examination, you are still unsure what the underlying cause for Jame’s pain is. You cannot safety net and discharge him home without further investigations even though you know taking bloods and performing X-rays will be challenging.

You do bloods and an X-ray which again have been a challenging exercise.

Blood results:
Hb   9.8, WCC  15.6, Plt    299, Na  131, K  haemolysed, Urea  2.4. Creat   15
ESR insufficient
LDH haemolysed

James has presented with atraumatic joint pain.

There is a wide-range of aetiologies but most are benign and self limiting. However nestled among these varied presentations are limb and life-threatening infections and non-accidental injuries. Getting a detailed history from an older child with learning difficulties is going to be challenging, as is getting a history from a preverbal child. One should always approach a scenario with a detailed history; and in this case the main aim would be to tease out red flags with the assistance of the parent/caregiver followed by an examination.

History

A systematic structure to history taking is the SOCRATES pneumonic for a pain focused history.

S: Site. Ask the child where it hurts. Children are more likely than adults to experience referred pain. Remember: knee pain emanates from the hip (in 35% of cases). Also pain from the spine can refer to the lateral thigh.

James rubs his right hip region when you ask him where it hurts.

O: Onset. Is the pain acute or chronic? Acute onset tends to be more concerning and suggests joint/bone infection, trauma, or with acute deterioration of a chronic problem. Chronic pain is more suggestive of an inflammatory process, overuse syndromes or an osseous cause such as SUFE or Legg-Calve-Perthes disease. Malignancy often has a delayed presentation with mild dull pain that may not be activity limiting in the initial stages. Nocturnal pain is a red flag and should always be asked about.

James is unable to answer your questions. Mum thinks James has been unwell since Monday (3 days ago), and says he doesn’t have problems sleeping.

C: Character. Dull ache (deep tissue pathology) or sharp sting (cutaneous involvement) can be helpful.

James is unable to answer both questions to character and radiation.

R: Radiation. Can be difficult to elicit exact origin of pain and radiation, especially in the younger child. Be aware of bilateral limb involvement as this may suggest a more central cause, such as cauda equina.

A: Associations.

Weight-bearing: non-weightbearing can suggest more serious pathology

Mono or polyarticular: polyarticular is generally less concerning and suggests an underlying systemic disease process. However, 8% of septic arthritis cases involve more than one joint and leukaemic infiltrates typically affect multiple joints.

Systemic illness: chronic features such as malaise, fatigue, weight loss could suggest underlying increase in catabolism from a systemic disease such as SLE, JIA, or anaemia from malignancy.

Dermatology: extra-articular features of inflammatory bowel disease (IBD) (eye pain, pyoderma gangrenosum, erythema nodosum, aphthous ulcers). Ask the parents about any new marks on the body and later during the examination look for a Salmon patch of juvenile idiopathic arthritis (JIA). Consider whether this presentation is associated with a recent upper respiratory infection or viral gastroenteritis which may be suggestive of reactive arthritis.

Mum says James is off his food but he hasn’t lost weight.

T: Time course. Note the pain progression over time and response to analgesics.

Mum says James is more comfortable after Ibuprofen which she started giving him 2 days ago.

E: Exacerbating or Relieving factors. Trauma and infection aggravate pain after activity and are relieved by rest. The presence of pain that is relieved by activity is more suggestive of an underlying inflammatory cause. Pain relieved with rest is pain from osteochondrosis in the adolescent experiencing growth spurts.

S: Severity. Severity is subjective but a surrogate of severity is the inability to walk or to tolerate examination with distraction.

Finish off the SOCRATES pain history with a FAST history:

F: Family history for autoimmune disease (IBD, psoriatic arthritis)

A: Adolescent screen. The sexually active teenager could present with joint infection due to gonococcus or joint inflammation due to chlamydia. Similarly ask about IV drug use as this increases the chance for infectious arthritis.

S: Safeguarding. Due attention should be maintained for a history that is not in keeping with the presentation or the child’s developmental age.

T: Travel history

Examination

Look. Inspection is non-invasive, interactive and can be used to establish rapport.

Feel for temperature changes, tender areas, effusions.

Move actively and passively with the aim of gently stressing the ligaments of which the joint is comprised.

It is always important to complete a comprehensive general examination especially in the presence of red flags or suspicion of a multisystem disease.

pGALS is a standardised musculoskeletal (MSK) basic examination. Free educational resources to demonstrate pGALS are available online. (www.pmmonline.org).

pGALS screen has the benefit of quickly assessing all joints, this is important given the sometimes vague presentation of MSK problems and the difficulty of localising the site of joint pathology from the history alone. Frequent practice of pGALS, especially on healthy children, is important to appreciate normal ranges of movement as joint ‘restriction’ – a common finding in JIA can be easily missed especially with symmetrical joint disease.

The x-ray is diagnostic and demonstrates a large pelvic Ewing’s sarcoma.

The blood tests (which were very difficult to obtain from James) reveal an anaemia and leukocytosis. A marginally elevated ESR and LDH may also be evident in Ewing’s sarcoma.

Ewing’s sarcoma typically presents with more systemic disease at presentation and localised pain. At diagnosis, the median duration of symptoms is 3-9months.

Any child or adolescent who’s pain involves any of these characteristics should be investigated to exclude a malignant pathology with at least a plain film X-ray.

–        A painful ‘injury’ which fails to resolve over a reasonable time (over 1 month)

–        Intermittent or persistent localised pain for one month with no history of trauma

–        Night pain that wakes you up from sleep or prevents adequate sleep

–        Fracture where history of force resulting in injury seems insufficient

Ewing’s sarcoma occur more commonly in the pelvic bones, diaphysis of the long bones of the leg, and bones of the chest wall.

At presentation 25% will have metastatic disease to the lung, bone or bone marrow or a combination of these.

Plain X-ray in 2 planes of the painful area remains the first line investigation of choice and is readily available to most clinicians. Ewing’s (as well as an osteosarcoma) can lead to a radiologically significant sign – the Codman triangle. It is a triangular area of new subperiosteal bone that is created when a lesion, often a tumor, raises the periosteum away from the bone. Ewing’s sarcoma traditionally demonstrates osteolysis, detachment of the periosteum and occasional calcification in any associated soft tissue mass.

There are no peripheral blood tests or tumor markers which are diagnostic of bone tumors.

Further imaging of the affected bone is required to adequately determine the true extent of the disease and staging.

Biopsy is the gold standard for histological diagnosis.

Whole body technetium-99m bone scans and CT chest are performed to assess metastatic disease at presentation.

Bone marrow aspirates and trephines are required for Ewing’s sarcoma patients as marrow involvement is a part of the disease process and for some high dose procedures requiring harvest of stem cells from the patient may be part of the treatment.

Referrals to a specialist orthopaedic sarcoma surgeon, paediatric oncologist, radiology services, paediatric surgeon, rehabilitative specialists and physiotherapists to name a few are required.

Important to note that although malignancy is rare, it should be actively excluded. Also, blood tests may be normal even in cases of inflammatory, infectious and neoplastic joint pain and peripheral blood films may not show blast cells in children with leukaemia cells.

Which of the following is NOT part of Kocher’s criteria for assessing the risk of septic arthritis in a limping child?

A: ESR >40

B: Range of movement <50% normal

C: WCC > 12×109

D: Fever >38.5oC

E: Inability to weight bear

The correct answer is B.

Although range of movement can be a useful part of the assessment, it is not part of the official Kocher criteria.

Which of these statements about SCFE/SUFE is TRUE?

A: It is most common in underweight children between the ages of 6-10. It can be a cause of chronic hip pain and is bilateral in approximately 10% of cases.

B: It is a cause of both acute and chronic hip pain, is rarely bilateral and typically occurs in overweight adolescents.

C: It is caused by avascular necrosis of the femoral epiphysis and usually presents as a chronic problem. Radiological detection is improved by requesting a ‘frog-leg lateral’ view.

D: It is most common in children over the age of 10 and can present with acute or chronic pain. It is bilateral in around 20% of cases and radiological detection is improved by a ‘frog-leg lateral’ view.

E: It is a common cause of limp and pain in underweight adolescents and is bilateral in one third of cases. Early detection and referral improves prognosis.

SCFE is most common in boys between the ages of 10-17 with a median age of 13. It is the most common cause of serious hip pathology in adolescents. 50% of them are >95th centile for weight and knee pain is a common initial presentation. Pain and limp may be entirely acute but often presents with an acute on chronic picture with long term low level pain suddenly becoming more acute with a large epiphyseal slip

In a classical antalgic gait, which phase of walking is affected?

A: Strike

B: Contact

C: Stance

D: Propulsion

E: Swing

The correct answer is C.

The stance phase is shortened in an antalgic gait as the patient tries to minimise the amount of time that weight is placed through the painful leg. (https://pemplaybook.org/podcast/please-just-stop-limping/ for diagram of phases of gait and fuller explanation)

Which of the following bacteria is the most likely to cause septic arthritis?

A: E. Coli

B: Streptococcus pneumoniae

C: Haemophilus Influenza B

D: Staphylococcus aureus

E: Salmonella

The correct answer is D.

Although all of the organisms above can cause joint pathology, the most common is Staph aureus. Previous studies suggest it is responsible for over half of all cases of septic arthritis.

Which of the following statements about Perthes disease is FALSE?

A: It is more common in boys than girls

B: It is bilateral in 10% of cases

C: It is defined by avascular necrosis of the femoral head

D: An older age at diagnosis is associated with a more favourable prognosis

E: Physiotherapy, casting and surgery may all form part of the treatment regimen

The correct answer is D.

Perthes disease is five times more common in boys than girls although damage is often more severe in affected girls. It may be bilateral in around 10% of cases and is defined by avascular necrosis of the femoral head. The younger a child is diagnosed the more favourable the prognosis owing to a greater potential for bone remodelling. Children under the age of 6 do especially well. Management is multidisciplinary and physio, casting and surgery may contribute at various stages of the disease process.

A 10 year old presents with an acute onset of right hip and wrist pain following a very minor trip and fall onto the ground. Since the incident she has been unable to bear weight. On examination the right hip and wrist showed no obvious deformity and range of movement were normal after her pain was addressed. During the last 2 years she had not presented to the GP but recently she had complained of poor sleep, leading to daytime somnolence, palpitations, anxiety and sweating. A fall in her weight growth curve was noted after plotting her on a growth chart.

Which statements are FALSE?

A: This is a ‘red herring’ injury commonly reported by patients and their parents and will not require further investigations.

B: For children over the age of 8 years or limping > 7 days an X-ray is an adequate imaging modality as it has a relatively low dose of radiation but is also very likely to show the pathology causing the pain.

C: Blood tests are indicated including thyroid functions because the minor fall is not in proportion to the severity of her symptoms and her unexplained weight loss is of concern

D: Transient synovitis is most common in this age group so cooling, rest and pain relief are adequate therapy.

The correct answers are A and D.

The most common cause for hip pain (in children aged 3-10years) is transient synovitis. Even though this is a benign cause not requiring further treatment, other more severe differential diagnoses need to be considered. A ‘red herring’ injury is commonly reported by patients and their parents but in this case the minor fall was not in proportion to the severity of her symptoms. Similarly, X-ray and blood tests including thyroid functions are indicated due to the red flags of not weight bearing, disproportionate severity of her pain and unexplained weight loss. The indications for a CT scan are limited in this context. In this case, she had a  pathological fracture due to endocrine abnormalities. Hyperthyroidism is rare but a severe disease in children and mostly autoimmune.



Please download our Facilitator and Learner guides

Asthma Module

Cite this article as:
Miriam Saey Al-Rifai. Asthma Module, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27232
TopicAsthma
AuthorMiriam Saey Al-Rifai
DurationUp to 2 hours
Equipment requiredNone
  • Basics (10 mins)
  • Main session: (2 x 15 minute) case discussions covering the key points and evidence
  • Advanced session: (2 x 20 minutes) case discussions covering grey areas, diagnostic dilemmas; advanced management and escalation
  • Sim scenario (30-60 mins)
  • Quiz (10 mins)
  • Infographic sharing (5 mins): 5 take home learning points

We also recommend printing/sharing a copy of your local guideline.

Joseph, a 10 year old boy comes into the ED. He is a known asthmatic on treatment. He appears breathless with an audible wheeze. He is able to talk in complete sentences. He has a RR of 25, sats of 94%, pulse of 100 and his PEF is 60% of normal.

What is the severity score of this child’s asthma presentation?

What investigations and treatment options should you consider?

How do you decide when it is safe to discharge home?

The boy is 3 years old with the same presentation – his mum asks you if her son has asthma. What is your response?

When seeing a child with an acute asthma attack, the initial assessment is key to establishing the severity of the attack as this influences ongoing management. 

The following clinical signs should be recorded:

Pulse rate – Increasing tachycardia generally denotes worsening asthma; severe airway obstruction can result in pulsus paradoxus and a fall in heart rate in life-threatening asthma is a preterminal event.

Respiratory rate and degree of breathlessness –  Ie too breathless to complete sentences in one breath or to feed.

Use of accessory muscles of respiration – subcostal, intercostal recessions, tracheal tug. You can also assess by palpation of neck muscles. Also consider including a prolonged expiratory phase.

Amount of wheezing – which might become biphasic or less apparent with increasing  airways obstruction. Silent chest is an indicator of life threatening asthma. It is important to auscultate and document any improvement with treatment.

Degree of agitation and conscious level – always give calm reassurance.

Observations

  • Include general observations.

CXR

  • NOT routinely advised. A chest X-ray should be performed if there are persisting unilateral signs suggesting pneumothorax, inhaled foreign body, lobar collapse or consolidation and/or life-threatening asthma not responding to treatment.

Blood Gas

  • Only indicated if not responding to treatment or needing further escalation of care

Oxygen 

  • If any life threatening features or sats <94%. Aim for sats 94-98%

Inhaled β2 agonist 

  • Salbutamol up to 10 puffs via spacer (1 puff = 5 breaths) assess after 15 mins and repeat if necessary. If sats <94% use,or patient refusal/poor inhaler technique use salbutamol nebulisers (2.5 – 5mg).
  • Continuous nebulisation may be better, as intermittent may result in rebound bronchoconstriction. 

Ipratropium Bromide 

  • If symptoms are refractory to initial β2 agonist treatment, add ipratropium bromide (250 micrograms/dose mixed with the nebulised β2 agonist solution) every 20-30 mins for the first two hours in severe asthma attacks. This should then be tapered to 4-6hrly before being discontinued. However, there are no clinical trials supporting ipratropium use beyond the first hour or first 3 doses in children (EMCases).
  • In a systematic review and meta-analysis comparing the use of beta-agonists plus anticholinergics with beta-agonists alone, combination therapy was associated with significantly lower hospitalisation rates and improvements in asthma scores and pulmonary function test results (EMCases).

Oral steroids 

  • Give oral steroids in the management of acute asthma attacks. Dexamethasone is starting to be used more, as a once only dose, but there is no evidence for benefit over Prednisolone, so not recommended yet. 

Nebulised Magnesium 

  • Nebulised magnesium sulphate is not recommended for children with mild to moderate asthma attacks. The RCT entitled MAGNETIC trial in 2013 of about 500 children showed that MgSO4 nebulisers added to the salbutamol and ipratropium bromide nebuliser in the first hour, for kids with acute severe asthma, significantly improved asthma severity scores without any increase in adverse events.

Antibiotics 

  • Insufficient evidence to refute or recommend.

Burst therapy – improves forced expiratory volume with an earlier peak response, and prevents deterioration between doses. Salbutamol 100 mcgs x 10 puffs via inhaler & spacer every 20 mins for 1 hour. Add ipratropium bromide 20 mcgs (x 4 puffs < 5 years, x 8 puffs > 5 years) together with salbutamol as above for severe cases.

BTS/SIGN – Children can be discharged home once requiring no more than 3-4 hourly inhalers (based on a randomised controlled study in 1999), PEF >75% and sats >94% . 

Safe follow up

  • Reducing regime of salbutamol inhaler therapy with a clear plan as to when to come back to hospital (ie. requiring >10 puffs in 4 hours)
  • Ensure good inhaler technique/correct fitting spacer mask. Advise to use the B-agonist BEFORE the inhaled steroid and to wash the mouth out after the steroid inhaler to prevent thrush.
  • If the parent/carer of the child smokes, advise them to stop.
  • Address potentially preventable contributors to the exacerbation, such as exposure to trigger factors
  • Ensure the patient is discharged home with 3-5 days oral steroids. Some trusts are now given single dose Dexamethasone, although prednisolone is still in the national guideline (https://www.stemlynsblog.org/dexamethasone-asthma-children/). 
  • Primary care follow-up in 24-48hrs
  • If second attack in 12 months refer to a secondary care asthma clinic.

Wheeze is a common presentation in the ED and its diagnoses and management differs depending on the age of the child and the detail in the history (Snelson et al, 2019). 

An age based approach to wheeze in children

Bronchiolitis

  • Slow onset of symptoms. 3-4 day period of worsening cough, poor feeding, wheeze and respiratory distress due to inflammation of the airways.

Viral Wheeze

  • Rapid onset of wheeze and respiratory distress over hours due to bronchospasm.

Asthma

  • Described above. 

The age based approach to wheeze can be explained by the changes in a child’s immune system:

  • At birth and in the first few months, immunity is largely provided by maternal antibodies. These antibodies offer protection from most simple viral infections. Acute atopic IgE mediated reactions are very rare. If infections do occur it is likely to be serious bacterial infections. In addition the baby’s own immune system is not yet fully turned on and the response to infection is therefore muted, making the recognition of sepsis difficult in this age group.
  • Preschool age children no longer rely on maternal antibodies. However, their own immune system is still not fully developed. They compensate for this by having heightened and indiscriminate responses to infections. They produce lots of white blood cells, but do not yet have circulating antibodies. You are more likely to see associated problems of viral infections in this age group like transient synovitis. Atopy is becoming more common now. Sepsis is also difficult to recognize in this age group due to the extreme reaction to often uncomplicated viral infections. These children present with viral wheeze. It is worth knowing that there are wheezy presentations in this age group that can look a lot like viral wheeze.  These include bronchomalacia, acute allergy, and cardiac failure due to e.g. acute myocarditis.
  • Older children have a more mature immune system and response to infection is like that of an adult. As the response to infection is less vigorous and indiscriminate than the pre-schoolers, some specific infections like Varicella can cause severe reactions in these children. These children are more likely to have asthma. True asthma is rarely seen under the age of 5 as it requires a fully matured immune system to develop.

Management

  • By looking at the history we can direct our inhaled beta agonist treatment to one that matches a story consistent with bronchospasm. This would include children with likely viral wheeze and asthma.  
  • The best evidence for the use of oral steroids for viral wheeze between the ages of 1 and 5 would suggest that the following group are most likely to have a small benefit (https://gppaedstips.blogspot.com/search/label/Asthma):
  • Children with a diagnosis of asthma
  • Children who have required substantial amounts of inhaled beta-agonist prior to presentation
  • Children whose severity and lack of response to treatment with beta-agonists requires admission to hospital
  • Joseph has presented with features of a moderate asthma attack
  • This can be managed with beta 2 agonist therapy and oral steroids
  • Once Joseph does not need beta 2 agonist bronchodilation for more than 4hrs and obs remain stable he can be safely discharged home with safe follow up.
  • The 3 year old presenting with the same symptoms of sudden onset wheeze and breathlessness, likely has a diagnosis of viral wheeze. They would benefit from beta 2 agonist bronchodilation. They are too young to be diagnosed with asthma, but risk factors for developing asthma could be explored in the history.

Leila, a 13 year old female, known asthmatic on treatment, presented to ED breathless and finding it hard to speak in full sentences. Her oxygen saturations are 92%, HR 130 and RR 35

What is the severity score of this child’s asthma presentation?

What investigations and treatment options should you consider?

When do you need to re-assess response to treatment to decide on discharge vs escalation?

  • In this instance, Leila falls into the acute severe asthma presentation. 
  • As her sats <94% oxygen needs to be given via a facemask. 
  • Beta 2 agonist bronchodilator via a nebuliser (preferably oxygen driven) to be given due to sats <94% and she falls into the severe category. 
  • Oral steroids must be given. This can be given as IV Dexamethasone if too unwell/vomiting.
  • Re-assess response to treatment after 15 minutes. 
  • If no improvement after 15 minutes give a further two beta 2 agonist nebulisers and add Ipratropium Bromide nebuliser. 
  • A consideration of nebulised Mg can be given in acute severe asthma.
  • Plan for admission, escalate and refer to paediatrics for consideration of second line treatment.

Do you know how to use a spacer?

Leila has not improved despite the treatment given in ED as outlined in case 2. Her sats are now 89%, she appears cyanosed and has a poor respiratory effort. On auscultation her chest is quiet. What are the next steps that need to be taken?

How would you rate the severity score of this presentation?

What investigations or treatment needs to be considered?

Which IV medications if any should be used? 

Which important differentials need to be considered?

What escalation plans need to be put in place?

Children with continuing severe asthma despite optimal first-line treatments, frequent nebulised β2 agonists and ipratropium bromide plus oral steroids, and those with life-threatening features, need urgent review by a specialist with a view to management in an appropriate high-dependency area or transfer to a paediatric intensive care unit to receive second-line intravenous therapies. It is important to do a blood gas prior to starting bronchodilators to measure the pCO2 and also to monitor side effects of salbutamol (decreasing potassium and lactic acidosis).

PERUKI (Paediatric Emergency Research in the UK and Ireland network) is a research collaborative of paediatric-specific and mixed adult and paediatric emergency departments (EDs). In 2015 PERUKI carried out a study looking at the variation in practise of the use of IV bronchodilators as a second line treatment in the management of acute asthma in children. There was a large discrepancy between what clinicians felt was the appropriate management and what they actually administered. A survey of 183 clinicians in 30 EDs revealed that when escalating to intravenous bronchodilators, 99 (54%) preferred salbutamol first line, 52 (28%) magnesium sulfate (MgSO4) and 27 (15%) aminophylline. 87 (48%) administered intravenous bronchodilators sequentially and 30 (16%) concurrently, with others basing approach on case severity. 146 (80%) continued inhaled therapy after commencing intravenous bronchodilators. 

Of 170 who used intravenous salbutamol, 146 (86%) gave rapid boluses, 21 (12%) a longer loading dose and 164 (97%) an ongoing infusion, each with a range of doses and durations. Of 173 who used intravenous MgSO4, all used a bolus only. What this demonstrates is the considerable variability in practise and opinion. 

So what is the evidence? (Cochrane review)

IV salbutamol 

  • There have not been enough trials to form a robust evaluation of its benefits.

IV MgSO4 

  • Appears to be safe and beneficial in severe asthma

IV aminophylline 

  • Improves lung function within 6hrs. However, there is no apparent reduction in symptoms, number of nebulised treatments or length of hospital stay. We do not know the impact on oxygenation, PICU admissions or need for NIV. 

IV ketamine 

  • There has only been 1 study conducted, which reveals no known benefit in non intubated children. 

In one RCT comparing IV aminophylline, salbutamol and magnesium in 100 children, a bolus of magnesium sulphate was shown to reduce clinical symptoms faster than the other treatments. There were no significant side effects documented in the magnesium sulphate group. A systematic review of four paediatric trials comparing IV salbutamol with IV aminophylline demonstrated equivalence.

In children who respond poorly to first-line treatments, consider the addition of intravenous magnesium sulphate as first-line intravenous treatment (40 mg/kg/day).

Consider early addition of a single bolus dose of intravenous salbutamol (15 micrograms/kg over 10 minutes) in a severe asthma attack where the child has not responded to initial inhaled therapy. It is not clear whether IV bolus vs infusion is more beneficial. Prior to IV salbutamol administration insure blood potassium is checked and on cardiac monitor. If using an IV infusion monitor lactate to check for toxicity. 

Consider aminophylline for children with severe or life-threatening asthma unresponsive to maximal doses of bronchodilators and steroids. Some of the side effects include abdominal pain, anxiety, headache, nausea, palpitations and seizures. Toxicity can occur with aminophylline. This presents as vomiting (which may be severe and intractable), agitation, restlessness, dilated pupils, sinus tachycardia, and hyperglycaemia. More serious effects are haematemesis, convulsions, and supraventricular and ventricular arrhythmias. Severe hypokalaemia may develop rapidly especially in combination with salbutamol.

Ensuring you have appropriately assessed and optimised their condition

Reassess the patient?

  • Consider revisiting history, respiratory examination and consider adjuncts to assessment such as a capillary or venous blood gas.

Have you exhausted medical management?

  • ? adrenaline ? ketamine ?heliox 

What could be missing? 

  • Consider your confidence of whether you have the right diagnosis or if there is a need to assess for a secondary pathology such as pneumonia, foreign body, anatomic airway anomalies, airway compression by masses/lymph nodes, cardiac disease? Some can be excluded with a good history. Do you need to further investigate with bloods, CXR? Do you need to append your management and provide antibiotic coverage? Do you need to assess for a complication from treatment e.g. pneumothorax.

Escalation options

  • Have you sought a senior review/notified the admitting paediatrician?
  • Do you need an ICU consult, NETS consult or retrieval to a tertiary centre?
  • How long are you comfortable to wait to see if there is a response to IV bronchodilation?

Non invasive ventilation 

  • Is there any evidence in acute asthma attack?
  • What settings/mode would you use?

Does this child need to be intubated?

  • How would you determine this?
  • Who should be involved in the conversation? Who should perform the intubation?
  • What sedation would you use?
  • What equipment would you use?
  • What settings would you use?

Alternative treatment options

Adrenaline

Give for severe or life threatening asthma – if the diagnosis is in doubt. 

Asthma and atopy often co-exist – and in these patients death from anaphylaxis is more likely. So if a patient fails to respond to initial therapy, the diagnosis of anaphylaxis needs to be considered. In addition nebulised Adrenaline causes bronchodilation.  

Heliox 

May improve respiratory score, but it probably won’t reduce the risk of admission. Nor should you use it in routine asthma to stave off intubation (PEMBlog). Can be considered in the ICU setting with maximum oxygen therapy has failed. 

Ketamine

Limited number of trials with mixed outcomes on the benefits of Ketamine. However, it is safe at dissociative dosages, and is a reasonable option when all others measures have failed.

NIV

A few case reports and observational studies of the use of BiPAP in pediatric asthma show some promise. The one RCT of only 20 patients does show a benefit in clinical asthma scores, respiratory rate, and supplemental oxygen need. There is no evidence that it prevents the need for intubation (Basnet S et al, 2012).

Critical care input is the next step for children with severe asthma not responding to treatment or with any life threatening features. There are a number of ongoing trials on the use of ketamine, sevofluorane and NIV, but the evidence is currently lacking so they’re not recommended by BTS/SIGN.

A 15 year old male has been brought into resus with features of life threatening asthma. Pre hospital the paramedics gave continuous salbutamol nebulisers, 500mcg Ipratropium nebulisers and 0.5mg IM Adrenaline. The attending medical team in resus administered 2g IV Mg over 20 mins and a bolus of 250mcg IV Salbutamol. The patient then became unresponsive with no respiratory effort.

What are the next steps that need to be taken?

What is the ‘deadly triad’ in asthma?

What are the key ALS modifications in asthma arrest?

In the pre-hospital setting, paramedics usually give IM Adrenaline to cover for the possibility of a diagnosis of anaphylaxis. 

In this case the patient has arrested. As soon as this has been identified, CPR needs to be initiated as per the ALS guidelines.

The cause of cardiac arrest in asthma is a result of the ‘deadly triad’:

Important modifications and considerations in managing cardio respiratory arrest in asthma (RCEMLearning – https://www.rcemlearning.co.uk/foamed/arrest-asthma/):

  1. Intubate Early

Due to the need for high inflation pressures, an endotracheal tube (ETT) is needed. In addition this protects the airway from the increased risk of regurgitation and aspiration.

  1. Ventilate with caution

The European Resuscitation Council recommends 8-10 breaths per minute with the lowest tidal volume required to see the rise and fall of the chest, to avoid dynamic hyperinflation. Tachypnoea must be avoided as this reducses expiratory time, thus increasing the residual volume in the alveoli. This auto PEEP increases intrathoracic pressure which reduces venous return, impeding CPR. 

  1. Manual chest deflation

If the patient has a hyperinflated chest/poor excursions of the chest wall, disconnect the ETT and apply manual pressure to the patient’s chest to expel the trapped air. 

  1. Consider tension pneumothorax

If ETT disconnection does not improve ventilation, consider performing a bilateral thoracostomy.

  1. Rehydrate

Dehydration and reduced intravascular volume compromises effective CPR. It also causes mucus to be thicker which can plug small airways. So ensure you give IV fluids. 

  1. GIVE ADRENALINE! – Utilise its bronchodilator effect. 

In an acute asthma exacerbation in children, monitoring the oxygen sats is important because:

A: Hypoxaemia is an early sign of clinical deterioration 

B: Sats <95% may suggest the need for prolonged bronchodilator therapy

C: Hypoxaemia occurs in the presence of life threatening asthma. Children may have normal sats for some time before critical desaturation occurs.

D: Sats >96% supports the decision to safely discharge home

The correct answer is C.

In an acute asthma attack hypoxic vasoconstriction occurs. This is coupled with decreased blood flow to the under ventilated lung (matching pulmonary perfusion with alveolar ventilation). 

In the hospital setting SaO2<91% may be a helpful predictor of prolonged frequent bronchodilator therapy more than 4 hours and SaO2 of <89% is associated with a need for bronchodilator therapy over 12 hours.

Hypoxaemia and hypocarbia only occur in the presence of life threatening asthma. Children may have normal sats for some time before critical desaturation occurs. Whilst low oxygen saturations mean that a patient is unwell it should be clinically obvious at this point.  Low oxygen saturations may also represent a degree of mucus plugging that may be helped with repositioning.

Hyperoxia can lead to absorption atelectasis as well as intra-pulmonary shunting with subsequent reduction in cardiac output. In addition concerns have been raised that oxygen administration may lead to potential delay in recognising clinical deterioration.

What is an appropriate length of time to stretch children in the ED prior to discharge?

A: After two sets of 3-4hrly inhaler/nebulisers

B: After they reach the first 3-4 hrs post last inhaler/nebuliser

C: After two sets of 3hrly

D: After 1 hour, if obs are completely normal and has had a consultant review

The correct answer is B.

BUT this is based on a randomised control trial in 1999. The most recent study in 2018 suggests that there is no benefit to 4hours vs 3hrs, and in fact 3 hrs post inhalation resulted in a reduction in length of stay. A recent retrospective analysis study in Australia looked at discharging children after 1 hour. They suggested that children that were clinically ‘well’ at 1 hour were likely to go home and if they were showing any moderate symptoms at one hour would likely need to be admitted. There is no strong evidence or recent studies, which is why there is such variation in practice. 

Under what circumstances would you choose to administer a beta agonist via nebuliser as opposed to a pMDI with a spacer?

A: When the child has become more tachycardic with worsening salbutamol induced tremor

B: In severe or life threatening asthma or when under the age of 1yrs old/learning difficulties

C: If the pMDI is ineffective

D: Some departments prefer nebulisers as it is cheaper than inhaled preparations

The correct answer is B.

Cochrane review 2013 – “Metered-dose inhalers with a spacer can perform at least as well as nebulisation in delivering beta-agonists in children with acute asthma”

Salbutamol has systemic side effects – tremor and increased pulse rate were more common when using nebulisers. SIGN/BTS guidelines state to give nebulisers in severe or life threatening asthma. Nebulisers are also preferential in very young children, or those with learning difficulties, as coordinating breathing with an inhaler can be difficult. Cost savings can be made with inhaled preparations. 

When is intubation indicated in paediatric asthma presentations?

A: When the HR > 160 OR the RR > 60

B: When you have given all first line and second line treatment and trialled NIPPV and the patient has still not improved. 

C: The child looks exhausted with worsening hypercapnia and changes in mental status. 

D: When the child has a history of fast deterioration and need for intubation

The correct answer is C.

Up to 26% of children intubated due to asthma suffer complications including pneumothorax, impaired venous return, and cardiovascular collapse because of increased intrathoracic pressure. Mechanical ventilation during an asthma exacerbation is associated with an increased risk of death and should therefore be a last resort. The decision to intubate should be based on clinical judgement as opposed to any one observation or blood result. Some variables to consider for intubation are worsening hypercapnia, patient exhaustion and changes in mental status (EMCases).

You have a 4 yr old, with two days of wheeze, coryzal symptoms and one day of increased work of breathing symptoms. You suspect that this may be viral induced wheeze. How do you manage this child?

A: Burst therapy with salbutamol. 

B: 6-10 puffs of salbutamol and reassess. If severe symptoms give oral steroids. 

C: Humidified air nebuliser and antipyretics for fever. 

D: 6-10 puffs of salbutamol and Ipratropium bromide nebuliser. If severe symptoms give oral steroids.

The correct answer is B.

At what age would it be appropriate to consider a trial of ventolin for potential viral induced wheeze? 

  • (Note – This is a good opportunity to survey your team and colleagues to see what the practice is at your local department). 
  • Regarding this grey area question, in Australian practice, some clinicians will trial salbutamol for potential viral induced wheeze if the child is 12 months or older. Other doctors may wish to trial if the child is slightly younger (e.g. from 10 months) if they have a strong family history of asthma and atopy or if they have had previous ventolin use reported by their family with good effect. The younger the child is, the less likely that the story and case is to fit viral induced wheeze.

If you are not sure if the child is presenting with asthma or viral induced wheeze, but they are displaying severe symptoms – it is advisable to give steroids. But be cautious in giving too many courses of steroids if presenting frequently to the ED.

M Balfour-Lynn (1996) Why do viruses make infants wheeze?, Archives of Disease in Childhood  74: 251-259

MO Stormon, CM Mellis, PP Van Asperen, HA Kilham (2002) Outcome evaluation of early discharge of asthmatic children from hospital: A randomized control trial, Journal of quality in clinical practise, Vol 19, issue 3, 149-154

Huay-ying Lo, Amanda Messer, Jennifer Loveless, Esther Sampayo, Robert H. Moore, Elizabeth A. Camp, Charles G. Macias and Ricardo Quinonez (2018) Discharging Asthma Patients on 3-Hour β-Agonist Treatments: A Quality Improvement Project, Hospital Pediatrics, 8 (12) 733-739

Basnet S, Mander G, Andoh J, Klaska H, Verhulst S, Koirala J (2012) Safety, efficacy, and tolerability of early initiation of noninvasive positive pressure ventilation in pediatric patients admitted with status asthmaticus: a pilot study. Pediatr Crit Care Med 13(4):393-8.

Snelson, E (2019) A simple model for understanding the causes of paediatric wheeze, Paediatrics and Child Health, Volume 29, Issue 8, Pages 365-368

DFTB – Managing acute asthma, Simon Craig (2017)

DFTB – Asthma for ambos (2016)

DFTB – Are nebulisers or spacers better for managing acute asthma (2013)

DFTB – The curious incident of the wheeze in the night

PEMBLOG – Heliox in the emergency department (2017)

EMCases – Management of acute paediatric exacerbations (2016)

BTS/SIGN British guideline on the management of asthma in children (2019)

PaediatricFOAM – ventilation strategies for the critically ill asthmatic (2019)

RCEMLearning – Arrest in asthma

gppaedstips.blogspot.com – The NYCE guideline for viral induced wheeze – Let’s clear a few things up (2019)



Please download our Facilitator and Learner guides

Inherited Metabolic Disorders Module

Cite this article as:
Taciane Alegra. Inherited Metabolic Disorders Module, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27425
TopicInherited metabolic disorders
AuthorTaciane Alegra
Duration1 to 2 hours
Equipment requiredNone
  • Basics (10 mins)
  • Main session: (5 x 20 minute) case discussions covering the key points and evidence
  • Quiz (10 mins)
  • Infographic sharing (5 mins): 5 take home learning points

We also recommend printing/sharing a copy of your local guideline.

This module presents an approach to acute metabolic presentations, how to identify potential problems and emergency treatment in the ED. You don’t need to make a diagnosis (bonus points if you do) but do need to remember that spotting the zebra will lead to more favourable outcomes. Metabolic diseases / disorders are also called inborn errors of metabolism (IEM).

How common are they?

Individually, metabolic conditions are rare, most having an incidence of less than 1 per 100,000 births. However, when considered collectively, the incidence may reach 1 in 800 to 1 in 2500 births (Applegarth et. al, 2000; Sanderson et.al, 2006). 

Remember: some symptoms can be unspecific and can mimic sepsis; or a child with an undiagnosed metabolic condition can decompensate with an intercurrent infection. 

An easy-to-understand classification by Saudubray divides the IEM in three groups of disorders, depending on how they present. 

An acute or progressive intoxication from the accumulation of toxic compounds, usually small molecules. 

These usually present with a symptom-free interval and clinical signs of ‘intoxication’, which may be acute, although can be intermittent.

  • disorders of amino acid catabolism: e.g. phenylketonuria, maple syrup urine disease, homocystinuria, tyrosinemia 
  • most organic acidurias: e.g. methylmalonic, propionic, isovaleric acidaemia
  • urea cycle defects: e.g. Ornithine transcarbamylase deficiency (OTC deficiency), Citrullinemia type I (ASS1 deficiency).
  • sugar intolerances: galactosemia
  • metals: Wilson’s, Menkes, hemochromatosis
  • Porphyrias.

A deficiency in energy production or utilization, within the liver, myocardium, muscle, brain or other tissues. 

Common symptoms include hypoglycemia, hyperlactatemia, hepatomegaly, failure to thrive and cardiac failure. 

  • Mitochondrial defects: congenital lactic acidemias (defects of pyruvate transporter, pyruvate carboxylase, pyruvate dehydrogenase, and the Krebs cycle), mitochondrial respiratory chain disorders and the fatty acid oxidation defects (MCAD deficiency).
  • Cytoplasmic energy defects: disorders of glycogen metabolism (collectively known as glycogen storage diseases), hyperinsulinism.  

Problems in the synthesis or catabolism of complex molecules, leading to storage of big molecules. 

Symptoms are chronic, progressive and independent of intercurrent events or food intake. 

  • Mucopolysaccharidosis (I-IV, VI and VII). The eponymous names are used less frequently now, particularly in the literature, but you might come across them in clinical practice (MPS I, Hurler’s Syndrome; MPS II, Hunter’s Syndrome; MPS VI, Maroteaux- Lamy) 
  • Gaucher disease
  • Peroxisomal disorders: e.g. X-linked adrenoleukodystrophy (X-ALD) and Zellweger’s Syndrome.

Remember your biochemistry: a substrate is transformed by an enzyme into a product.

If there is a problem with the enzyme, there will be more substrate. If accumulation of the substrate is the problem, we remove it (like avoiding protein in the diet).  Or, if the problem is the lack of the product, we can supplement it. And for some diseases the  enzyme can be “corrected” (by organ transplantation, enzyme replacement).

Due to accumulation of “unusual” products in their body fluids, people with certain metabolic conditions have distinctive odours (better observed in urine, for practical reasons):

  • Maple syrup, burnt sugar, curry: Maple syrup urine disease
  • Sweaty feet: glutaric aciduria type II, isovaleric acidaemia
  • Cabbage: tyrosinemia
  • Mousy, musty: Phenylketonuria
  • Rotting fish: Trimethylaminuria
  • Swimming pool: Hawkinsinuria 

It’s early morning in the ED and you are enjoying your coffee. You’re called in to see a neonate with a history of irritability and seizures. You enter the room and are told the following: “Emma is a 3 day old, term baby who has been refusing feeds and crying excessively. There has been no history of fever or cough. At home she had seizure-like activity with tonic posturing”. 

First pregnancy, no antenatal or perinatal problems. Birth: Weight: 2950g,  Apgar 9/10. Discharged home on day 2. Irritability since birth. Vomiting after feeds (mixed: breast and formula). 

Examination: Awake, extremely irritable, upper limbs flexed, lower limbs extended, global hyperreflexia. No dysmorphic features. Otherwise no positive findings. Weight: 3050g

Vitals: Temp 36.8ºC, HR 155, RR 48, O2 sats 99%, BP wasn’t checked.

What are the red flags in Emma’s story?

What tests do you want to send?

  • Irritability and excessive crying
  • Acute onset of seizures, without any obvious trigger. 
  • Blood gas, glucose, U&E, LFTs, CRP, blood culture, urine ketones and MC&S, metabolic screen. Consider CT brain.

FBC, CRP, U&E, LFTs  – normal

Venous blood gas:

  • pH: 7.33 
  • pCO2: 3.1 kPa*
  • HCO3: 14 mmol/L
  • Na+: 142 mmol/L
  • K+: 4 mmol/L
  • Chloride: 100 mmol/L

Glucose: 5 mmol/L

Ketones: 2.1mmol/L

Ammonia 184

Urine: Ketones +2, and smells of sweaty feet.

Metabolic screen: plasma amino acids, urine organic acids, acylcarnitine profile sent 

*1kPa = 7.5mmHg

This baby has an acute neurological presentation, with metabolic acidosis, increased anion gap and mildly elevated ammonia –  suggestive of an organic acidemia

  • A normal ammonia level is <50 mol/l but mildly raised values are common, up to 80 mol/l. 
  • Artifactually high values can be caused by muscle activity, haemolysis or delay in separating the sample. Capillary samples are often haemolysed or contaminated and therefore should not be used. 
  • In neonates, any illness may be responsible for values up to 180 mol/l. 
  • There’s debate as to whether a level of >100 or 200 should be discussed with a metabolic specialist, but if in doubt, follow the RCPCH DeCon guideline and seek advice for any patient presenting with a level >100.
  • The AG is raised at 32mEq/L [(Na + K) – (Cl + HCO3)]. 
  • (142 + 4) – (100 + 14) = 146 – 114 = 32
  • PEMinfographics have a nice infographic explaining interpretation of anion gaps in children. In the context of a sick neonate with a raised AG, a normal lactate and normal ketones, think organic acids.
  • Urine organic acids and blood acylcarnitines will also be sent as part of this baby’s metabolic work-up. Although the results won’t be available to us in ED, the urine organic acid profile will confirm a diagnosis of an organic acidaemia, while the blood acylcarnitine profile will support the diagnosis as the organic acids conjugate with carnitines creating compounds such as isovalerylcarnitine.
  • It’s important to think about your differentials. Sepsis is the most common – these conditions can mimic sepsis, or decompensation can be triggered by an infection, always cover with broad spectrum antibiotics. But don’t forget non-accidental injury and other differentials – the baby is likely to need a CT head if presenting encephalopathic or with seizures.
  • Manage seizures in the usual way. 
  • Specific emergency treatment of her metabolic presentation requires 
  • stopping sources of protein (milk)
  • avoiding catabolism (by giving glucose IV – 2mL/kg 10% glucose) 
  • rehydration (IV fluids resuscitation and maintenance)
  • The “sweaty feet” smell is a clue to the diagnosis of Isovaleric Acidaemia. Remember that this condition can be part of the Newborn Screening in some countries (Ireland, UK, Australia, New Zealand).
  • Isovaleric acidaemia is a type of organic acidemia, inherited in an autosomal recessive way. It is caused by a problem with the enzyme that usually breaks down the amino acid leucine. This amino acid accumulates and is toxic at high levels, causing an ‘intoxication’ encephalopathy. The sweaty feet smell is stronger without treatment or  during acute exacerbations. 
  • Maple Syrup Urine Disease (MSUD) is another organic acidaemia, associated with sweet smelling urine during decompensation. These children cannot break down leucine, valine and isoleucine. They may not have hypoglycaemia, hyperammonemia or acidosis and, if not picked up on newborn screening, can be diagnosed late, resulting in neurological sequelae.
  • Sick neonates with metabolic acidosis, increased anion gap and mildly elevated ammonia may have an organic acidemia.
  • Treatment is to stop feeds, prevent catabolism with 10% dextrose (and standard electrolytes for IV maintenance) and cover for sepsis with IV antibiotics, whilst considering other differentials.

The next baby you see is remarkably like Emma but with a subtle difference.

Lucy is a 3 day old baby, presenting with poor feeding, irritability and seizures at home. There has been no fever, cough, coryza, or sick contacts. 

Examination:  Awake, extremely irritable, upper limbs flexed, lower limbs extended, global hyperreflexia. No dysmorphic features . You notice that she seems tachypnoeic, although lungs are clear. 

Vitals: Temp 36.8ºC, HR 155, RR, O2 sats 98%, BP wasn’t checked. 

Glucose = 5 mmol/L Ketones = 0.1 mmol/L

VBG: respiratory alkalosis 

Venous blood gas:

  • pH: 7.48
  • pCO2: 3.1 kPa*
  • HCO3: 24 mmol/L
  • Na+: 135 mmol/L
  • K+: 4 mmol/L
  • Chloride: 99 mmol/L

*1kPa = 7.5mmHg

What are the key differences between Lucy’s and Emma’s presentations?

What is the anion gap? 

What does a respiratory alkalosis make you suspicious of?

  • Lucy is tachypnoeic and has a respiratory alkalosis
  • Emma, on the other hand, had a metabolic acidosis with a normal respiratory rate
  • AG = 16 mEq/L
  • (Na + K) – (HCO3 + Cl) = (135 + 4) – (99 + 24) = 139 – 123 = 16
  • Unlike Lucy’s case, this baby has a normal anion gap.

Hyperventilation

The lab phones you with Lucy’s ammonia result. It’s 1250.

  • This baby have a neurological acute presentation, with respiratory alkalosis and extremely elevated ammonia –  suggestive of a urea cycle disorder
  • High ammonia stimulates the brain stem respiratory centre, causing hyperventilation and, as consequence, respiratory alkalosis 
  • Overall treatment is similar to case 1: cover for sepsis, manage seizures and consider differentials. 
  • As with organic acidaemias, the initial (specific) treatment requires 
  • stopping sources of protein (milk)
  • avoiding catabolism (by giving glucose IV – 2mL/kg 10% glucose) 
  • rehydration (IV fluids resuscitation and maintenance).
  • In urea cycle disorders, the toxic metabolite is ammonia, so ammonia scavengers are used, all given intravenously:
  • sodium benzoate
  • phenylbutyrate 
  • arginine
  • Urea cycle disorders are autosomal recessive inborn errors of metabolism. A defect in one of the enzymes of the urea cycle, which is responsible for the metabolism of nitrogen waste from the breakdown of proteins, leads to an accumulation of ammonia as it cannot be metabolised to urea. The urea cycle is also the only endogenous source of the amino acids arginine, ornithine and citrulline. 
  • The most common urea cycle disorder is OTC deficiency. Unlike the other urea cycle disorders (which are autosomal recessive), OTC deficiency is x-linked recessive, meaning most cases occur in male infants. Female carriers tend to be asymptomatic.
  • Classically, urea cycle disorders present in the neonatal period with vomiting, anorexia and lethargy that rapidly progresses to encephalopathy, coma and death if untreated. In these circumstances, ammonia accumulates leading to a very high plasma ammonia. 
  • Respiratory alkalosis is a common early finding caused by hyperventilation secondary to the effect of hyperammonemia on the brain stem, although later the respiratory rate slows as cerebral oedema develops and an acidosis is seen.
  • Children presenting in infancy generally have less acute and more variable symptoms than in the neonatal period and include anorexia, lethargy, vomiting and failure to thrive, with poor developmental progress. Irritability and behavioural problems are also common. The liver is often enlarged but, as the symptoms are rarely specific, the illness is initially attributed to many different causes that include gastrointestinal disorders. The correct diagnosis is often only established when the patient develops a more obvious encephalopathy with changes in consciousness level and neurological signs. 
  • Adolescents and adults can present with encephalopathy and or chronic neurological signs. 

Ammonia scavengers

  • In urea cycle defects, ammonia cannot be converted to urea so instead is converted to glutamine and glycine. 
  • Ammonia scavengers phenylbutyrate and sodium benzoate can be given – they offer alternative pathways for ammonia excretion through urinary pathways.
  • Phenylglutamine and hippurate are produced and are excreted in urine.
  • Sick neonates with respiratory alkalosis, normal anion gap and very elevated ammonia may have a urea cycle defect. 
  • Emergency treatment is the same as for an organic acidaemia plus ammonia scavengers.

Jane, 14 years old, is brought in by ambulance unconscious after a generalized tonic clonic seizures at home lasting at least 20 minutes. While doing the standard resuscitation steps, you talk to her mother. You learn that she has been a healthy child with no chronic conditions, no history of drug abuse, no acute illness. She’s a vegetarian and enjoys dancing. It’s the Coronavirus pandemic, so she has been at home for the last 3 weeks. She’s started a new ‘intermittent fasting diet’ and yesterday, hadn’t eaten since brunch. She went to bed early and this morning her mother was woken early by strange sounds coming from Jane’s room and found her seizing on the floor. 

Physical exam:  GCS 10/15, hyperreflexia. No dysmorphic features . You notice that she seems tachypneic, although lungs are clear. 

Vitals: Temp 37.4ºC, HR 112, RR 30, O2 sats 100% on supplemental oxygen (started at the ambulance),  BP 110/70 mmHg.

You send some bloods:

Glucose = 5 mmol/L Ketones = 0.1
VBG: respiratory alkalosis 
Ammonia = 650 (normal <40)
Anion gap = 15 (normal)
LFTs: slightly above reference levels
FBC, U/E, CRP  normal

What are your differential diagnoses?

What key points in this case point you towards a metabolic disorder?

  • This adolescent has an acute onset of neurological symptoms. The differential diagnoses are broad but a red flag for a metabolic condition is that her encephalopathy was precipitated by prolonged fasting. 
  • The RCPCH decon guideline lays out an approach to the child with a decreased conscious level, including differentials, investigations and management (take a look at the DeCon poster and summary guidance). 
  • All children presenting with a decreased conscious level, regardless of age, should have an ammonia sent as part of their initial investigation in ED.
  • In late onset urea cycle defects, acute metabolic encephalopathy develops following metabolic stress precipitated by a rapid increase in nitrogen load from
  • infection, trauma, rapid weight loss and auto-catabolism, increase in protein turnover from steroids, surgery, childbirth or other precipitants of protein catabolism.
  • Adolescents and adults with an undiagnosed urea cycle defect may be completely fit and well, but may have chronic symptoms such as headache, cyclical vomiting, behavioural difficulties, psychiatric symptoms or mild learning difficulties.
  • They may be selective vegetarians, restricting their protein intake.
  • Between episodes patients are relatively well. However, acute presentations can be fatal or patients may be left with a neurological deficit, so the learning point is to always send an ammonia in any child presenting with an acute encephalopathy.
  • Two cases reports your team may find interesting

Send ammonia as part of your investigation of adolescents presenting with a decreased conscious level 

It’s 11am on Easter Monday in Dublin. Ellie-Mae is a 6 day old baby, born at 37 weeks via SVD,  in Wales while her mother was visiting some friends. When Ellie-May was 3 days old her mother returned to Ireland to stay with her own mother, for some early baby support. Since day two of life Ellie-Mae has been vomiting after feeding. She is bottle fed and since yesterday she has only been accepting half of each bottle, but mother thought it was tiredness from the long trip.

Ellie-Mae’s mother brought her to the ED this morning because she has been quiet, hasn’t been crying as usual with nappy changes and seemed too sleepy to take this morning’s bottle. 

Pregnancy: Mother 21 years old, G1P1, no problems. 

Birth: SVD at 37/40, BW 2.9kg, no resus, no NICU.She was jaundiced on the second day of life, but below phototherapy levels. 

Family history: healthy parents from the Irish Traveller Community. 

Physical exam: Weight 2.45kg (16% below birth weight), jaundiced, lethargic. Anterior fontanelle is sunken, and Ellie-Mae looks dehydrated. You can palpate the liver 2 cm below the right costal margin. No spleen palpable. Otherwise no positive findings.

Vitals: Temp 37ºC, HR 185, Capillary refill time 3 seconds, RR 55, BP systolic = 102 mmHg (crying), O2 sats 97%

What are the red flags in Ellie-Mae’s case?

  • History: vomiting and lethargy
  • 16% weight loss by day 6 of life
  • Examination: jaundice and a palpable liver

You take some bloods:

Glucose 2.0mmol/L
Ketones = 6 mmol/L
VBG metabolic acidosis – hyperchloremic

Venous blood gas:

  • pH: 7.32
  • pCO2: 4 kPa
  • HCO3: 20 mmol/L
  • Na+: 135 mmol/L
  • K+: 3.5 mmol/L
  • Chloride: 95 mmol/L

When you see Ellie-Mae’s low glucose level you send a hypoglycaemia screen.

You also send FBC, U&E, LFTs, clotting, ammonia and blood culture.

LFTs: AST 70U/L, ALT 75U/L, Bilirubin total 255 µmol/L, direct 60µmol/L,  Alkaline phosphatase  270U/L
INR 1.8
Ammonia 47

How do you investigate hypoglycaemia?

What treatment do you want to start in ED?

Do these tests make you suspicious of any diagnoses?

  • Discuss your institution’s hypoglycaemia guideline – which tests to send, where to find the bottles and Guthrie cards.
  • Hypoglycaemia, this neonate has hepatomegaly and raised liver enzymes point towards a diagnosis of galactosaemia.
  • Some countries screen for galactosaemia in their newborn screening programmes (Ireland, UK, New Zealand, some parts of Australia). Because of its autosomal recessive inheritance, galactosaemia is more common in some ethnic groups. 
  • In the Irish travelling community, for example, the incidence is higher than the rest of the populations, so babies born to parents from the travelling community are specifically screened on day 1 of life in Irish maternity hospitals. The baby’s diet should exclude galactose, so newborn babies of Irish travelling families are given soy-based formula rather than breast feeds or standard formula until their screening test result is known.
  • The initial investigation and management of hypoglycaemia: this baby needs Glucose 10% 2mL/kg IV as soon as possible. Collect blood prior to treatment.
  • Management is similar to the previous cases: 
    • Clinical stabilisation
    • Antibiotics
    • stop feeds
    • Correct hypoglycaemia with 2ml/kg 10% 
    • Give maintenance fluids with electrolytes to maintain hydration as per your local policy

Galactosaemia occurs due to a defect in the enzyme galactose-1-phosphate uridyl transferase (GALT). It presents after the affected patient receives the sugar galactose, present in milk. Accumulation of galactose-1-phosphate results in damage to the brain, liver, and kidney. The affected neonate presents with vomiting, hypoglycaemia due to an inability to metabolise glucose, feeding difficulty, seizures, irritability, jaundice, hepatomegaly, liver failure, cataracts, splenomegaly, and Escherichia coli sepsis. The condition presents with metabolic acidosis. Source: Gene Reviews 

Liz is a 3 year old girl from the countryside, who is visiting her grandmother in the city. She has been having diarrhoea since yesterday and started vomiting last night. In the last 3 hours she hasn’t been able to tolerate anything orally. There has been no fever or respiratory symptoms and she is passing urine as normal. Her 5 years old cousin has similar symptoms. 

Her Grandmother informs you that Liz has MCAD deficiency and her emergency plan was tried at home, without success. Liz is not usually treated at your hospital and you don’t have her chart. Unfortunately Liz’s grandmother didn’t think to bring the plan to hospital. 

Physical exam: Liz looks tired and is mildly dehydrated, but smiles at you. Her heart sounds are normal and her chest is clear. She has increased bowel sounds, a soft abnormal with mild diffuse pain on deep palpation and no masses or organomegaly. 

Vitals: Temp 37ºC, HR 165, capillary  refill time 3 seconds, RR 32, BP systolic = 104mmHg, O2 sats 97% in air.

Glucose 2.5 mmol/L, Ketones 0.4 mmol/L

What is the priority in Liz’s treatment?

Is her ketone response appropriate to the degree of hypoglycaemia? 

Liz’s grandmother told you Liz has MCAD Deficiency, but what is it?

Where can you find resources to help you manage Liz?

Liz has MCADD and needs extra calories when she is sick. The most important intervention is to give simple carbohydrates by mouth (e.g. glucose tablets or sweetened, non-diet beverages) or intravenously if needed to reverse catabolism and sustain anabolism. Liz is vomiting all oral intake so cannot tolerate oral carbohydrates, so the intravenous route is necessary.

No, it’s not. The body’s response to prolonged fasting is to break down fat to create ketones to be used as an alternative source of energy. Liz has not produced ketones, because she is unable to break down fat.

  • Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common fatty acid oxidation disorder in Caucasians in Northern Europe and the United States. Most children are now diagnosed through newborn screening
  • Children with fatty acid oxidation disorders (medium, long and short chain defects) have typical acylcarnitine patterns. This is one of the reasons acylcarnitines are sent as part of metabolic and hypoglycaemia work-ups. 
  • Clinical symptoms in a previously apparently healthy child with MCAD deficiency include hypoketotic hypoglycemia and vomiting that may progress to lethargy, seizures, and coma, triggered by a common illness. Hepatomegaly and liver disease are often present during an acute episode. 
  • Children appear well at birth and, if not identified through newborn screening, typically present between three and 24 months of age, although presentation even as late as adulthood is possible. 
  • The British Inherited Metabolic Disease Group, BIMDG, has specific guidance on their website, including
    • Correct hypoglycaemia immediately with 200mg/kg glucose: 2 ml/kg of 10% glucose or 1ml/kg of 20% glucose, over a few minutes. 
    • Treat shock or circulatory compromise with a bolus of 20ml/kg 0.9% sodium chloride. 
    • Give maintenance fluids with potassium once the plasma potassium concentration is known and the child is passing urine. 

Mike is 12 years old, presenting to the ED with cough and fever. He has been coughing for 10 days, worse progressively in the last five and febrile in the last 3 days. Since yesterday he just wants to sleep and even when afebrile he looks unwell. Appetite is poor and he has been “sipping some apple juice”. You learn from his mother that he has a condition called Mucopolysaccharidosis (MPS) type I and is on treatment with “the enzyme”. Every now and again, “he is chesty and needs to come to hospital”. 

Physical exam: Pink, hydrated, but looks sick. You notice that he is shorter than an average 12 year old boy, has hand contractures and coarse facial features. 

Cardiovascular: systolic murmur, +2/+6. Good pulse volume. Respiratory: creps and rhonchi on the right side. Abdominal exam: mild hepatomegaly. Umbilical hernia. 

Vitals: Temp 37.5ºC, HR 132, RR 30, BP systolic = 112mmHg, O2  sats 88% in air.

What is Mike’s clinical diagnosis and what treatment do you want to start in the ED?

  • Patients with Mucopolysaccharidosis don’t require any emergency treatment in the ED for their underlying metabolic disease. They are, however, at increased risk of respiratory infections.
  • Mike is likely to have a community acquired pneumonia and needs to be treated accordingly with oxygen and antibiotics.

  • In mucopolysaccharidosis disorders, the body is unable to break down mucopolysaccharide sugar chains. These mucopolysaccharide sugars buildup in cells, blood and connective tissue: hence the name, ‘storage disorders’.
  • In general, most affected people appear healthy at birth and experience a period of normal development, followed by a decline in physical and/or mental function.
  • As the condition progresses, it may affect appearance; physical abilities; organ and system functioning; and, in most cases, cognitive development. 
  • Most cases are inherited in an autosomal recessive manner, although one specific form (Type II) follows an X-linked pattern of inheritance. 
  • Specific treatment can be provided via Enzyme replacement therapy or haematopoietic stem cell transplantation in the early stages. 
  • Presently, enzyme replacement therapy is available for MPS I, II and VI and is given as an intravenous infusion either weekly or biweekly, depending on the disease. 
  • Both enzyme-replacement and haemotopoietic stem cell treatments still have gaps and few clinical trials supporting them. (rarediseases.info; Dornelles et.al, 2014).

See the American APLS online sim scenario, page 54-57:

https://www.aplsonline.com/pdfs/Simulation_Scenarios.pdf

A neonate presents with extreme irritability and vomiting. Which laboratory tests can be most helpful in identifying an underlying inherited metabolic condition?

A: Ammonia

B: Glucose

C: LDH

D: Coagulation profile

The correct answer is A.

Irritability and vomiting are unspecific presentations for a broad range of neonatal conditions. Elevated ammonia can help differentiate towards a metabolic condition, such as organic acidemias and urea cycle disorders.

Hypoglycaemia with low ketones are an _______ response, it can lead us to think of _______ diagnosis. 

A: Appropriate, sepsis

B: Appropriate, diabetes

C: Inappropriate, diabetes

D: Inappropriate, fatty acid oxidation disorders.

The correct answer is D.

The body’s response to prolonged fasting is to break down fat to create ketones that will be used as an alternative source of energy. So in hypoglycaemic states, high ketones will be observed. If ketones are low, it’s because the body is unable to break down fat properly, such as in fatty acid oxidation disorders.

Which tests are part of the investigation of hypoglycemia?

A: Insulin and GH

B: Amino acids (plasma)

C: Ketones

D: All the above

The correct answer is D.

The basic screen aims to identify the most common endocrine or metabolic conditions responsible for hypoglycemia. Usually it involves: glucose, ketones (Beta-hydroxybutyrate), insulin, cortisol, Growth Hormone (GH), ammonia, lactate, free fat acids, serum amino acids, acylcarnitines profile (Guthrie card) and urine for organic acids and ketones.

Extremely high ammonia can be usually found in which condition?

A: Hyperinsulinism

B: Phenylketonuria

C: Urea Cycle disorders

D: MSUD

The correct answer is C.

Although ammonia can be increased for a range of reasons (muscle activity, haemolysis, neonatal sepsis), however in urea cycle disorders these levels are the highest observed. The urea cycle is responsible for the metabolism of nitrogen waste from the breakdown of proteins, as one of these enzymes are deficient, it leads to an accumulation of ammonia as nitrogen cannot be metabolised to urea.

Which of the following is incorrect regarding Anion Gap (AG)?

A: The AG is the difference between primary measured cations and the primary measured anions.

B: Potassium (K+) is the most important cation for AG calculation. 

C: Commonly measured anions are Chloride and Bicarbonate.

D: AG is useful in understanding causes of metabolic acidosis. 

The correct answer is B.

If not available, the anion gap can be calculated without potassium, in this situation the reference range will be different (12 ±  4mEq/L).   

Adam , HH. Ardinger, RA. Pagon, S. E. Wallis, L. J. H. Bean, K. Stephens, & A. Amemiya (Eds.), GeneReviews® [online book].

Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics. 2000 Jan;105(1):e10.

Dornelles AD, de Camargo Pinto LL, de Paula AC, Steiner CE, Lourenço CM, Kim CA, Horovitz DD, Ribeiro EM, Valadares ER, Goulart I, Neves de Souza IC, da Costa Neri JI, Santana-da-Silva LC, Silva LR, Ribeiro M, de Oliveira Sobrinho RP, Giugliani R, Schwartz IV. Enzyme replacement therapy for Mucopolysaccharidosis Type I among patients followed within the MPS Brazil Network. Genet Mol Biol. 2014

Sanderson S, Green A, Preece MA, Burton H. The incidence of inherited metabolic disorders in the West Midlands, UK.Arch Dis Child. 2006 Nov;91(11):896-9. 

Saudubray J-M, Baumgartner MR, Walter JH. (editors) Inborn Metabolic Diseases. Diagnosis and treatment. 6th Edition. Springer 2016. 



Please download our Facilitator and Learner guides

Constipation Module

Cite this article as:
Team DFTB. Constipation Module, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27243
TopicConstipation
AuthorRebecca Paxton
Duration30-60 mins
Equipment requiredNone
  • Basics (10 mins)
  • Main session: (2 x 15 minute) case discussions covering the key points and evidence
  • Advanced session: (2 x 20 minutes) case discussions covering grey areas, diagnostic dilemmas; advanced management and escalation
  • Quiz (10 mins)
  • Infographic sharing (5 mins): 5 take home learning points

We also recommend printing/sharing a copy of your local guideline.

Billy is an otherwise well 4 year old boy who presents to A&E with a 4 week history of abdominal pain. His pain comes and goes, and seems to be worse after eating. Today he has been doubling over with pain and crying inconsolably.

He has had no fevers or vomiting. He is drinking well but parents think he is a bit off his food. His last poo was 3 days ago, and parents think it was normal but aren’t sure.

What else would you like to know?

What would you look for on examination?
How would you treat Billy?

When should he be seen again?

What is your next step if he doesn’t respond to your treatment?

Red flags – make sure learners have thought to exclude red flags in their history and examination. These include:

  • History of delay more than 48hours in passing meconium
  • Ribbon stools
  • Faltering growth
  • Abdominal distension and vomiting
  • Abnormal anatomical appearance of the anus
  • Severe abdominal distension
  • Abnormal motor development
  • Abnormal gluteal muscles or sacrum
  • Spine or limb deformity (including talipes)
  • Abnormal power, tone or reflexes
  • Safeguarding concerns
  • Ensure external examination of anus for haemorrhoids/fissures that may need treatment 
  • Treatment – assess Billy for signs of impaction and start disimpaction regime if indicated. Discuss non pharmacological treatments.
  • Counselling – prepare parents for duration of treatment, possible side effects and importance of adherence
  • Follow up – prompt and regular follow up, tailored to the families needs
  • Treatment failure – discuss reasons for treatment failure, methods to tackle common problems
  • Red flags
  • Not responding to treatment after 3 months (thyroid, coeliac, allergy) 
  • Failure to thrive
  • Safeguarding concerns

Jakob is a  9 day old baby boy who is brought to the emergency department with vomiting. He is mum’s 3rd baby. Mum is worried that he is vomiting everything he drinks, and is sleepier than she would expect. He seems distressed when awake. He is having 3-4 light wet nappies per day but has only passed a few small stools in his short life.

What else would you like to know? 

What would you look for on physical exam?

Would you order any investigations?

What is your initial management?

  • Red flags on history – delayed passage of meconium and bilious vomiting
  • Examination- look for abdominal distention, careful examination of external genitalia and anus. Document weight and weight loss.
  • Discussion of PR examination – should only be performed by experienced practitioner. May result in forceful expulsion of gas/stool (highly suggestive of Hirschsprung’s). 
  • Investigations – order in consultation with surgical team. Consider abdominal XR to assess for obstruction but keep in mind the surgical team will likely perform contrast study. Rectal biopsy (under surgeons) for definitive diagnosis. 
  • Initial management – resuscitation. NG tube and IV fluids, correction of any electrolyte abnormalities. Look for signs of sepsis (enterocolitis).

Lily is an 8 year old girl with Trisomy 21. She had an AVSD repair as an infant, and is otherwise well and takes no medications. She has been referred to A&E by her GP with worsening constipation. She has been constipated on and off for most of her life, but this has usually been easily managed with movicol. This time around, she has been constipated for 3-4 months and is passing painful, hard stools approximately once per week. Her GP started her on movicol 3 months ago, which parents say she has been happily taking but it doesn’t seem to be working. 

What else would you like to know?

What investigations would you order?

What do you think might be going on?

How would you treat Lily?

T21 and constipation. Constipation is very common in Trisomy 21. Most often it is not due to an underlying disease, but a combination of low muscle tone, decreased mobility and/or a restricted diet. However, T21 is associated with an increased risk of autoimmune disease, including thyroid dysfunction, diabetes and coeliac disease – all of which might cause constipation.

Investigations can be done in an outpatient setting, in this scenario should be followed up by a community paediatrician. Screen for all of the above.

Laxative treatment is unlikely to be entirely effective until the underlying problem is corrected. However, depending on the severity of symptoms treatment escalation is appropriate. Lily doesn’t have any symptoms if impaction, but it may be worth escalating her movicol dose or considering the addition of a stimulant laxative whilst awaiting test results.

Advanced Case 2 (20 minutes)

Georgie is a 12 year old girl with severe autism. She is non verbal. She is otherwise well, but has had trouble with constipation in the past. Her parents attribute this to her being a “picky eater”. Georgie has had abdominal pain for the last 2 weeks, and has been passing small, pellet – like stools every 4-5 days. She has been having more “accidents”, and has been back in nappies for the last 7 days. She has been seen by the GP who has diagnosed constipation and prescribed movicol. She took this as prescribed for the first couple of days, but she is now refusing her medications. Over the past 4 or 5 days, Georgie has begun to refuse all food and will only drink sips of juice with a lot of encouragement. When parents try to give her medications or take her to the toilet, Georgie becomes very upset and aggressive. Her parents are very distressed and not sure what to do.

What are your management options for Georgie? 

Children on the autistic spectrum are more likely to have problems with constipation. Often this is due to a restricted diet, but may also be due to increased levels of anxiety around toileting.

  • Georgie requires disimpaction and this is not being achieved despite the best efforts of the family. There is no right approach to this scenario. Options include
    • Optimise setting and motivators for toileting
    • Change/optimise medications – try mixing movicol into juice, try changing to lactulose, add stimulant laxative
    • Admission for washout – nasogastric tube for washout +/- enema. Strongly consider sedation
    • General anaesthetic for manual disimpaction + washout
  • Support parents and empower them in decision making process
  • Involve multidisciplinary team – community supports will be important on discharge

Macrogol laxatives may cause “lazy bowel” if used for more than 2 months. True or false?

The correct answer is false.

There is some evidence of patients developing dependence on stimulant laxatives if used long term. However, macrogols are safe to use indefinitely without complication.

Which of the following is NOT supportive of a diagnosis of idiopathic constipation?

A: Loss of appetite

B: Ribbon like stools 

C: Urinary incontinence

D: Faecal incontinence

The correct answer is B.

Ribbon like stools suggest an anorectal malformation, and any history of this warrants further investigation. Loss of appetite, urinary and faecal incontinence can all be the result of constipation or faecal impaction. 

In a child with abdominal pain, the diagnosis of UTI makes constipation less likely. True or false?

The correct answer is false.

Constipation can lead to urinary retention and UTI, and as such the two can, and often do, co-exist.  A positive urine dip or culture doesn’t rule out constipation as a cause of abdominal pain. Don’t forget to think about constipation in the child with a history of recurrent UTI. 

National Institute for Health and Care Excellence. Constipation in children and young people. London: NICE, 2014. Available at www.nice.org.uk/guidance/qs62 

The Royal Children’s Hospital. Clinical practice guideline on constipation. Melbourne: RCH, 2017. Available at www.rch.org.au/clinicalguide/guideline_index/Constipation

Zeevenhooven J, Koppen IJ, Benninga MA. The new Rome IV criteria for functional gastrointestinal disorders in infants and toddlers. Pediatr Gastroenterol Hepatol Nutr 2017;20(1):1–13.

Sampaio C, Sousa AS, Fraga LGA, Veiga ML, Netto JMB, Barroso Jr U. Constipation and lower urinary tract dysfunction in children and adolescents: a population-based study. Frontiers in pediatrics 2016;4:101.

Youssef NN, et al. Dose response of PEG 3350 for the treatment of childhood fecal impaction. Journal of Pediatrics. 2002;141(3):410-4



Please download our Facilitator and Learner guides

Headaches Module

Cite this article as:
Anna McCorquodale. Headaches Module, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27380
TopicHeadaches
AuthorAnna McCorquodale + Arie Fisher
Duration1-2 hours
Equipment requiredNone
  • Basics (10 mins)
  • Main session: (2 x 15 minute) case discussions covering the key points and evidence
  • Advanced session: (2 x 20 minutes) case discussions covering grey areas, diagnostic dilemmas; advanced management and escalation
  • Sim scenario (30-60 mins)
  • Quiz (10 mins)
  • Infographic sharing (5 mins): 5 take home learning points

We also recommend printing/sharing a copy of your local guideline.

https://www.headsmart.org.uk/symptoms/sam-animation/ (2 min video) headsmart website contains around 20 min of reading around symptoms which could suggest an intracranial tumour

https://pemplaybook.org/podcast/pediatric-headache-some-relief-for-all/ (30 mins)
A good podcast including risk stratification, diagnosis and management of headache 

https://www.nice.org.uk
Quality standard 42 and clinical guideline 150

https://pemcincinnati.com/blog/headaches-in-the-pediatric-ed/

https://www.pemcincinnati.com/podcasts/?p=89

This is a lecture and a podcasts from PEM Currents which talks succinctly about the emergency management of migraine in ED and the likely treatment outcomes.

https://www.researchgate.net/publication/327473427_Cognitive_bias_in_clinical_medicine

https://miro.medium.com/max/800/1*yN2Xhv-M5PPerWzDVNt3sw.jpeg

Lecture by a US doctor specialising in headaches. Great review over the first 18 min of both the history and examination red flags and where she considers imaging. The second half is a question and answer session which is less useful.

(30 min video)

This is a lecture from a 2016 conference. It is pretty involved in the chronic management of headaches in children so quite advanced for the majority of attendees but might interest paediatricians who run follow up with outpatient clinics.

Headaches are common in children with 75% of children having experienced a headache by age 15. Our primary jobs in emergency are to provide effective symptom relief and filter out the headaches that are more likely to be concerning in their origin. The aetiology of headaches relies enormously on the history and, even in sinister causes, there are often few or no examination findings.

The most common cause of headache in children is a viral infection and the most worrying an intracranial space occupying lesion. Happily the latter is rare.

A good history is key:

  1. Onset, gradual or sudden?
  2. Location & severity, these questions will be incredibly age dependent. Younger children find localisation of pain difficult.
  3. Duration of the problem? How many times has this been reviewed and by who. Is there a lead professional. Be aware of cognitive bias created at this point by knowing what labels others have used. Here there should also be some investigation into what treatment strategies have been tried previously.
  4. Timing and associated symptoms? Compare a morning headache with some nausea/vomiting to one which worsens during the day and is relieved with sleep.
  5. Background medical history
  6. Family history sp of migraines. The presence or absence of this can be incredibly important when establishing aetiology. High prevalence of migraines running in families.

Full examination is necessary but here it should be stressed that abnormal neurological findings are rare in children with headaches. Where they exist there is a clear reason to pursue investigation by imaging, however, their absence cannot be wholly reassuring.

A 12 year old boy is brought to ED with a headache. He does not ordinarily suffer from headaches but today came home from school with a throbbing headache on the right side of his head. It is now 8pm and there has been no change. He has never been seen for headaches before but had a number of attendances for abdominal pain between the ages of 5 & 9 years.

On examination  you see an afebrile child, holding his head with his eyes closed. His neurology is otherwise normal (GCS 14 M 6 V 5 E 3).

What additional information would you consider important in the history?

What would be your next management steps?

Would you discharge this child?

With the additional history what are we trying to establish? Is this a primary or secondary headache. Here the presence of a family history of migraine can contribute to a likely ‘primary headache’ history. We also need to be clear about whether there is any possible infectious aetiology. How do we distinguish between a viral infection with a headache and meningitis? 

Clinical features suggestive of meningitis in children: a systematic review of prospective data, Curtis et al, Pediatrics 2010 – Having either a bulging fontanelle or neck stiffness (older child) increases the likelihood of meningitis by 8 fold

Without either of the above treating symptoms and re-evaluating seems reasonable.

  • The ongoing management of this child is based around clinical judgement of the underlying cause. There aren’t any features of space-occupying lesion (SOL) so it seems reasonable to proceed with either simple analgesia (with an antiemetic if migraine seems likely).

Treatment of pediatric migraine headaches: a randomized, double-blind trial of prochlorperazine versus ketorolac, Brousseau et al, Annuls of Emergency Medicine 2004

  • Migraine symptoms more optimally treated with analgesia with additional antiemetic with >90% resolution of symptoms at 3 hours compared to either analgesia alone (55% symptom resolution) or antiemetic alone (85% resolution)
  • https://bpna.org.uk/uploads/pet/chat-pre-course-june-2017.pdf Offer combination therapy with an oral triptan and an NSAID,or an oral triptan and paracetamol,for acute treatment of migraine with or without aura.
  • https://www.rch.org.au/clinicalguide/guideline_index/Headache/ Acute migraine management on presentation to ED to consider is Chlorpromazine 0.25mg/kg (max 12.5mg) IV over at least 30 minutes with 10 – 20mL/kg sodium chloride 0.9% (max 1L); may cause hypotension, monitor BP.

A 2 year old girl is brought to your emergency with a headache. She has been unsettled at night and wakes slapping the back of her head. She has been seen on four previous occasions over a 5 month period with similar presentations (varying grades of staff involved including a paediatric consultant).

The first presentation was related to the appearance of her molars, an MRI was booked but cancelled as symptoms had resolved when the molars erupted. Subsequent attendances have been documented as teething.

The parents history corroborates the above. She is waking at night with increasing frequency and have come today because it has been worse over the past week. Full neurological examination is normal and she is developing normally. There are some areas of white bulging on the lower gums.

Are there any features here which suggest additional investigation is necessary?

  • If so, what would you plan?
  • If not, how do you proceed

What non-medical features of this cases should we be aware of?

  • There are red flags in this history, however, due to the ages of the child these are difficult to clearly elicit through the history. Waking at night holding the occiput would seem unusual and a primary headache at this age is less likely.
  • Given that clinical examination findings are unlikely even in sinister diagnoses, we should endeavour to find those red flags embedded in the history.
  • There are no neurological examination findings and the behaviour change is not sustained so here evidence would suggest that, although imaging is required, it should be of the most optimal type ie MRI

Children with headache suspected of having a brain tumor: a cost-effectiveness analysis of diagnostic strategies, Medina et al, Pediatrics 2001

  • Here is an optimal time to discuss cognitive bias. Many people had seen this child before, it is easy to ‘plan’ an MRI in a teaching session on headaches but in reality, if your consultant had seen and discharged this child with a diagnosis of teething how would you actually feel?
  • Much has been written on cognitive bias in business and it has been extrapolated to clinical medicine.  It could be useful to explore way we can individually become more aware of this as a process in day to day practice. (www.researchgate.net/publication/327473427_Cognitive_bias_in_clinical_medicine)

A 13 year old boy presents with a headache. He has been seen on four previous occasions spanning your hospital and another local emergency department over a 6wk period. His mother is particularly distressed by the headaches as she has previously lost a child. The boy’s mother clearly voices her anxieties and feels that things are worsening. This morning she reports witnessing an episode of vomiting with some ‘shaky walking’.

It is clear during your assessment that the boy is less concerned than his mother about these headaches. Neurological examination is normal while seated as he fears this will bring the headache back on lying down.

How do you proceed, is any further information required?

What investigations are indicated?

In practical terms this history and examination will need elucidating from both the mother and child independently being sympathetic to the overlying anxieties this mother is carrying from her deceased child. In saying this, there are already red flags appearing here:

  • Worsening headaches
  • Morning vomiting
  • Shaky walking (might indicated cerebellar signs)
  • Refusal to move to a supine posture

Again, we have a normal neurological examination (aside from the whole examination being conducted in a seated position).

How is imaging arranged within your department? This boy does require neuroimaging, but what would happen, CT or MRI? Does a refusal to lie down constitute enough information for a non-contrast CT head in emergency?

As you are deciding to neuroimage this child, you may wish to discuss:

  • Process of gaining CT at different times of day
  • Who reports this
  • If there are abnormalities on the imaging suggestive of raised intracranial pressure, what are the local arrangements to discuss this and where will definitive treatment be arranged?

A non-contrast CT head was undertaken which showed an obstructive posterior fossa mass requiring intervention by neurosurgery. The child required urgent transfer to a different unit for definitive treatment. Some further discussion points could be:

  • How is a time critical transfer arranged in you department?
  • What staff should go and what skills set would be required?
  • What would you prepare for if you were transferring this child (not ventilated, with a 6 week history of headaches but whom you now know has significant hydrocephalus)?

A 14 year old girl arrives immediately following an ophthalmology appointment for a general paediatric review. She has been suffering from mild headaches which have been controlled with simple analgesia for 2 months. These last from 1-4 hours, usually after school and have not worsened over this period. In the past 4 weeks she has become more aware of intermittent visual changes. She sees flashes of colour or ‘lego bricks’ which fall across her vision. This occurs daily, usually in the afternoon. Her ophthalmology appointment was unremarkable, including fundoscopy.

She is afebrile and lucid with no headache currently. Full neurological examination including co-ordination is normal.

Does this girl fit criteria for additional investigations?

What would you do?

You are intending to discharge her, what follow up should be arranged?

We refer back to:

Children with headache suspected of having a brain tumor: a cost-effectiveness analysis of diagnostic strategies, Medina et al, Pediatrics 2001

as an evidence base for imaging. She would not meet the criteria for urgent imaging. Consensus opinion from the American Academy of Neurology would suggest neuroimaging should be considered on the basis of new headaches with some features suggestive of neurological dysfunction. With a normal neurological examination, which here includes fundoscopy by an ophthalmologist, time is on our side so if imaging is pursued this should be MRI. Here it might be pertinent to consider other investigative strategies:

  • Would blood tests offer additional value? If not in this particular case then might they help in the context of low grade fever?
  • Would you consider an EEG?

In this case headaches aren’t really the major feature as they are easily controlled with analgesia. These do not sound epileptic – episodes are too frequent to not have a non-visual epileptic manifestation by now and the associated headache is not severe so an EEG may not be helpful. In childhood, migraine can encompass many other features and headache may not be the most prominent. Where patients are being discharged counselling/advice cannot be underestimated. A headache (or symptom in this case) diary can be a fast track to diagnosis in the outpatient setting and can easily be started from an emergency setting. Taking the time to talk about what your number one diagnosis is, and what environmental strategies might help and what features should prompt a further review, prior to discharge is vital.

A 10 year old boy presents with a 2 day history of a headache. He was referred by the GP to rule out meningitis. He appears uncomfortable but is alert and cooperative. The pain is throbbing and bilateral with a degree of photophobia. There is nausea but no vomiting. He is coryzal and has a temperature of 37.8C. The heart rate is 105 BPM and oxygen saturation rate 99% in room air. Neurological examination does not reveal any abnormalities and he has no problem lying flat for the exam. There is no meningism. On systemic examination there is only mild costophrenic tenderness.

What is the next best step in the management of this patient?

If a urinalysis is requested it shows microscopic haematuria and microscopic proteinuria but no pyuria.

What is the next step?

Participants may become fixated on headache characteristics at this point and may wish to ask additional questions about the character, timing and intensity and about associated symptoms. But these are vague and unspecific in this case. There is a heavy clue in the systemic findings including a mild tachycardia, low grade pyrexia and costophrenic tenderness. This is where the focus should shift towards investigating the cause of all of the patient’s findings, not just the headache.

The blood pressure was intentionally omitted from the vignette, an omission which also occurs frequently in real life. If it is requested it’s revealed to be 161/102. If it is not requested the vignette can continue with the patient developing seizures, which constitutes hypertensive emergency. The cause appears to be renal and the history, clinical findings and urinalysis are more in keeping with glomerulonephritis then acute infection. The most likely is IgA nephropathy. The management is behind the scope of this discussion – starting an anti-hypertensive and consulting a renal service is appropriate in the first instance. Here it is demonstrated that headache can be a sign of systemic illness and a thorough history and exam is always required including a full set of vital signs.

A 12 year old girl presenting with a 2 month history of headache. The pain is throbbing, bilateral, worse at night and is accompanied by nausea. She is anxious as the headache is now affecting her sleep. The GP started her on Amitryptiline but she stopped it due to daytime somnolence. She has a history of chronic abdominal pain. There is a family history of essential hypertension and diabetes. She has long been bullied about her weight. Her BMI is >99th centile.

Her fundscopy examination is shown.

Are there any red flags in the history?

What is the most likely diagnosis and the differential diagnosis?

What are the most important aspects of the exam?

This patient has symptoms which could suggest increased intracranial pressure. Given the history idiopathic intracranial hypertension is probably most likely but other causes like mass or syringomyelia must be considered. If these are ruled out than a primary headache disorder is most likely. Participants will likely list important aspect of the neurological examination. Visual fields and extraocular movements are of particular importance to screen for complications of ICP and a thorough screen for lateralizing signs to outrule mass. Ultimately this patient will need a scan prior to lumbar puncture but these findings will determine urgency.

A bedside fundoscopy can be used as a test for papilloedema but is it really possible? Most children are not fully cooperative and most ED are equipped with direct ophthalmoscopes which give a very small field of view (a panoptic ophthalmoscope is better). Additionally, the exam is usually undilated, adding another layer of difficulty. Overall a reliable ophthalmoscopy under these conditions requires significant expertise, so it should not be relied on unless a specialist is available. If the history is concerning, than the child should be worked up.

Which of the following is not a sign of raised intracranial pressure when co-existing with a headache?

A: Increasing head circumference in <1 year old

B: Vomiting

C: Behavioural change/irritability

D: Fever

E: Waking from sleep with pain

The correct answer is D.

Fever may suggest meningism but not raised ICP. All the others are concerning features of raised ICP.

What is the investigation of choice in headaches with clinical neurological signs?

A: MRI

B: Non-contrast CT

C: EEG

D: Bloods including infection markers/clotting profile

The correct answer is B.

Children who present with headaches and clear neurological signs are the cases where an in department non-contrast CT is indicated. Where there are no clinical findings MRI is the preferred imaging modality.

In paediatric migraine, what is the most effective single treatment for children presenting to emergency?

A: Analgesia

B: Rest and reassess

C: Modify environmental factors

D: Antiemetic

E: Keeping a headache diary

The correct answer is D.

All of the above have a role in the treatment of migraine, however, in the acute setting evidence points to antiemetics are most effective in symptom relief. Analgesia and antiemetics together are even more beneficial. Modification of environmental factors, including rest/exercise/diet and keeping a diary of symptoms will not help acutely but hand some control to the patient in the long term management of symptoms.

https://www.headsmart.org.uk/

Clinical features suggestive of meningitis in children: a systematic review of prospective data, Curtis et al, Pediatrics 2010

Treatment of pediatric migraine headaches: a randomized, double-blind trial of prochlorperazine versus ketorolac, Brousseau et al, Annuls of Emergency Medicine 2004

https://bpna.org.uk/uploads/pet/chat-pre-course-june-2017.pdf

https://www.rch.org.au/clinicalguide/guideline_index/Headache/ www.researchgate.net/publication/327473427_Cognitive_bias_in_clinical_medicine

Children with headache suspected of having a brain tumor: a cost-effectiveness analysis of diagnostic strategies, Medina et al, Pediatrics 2001

https://pemplaybook.org/podcast/pediatric-headache-some-relief-for-all/

https://pemcincinnati.com/blog/headaches-in-the-pediatric-ed/

https://dontforgetthebubbles.com/non-specific-symptoms-in-the-emergency-department-are-you-headsmart/



Please download our Facilitator and Learner guides

Febrile Child Module

Cite this article as:
Team DFTB. Febrile Child Module, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27356
TopicFebrile child
AuthorSarah Timmis
DurationUp to 2 hours
Equipment neededNone
  • Basics (10 mins)
  • Main session: (2 x 15 minute) case discussions covering the key points and evidence
  • Advanced session: (2 x 20 minutes) case discussions covering grey areas, diagnostic dilemmas; advanced management and escalation
  • Sim scenario (30-60 mins)
  • Quiz (10 mins)
  • Infographic sharing (5 mins): 5 take home learning points

We also recommend printing/sharing a copy of your local guideline.

The expectation is for the learners to have watched or read one of the basic links before the session.

What is the deal with fever? a good overview of the approach to a febrile child

NICE fever guidelines for kids • LITFL covers the NICE guidelines, plus a bit more

If you prefer to listen rather than read, there is a podcast that although long, is worth listening to and covers the approach to a febrile child: (1hr 14 minutes)

Pediatric Fever Without A Source

Fever is one of the most common presentations to the paediatric emergency department; it scares parents and it makes children miserable. So why does fever occur? A fever is a natural physiological response to infection. It occurs when either an exogenous (eg micro-organisms) or endogenous (eg TNF, interleukin-1 or 6) pyrogen is activated. These pyrogens, via a number of mechanisms, activate the anterior hypothalamus which ultimately results in an increase in body temperature (The pathophysiological basis and consequences of fever).  

This is crucial to understand – your body is in control of your temperature. This is not something an infection is doing to your body; it is something your body is doing to the infection. Of note- this is different from pathological hyperthermia, where your temperature is elevated by either hypothalamic dysfunction or external heat. These are extremely rare. (Hot Garbage: Mythbusting fever in children)

The process of having a fever is believed to be a beneficial response to an infection. The mechanisms by which a fever helps protect you from infection include:

  1. Higher temperatures inhibiting growth/replication of pathogens
  2. Higher temperatures promoting the immune response to infection
  3. It is also worth noting that bacteria are killed more easily by antibiotics at higher temperatures, so there is also a potential third mechanism.

With all this considered, it is not the presence of the fever that is the issue, but what the reason behind the fever is. This is what we, as clinicians, need to discern. First of all, is it infection (most likely in the paediatric population), if so, is this a serious infection? Or is the fever caused by something else (malignancy, drugs, autoimmune, endocrine)?

A father attends the ED with his 4 year child, who has a 2 day history of fever, his most recent temperature was 39.9oC and this has prompted his visit to the emergency department. The father describes his child as being otherwise well, but is extremely concerned about the height of the fever.

Describe how you would assess the child?

What investigations and treatment options would you consider?

You are happy with your assessment of the child, and would like to discharge him, however his temperature is 38.5oC. How do you proceed?

Is this child sick?

The Paediatric Assessment Triangle (from DFTB)

In some instances it will be fairly obvious if the child is unwell, they just ‘look unwell’. A tool that can help you put a system to this assessment is the paediatric assessment triangle. Which considers the childs: appearance, breathing and circulation. This will let you consolidate what you are worried about and allow you to communicate this to your colleagues. 

If all these appear to be in order, this is a reassuring sign. A happy child playing in the waiting room, whilst eating a packet of crisps is much less likely to be unwell with a serious bacterial infection than one that is quiet. Remember to write what you have observed in your notes. 

NG143 Traffic light tool (from NICE)

Once you have some observations you can also use the NICE traffic light table – which helps categorise children into green (well), amber or red (potentially unwell). If they score red, you know they need further workup, and potentially quickly. Green, then they can probably wait a bit to be seen. 

Take a full paediatric history, specifically asking about:


Normal self?
Eating and drinking?
Passing urine?
Bowels opening?
Drowsy?
Pulling at ears?
Vomiting?
Rash/ lumps and bumps?
Siblings, anyone else unwell?
Travel?
Immunisations?

This should also give you an idea about how worried the parents are, is it just the temperature, or is it something else? A high fever with a child who seems their normal self is far less concerning than a child with a normal temperature that just isn’t right.

This needs to be thorough, given that the majority of these kids will be discharged without further investigation. This means looking in ears and throats, looking at the skin hidden under clothing, looking at joints, feeling pulses. So undress the child. You may find a petechial rash, a lump, or more likely, some very enlarged tonsils. Get the child to walk if they are old enough, and stand on one leg and then the other. And when it comes to ears and throats get the parent on board and show them how to hold the child properly. 

Whilst you are hunting for the source, also note the absence of one- look for the signs of the scary infections, the petechiae, the reduced air entry on a lung base, the red knee.

Are you happy examining a child? https://vimeo.com/60599216 gives some top tips on how to examine different age groups

Also read https://dontforgetthebubbles.com/finding-fever/ for a step by step fever focussed examination guide

This step depends very much upon your assessment of the child. If you have found a source-treat that as appropriate. If full history and examination does not provide you with an answer, you have a fever with an unclear source. NICE helpfully has a set of guidelines for these: (NICE fever guidelines for kids • LITFL)

  • Investigate fever with no source if they have any red features –  this includes FBC, CRP, B/C and urine.  Consider LP, CXR, UEC and gas if indicated. 
  • Investigate fever with no source if there are any amber features unless deemed unnecessary by an experienced paediatrician. (this is the bit that could cause you to become unstuck, and you may want a senior to look over these)
  • Check urine for all children with fever (over 37.5) and no source, even if they are green (on the NICE traffic light systemt).

Consider the use of paracetamol or ibuprofen to bring down a high temperature in a hot and miserable child. If it makes the child feel better, it will make the examination process easier for everyone. NICE advises alternating antipyretics.

In many children with fever, the cause will be viral, the source of which may be obvious, or may still be unclear. If they are in a low risk group with a normal urine, they may be ok to go home with advice and a leaflet on the use of antipyretics, fluid management and safety netting advice. However as stated above these are only guidelines, if you are not happy you can always investigate, or admit for observation, and parents can always come back.

If the child has a fever but you have a well child that you have no concerns about then you do not have to wait for the temperature to come down before discharge. 

Give the parents advice on recognising red or amber signs by providing written information and/or arranging follow-up- most EDs will have a ‘fever’ leaflet to give to parents. 

Educating the parents about the nature of fever is important. Explain that “We treat fever with anti-pyretics because it makes the child feel bad, not because fever itself is bad.” Fever is due to a functional immune response. It is what is causing the fever that has the potential to do harm. As a result what the fever is, is not nearly as important as how the child looks or behaves. (The caveat being an under 6 month old where the height of fever is relevant)

On discharge tell them If the fever lasts for more than 5 days, the child should at least have a repeat physical exam by a clinician.

Finish with “But come back if you are worried about the child, even if you have only made it to the car park/ house/ doors of the ED”  
A good summary in video form on seeing a feverish child: https://rolobotrambles.com/listen-look-locate-an-approach-to-the-febrile-child-tipsfornewdocs/

A 5 week old girl has been brought in by her mother. Her mother reports the child seemed irritable so she took her temperature and it was 38.2oC. Pregnancy and birth was unremarkable and there have been no concerns since her birth. The child is feeding well and the history and examination are unremarkable, observations in the ED have been within normal limits, apart from her current temperature which is 38.5oC. Your initial assessment has not provided you with an obvious source for the infection.

When is a temperature classed as a fever?

How would you investigate this child?

How would you manage this child if they had a white cell count of 17 x109/L?

NICE consider >38oC to be a fever

RCEM considers a temperature of 37.5-38oC to be a low grade fever 

However, most people would agree that the difference between .1 of a degree is not significant, therefore infants with a temperature of 37.9 vs 38oC should be managed in the same way.

This child is under 3 months old

Any child with a fever >38oC that is under 3 months old is at ‘high risk’ of serious illness (‘red’ on NICE’s traffic light table NICE fever guidelines for kids • LITFL). If they have a history of fever, but none on assessment remember to ask about antipyretics.

According to NICE this child requires bloods (FBC, CRP, Blood cultures), a urine sample and if the history and exam suggests, a chest X-ray and/ or a stool culture.

A lumbar puncture should be considered and is indicated if the child is:

  • less than 1 month 
  • 1-3 months and unwell; 
  • or 1-3 months with WCC<5×109/L or >15×109/L.

The discussion here is if the child is ‘unwell’, or not. You have a few tools that can help you – the paediatric assessment triangle and the NICE traffic light table (referenced in the above case) can help you decide. However if in doubt, the child will be investigated, and you should be speaking to the paediatric seniors.


If this child had a WCC of 20 then this is an indication for IV antibiotics. 

IV antibiotics are required for children under the same criteria that a lumbar puncture is indicated: 

  • if less than 1 month; 
  • 1-3 months and unwell; 
  • or 1-3 months with WCC<5×109/L or >15×109/L.

The choice of antibiotic will come down to trust guidelines.

A 7 week old has been brought in by her mother because she felt very hot today, and has been ‘a bit grizzly’. Mum has given paracetamol and brought her to ED. Her temperature is 37.6oC on triage. On initial assessment you have no concerns and remaining observations are within normal limits. 

How should a temperature be taken? 

How would you investigate and manage this patient?

NICE has recommendations on this:

Do not routinely use the oral and rectal routes to measure the body temperature of children aged 0–5 years.

They advise in infants under 4 weeks: 

  • measure body temperature with an electronic thermometer in the axilla 

In children aged 4 weeks to 5 years use one of the following:-

• electronic thermometer in the axilla

• chemical dot thermometer in the axilla

• infra-red tympanic thermometer

It’s worth checking what your department uses and what the parent has been using. 
There are some small studies with low numbers of patients that suggest that layers of clothing can raise the skin temperature by up to 2.5°C with a minimal rise in rectal temperature in the very young (Feel the heat). Therefore undress children who seem inappropriately overdressed.

For this patient, guidelines are helpful, but they will not tell us what to do.

We know that 

1. Any child with a fever >38°C under 3 months old is a ‘red’ on NICE’s traffic light system, and this makes them at high risk of serious illness.

2. NICE guidelines suggest that the parents subjective perception of a fever should be considered valid and taken seriously by healthcare providers. 

There is a temptation to treat a child who is apyrexial in the department differently to one that does have a fever. Consider:

  • Has this child had an antipyretic? 
  • In the young, mums are usually right (There is a study from 1984 that shows in children under 2 yrs, mums were correct 90% of the time when they thought their child had a fever, although this dropped to 50% accuracy in over 2 year olds.)
  • Those with fever at home are equally at risk as those with fever in the department (A BMJ study reports that infants <60 days of age, with a history of documented fever are at equal risk for bacteraemia or meningitis as those with fever in the department. https://adc.bmj.com/content/103/7/665.)

So in summary, we have an infant with a normal temperature, who probably had a fever this morning. There are at least two ways of managing this, one is to treat as a fever which therefore means bloods (FBC, CRP, B/C), urine and if history suggests, a CXR and or stool culture. Given that there was parental concern this is probably the preferable option. The other is a period of observation to see how the child progresses, and see whether or not they spike a fever. 

Given that there are no clinical concerns at present, antibiotics prior to blood results are not indicated.

For a debate surrounding overtreating infants read https://dontforgetthebubbles.com/fever_under_60_days_of_age/

A 3 year old boy has returned to ED with a history of 6 days of fever, they have seen the GP twice, two and four days ago, and told it was a viral illness. However the fever is persistent and his parents are concerned. His past medical history includes two admissions for viral wheeze when he was younger, but is otherwise unremarkable. All immunisations are up to date, he goes to nursery and lives with his parents, he has no siblings but his mother is 9 weeks pregnant. On examination the child seems grumpy, he has a fever of 38.8 and a HR of 150 he has a rash across his face and torso and evidence of conjunctivitis.

You think the rash looks morbilliform, what are your concerns and how will you proceed?

What other differentials should you consider, and what examination findings would you be looking for?

How would you work this patient up?

Measles – A brief historical & clinical review

The MMR in the UK is given at 12 months and 3yrs 4 months, so this child will have had the first immunisations affording him 80-95% protection, https://em3.org.uk/foamed/15/7/2019/lightning-learning-measles. Measles therefore is unlikely but possible. Once he has had the second vaccination, this is quoted to afford 99% protection.  

Hopefully you are seeing this child in a side room, as measles can survive for up to 2 hours in air and is very contagious in the un-immunised population. 

It is likely wherever you are in the world, you will need to report this to your public health body. 

His mother is pregnant, check her vaccination status, if this is not complete and she has no history of disease, you need to advise her to see her GP ideally today, she may need a measles titre and, if this does not show previous exposure to the disease, human normal immunoglobulin (HNIG). You also need to enquire about other immunosuppressed/ non immunised contacts. 

A patient is infectious from 4 days before the onset of rash to 4 days afterwards, therefore he will need to be isolated until this period is up and nursery and other contacts need to be informed. 

Serum and saliva testing for measles is available.

Most children with measles can be discharged home

UK guidelines on managing measles exposure : Guidelines on Post-Exposure Prophylaxis for measles June 2019 

Poster: https://em3.org.uk/foamed/15/7/2019/lightning-learning-measles

Recurrent or Periodic Fevers – investigate or reassure? 

Think infection, inflammation or neoplastic. We know infection is common in paediatrics, and the other two are less so. The list of differentials is probably almost endless. There is a good article which lists a whole heap of causes of fever in children, and investigations which can be performed. 

However with this presentation, it is important to consider Kawasaki disease with this time scale of fever and measles. Other conditions worth considering are listed below: 

• Streptococcal disease (e.g. scarlet fever, toxic shock syndrome)

• Staphylococcal disease (e.g. scalded skin syndrome, toxic shock syndrome)

• Bilateral cervical lymphadenitis

• Leptospirosis and rickettsial diseases

• Stevens-Johnson syndrome and Toxic Epidermal Necrolysis

• Drug reactions

• Juvenile Chronic Arthritis

Kawasaki Disease 

You are looking for evidence of Kawasaki disease: The diagnosis is made on the basis of the following clinical criteria (A + B):

A. Fever ≥5 days

B. At least 4 of the 5 following physical examination findings:

  • 1.Bilateral, non-exudative conjunctivitis
  • 2.Oropharyngeal mucous membrane changes – pharyngeal erythema, red/cracked lips, and a strawberry tongue
  • 3.Cervical lymphadenopathy with at least one node >1.5 cm in diameter
  • 4.Peripheral extremity changes 
    • acute phase: diffuse erythema and swelling of the hands and feet
    • convalescent phase: periungual desquamation (weeks 2 to 3)
  • 5.A polymorphous generalised rash – Nonvesicular and nonbullous. There is no specific rash that is pathognomonic for KD

This child has had a fever for 6 days, is tachycardic and the source currently is unclear. It may be measles, however this is not clear cut. He is therefore not going home. Depending on other findings on examination he may also fit the criteria for Kawasaki disease he certainly needs bloods, FBC, U+E, LFTs, CRP, ESR, cultures and a urine dip. He does not require IV antibiotics at this point.

Kawasaki Disease the first 4 minutes covers the presentation and investigation of Kawasaki disease

Communication: Septic screen , taken from  Simulation Library, PaediatricFoam

Which of these is true, a 60 day old with a temperature of 38.5oC:

A: Fulfils the criteria for a lumbar puncture

B: Can be discharged without further investigation 

C: Needs IV antibiotics

D: Needs urine sent for urgent microscopy and culture

The correct answer is D.

This child will need further investigation, at the least bloods and serum cultures, however if they are well they may not necessarily need antibiotics or a lumbar puncture. All children under 3 months need urine sent, not dipped. Use dipstick testing for infants and children 3 months or older.

Which of these is false?

A: The height of the fever can make a difference to the how the child is managed

B: If a fever doesn’t reduce with an antipyretic the child needs admission to hospital

C: A 28 day old with a temperature of 38.5oC will need FBC, CRP and Blood cultures

D: It is recommended that children aged 4 weeks to 5 years have their temperature taken with an axillary probe or tympanic thermometer

The correct answer is B.

A is true because the height of the temperature does make a difference to the management of those under 6 months old

Presence of a fever, even one that does not reduced with an antipyretic is not an indication of a serious infection. It is perfectly acceptable to discharge a well child with a fever, with good safety netting. 

Which of these is true?

A: Kawasaki disease can be diagnosed with fever for > 5 days plus 3 of the B symptoms

B: Fever of over 39oC in a 3-6 month old automatically needs a full septic screen 

C: The higher the fever, the more likely it is to be a serious bacterial infection

D: Measles is infectious from 4 days before the onset of the rash to 4 days afterward

The correct answer is D.

Kawasaki disease is diagnosed with fever >5 days and 4 out of 5 B symptoms

A fever of >39 in a 3-6 month may need a full septic screen, the temperature alone would push them into NICE’s ‘amber’ category. However it depends on a few factors, including whether there is an obvious source and NICE recommends a review by an experienced paediatrician before performing a septic screen automatically on these patients. 

C is not true, there is no good consistent evidence to suggest a higher fever means a more serious infection 



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