Non Blanching Rashes Module

Sepsis in the setting of bacterial meningitis secondary to meningococcemia complicated by shock and raised ICP.

Neisseria meningitidis.

The rash may be absent in up to 50% of cases (in meningitis and the early stages of septicaemia). Be mindful of non-specific clinical features such as limb pain in the alert child which is present in 30 – 60% in the early stages of sepsis.

James is unstable, so do not do any investigations that would delay treatment. Do bloods (VBG, FBC, U+E, CRP, coagulation study), and take two EDTA tubes for meningococcal DNA PCR and blood culture. Microbiological confirmation is important for disease identification and the institution of public health measures. Blood cultures are positive in 50-80% of cases, and CSF cultures are positive in 80-90% of cases of meningitis. Meningococcal PCR is both sensitive (97%) and specific (99.6%) and will remain positive for several days after the start of antibiotics.

UpToDate – Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications 

Firstly, attend to ABCDEFG (don’t ever forget glucose!) H (and get help…). High-flow oxygen should be delivered routinely from the outset. If no major airway or breathing problem is present, priority is given to the assessment and treatment of the circulation. Give fluid resuscitation as required. Treat with a third-generation cephalosporin (Ceftriaxone or Cefotaxime). Add Vancomycin if Gram-positive cocci on Gram-stain. Add acyclovir if signs of encephalitis (fluctuating consciousness, motor or sensory deficits, altered behaviour and personality changes, speech or movement disorders).

Dexamethasone therapy should be administered to all patients early in the disease course with or before the initial IV antibiotics. In children with bacterial meningitis, dexamethasone appears to reduce the risk of hearing loss (particularly in those with Haemophilus influenzae type b [Hib] meningitis). However, it does not appear to reduce the risk of other neurologic sequelae or mortality.

Larger and more extensive rashes are an indicator of a greater degree of thrombocytopenia and coagulopathy (DIC) secondary to septicaemia.

UpToDate – Clinical manifestations of meningococcal infection 

UpToDate – Disseminated intravascular coagulation in infants and children 

This is purpura fulminans; it occurs in 15 to 25% of those with meningococcemia. It is the deadliest form of skin involvement secondary to meningococcal infection. It is characterized by the acute onset of cutaneous haemorrhage and necrosis due to vascular thrombosis and disseminated intravascular coagulopathy. Initially, there is cutaneous pain followed by erythema and petechiae. Ecchymoses develop and these lesions, if the course is not altered with therapy, evolve into painful indurated, well-demarcated purple papules with erythematous borders. These areas progress to necrosis with the formation of bullae and vesicles. Gangrenous necrosis can follow with extension into the subcutaneous tissue and occasionally involves muscle and bone.

These patients will benefit from fresh frozen plasma (FFP) and/or protein C concentrate. There have been no randomized controlled trials to study the efficacy of platelet, FFP, or cryoprecipitate transfusions in children or adults with DIC. Nevertheless, the use of these agents seems rational in patients with significant bleeding due to thrombocytopenia and clotting factor consumption. 

If soft tissue/skin necrosis is found, consultation with general surgery is recommended as debridement, fasciotomy, and/or amputation may be indicated based on the progression of the illness. Multi-disciplinary input from orthopaedic, vascular, and plastic surgeons may be needed for limb salvage.

Once elevated ICP is identified or suspected, time is of the essence, as it can progress to herniation and/or death.

Dexamethasone may reduce ICP by reducing inflammation as well as increasing vascular perfusion. Other strategies include head-of-bed elevation to 30 degrees, pain control, adequate sedation, fever control, hypertonic saline (2.7% in 3-5mls/kg boluses over 20 minutes) to aim for serum sodium levels of >140 or mannitol infusion and/or craniotomy.

Should intubation be required for airway protection, it should be performed by the most experienced physician, as you want to avoid hypoxia and recurrent attempts will potentially increase ICP. Once intubated, the patient should be adequately sedated with a fast-acting, easily titratable sedative such as propofol that allows for frequent repeat neuro exams such as checking pupil size and reactivity every 15 minutes. Ventilate to a lower limit of between 30-38mmHg (4-5kPa) with continuous capnography. 

James is clearly unstable so organising a CT head is not appropriate until he is stabilised. 

Symptoms of raised ICP are:

• Headache 
• Vomiting 
• Diplopia

Signs of raised ICP are:

• Decreased level of consciousness
• Tense cranial fontanelle
• Pupillary asymmetry 
• Seizures

Signs of brain herniation are:

• Pupillary dilatation
• Hypertension
• Bradycardia
• Respiratory depression

Urgent CT head is indicated in patients with these signs and symptoms once they are stabilised.  

Prophylaxis (Ciprofloxacin, Rifampicin, Azithromycin as an alternative in pregnancy) should be given to those who had prolonged close contact with the patient during the seven-day incubation period, intimate contacts, and those exposed transiently to large droplets from the upper respiratory tract of the patients during their admission to hospital e.g. those intubating or suctioning the airway without wearing appropriate PPE. 

DFTB – Quadrivalent Meningococcal Vaccination What’s The Fuss About

The quadrivalent meningococcal vaccination (MenACWY) is effective against A, C, W₁₃₅ and Y serotypes. The aim of this vaccination is to stop transmission from asymptomatic colonised people and those who are susceptible and non-colonised. Vaccination is recommended for those most at risk of invasive meningococcal disease:

• Immunocompromised patients (e.g. those with complement disorders, functional or anatomical asplenia)
• Children <2 years and adolescents (age groups where there are high carriage rates of meningitidis)
• Those living in close quarters (e.g. boarding school or college accommodation)
• Travellers to endemic areas 

The meningitis B vaccination (4C-MenB) was approved for use in Europe in 2013. It was introduced onto the UK and Irish vaccination schedules in 2015 and 2016 respectively. The current Australian National Immunisation Program (NIP) funds the MenACWY vaccine, whilst the 4C-MenB vaccine can be purchased separately for $250 – $500. 

Preliminary results have been positive – in the UK, there was a 50% reduction in the incidence rate ratio of serogroup B IMD cases in the vaccine-eligible cohort compared with the pre-vaccine period. Cases in vaccine-eligible infants halved in the first 10 months of the program. However, at this stage, the effect of 4CMenB vaccination on meningococcal carriage is not known. Data on the effect on carriage will be important for vaccination scheduling. Adolescents have the highest carriage, and if the 4CMenB vaccination is found to disrupt it, vaccinating adolescents may be an effective vaccination strategy. Many countries are waiting for post-licensure studies from those countries that have universally introduced the vaccine, such as the UK, before continuing or starting an assessment of the vaccine. These studies will be vital to filling the existing data gaps, especially around vaccine impact.

ITP – because of an isolated thrombocytopaenia with no evidence of abnormal cells on the peripheral smear.

Yes, it could. Confirmation of ITP is based on excluding other differentials such as acute leukaemia, aplastic anaemia, HUS.  A full blood count and film are usually adequate to make the diagnosis. 

Red flags that may be present in leukaemia but not ITP include hepatomegaly, lymphadenopathy, fever, weight loss and musculoskeletal pain; pancytopenia is a sign of aplastic anaemia, while the diagnosis of HUS is clinically based on the classical triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. It is important to rule out conditions such as these before making a diagnosis of ITP. 

ITP is a reduction in platelet count in the absence of any other cause (<100 × 10⁹/L).  Whilst normal platelets last eight to ten days, in ITP there are autoantibodies that destroy them in the first few hours. 

The incidence in children is approximately 4 in 100,000 in the UK. It has a peak incidence of two to five years of age (chronic ITP peaks in adolescence).  There is often a recent history (one to six weeks) of a viral illness or immunisation.

The most common sign is petechiae on the skin or mucosa – these indicate capillary haemorrhages.  Some mucocutaneous bleeding is often seen, but it is rare for this to be severe (<5%).

Other symptoms of autoimmune disorders should NOT be present in ITP – e.g. no weight loss, rashes, alopecia, or joint swelling. The examination should be normal with no hepatosplenomegaly or lymphadenopathy.

The presence of systemic symptoms such as fever, anorexia, bone or joint pain, and weight loss warrant a workup for malignancy and are not typical of ITP. 

Pediatric EM Morsel – Wet Purpura and ITP 

• There is a proposed scoring system to help determine management (Buchanan 2002), which is also solely based on clinical findings.

• Skin (degree of petechiae and bruises)
• Epistaxis (mild to active bleeding)
• Oral (petechiae on the palate to mucosal bleeding)
• Overall (mild skin findings without mucosal involvement to internal haemorrhage)

It is diagnosed by having a low platelet count with normal haemoglobin (unlike in leukaemia, TTP, HUS, and DIC). If there is a history of previous bleeding then consider other diagnoses. Bone marrow aspirate is only recommended if there is persistent bleeding in spite of a platelet count >20 × 10⁹/L.

The answer is simple: treat the patient, not the platelet count. 

Assess if the patient has haematuria, melaena, menorrhagia, epistaxis, mucosal bleeding or tonsillar purpura/petechiae.

Although there is variation between specialists, they will all be more concerned with the signs of wet purpura or haematuria rather than just the petechiae on the skin. The majority of children do improve spontaneously in 6-12 weeks irrespective of treatment. Hence if there is no significant bleeding in the first week watchful wait is sufficient. Parents are advised to avoid medications such as ibuprofen, and aspirin as they increase the risk of further bleeding.

• Tranexamic acid
  
  Can be tried for 5-7 days to improve clot formation if there is a history of gum bleeds, epistaxis, or heavy periods
  Contraindicated in haematuria

• Steroids
  
  For mucocutaneous and severe visceral bleed
  
  – Prednisolone 1-2mg/kg OD for 7-21 days, followed by tapering 
  
  OR
  
  – Methylprednisolone 30mg/kg/day (up to 1g) IV for 3-4 days (no need to taper for this short course)

• IVIG (intravenous immunoglobin)
  
  Consider where there is life-threatening severe bleeding (0.8-1g/kg) – halt autoimmune destruction of platelets and can rapidly raise the platelet count. The effect takes place in one to five days and lasts for two to four weeks

• Platelets
  
  Only give platelets if there is an intracranial hemorrhage or significant bleeding. Can be effective after IVIG administration and this can prolong platelet survival (otherwise transfused platelets are quickly destroyed).

• Anti-D immune globulin
  
  Can be used as a reasonable alternative to IVIG for appropriately selected children. Anti-D is ineffective when used in patients with Rhesus (Rh)-negative blood type or those who have had a splenectomy. Anti-D should also be avoided in patients with underlying comorbidities such as renal abnormalities, cirrhosis, or acute febrile illness.
  

Admit if there is significant bleeding: epistaxis>1 hour; haematemesis; haemoptysis, intracranial haemorrhage (ICH), melaena.  Or if there is an unclear diagnosis or problematic social circumstances.

Most ITP self-resolves.  80% will have resolved by six months (with or without treatment).  5% of ITP patients will have a recurrence. Although it seems counterintuitive, the lower the platelet count at the beginning, the better.  Uncomplicated ITP normally has a platelet count of <20 × 109/L. Chronic ITP does not resolve within six months and accounts for 10% of ITP.

While the platelets are low, the patient is at risk of bleeding.  ICH is a serious but rare (1%) side effect.  Parents should watch out for any signs of ICH, urinary bleeding, GI bleeding, excessive mucosal bleeding, and menorrhagia (in older patients).

They should avoid NSAIDs while the platelet count is low.

Older children should avoid contact sports.  This is completely impractical for young children so is not helpful advice – will only stress out the parents!

She should be reviewed within two weeks of the initial presentation and have a repeat FBC. Aim for weekly GP follow-up initially and then PRN until resolution.

Paediatric outpatient review at six weeks three months and six months. Refer to haematology if an unclear diagnosis, unresolved after six months or a haematological malignancy is suggested by the blood count.

Blood – Intravenous immunoglobulin vs observation in childhood immune thrombocytopenia: a randomized controlled trial

DFTB – Childhood Immune Thrombocytopenia: To treat or not to treat?

This is not currently recommended. Many children can be safely managed with observation, advice about safety precautions, and carer education. 

Let’s delve a little deeper…

Katja et al. published a prospective randomised controlled trial (RCT) in 2018 which examined if IVIG treatment of ITP reduces the likelihood of developing chronic ITP. 

Patients were between three months and 16 years with a diagnosis of ITP, platelets ≤ 20 × 10⁹/L, and grade 1-3 bleeding on the Buchanan Bleeding Score. Exclusion criteria were: severe bleeding, receiving immunomodulatory drugs in the past month, or contraindications to IVIg such as renal failure or IgA deficiency.

Between 2009-15, 206 patients from 48 centres were randomly allocated within 72 hours of diagnosis to receive either a single dose of IVIg (at 0.8g/kg, 102 patients) or no treatment and observation (104 patients). The primary outcome was the development of chronic ITP. Secondary outcomes were the rate of recovery, safety, and efficacy of treatment choices.

The initial study design used a platelet count ≤ 150 × 109/L for chronic ITP; the study was modified to reflect current consensus since 2009 guidelines of ≤ 100 × 109/L platelets where possible.

Essentially, platelet recovery was significantly higher in the IVIG group at 1-week, 1, and 3-month intervals. However, there was no significant difference in presence of chronic ITP at 6 and 12 months (10% in IVIG group vs 12% without at 12 months)

Petechiae in well babies occur commonly; a study published in 2002 found a prevalence of 27.6% of a cohort of 116 babies less than twelve months of age at child health surveillance clinics, predominantly to the trunk and lower limbs. Observation is the mainstay of ruling out early septicaemia, in addition to blood tests if there is demonstrable or historical pyrexia.

The rash can result from the following mechanisms:

• mechanical capillary injury
• impaired haemostasis
• septic emboli or invasion of the capillary walls
• microbial toxin-induced capillary damage
• immune complex deposition

One study found a high proportion of children with non-accidental injuries were brought by a third party (extended family member or teacher, for example). There are well-documented prompts to consider non-accidental injury in event of;

• Delay in the presentation of the injury
• Discrepant or absent history
• History incompatible with the injury
• The pattern of injury more suggestive of abuse
• Repetitive injuries
• Unusual parental behaviour or mood
• Child’s demeanour, behaviour, or interaction with the parent/caregiver unusual
• Disclosure by child or witness

It is generally accepted that non-mobile children are unlikely to have bruises. Babies “do not injure themselves”, and blame attributed to siblings is rarely appropriate. A study of 973 well children under the age of 36 months found only 2.2% of non-mobile children had bruises, compared to 17.8% of cruisers and 51.9% who were walking. This systematic review of patterns of bruising found from pooled data that bruising in non-mobile babies was rare, occurring in <1%. ‘Can’t cruise, can’t bruise’.

In mobile children, bruises on bony prominences (particularly the anterior tibia and knee) and the forehead are common, reflecting frequent falls in those beginning to walk. Bruises in those aged 9 months to 4 years of age are more suspicious of non-accidental injury when found on other parts of the face, the head, neck, trunk, or buttocks.

“Normal” bruises are not associated with petechiae in a child without an underlying medical or haematological problem. Petechiae which coexist with bruises are considered to have a high positive predictive value for non-accidental injury (80%: 95% confidence interval 64.1%-90.0%)

Linear petechiae may suggest the shape of a hand, having been formed by capillary rupture at the edge of injury from a high-velocity slap. They may also represent specific mechanisms such as suction, squeezing, slapping, strangulation, or suffocation. Blunt trauma may generate a negative impact of the offending object, outlined by petechiae, or deep to a constricting ligature. Petechiae to the earlobe commonly represents non-accidental injury, and linear petechiae may be associated with cultural practices such as cupping or coining.

 A word of warning…

Beware, though: The consensus of medical opinion is that bruises cannot be accurately aged by clinical assessment either in vivo or by photograph, with one study finding that aging within 24 hours of occurrence is accurate less than 50% of the time, with poor interobserver reliability. There are no studies that discuss the changes in colour or appearance of petechiae over time.

Henoch-Schoenlein purpura (HSP)

HSP is an autoimmune, self-limiting, immunoglobulin A-mediated, small-vessel vasculitis. It typically affects children aged 2-8 years and is the most common vasculitis affecting children. It is often preceded by upper respiratory tract symptoms (occurring 1-3 weeks earlier).

The diagnosis is likely in the presence of the triad of:

• purpuric rash (commonly palpable) on the limbs (mainly lower) and buttocks (especially the dependent surfaces). This is the main diagnostic feature.
• joint pain/ swelling
• abdominal pain – diffuse, colicky, acute onset

Haematuria is present in 90% of cases, but only 5% are persistent or recurrent. Less common renal manifestations include proteinuria, nephrotic syndrome, isolated hypertension, renal insufficiency, and renal failure. Subcutaneous oedema of the scrotum, hands, feet, and sacrum may be present and can be very painful.

If atypical distribution or the child is unwell, consider meningococcaemia, thrombocytopenia (ITP), or other rare vasculitides. Other differentials include causes of an acute abdomen (e.g. bowel infarction or perforation), drug reactions, and systemic lupus erythematosus.

Suggested investigations for a child presenting with palpable purpura, suspected of having HSP include

• Blood pressure
• Urine analysis
• Full blood count
• Serum creatinine
• Urine protein: creatinine ratio

These are carried out in an attempt to exclude other diagnoses and to identify the presence of renal impairment. The FBC allows the detection of thrombocytopaenia. Renal involvement is common but usually limited to haematuria and/or mild proteinuria. More severe nephritis produces greater levels of proteinuria, but it is unusual for the serum creatinine to be raised at presentation.

Jack may require admission if symptoms of joint pain or abdominal pain are very severe and caused by gastrointestinal bleeding or more rarely intussusception. If a surgical review is needed to rule out a testicular torsion or if there is evidence of severe renal disease.

Children with haematuria and/or proteinuria should be kept under review and those with significant proteinuria (early morning urine protein:- creatinine ratio persistently greater than 50 mg/mmol), hypertension or impaired renal function should be discussed with a paediatric nephrologist, because of the risk of long-term renal problems.

HSP is a multi-system disease involving all organs:

• Renal  – haematuria (persistent or recurrent in 5%) is common and usually self-limiting; significant proteinuria (less commonly), acute nephritis (very rarely but can lead to renal impairment); nephrotic syndrome, isolated hypertension, renal insufficiency, and renal failure (<1%). May not be present acutely but become apparent during the convalescent period.
• Gastrointestinal – caused by inflammation of the intestinal mucosa including intussusception (rare), bloody stools, haematemesis, spontaneous bowel perforation, and pancreatitis.
• Subcutaneous oedema – particularly affects the scrotum, hands, feet, and sacrum can be very painful and may present as an acute scrotum in boys
• Rare CNS and pulmonary complications can also occur.
• Liver – cholecystitis
• Heart – rheumatic fever with complete atrioventricular block, pericarditis
• The recurrence rate is between 25-50%

Typically, a URTI may precede the onset of symptoms by 1-3 weeks. Joint pain has a short course and lasts <48 hours, abdominal pain lasts < 72 hours. The purpuric rash should resolve in 4-6 weeks.

In a large paediatric study by Allen et al, children older than 2 years had a recurrence rate of 50%, whereas those younger than 2 years had a recurrence rate of less than 25%.

Allen DM, Diamond LK, Howell DA. Anaphylactoid Purpura in Children (Schönlein-Henoch Syndrome): Review with a Follow-Up of the Renal Complications. AMA Am J Dis Child. 1960;99(6):833–854. doi:10.1001/archpedi.1960.02070030835021Available online:

https://jamanetwork.com/journals/jamapediatrics/article-abstract/499525

Management is typically supportive. Analgesia, education, and observation for complications. Most cases can be managed in the outpatient setting by the GP and general paediatrics. Concern about the possible development of renal complications is the main driver for the follow-up of children after an episode of HSP. Patients need to be followed for a minimum of 6 months.

DFTB – HSP –Are Steroids helpful in preventing neuropathy?

The role of corticosteroids in HSP to reduce the risk of developing nephropathy has always been controversial because there have never been good-quality studies.

The best study to date has just been published in Arch Dis Child and effectively demonstrates that steroids are either of no help or of sufficiently small effect not to justify treating large numbers of patients with HSP to prevent a small difference in the risk of developing renal complications in a small proportion of patients.

RCH Clinical practice guidelines outline: “The use of prednisolone has not been shown to make clinically important improvements in the rate of long-term renal complications. It has been shown to reduce the duration of abdominal and joint pain and may reduce the risk of abdominal complications. It may be considered for use in patients with more than mild joint or abdominal pain. Consider prednisolone 1mg/kg while symptoms persist.

Dudley J, Smith G, Llewelyn-Edwards A, Bayliss K, Pike K, Tizard J. Randomised, double-blind, placebo-controlled trial to determine whether steroids reduce the incidence and severity of nephropathy in Henoch-Schönlein Purpura (HSP). Archives of disease in childhood. 2013 Oct 1;98(10):756-63. Available online: http://europepmc.org/article/med/23845696 Weiss PF, Klink AJ, Localio R, Hall M, Hexem K, Burnham JM, Keren R, Feudtner C. Corticosteroids may improve clinical outcomes during hospitalization for Henoch-Schönlein purpura. Pediatrics. 2010 Oct 1;126(4):674-81 Available online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518383/

Which of these is a sign of raised ICP?

A: Diarrhoea

B: Vomiting

C: Non-blanching rash

D: Thrombocytopenia

The correct answer is B, vomiting.

Which of the following can be an appropriate treatment for ITP?

A: Tranexamic acid

B: Steroids

C: Platelet infusion

D: All of the above

The correct answer is D, all of the above.

Which of the following is not a side-effect of HSP?

A: Intussusception

B: Cholecystitis

C: Hearing loss

D: Rheumatic fever

The correct answer is C, hearing loss.

Which of the following would make you suspicious of NAI?

A: Bruising on the knees of a 5-year-old

B: Delay in presentation of the injury

C: Petechiae on the lower limb of a 6-month-old

D: Both B and C

The correct answer is D, both the delay in presentation of the injury and petechiae on the lower limb of a 6 month old.

Which of the following investigations is sensitive for diagnosis of invasive meningococcal disease?

A: Blood cultures

B: DNA PCR

C: CT head

D: Skin scrapings

The correct answer is B, DNA PCR.