Petechiae in Children – the PiC Study

Cite this article as:
Tessa Davis. Petechiae in Children – the PiC Study, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.30782

Today the Lancet has published the long-awaited results of the Petechiae in Children (PiC) study. Team DFTB got our hands on a pre-publication copy to read, summarise, and analyse for you. So let’s get to it.

This PERUKI study by Waterfield et al. is a prospective, multicentre cohort study:

Waterfield T, Maney J-A, Fairley D, Lyttle MD, McKenna JP, Roland D, Corr M, McFetridge L, Mitchell H, Woolfall K, Lynn F, Patenall B, Shields MD, Validating clinical practice guidelines for the management of children with non-blanching rashes in the UK (PiC): a prospective, multicentre cohort study, The Lancet, 2020

Why is this study needed?

We are all somewhat terrified of children with fever and a non-blanching rash. We don’t want to miss meningococcal sepsis. Current guidelines are based on data from before the introduction of the Meningococcal B (2015) and C (1999) vaccines and consider a prevalence of 10-20% of meningococcal infection in children with fever and non-blanching rash.

Who were the patients?

The paper looked at children under 18 years old presenting to 37 Paediatric Emergency Departments in the UK over a 16 month period. Children were included if they had a fever (>38oC) and new onset of a non-blanching rash or features suggestive of meningococcal infection. Children were excluded if they had a pre-existing haematological condition or if they already had a diagnosis of Henoch-Schonlein purpura.

1513 patients were screened. 179 were excluded due to not meeting the criteria, not consenting, or a language barrier. Five that were enrolled had incomplete data leaving 1329 children were enrolled and included – the median age was 24 months, and 59% were male. Most children were vaccinated with 73% having had at least one dose of the Meningococcal B vaccine, and 77% having had at least one dose of the Meningococcal C vaccine.

What was the intervention?

There was no intervention here. Included patients were recruited at the point of meeting the criteria, using ‘recruitment prior to consent‘ and then consent was obtained soon after (usually within 24 hours). Data were collected contemporaneously: patient symptoms, blood test results, and treatment. A positive case was identified by being positive on PCR, or with a positive growth from another body sample (e.g. blood culture, or CSF). Patients were also checked for re-attendance to the hospital within 7 days. Results were also confirmed with the Public Health Agency – as meningococcal disease is a notifiable condition, this was a good method of picking up any missed cases.

What were the outcomes measured?

The primary outcome was assessing the performance of eight clinical guidelines on identifying children with invasive meningococcal disease (NICE meningitis (CG102); NICE sepsis (NG51); London; Chester; Bristol; Nottingham; Newcastle-Birmingham-Liverpool; and Glasgow).

The secondary outcomes were: performance of the eight guidelines in identifying children with other bacterial infections; and also looking at a cost comparison of each of the eight guidelines.

What were the results?

Of all 1334 children, 86% had a blood test and 45% had antibiotics. For patients admitted to hospital, the median length of stay was one night. 11 patients were admitted to PICU (2%) and two patients died (<1%).

Eight of these 11 PICU patients had N. meningitidis as did both of the patients who died. Seven patients had invasive bacterial infection (five with pneumococcal infection, one with E. Coli, and one with Group A Strep).

19 (1%) of patients in the cohort had meningococcal disease. 17 of these had N. meningitidis B, one had N. meningitidis C, and one had N. meningitidis W. Overall there were 26 patients (2%) with invasive bacterial infection (19 with meningococcal disease and 7 with an invasive bacterial infection).

346 patients (26%) did not have standard testing, and of these 19 patients (5%) had one unplanned re-attendance within seven days. However, none of these required readmission, antibiotics, or bacterial infection.

And how did the guidelines do?

All eight guidelines identified all of the 19 cases of meningococcal disease and all 26 cases of invasive bacterial infection (so the sensitivity of all of them is 100%). Specificity varied though. The NICE sepsis guideline stratified every patient as having a bacterial infection and therefore had a specificity of zero, making it the lowest specificity out of all the guidelines (closely followed by NICE meningitis guidelines with a specificity of 1%). This strategy clearly has cost implications too which is why the two NICE guidelines were also the most expensive per patient (£660.41 for the NICE sepsis guidelines).

Coming out top of the guideline ranking was the Barts Health NHS Trust guideline with a sensitivity of 100%, a specificity of 36%, and a cost of £490.29. This makes it the most accurate and also the cheapest.

Here’s the Barts Health NHS Trust guideline:

What about when we don’t follow the guidelines?

In practice, the guidelines were adhered to in 46% of the patients in the cohort. Deviation from guidelines resulted in fewer antibiotics being given. However, it also resulted in two patients being discharged with early meningococcal disease (they were subsequently treated and did not need PICU admission). Clinician decision-making increased the specificity (i.e. clinicians treated fewer people with antibiotics who didn’t have an invasive bacterial infection), but unfortunately reduced the sensitivity to 89%. Clinician decision-making did have the lowest cost per patient.

You’ve heard the facts, but how good was the paper?

As Ken Milne says…let’s get nerdy (and consider the CASP checklist for cohort studies)

Yes.

Research without prior consent was used to avoid recruitment delaying any treatment plans. However consent was obtained as soon as possible after inclusion in the study (usually within 24 hours).

Yes. Objective measurements were used for a blood test and PCR results. Risk factors for meningococcal disease are subjective and were based on contemporaneous clinical assessment – but this is what we do in practice so is a good reflection.

Yes. Note, however, that two patients with meningococcal disease were not included – one was not enrolled and the other was deemed by local staff to be inappropriate for inclusion.

Yes.

Yes, and also results were also checked with the Public Health Agency which would have allowed pick up of any missed meningococcal positive results.

There is a 1% prevalence of meningococcal disease in a mainly immunised population of children with fever and a non-blanching rash. The Barts Health NHS Trust guideline was the most accurate out of all the guidelines and with the lowest cost per patient.

Yes.

Yes. However, they would not be transferrable to populations with lower rates of vaccine uptake or a higher disease prevalence. The data was not shared on whether those with meningococcal disease were unimmunised or not, and therefore it would be prudent to be more cautious if your patient is not vaccinated.

Previous data was from prior to the meningococcal vaccination so this is the first and largest study since then.

What did the authors conclude and what can we take away from this study?

Since the advent of a vaccination programme and increased vaccine uptake, the rates of meningococcal disease are lower. Although previous data suggested 10-20% of children with fever and a non-blanching rash had meningococcal disease, in fact this study shows that only 1% had meningococcal disease.

Using a cautious guideline like NICE results in a lower specificity and higher cost. Tailored guidelines can increase the specificity and reduce the cost per patient without compromising on 100% sensitivity. The Barts Health NHS Trust guideline was the top performing guideline.

And finally, a comment from the authors themselves:

From Tom Waterfield:

The Petechiae in Children study represents the best available evidence regarding the assessment and management of febrile children with non-blanching rashes in the UK and clearly demonstrates that a lighter touch, tailored approach, is favourable to a test/treat all approach as currently advised by NICE. Moving to a tailored approach will reduce the need for invasive procedures, improve antimicrobial stewardship and save money. 

In vaccinated populations where the prevalence of invasive meningococcal disease is low the presence of Petechiae alone should no longer be viewed as a red flag and should not be used to justify immediate treatment with broad spectrum antibiotics. The emphasis and teaching should shift away from worrying about all non-blanching rashes with greater emphasis on the importance of identifying purpuric rashes as they confer the greatest risk of invasive meningococcal disease. 

Finally the PiC study demonstrates the importance of well designed prospective research studies in identifying risk factors for sepsis. Traditional approaches utilising retrospective reporting of symptoms from convenience samples of children with sepsis results in an over estimation the risks. This in turn leads to the development of overly aggressive clinical practice guidelines that are poorly adhered to. 

Note from Tessa: I am an employee of Barts Health but was not involved in the PiC study or in writing the Barts Health NHS Trust guideline.

Paediatric dermatology

Cite this article as:
Andrew Tagg. Paediatric dermatology, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.26525

Whether it is the primary complaint or a symptom of the underlying disease many children present to health care practitioners with skin conditions.

The Skin Deep Project is a collection of photographs and descriptions of paediatric skin lesions led by Don’t Forget The Bubbles and the Royal London Hospital with contributors from all over the world. The project focuses on providing high quality, accessible images which improve the diversity available in paediatric skin images found online. This will improve identification and patient care.

But first in order to help identify skin lesions it is helpful to know the right terms to use. So let’s start there…

Basic skin anatomy

The skin is made up of three layers: the epidermis. the dermis and a layer of subcutaneous fat. The epidermis is made of many layers of epithelial cells. Near the bottom of the epidermis are melanocytes. These are a special type of cell that produces melanin, a dark pigment responsible for giving skin it’s colour. The dermis is made up of connective tissue and contains hair follicles, sweat glands, sebaceous glands, branches of blood vessels, and nerve endings. The subcutaneous fat layer below the dermis helps to give our bodies protection, regulate temperature, and anchor the dermis to structures below such as muscle or bone. It also contains blood vessels.

Skin forms a protective barrier for the body but also has multiple other functions including immunological protection, temperature regulation, synthesis of vitamin D, sensation, secretion, and excretion.

Whilst history is very important, paediatric dermatology is often truly down to the spot diagnosis. It would be great if we could just send pictures straight to the electronic medical record but this is not always possible.

Distribution pattern

Some rashes are easily diagnosed by their location – why do you think it is called Hand, Foot and Mouth? These are LOCALIZED rashes. Are they in a DERMATOMAL distribution, like in shingles or in a sun-exposed area. PHOTOSENSITIVE ares. Others are harder to place and are more GENERALIZED in their location.
The skin changes associated with eczema are more commonly seen on FLEXURAL surfaces (i.e. the creases) whereas the plaques of psoriasis are more likely to be found on EXTENSOR surfaces.

Configuration

Having figured out the distribution of the lesion it is then time to figure out the configuration. This is the pattern or shape.

Are the lesions DISCRETE (separate) or CONFLUENT (joined together)? Are they LINEAR or not? Are the TARGET lesions, ANNULAR, or DISCOID?

Primary skin lesions

Skin lesions can be primary or secondary. Primary lesions arise directly from a disease process/cause. Secondary lesions progress from a primary lesion or due to transformation from interacting with the environment (eg. heat, chemicals) or a patient’s actions (eg. picking, rubbing) .

Primary skin lesions include:

CRUST: The skin is covered in a layer of dried matter – usually serum, blood, pus, or a combination of these.


CYST: A closed cavity, filled with semi-solid or liquid material such as fluid or blood. It can be lined with epithelium or endothelium. A Cyst which is filled with pus is a PUSTULE.


MACULE: A small, flat, non-palpable skin lesion that is less than 1 cm diametre in size. Note that this type of lesion which is >1cm is usually referred to as a PATCH.


PUSTULE: A pus filled elevated skin lesion, often with surrounding erythema.


ULCER: A defect in the skin or mucous membranes (loss of epidermis +/- deeper layers. They are deep and often leave a scar when they heal


VESICLE: A well rounded, raised, fluid filled lesion which is <1cm in dimaetre (a BULLA is >1cm in size)


WHEAL/HIVE: A pink, oedematous papule from swelling in the dermis that can vary in size and shape. They are usually erythematous but can have a paler centre.

The only way to be better is to practice so dive into our gallery.

Eczema Management: Jean Robinson at DFTB19

Cite this article as:
Team DFTB. Eczema Management: Jean Robinson at DFTB19, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.21638

Jean Robinson is paediatric dermatology nurse specialist working at the Royal London Hospital. Her area of expertise is something we could all be a bit better managing – eczema. She might be one of the few people that can actually describe a rash in twenty words or less. She also knows more than just steroids and wet dressings.

 

 

 

 

 

 

This talk was recorded live at DFTB19 in London, England. With the theme of  “The Journey” we wanted to consider the journeys our patients and their families go on, both metaphorical and literal. DFTB20 will be held in Brisbane, Australia.

If you want our podcasts delivered straight to your listening device then subscribe to our iTunes feed or check out the RSS feed. If you are more a fan of the visual medium then subscribe to our YouTube channel. Please embrace the spirit of FOAMed and spread the word.

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Eczema

Cite this article as:
Davis, T. Eczema, Don't Forget the Bubbles, 2019. Available at:
https://dontforgetthebubbles.com/eczema-2/

This post is based on teaching by Jean Robinson, Clinical Nurse Specialist in Paediatric Dermatology at the Royal London Hospital; and notes by Joe Piper.

The broad principles are of eczema are:

Emollients are to put moisture into the skin

Steroids are to reduce inflammation

Note: a skin flare up is always itchy – if it’s not, then question the diagnosis.

 

Can we cure it?

Atopic eczema is seen in 15-20% of children. There is no cure, and so treatment aims to control rather than cure the eczema. The aim is to get it under control. 80% will improve by puberty/teenage years with topical treatments. There will be remits and relapses, and children and families require education and support.

50% will resolve by age 7, but be careful with the figures you share with parents, as they may be disappointed when it does not improve. 85% of eczema sufferers have mild eczema, and most start with symptoms after one year of age.

 

Bad disease is usually due to poor management from the practitioner, or being on the right treatment but having poor compliance.

Poor adherence is the number one reason for a flare. There are often lots of psychological issues: embarrassment; bullying; confusion around treatment. Well-meaning relatives/friends can give contradictory advice and suggests alternative therapies.

Families will present with a mixture of frustration, stress, reduced quality of life, and are often miserable, with sleep disturbance. Eczema needs to be taken seriously and managed well. There is a similar reduction in quality of life to families of other chronic disease patients – partly due to sleep disturbance, but also a because it is a very visible disease.

 

Management principle 1 – Bathing

Bathing was previously advised for 15 minutes daily, in lukewarm water, with added oil.

The recent publication of the BATHE trial has turned this advice on its head. The Southampton-based trial randomised 483 children with atopic dermatitis to either have emollient added to the bath for 12 months or no emollient added to the bath for 12 months. Outcomes were eczema control and eczema severity. The BATHE trial showed no benefit in adding emollients to the bath.

However, there is ongoing debate amongst dermatologists as to whether this study is applicable to those being treated by specialist dermatology teams.

  1. The BATHE trial was conducted in patients being managed in primary care.
  2. No benefit was shown in the group who bathe 4 times or less per week; however, when looking at those who bathed more frequently, a clinically meaningful benefit was demonstraed (although it was small).

So for now, our hospital-based dermatology team at my own hospital in London, still recommends emollients in bath oils.

For bath oil, use Oilatum Junior or Hydromol. Use one capful for one baby bath. If a normal bath is being used, then use two to three capfuls and make sure it is mixed in well.

Oilatum Plus has antiseptic in it, and hence can cause bad dermatitis if not mixed in water well. Many centres do not recommend this version any more.

When washing with water – use a soap-free cleanser when washing as the water on its own will dry out the skin. The most infected use Dermol 500 as a soap substitute, and it can be used on the face. Consider applying this after washing hands, at nursery (this can be hard to do at school).

These are all prescribable: we should encourage GPs and us to prescribe it, so that parents do not have to buy it (to improve compliance)

Reactions to aqueous cream in children are so common that it should only be used as a soap substitute, and not as a leave-on emollient.

 

Management principle 2 – Steroids

There are four different strengths:

Mild: 1% hydrocortisone, (Fucidin H: Fucidin & Hydrocortisone)

Moderate: Eumovate (clobetasone butyrate 0.05%) – this is the strongest you should use on the face, Betnovate RD (reduced dilution 0.025%). These can be used for those over one year (if repeated courses are needed despite the eczema not improving then the patient should be refered to dermatology)

Potent: Betamethasone 0.1%, Fucibet (fucidin & betamethasone) –  microbial resistance is high in the UK, so only use for 14 days),  Elocon (mometasone furoate). These are the strongest for the body. They can be used for short term treatment i.e. one to two weeks, but you probably need a dermatology opinion if there is no response to the initial course.

Super-potent: Dermovate (clobetasol propionate), Clobaderm. These are dermatology recommended only.

 

Know the generic names as well as the brand names and check the percentage.

Hydrocortisone cream vs ointment – ointment is oilier and better.

The cream has more water and more additives. Only give the cream if the patient doesn’t  like ointments.

Note: If very very infected and ointment will slide off, then cream has better application, but this is very rare, even within dermatology (<2%).

 

How do you apply steroids?

As a rough guide – one finger tip unit (i.e. squeezed over adult finger) should be enough to cover two adult palm-sized areas.

It is much easier to say ‘apply enough so it looks shiny’. Do all the application with a finger, not with the hand, otherwise the majority will be absorbed before it reaches the child.

Make sure steroids are applied to inflamed areas, including open areas. But don’t apply it on surgical wounds or ulcers.

Skin thinning is rarely an issue (we hardly ever see skin thinning from topical steroid use, but we see loads of under treated children) – so avoid saying ‘apply a thin layer’.

The advice should be:

  • Start with pea-sized lump
  • Apply to all of the active area, including lichenified areas, hyperpigmented areas
  • Leave the healthy bits
  • For papular areas – anything that is thickened is inflamed and needs treating with steroids

Apply steroids twice a day in general, but there is a move to use them once a day (Mometasone is once a day)

 

Which steroids to choose?

Start with hydrocortisone on the face. If the eczema is severe, you can go up to a moderately potent steroid (e.g. Eumovate) on the face and potent on the body, but often this should be discussed with dermatology, and should certainly be discussed if it is not improving after two weeks. However, be more cautious in babies – from four months of age, you can use Eumovate (moderately potent) on the body.

Do not use potent steroids without specialist advice.

Only apply the steroids to active eczema. Use the steroids for seven days, and you can stop if it has completely cleared with no inflammation. There may be a need for longer steroid use e.g. for 14 days, 28 days, or 33 days for small, persistent parts.

Chronic relapse is very common and people struggle on for long time with too weak steroids. Often it is better to then try short dose of stronger steroids. Moderate or potent steroids for short periods only can be used in the axillae and groin – it can be difficult with skin folds to get to the active area. Generally, do not use potent steroid in children (e.g. Betnovate) without specialist advice. You can go up to potent/moderately potent on scalp.

Make sure you show people how to use the steroids i.e. consider it the same as checking inhaler technique.

 

Management principle 3 – Emollients

Use the greasiest the family are happy to use. If the child has very sore skin, then 50/50 is the greasiest.

With paraffin, beware of smoking, and open fires.

Lotions are acceptable, but not as greasy, so should be used only if the family are finding a greasy emollient too difficult.

The rough estimate is using one pot every two weeks (250g-500g), and use it four times a day if it’s bad enough for hospital presentation, otherwise they can step it down to twice a day

Pump dispensers are cleaner, but you cannot use emollients in a pump dispenser. From a tub, use a clean spoon at home, ideally with a saucer. Apply the emollient in the direction of hairs, so that it does not upset hairs and potentially lead to folliculitis. After a bath, the skin is very moist and so there is better absorption.

Put the steroid on first and then wait for 20-30 minutes and then put the emollient on top.

Keep going with emollients even when the eczema is clear. If the child is still scratching, use emollients.

 

 

If you want to dive a little deeper then read these previous posts…

The basics by Dilshad Marikar

Living with eczema by Andrea Coe

Complications by Andrea Coe

Lyme Disease

Cite this article as:
Emily O'Connor. Lyme Disease, Don't Forget the Bubbles, 2018. Available at:
https://doi.org/10.31440/DFTB.16210

A nine year old girl, Skye, comes to see you with her parents. She has a two day history of a red, circular and enlarging rash on her right calf, which they describe as looking like a ‘bull’s eye’.  She has also been feeling generally unwell with headaches, muscle aches, fatigue and a fever. They tell you in passing that they came back from holiday, in Scotland, a week ago.

Scarlet fever

Cite this article as:
Tessa Davis. Scarlet fever, Don't Forget the Bubbles, 2018. Available at:
https://doi.org/10.31440/DFTB.15511

The start of 2018 has seen UK hospitals receiving an alert from Public Health England about the rise in cases of suspected scarlet fever. What is the extent of the problem and how good are we at actually diagnosing scarlet fever?

Atopic dermatitis

Cite this article as:
Pascoe, E. Atopic dermatitis, Don't Forget the Bubbles, 2017. Available at:
https://dontforgetthebubbles.com/atopic-dermatitis/

This month’s Podcast of the Month is from The Medical Journal of Australia.

In a 15 minute podcast Prof Alan Cooper (Dermatologist, Royal North Shore Hospital) discusses what’s new in eczema management and, perhaps more importantly, what hasn’t changed.

Which kids respond well to ultraviolet light therapy?

If you only get the itch to listen to one podcast this month, make it this one.

Listen to the podcast.

Kawasaki’s Disease

Cite this article as:
Alyssa Courtney. Kawasaki’s Disease, Don't Forget the Bubbles, 2017. Available at:
https://doi.org/10.31440/DFTB.12282
A four-year-old Japanese boy was brought into Emergency with 5 days of fevers, non-exudative bilaterally injected sclerae, erythematous pharynx and irritability.

Wondering about the possibility of Kawasaki Disease, I turned to check the 2017 update of the American Heart Association Scientific Statement, focusing on considering a diagnosis of Incomplete Kawasaki Disease.

 

Bottom line:

  • Unchanged diagnostic criteria of complete Kawasaki Disease (KD)
  • Refined algorithm for evaluation of suspected incomplete KD (15-20% of cases)
  • Recommended ECHO at diagnosis, and repeated at 1-2 weeks and 4-6 weeks after treatment
  • Unchanged acute management– Intravenous immunoglobulin (IVIG) single dose 2g/kg over 10-12 hours. Ideally prior to day 10. Some countries continue to use high dose aspirin for varying durations.
  • Additional therapeutic options are outlined for the 10-20% with persistent or recurrent fever
  • New model of KD vasculopathy

 

What is Kawasaki Disease?

An acute, self-limited febrile illness of unknown cause, predominantly in children <5 years. It is the most common cause of acquired heart disease in developed countries. Without pathognomonic tests, we need to detect it clinically!

 

Epidemiology

  • Most common in Japan (where it was first described) with an annual incidence of 264.8 per 100 000 children in 2012. The estimated incidence in North America is 25 cases per 100 000 children <5 years of age per year. Australia has one of the lowest reported rates (3.7 per 100 000 <5 years of age), equivalent to 50–60 cases Australia-wide per year. It is likely that the current Australian incidence is higher.
  • Highest relative risk is in Asian children, especially of Japanese ancestry
  • The ratio of males to females is 1.5:1
  • Predominantly affects children 6 months to 4 years
  • Predisposing factors have been reported inconsistently
  • In Japan, the recurrence rate is 3%, and the relative risk in siblings is ten-fold higher

 

What is the aetiology?

We have no idea why…. BUT the resultant systemic inflammation leads to associated clinical findings: liver (hepatitis), lung (interstitial pneumonitis), gastrointestinal tract (abdominal pain, vomiting, diarrhoea, gallbladder hydrops), meninges (aseptic meningitis, irritability), heart (myocarditis, pericarditis, valvulitis), urinary tract (pyuria), pancreas (pancreatitis), and lymph nodes (lymphadenopathy).

A new model of Kawasaki disease vasculopathy involves three processes impacting muscular arteries. The first is a necrotising arteritis, followed by subacute/chronic vasculitis. The final process is luminal myofibroblastic proliferation.

 

How do we diagnose it in Australia?

Diagnostic Criteria

Fever for 5 days or more (typically high spiking (>39°C to 40°C) and remittent)

Plus 4/5 of:

  • polymorphous rash (usually within 5 days of fever onset)
  • bilateral (non-purulent) conjunctival injection (usually begins shortly after fever onset and often spares the limbus, an avascular zone around the iris)
  • mucous membrane changes e.g. reddened or dry cracked lips, strawberry tongue, diffuse redness of oral or pharyngeal mucosa (oral ulcers and pharyngeal exudates are not consistent with KD)
  • peripheral changes, e.g. erythema of the palms or soles, oedema of the hands or feet, and in convalescence desquamation
  • cervical lymphadenopathy (> 15 mm diameter, usually unilateral, single, non-purulent and painful in the anterior cervical chain)

AND exclusion of diseases with a similar presentation

  • Staphylococcal infection (e.g. scalded skin syndrome, toxic shock syndrome)
  • Streptococcal infection (e.g. scarlet fever, toxic shock-like syndrome not just isolation from throat)
  • Measles
  • Viral exanthems
  • Steven’s Johnson syndrome
  • Drug reactions
  • Juvenile rheumatoid arthritis.

Trickily, these children may have a concurrent viral infection, often adenovirus. Adenovirus is more likely with exudative pharyngitis and conjunctivitis and positive PCR assay. Kawasaki disease is more likely with erythema/swelling of hands and feet, a strawberry tongue, and a desquamating groin rash.

Inflammation and crusting of a recent Bacille-Calmette-Guérin (BCG) injection site may occur.

Consider an alternative diagnosis to Kawasaki Disease if there is exudative conjunctivitis, exudative pharyngitis, ulcerative intraoral lesions, bullous or vesicular rash, generalized adenopathy, or splenomegaly.

 

What is Incomplete Kawasaki Disease?

Scarily, this is so easily missed. They make 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

Evaluation of suspected incomplete Kawasaki disease (via McCrindle BW et al. 2017)

What can we investigate?

As suggested by RCH Melbourne guidelines, all patients should have

  • ASOT / Anti DNAase B
  • Echocardiography (at least twice: at initial presentation and, if negative, again at 6 – 8 weeks).
  • Platelet count (marked thrombocytosis common in the second week of illness)
  • Consider Mycoplasma

In addition, findings can provide support when considering Incomplete Kawasaki Disease – refer to the above algorithm.

Evolution of laboratory findings via Tremoulet et al.

  • KD is unlikely if ESR, CRP, and platelet count are normal after day 7 of illness.
  • Low WBC and lymphocyte predominance suggests an alternative diagnosis
  • Leukocytosis is typical in the acute stage, with granulocyte predominance
  • Normocytic, normochromic anaemia is common during inflammation
  • CRP and ESR elevation is nearly universal, CRP normalizes more quickly with inflammation resolution. ESR is elevated by IVIG therapy.
  • Minimally elevated ESR in the setting of severe clinical disease should prompt investigation for disseminated intravascular coagulation.
  • Thrombocytosis is a characteristic feature that generally doesn’t occur until the second week, peaking in the third week, normalizing by 4 to 6 weeks
  • Thrombocytopenia can be a sign of disseminated intravascular coagulation and is a risk factor for the development of coronary artery abnormalities
  • Mild to moderate elevations in serum transaminases or gammaglutamyl transpeptidase occur in 40% to 60% of patients, and mild hyperbilirubinemia occurs in ≈10%.
  • Hypoalbuminaemia is common and associated with more severe and more prolonged acute disease
  • Urinalysis may show pyuria in up to 80% of children, non-specific for KD
  • In children who undergo lumbar puncture, ≈30% demonstrate pleocytosis with a mononuclear cell predominance, normal glucose levels, and generally normal protein levels

 

Pitfalls

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.

 

What is the treatment?

We’re aiming to prevent important coronary artery abnormalities. Timely (as soon as possible, ideally within 10 days) IVIG treatment reduces the incidence of coronary artery aneurysms (defined from absolute luminal dimensions) from 25% to 4%. Studies with additional therapies to IVIG have not substantially reduced this residual risk of 4%. Adverse effects are rare but include Coomb’s positive haemolytic anaemia and aseptic meningitis. The measles, mumps, and varicella vaccine should be deferred for 11 months unless at high risk (seek advice, may need repeat vaccination). If the diagnosis is delayed, IVIG should still be given (after the tenth day of illness) IF there is presence of fever, or continued elevation of ESR or CRP>3, indicating ongoing inflammation. Aspirin is used with the theoretical rationale of reducing coronary artery aneurysms (although there is no well-established evidence for this). In Australia, a dose of 3-5mg/kg daily from diagnosis until cardiology review at 6 weeks is routine. The newly released statement advises the administration of moderate to high-dose (80–100 mg/kg/day) aspirin is reasonable until the patient is afebrile. Patients should receive a seasonal influenza vaccination.

Fever usually resolves within 36 hours after IVIG infusion has been completed; if not, the patient is considered to have resistance to IVIG. 10-20% of patients will not respond to the single IVIG treatment dose. There is minimal data to support therapeutic agents for the child with IVIG resistance. Repeating the IVIG dose, 3 days of high-dose pulsed steroids, or 2-3 weeks of tapering prednisolone are all options. There are lower levels of evidence for infliximab and cyclosporine.

 

Coronary artery abnormalities

An angiographic study of 1100 patients showed coronary artery lesions in 24%, with aneurysms in 8% and a number of patients with stenoses and occlusions. Valvular regurgitation is usually mild to moderate in severity and resolves prior to follow-up. MR can occur after the acute stage from myocardial ischaemia. Patients after KD have been shown to have functional and anatomic abnormalities of the aorta with unknown long-term implications. Myocarditis is common during the acute illness but complete resolution is expected. Risk stratification for long-term management is based primarily on maximal coronary artery luminal dimensions, normalized as Z scores, and is calibrated to both past and current involvement. Patients with aneurysms require life-long and uninterrupted cardiology follow-up.

 

What is the prognosis?

  1. The case fatality rate is <0.1% in Japan, virtually all from cardiac sequelae.
  2. Peak mortality occurs 15 to 45 days after onset of fever, during which time well-established coronary artery vasculitis occurs concomitantly with marked elevation of the platelet count and a hypercoagulable state
  3. Coronary artery aneurysms from KD account for 5% of acute coronary syndromes (ACS) in adults <40 years of age

 

In Summary:

  • Be aware of the diagnostic criteria of complete Kawasaki Disease (KD)
  • Highest relative risk in Asian children, especially Japanese ancestry
  • Always consider incomplete KD (15-20% of cases) and refer to the algorithm if concerns, there are pitfalls!
  • Liaise with cardiology regarding an ECHO
  • Unchanged acute management– Intravenous immunoglobulin (IVIG) single dose 2g/kg over 10-12 hours. Ideally prior to day 10. Some countries continue to use high dose aspirin for varying durations.
  • Additional therapeutic options are outlined for the 10-20% with persistent or recurrent fever, minimal evidence for these
  • New model of KD vasculopathy but we are still in the dark regarding aetiology
  • Coronary artery aneurysms from KD account for approximately 5% of acute coronary syndromes (ACS) in adults <40 years of age

 

 Selected references

McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation2017;Mar 29

Yim D, Curtis N, Cheung M, Burgner D. Update on Kawasaki disease: Epidemiology, aetiology and pathogenesis. Journal of Paediatrics and Child Health 49 (2013) 704–708

Clinical Practice Guidelines, Royal Children’s Hospital, Melbourne

Kim DS, Kawasaki Disease. Yonsei Medical Journal. 47 (2006) (6): 759–72. PMC 2687814 PMID 17191303. doi:10.3349/ymj.2006.47.6.759

Yim D, Curtis N, Cheung M, Burgner D. An update on Kawasaki disease II: Clinical features, diagnosis, treatment and outcomes. Journal of Paediatrics and Child Health 49 (2013) 614–623

Tremoulet AH, Jain S, Chandrasekar D, Sun X, Sato Y, Burns JC. Evolution of laboratory values in patients with Kawasaki disease. Pediatr Infect Dis J. 2011;30:1022–1026

Dengler LD, Capparelli EV, Bastian JF, Bradley DJ, Glode MP, Santa S, Newburger JW, Baker AL, Matsubara T, Burns JC. Cerebrospinal fluid profile in patients with acute Kawasaki disease. Pediatr Infect Dis J. 1998;17:478–481

 

Teething trouble

Cite this article as:
Andrew Tagg. Teething trouble, Don't Forget the Bubbles, 2017. Available at:
https://doi.org/10.31440/DFTB.12002

As the smallest member of the clan grows older it’s time for my reality based revision to move on from normal neonates to something else. We’ve made it through neonatal nasties and tourniquets on toes. It’s something more commonplace that keeps us up at night – something we’ve all been through – teething.

Molluscum contagiosum

Cite this article as:
Andrew Tagg. Molluscum contagiosum, Don't Forget the Bubbles, 2017. Available at:
https://doi.org/10.31440/DFTB.10484

 

It started as one or two raised little bumps under her arm. They didn’t seem to bother her but as time went on they seemed to increase in number.  As a handful became too many to count her parents became concerned. What were these fleshy little lumps? Why wouldn’t they go away? Could they be catching?