Category Archives: General paediatrics

Capillary refill time (CRT)

Clinical, General paediatrics

In children over 7 days of age, the upper limit of normal CRT is approximately 2 s when measured on a finger, and 4 s when measured on the chest or foot, irrespective of whether the child is feverish or not. Longer pressing times and ambient temperature outside 20°C–25°C are associated with longer CRT.

Evidence suggests that the use of stopwatches reduces variability between observers.

Recommend following standardised CRT method: press on the finger for 5 s using moderate pressure at an ambient temperature of 20°C–25°C. A capillary refill time of 3 s or more should be considered abnormal.  Other timings apply to other sites.

[Systematic review – 21 studies on 1915 children.  Arch Dis Child doi:10.1136/archdischild-2014-307079]

Blood Culture

Clinical, General paediatrics, Infectious disease

Essential investigation in sepsis, particularly where unusual organisms or deep seated infection eg endocarditis.

The volume of the sample is important. Small volumes have higher false negative rate, and are slower to become positive – 6ml superior to 2ml [j Peds 1996].

Traditionally, thought to be most effective when done at time of pyrexia, but there is little evidence for this.  In a study of 1,436 adult patients with bacteremia and fungemia, the likelihood of documenting bloodstream infections was not significantly enhanced by collecting blood specimens for culture at the time that patients experienced temperature spikes. Nor was there any benefit for any subgroup eg patient age, gender, white blood cell count and specific cause of bacteremia. [J Clin Microbiol. 2008 Apr; 46(4): 1381–1385.  doi:  10.1128/JCM.02033-07]

Also traditionally, considered negative at 48 hours. Canadian study of 98 positive blood cultures in babies up to 90 days of age found 96% of true pathogenic cultures were positive at 24 hours, with 100% positive at 36 hours. Mean time to positivity was 14.4 hours in pathogenic bacteria and 23.2 hours in contaminants.  [DOI: 10.1093/jpids/piv078]

US study of 256 non-critically ill babies up to 60 days of age found median time to positive blood cultures of 16.6 hours for pathogens cf 25.1 for contaminants, for CSF cultures 14 hours for pathogens cf 40 for contaminants. 82% of pathogens positive within 24hrs for both blood and CSF [can’t see figures for 36/48hrs yet, full text embargoed?][Hosp Peds 2020]

Another US study of 392 cases (outside of PICU) found 96% of pathogens positive by 36hrs (95% CI 95-98), and 99% at 48hrs. But not clear how many of these would have been well enough to go home at 36 hours.  Estimated that observation >36hrs would identify 1 bacteraemic infant for 1250-2778 infants [Biondi, JAMAped2014]. Note that there were significant differences between organisms (E coli faster, staph slower), and between sites (sample volumes? time to inoculation?). No correlation with degree of fever, interestingly.

Current Western Australian guideline, FeBRILe3, appears to be safe.

Canadians have published a new position statement too.

In a tertiary neonatal unit, 72 hours was considered necessary. [ADC Fetal & Neonatal 2001]

Plagiocephaly

Clinical, Common, General paediatrics, OPD

Differential

The clinical criteria for a unilateral lambdoid synostosis consist of an ipsilateral occipital flattening, a depressed ipsilateral ear lobe (inferior movement) and a parallelogram-like shape in the posterior view. All three of these signs were present in the eight synostotic infants. Furthermore, all children had developed a compensatory contralateral parietooccipital bulging that led to a slanted tree top-like shape of the head at follow-up. Normal posterior view (ie ears level) and anterior movement of the ear excludes LS [but photo looks like ipsi anterior movement in LS – is it contralat in PP??? No mention of anterior bossing, not obvious in photo].

German study – all LS cases obvious clinically. Where positional plagiocephaly was doubted, USS demonstrated patent sutures.

[Arch Dis Child 2015;100:152-157 doi:10.1136/archdischild-2014-305944]

Monitoring

Measure the oblique diameter left (ODL) and oblique diameter right (ODR) lines are drawn from points located 40° either side of the antero-posterior (AP) line. 40° is typically where deformation most notable.  Express as difference (the Oblique diameter difference (ODD) = ODL−ODR) or else ratio between the ODL and the ODR (oblique diameter difference index, or ODDI).

[European Journal of Pediatrics March 2006, Volume 165, Issue 3, pp 149-157]

Treatment

Dutch RCT of 6 months of helmet therapy (n=84 infants aged 5 to 6 months with moderate to severe skull deformation, exclusions were prems, muscular torticollis, craniosynostosis, or dysmorphic features). Full recovery was achieved in 10 of 39 (26%) participants in the helmet therapy group and 9 of 40 (23%) participants in the natural course group (odds ratio 1.2, 95% confidence interval 0.4 to 3.3, P=0.74). All parents reported one or more side effects.

[van Wijk RM BMJ 2014; 348 (); g2741]

Some evidence for bedding pillows (but SUDI risk?) and stretching exercises.

Haemangiomata

Clinical, Common, Dermatology, General paediatrics

2018 classification (ISVVA.org) – rather functional and lacking in poetry!

Basically benign tumours, involving blood vessels.  Seen in 12% of all infants  – more common in girls, whites, premature infants, twins and are babies born to mothers of higher maternal age!  Mostly seen in head and neck region, including the face, but can be anywhere.

Tumours distinguished from malformations.

Infantile Haemangioma

Cutaneous/mucosal haemangiomata usually develop after birth, appearing in the first 8 weeks of life.  They then develop and grow for 6-12 months, often resembling a strawberry.  Most then start to reduce and fade gradually, although it can take up to 9 years.   Often there will be complete disappearance with no cosmetic defect, but there may well be scarring, telangiectasia, or loose fibro-fatty tissue.

Can be further differentiated by depth (superficial tend to be raised and bright red, deep are generally darker red or even purple/blue, they can also be mixed) and extent/pattern (focal or segmental).

Typically they are in the skin and soft tissues, but can sometimes affect the liver or airways.  Associated with GLUT-1 positive staining on biopsy.

Congenital Haemangioma

Much less common. Present at birth and do not progress, although they may grow proportionally with child.  Oval or round, plaques or exophytic.  Some rapidly involute during the first year of life but otherwise they are permanent.

Vascular malformations

Grow slowly compared with vascular tumours.  Usually present at birth but perhaps inconspicuous until child grows.  Can involve arteries, veins, lymphatics in various combinations.

Capillary malformations most common – dilated capillaries, classic port wine stain (naevus flammeus).  Darken over time, do not regress.  Can be associated with bone or soft tissue overgrowth. Multiple can be associated with underlying AVM!

Nevus simplex is the classic “stork bite” at the nape, eyelid or forehead at birth. Lighter, regress.

Venous malformation more ill defined, bluish, easily compressible.  Multifocal tend to be autosomal dominant.  Some syndromes eg Blue rubber bleb naevus syndrome (widespread, including palms/soles).

Lympoedema and cystic hygroma are the lymphatic versions.

Others

  • Pyogenic granuloma – reaction to trauma, well demarcated, raised or even pedunculate
  • Telangiectasia eg Hereditary haemorrhagic telangiectasia (HHT)
  • Angiokeratoma – characteristic of tubersclerosis
  • PHACE syndrome (post fossa malformations, haemangiomata, arterial anomalies, cardiovascular defects, eye anomalies – but also midline defects)
  • Tufted angioma and Kaposiform haemangioendothelioma – similar histologically, but latter bruised, purpuric appearance, infiltrate into muscle/adipose tissue and associated with Kasabach-Merritt syndrome (consumptive coagulopathy).
[Seminar intervent radiol 2017][Ped dermatology 2016]

Angioedema

Allergy, Clinical, Common, General paediatrics, Immunology

Swelling, usually acute, non-pitting.  May be erythema too.  Typically affects face, especially lips, tongue, eyes, but can be limbs, even internal!

Usually related to urticaria (wheals). As with urticaria, can be allergy – clue is consistent trigger, pattern of recurrent episodes – but can have other causes.

Angioedema without urticaria – consider hereditary or drugs, especially NSAIDs and ACE inhibitors.

Autoimmune Hepatitis

Gastro, General paediatrics, Immunology

Presents with anything from subtle anorexia, fatigue, rashes, abdo/joint pain to acute liver failure.  Jaundice does not relate to degree of histological fibrosis.

Check Prothrombin time, glucose, ammonia, lactate to monitor liver disease. Response to Vitamin K at 8 hours is prognostic, so refer to specialist centre if poor.

Type 1 (60%) is ANA/SMA (=small muscle) positive, usually presents as a viral hepatitis ie jaundice, raised transaminases, but can present insidiously, even with established portal hypertension, or as acute on chronic. Type 2 is LKM1 (liver/kidney/microsomal) positive, similar clinical presentation but probably more jaundice and cirrhosis, less impairment in synthesis. Seronegative hepatitis has been described in up to 20%.  Antibodies to soluble liver antigen described.  Quite common to see pANCA, too (not sensitive or specific).  The role of these autoantibodies in disease is unclear!

As with other autoimmune diseases, strong association with HLA types.  DR4 associated with less severe disease, lower rate of relapse (but older presentation).  Has been reported in association with immune disorders eg autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).

Alkaline phosphatase rarely exceeds 4x normal and generally remains less than 2x normal. Raised immunoglobulins are a clue, with a selective increase in IgG (up to 3x higher than the upper level of normal) seen in 75-85% (kids and acute less likely).  But not specific – also seen in Wilson’s disease; other causes should be excluded too. Interface hepatitis on biopsy, with sharp differentiation between inflammatory zone and normal liver tissue.  Findings don’t always match biochemistry.  Nonetheless, diagnosis is ultimately clinical!  Diagnostic scoring system available.  Differential also includes chronic hepatitis C and drug induced liver injury.

Treat with steroids, azathioprine (remember TPMT polymorphisms)  when improving, else mycophenylate. 85% achieve remission, biochemically within 6-12 weeks, histologically 6-12 months.  More than double normal enzymes is an indication for treatment, else bridging or multilobular necrosis.  Progressive fibrosis is associated with liver inflammation, and poor response to treatment (inability to suppress inflammation within 12 months) is associated with progression to cirrhosis (54%) and transplantation (15%).  But fibrosis can be stopped or slowed in the majority, and even cirrhosis can regress with treatment.  Aim is normal transaminases, immunoglobulins, histology – biopsy is still gold standard for assessing fibrosis.

Unlikely to outgrow.  Some trials of withdrawing treatment after remission, only a minority manage more than a year without relapse.  Azathioprine 2mg/kg daily effective.  Ciclosporin and MMF are second line agents.  Hepatobiliary cancers and lymphoma risk is increased and should be screened for.

Transplant may be necessary eg severe acute presentation with poor response to treatment.  Results are good, recurrence is rare but well described.

Variants

Can be features of other disorders eg primary biliary cirrhosis, primary sclerosing cholangitis.  Biliary changes are commonly seen in autoimmune hepatitis in any case.

Can be part of polyendocrine syndrome type 1.

[Heneghan, Lancet 2013; 382: 1433–44 http://dx.doi.org/10.1016/S0140-6736(12)62163-1]

See also PMID 22495399

Valproate – MHRA warning

General paediatrics, Neurology,

Updated December 2023 –

High risk of serious developmental disorders if exposed in womb (up to 30-40% risk, including 5x higher risk of autism) and congenital malformations (10%), including:

  • Spina bifida
  • face/skull malformations, including cleft lip/palate
  • Limb, heart, kidney, genital abnormalities
  • Deafness

In boys, pre-clinical data on transgenerational risks, and animal studies suggesting infertility.

Oral Valproate must not be started in new patients (male or female) younger than 55 years, unless two specialists independently consider and document that there is no other effective or tolerated treatment, or there are compelling reasons that the reproductive risks do not apply.”

Patient guide and checklist available.

Testing for antibiotic allergy

Allergy, General paediatrics

See also Penicillin allergy.

Systematic review – just 0.21% of unselected general paediatric outpatients exhibit positive antibiotic allergy tests, and only 6.8% of those with suspected allergy test positive.

No evidence to support using skin prick testing.  Intradermal testing has high false positive rate (64-67% for penicillin and clarithromycin). Caubet did oral provocation test (OPT) regardless of intradermal result to beta lactam, NNT=11 to avoid one OPT! [Ped All Immun 2015 ]. OPT reactions tend to be cutaneous and mild, usually more than 1hr post administration.

Where reaction is severe but non-immediate, eg Stevens Johnson syndrome, Toxic Epidermal Necrolysis (TEN), Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), care needs to be taken with investigation, but studies have reported intradermal and OPT without unsafe adverse effects.  If reaction is anaphylaxis with first dose, then OPT contraindicated.

Wide variety in regimens.  Suggests 1-5 incremental doses of amoxicillin for mild reactions (timing not specified), giving cumulative dose appropriate to child, then continuing for 3 days.  Skin testing may be appropriate for severe reactions according to risk:benefit balance.  Check asthma well controlled, no antihistamines.  Warn that low risk of false negative result (absent co-factors) and low risk of re-sensitization.

Intravenous provocation only where PICU!

[Marrs, ArchDisChild 2015]

Macy article says any rash can have OPT! 5mm pos SPT for penicilloyl-polylysine has good negative predictive value for anaphylaxis with OPT. Recommends 5 days amoxicillin.

[Ann Allergy Asthma Immunol 121(2018):523−529]

Mirakian article suggests SPT for all immediate reactions! Split dose challenges, with a week between first and second doses!

For non immediate reactions (1-72hrs), OPT confirmed in 59%, ID less than 40%.

6 studies showing that benign reactions (ie witnessed macpap or urticarial, no pain/burning, <50% skin surface etc) do not need skin testing.  Geneva have done more than 800 straight to OPT.  New EAACI guidelines in press.

If delay in reaction is unclear, assume immediate.  SPT vs amoxicillin, PPL, MDM.  IgE vs BPL.  0.04ml ID volume.  Note different reference ranges!  See Brockour, Allergy 13

Recent letter claimed OPT after skin test was “unnecessary, dangerous, unethical”!  But 30-100% false negatives!

Clavulanate allergy described.

Test sensitivity falls more than 4/12 after episode, ideally do within 4-6/52????

Basophil activation test using flow cytometry looking promising for IgE mediated drug reactions.  EAACI interest group working on Drug Allergy Passport.

Atypical HUS

General paediatrics, Genetics, Haem/Oncology, Renal

Most Haemolytic Uraemic Syndrome is associated with a diarrhoeal illness (D+ HUS), esp E coli O157.

Atypical HUS is a bad name for HUS that develops in certain individuals due to a genetic, complement disorder.  Disease is typically triggered by infection, esp respiratory tract, else diarrheal illness in 80% of pediatric forms.

Consider in young infants (less than 5% of D+HUS cases occur before the age of 6 mo), severe cases, non-colitis.

The penetrance of the disease among carriers of mutations in CFH, CFI and MCP genes is approximately 50%-60%.

Low C3 levels are a clue (seen with mutations in CFH, CFI and MCP).  In almost all cases of aHUS C4 levels are normal. Normal C3 levels do not however exclude a mutation.  Check factor H and factor I too.

Diagnosis

Measure CFH, CFI and MCP levels using radio-immune-diffusion assay (RIDA) or FACS. This however fails to detect low protein levels in 25%-75% of mutations, so genetic analysis also needed.

Check ADAMTS13 activity (as seen in thrombotic thrombocytopaenic Purpura, TTP) as part of differential.

Make sure you have enough blood samples before plasma exchange!

In neonates, screen for defective cobalamin metabolism (excess homocystine and methylmalonate in urine ).  These babies have high mortality from multiorgan failure, a prompt diagnosis and B12 supplementation is their only hope.

Haemolytic Uraemic Syndrome

Gastro, General paediatrics, Infectious disease, Renal

Or HUS for short.  Mainly caused by VTEC (Verocytotoxin producing E coli), esp serotype O157.  But note also:

  • Occasionally Pneumococcal
  • Atypical HUS – not infective, but a genetic complement disorder
  • D- HUS is the shorthand for HUS which manifests in absence of diarrhoeal illness.  Still worth looking for E coli O157, but need to look at other possibilities.

Clinically

What it says on the tin!

  • Haemolysis
  • Uraemia

Mechanism is Thrombotic Microangiopathy, with microthrombi circulating that affect not just kidneys (producing uraemia) but also:

  • Thrombocytopenia,
  • MI/stroke/infarction
  • Encephalopathy

Differential

  • Acute dysentery eg campylobacter, shigella
  • Intussusception
  • Atypical HUS
  • Acute colitis (Ulcerative Colitis)

Although atypical HUS has a genetic cause, it is typically triggered by infection, esp respiratory tract, else diarrheal illness in 80% of kids, so may be difficult to exclude.  Consider in young infants, severe cases, non-colitis. Low C3 levels are a clue.

Acute colitis will usually have more extensive history or other clues.  The emphasis on managing these cases is on identifying toxic megacolon, and surgical intervention if necessary.  Antibiotics are recommended if high risk of infection (eg signs of sepsis) and/or immediately pre-surgery.

Diagnosis

Features of established disease are:

  • Microangiopathic haemolysis
    • Falling Hb, Plts – clinically pallor, petechiae and bruising
    • Fragmented rbc’s on film
    • High LDH
    • Blood/protein on urinalysis (if there’s any urine being produced to collect)
  • Rising Urea/Creatinine

But ideally you get the diagnosis early, before too much damage has been done.  Clues are:

  • Rising LDH
  • Falling Plts
  • Oliguria
  • Blood/protein on urinalysis

Stool results, to confirm E coli O157, take 24-48hrs (culture and toxin test). Discuss with microbiology if stool culture negative, consider gene PCR, serology.

[Pediatr Int. 2009 Apr;51(2):216-9 PMID 19405919]

Progression

But not everyone who gets E coli O157 gets HUS. Some people get diarrhoea without progressing to colitis (prob the majority), some get colitis without progressing to HUS (only a minority).  Predictors of progression to HUS are:

  • Fever (usually not at presentation, but in history – not very specific)
  • WCC >11
    • Normal WBC provides reliable reassurance against progression to HUS in 9/10
    • WCC>11 predicts progression to HUS in 70–90% of children
  • Raised CRP

[Ikeda, Epid infection 2000; 124:343.  Archimedes, Arch Dis Child 2007]

Ikeda proposes scoring system of 2+ features of fever, high CRP and WCC – 32% sens cf 98% spec.

Public Health

Preventing further cases is as important as managing your case.  About 20% of cases in outbreaks are secondary, but this increases to over 50% of cases in under 6yrs.  Interestingly, secondary cases are usually other children in the nursery (but rarely adults) if pre-school, but family members if primary/secondary school age!  [BMC Infect Dis. 2009 Aug 28;9:144. doi: 10.1186/1471-2334-9-144] Notify Health Protection team on suspicion of E. coli O157 syndrome.

Antibiotics?

Controversial.  Would be considered for other infective dysenteries viz Clarithro for campylobacter, Cipro/cef for salmonella, Azithro for shigella.

But do they precipitate HUS in E coli O157? “Exposure to antibiotics (aOR 3.62; 95% CI, 1.23–10.6) in 1st week independently associated with development of HUS” [Wong 2012].  Current 2011 UK guidance states “The use of antibiotics should, therefore, be governed by good paediatric practice as indicated by needs other than the suspicion of enteric VTEC infection”.

Fluids etc

Loperamide has traditionally been associated with toxic megacolon in acute dysentery so is not advised.

Pain – can be significant with colitis.  Opiates, NSAIDs contraindicated given potential for megacolon or nephropathy.

IV fluid volume and sodium during E coli O157:H7 infections, esp in first 4 days of illness, associated with oligoanuric HUS:

  • 1.6x more likely to become oligoanuric if no IV fluids were given during the first 4 pre-HUS days

[Christina Hickey (St Louis) and Jim Beattie, prospective study Arch Pediatr Adolesc Med. 2011;165(10):884-889. doi:10.1001/archpediatrics.2011.152]

Hence, seems reasonable to:

  • Give 20ml/kg at presentation
  • Rehydrate aggressively eg correct over 6-8hrs
  • Repeat boluses if urine output reduces

Monitoring

Since onset of HUS is from 5 to a maximum of 13 days into diarrhoea illness, there is a need to monitor those with suspected or proven E coli O157 without HUS viz repeat bloods at 5-7 days or earlier if symptoms worsen.  Consider admission if significant infection control issues eg young children/siblings.

Advanced Measures

  • Renal replacement therapy
  • Plasmapheresis (not done in Glasgow)
  • Eculizumab – drug of choice for aHUS, recommended for children in whom plasma exchange is technically difficult
  • Monoclonal antibodies vs STX1/2

Eculizumab = Recombinant monoclonal anti-C5 antibody. Orphan drug.  No good evidence from Germany, but they had good results from plasma exchange anyway.  Evidence from severe TTP that it is effective in cases resistant to immunosuppression and plasma exchange.