Category Archives: General paediatrics

Food protein–induced enterocolitis syndrome (FPIES)

Allergy, Gastro, General paediatrics, Immunology, Neonatology, Nutrition

Non–IgE-mediated severe gastrointestinal food hypersensitivity, typically presents in early infancy with repeated vomiting, dehydration, lethargy, metabolic acidosis (even mimicking sepsis).  Watery diarrhoea (sometimes with blood and/or mucus) can develop in some cases. The severity is really what makes it worthy of a distinct name, debatable if it is actually distinct from other non-IgE mediated food allergy.

Probably underdiagnosed.

A few unusual features cf type 1 allergy.

The most common offending foods are cow’s milk and soy in young infants; in older infants, there are a range of food triggers including some foods usually not considered allergenic eg rice, oat, chicken, sweet potato!  Egg an unusual cause in some countries!  Cases in breastfed infants have been reported, even severe hypotension requiring intensive care.

Acute symptoms occur 1 to 5 hours after ingesting the offending food.  Lasts up to 24 hours. Not always consistent, which might suggest co-factors important.

In Europe, rare to get multiple food FPIES but in UK/US/Australia about 25% (English speaking!?).

Diagnosis

Diagnosis is based, predictably for a non-IgE condition, on clinical history and food challenges. Leucocytosis and methaemoglobinaemia are associated but low specificity/sensitivity.  

2017 Consensus out of date but diagnostic criteria still used – 

  • Major – vomiting at 1-4 hours in absence of type 1 skin/resp symptoms.
  • Minor – at least 3 minor criteria eg second episode of repetitive vomiting after same food; extreme lethargy; hypotension; need for hospital care or IV fluids; etc

Probably mild, mod and severe! Proposed BIO-FPIES criteria includes abdominal pain, nausea, increase in neutrophil count (but 3 points for second episode of repetitive vomiting after same food).

Phenotype switching

Egg and nut FPIES often go on to develop IgE sensitisation (about 20%), less for others. Of those, about 30% of milk FPIES will switch to type 1 phenotype, 15% for egg, less for other foods. But overall, unlikely to make much of a difference to care (and doesn’t help predict resolution).

Management

No role for antihistamine/adrenaline!

BSACI has FPIES plan.

Family support at www.fpiesuk.org.

For introducing weaning foods, when known FPIES to one food, start with low risk foods, supervise common triggers eg rice/egg.

Challenge

Challenge is necessary to decide whether things are getting better or not. Consensus is that 12-18 months after last reaction is a good balance between chances of things being better, and risk of causing severe reaction.  

50% milk/soya resolve by age 3-4, more like 4-5 years for other foods. 

Traditional protocol is 0.3g/kg protein, divided into 3 doses over 30 mins.  But unrealistic for low protein foods eg fruit. And doesn’t really make sense to split dose when you don’t expect a reaction for hours (but risk of switch to type 1 allergy for egg/nuts).

2 day protocol (25% portion then whole portion next day) had less severe reactions. 

25-30% of age appropriate portion triggers reaction in most children. [Baked???] Over 50% react after at least 2 hours. 

Beaudoin 2024 has home challenge protocol but brave… 

[Marta Vazquez-Ortiz systematic review]

[BSACI FPIES grand round – Marta Vazquez-Ortiz (Imperial/St Mary’s, BIO-FPIES research network)] [2025 Shaker shared decision making] [2024 Anvari]

Obesity management

Common, General paediatrics, Nutrition, OPD

Public health surveillance use 85th centile as definition for overweight, and 95th centile for obesity (UK says “at risk of obesity”…). Clinical definitions (SACN/RCPCH 2012, NICE) however are different: (UK 1990, use special BMI chart)

  • Obesity = BMI >98th centile for age (2 standard deviations, one tail)
  • Overweight = >91st centile (1.3 SD)

Growth charts then label:

  • Severe obesity = 99.6th centile (2.67 SD)
  • Morbid obesity = 3.33 SD.  High probability of co-morbidity, unlikely to improve by age 16.
  • (some guidelines use Extreme = 4 SD)

Cut off for overweight/obesity high in babies, starts at 18/20 age 2, nadir of 17/19 at age 5, rising to 20/24 at 10 then usual 25/30 at age 18. Girls same as boys, slightly fatter after 10 yrs. [International data, BMJ 320:1242.] Charts are available at the RCPCH.

Centile charts show centile spaces that are equivalent to 2/3 of a standard deviation.  When you get to high centiles, you need something better than “above the 99.8th centile” so you use Z score, which is the number of standard deviations above the mean

Calculators available to calculate BMI and Z-scores eg Phsim.man.ac.uk/SDSCalculator

So secondary referral for:

  • extreme, or
  • ?secondary obesity, eg
    • under 2 yrs with severe (>99.6th centile) obesity
    • short for age
  • co-morbidity eg strong FH type 2 DM, sleep apnoea, idiopathic intracranial hypertension, orthopaedic probs
  • psychological comorbidity,
  • safeguarding.

2nd care history –

  • menstrual hx,
  • sleep eg Chervin questionnaire (adds anything?)

Examination

  • acanthosis nigricans (neck, flexures) – highly associated with insulin resistance
  • buffalo hump.  Striae and obesity as only signs of Cushings v rare. Striae in Cushings more intense red!?
  • Mid-Parental Height – endocrinopathy unlikely if normal growth
  • Waist circumference
  • Goitre – hypothyroidism
  • BP
  • Peak flow
  • Syndrome eg BWS
  • Acne, Hirsutism – polycystic ovary syndrome
  • Telangiectasia

Investigations

Little evidence for investigations, not routine.

  • Fasting glucose, insulin, lipids
  • FBC, U&Es, LFTs
  • TFTs
  • HBA1c
  • SHBG (marker of insulin resistance)

For more severe cases, consider:

  • OGTT – 2hr glucose >11.1=diabetes, 7.8-11.1 = impaired glucose tolerance.  Esp if S Asian, other signs/risks of insulin resistance.
  • ECG
  • Sleep study
  • Molecular genetics (EDTA) eg Prader Willi, Bardet-Biedl syndrome, Cohen syndrome, MOMO syndrome.
  • Urinary cortisol/creatinine
  • Low dose dexamethasone test (more sensitive than above but needs overnight admission) – cortisol should suppress below 100, else suggests Cushings
  • CT head (if suspicion of raised intracranial hypertension

Homa-IR >4.5 for insulin resistance [Score = (Fasting insulin)*(Fasting glucose) / 405, measuring in mg/dl].  Transient increase in insulin resistance seen in puberty, independent of BMI.

Total choles:HDL 3.6 95th, 4.3 99th but no great paed data.

ALT>70 twice should proceed to USS to look for fatty liver, >100 urgent (for differential more than anything, although non alcoholic fatty liver disease can be progressive).

Communication

Delicate! Moral issue too – for example:

  • uncertain benefits on physical health
  • negative psychosocial consequences including uncertainty, fear, stigmatization
  • aggravating inequalities
  • disregarding the social and cultural value of eating
  • infringement upon personal freedom regarding lifestyle choices and raising children

Addressing these issues may avoid resistance [Erasmus medical centre, Obes Rev. 2011 Sep;12(9):669-79. doi: 10.1111/j.1467-789X.2011.00880.x. Epub 2011 May 4]

PHE “All our health” has child (and adult) obesity thread– use opportunistic moments to open up conversations around weight. “Let’s talk about weight” = short conversations guide.

  • Initiate a conversation. Anticipate defensiveness
  • Discuss “healthier weight” concept
  • Positive, non-judgmental language
  • Terms such as ‘obese’ are not generally well accepted by parents/carers

Opportunistic is good, but probably sensible to check that this is a good time, or at least create an invitation to start this conversation. And then, do more questioning and listening than advising.

What works?

The above section may already have brought up issues of low self-esteem and poor motivation. Building a therapeutic relationship, using motivational interviewing skills, is key then, especially where parents/children may have sensed discrimination and bias in the past.

General advice should include: (SIGN)

  • Healthier eating, and decreased calorie intake
  • At least 60 mins of moderately vigorous activity per day, pref habitual eg brisk walking! Given that evidence that moderate/high levels of cardiorespiratory fitness appear to attenuate or even eliminate the risks, just as important to emphasize fitness as weight loss? 
  • Max 2 hours screen time per day!

But as indicated above, probably more important to ask about the blocks, than to say “eat less, move more”.

OSCA 2012 Viner, arch dis child educ (paeds network)

See Prevention and Treatment.

Urticaria

General paediatrics, Immunology

Or “hives” – itchy plaques or papules (weals), with surrounding flare, typical of histamine reaction in skin. Urticaria can also be accompanied by angioedema – although angioedema on its own may point to hereditary angioedema (else drugs eg NSAID, ACE inhibitors, oestrogens, statins), and absence of angioedema may suggest urticarial vasculitis, Schnitzler syndrome, cryopyrin associated periodic syndromes.

Not always allergy, although it is the classic rash of type 1 (histamine and IgE mediated) allergy.  Can be inducible or spontaneous.  Can be transient, intermittent or chronic (6 weeks minimum).

Burden on quality of life and health services can be substantial.

Inducible

Various kinds of physical stimuli can trigger urticaria, including:

  • Dermatographism – within 10 minutes of pressure
  • cf Delayed pressure type – tight clothing, sitting
  • Heat (including exercise and emotion)
  • Cold – can be secondary to autoimmune conditions or infection. Anaphylaxis risk from swimming!?
  • Sunshine (solar)
  • Water (aquagenic) – cold, hot, even rain…
  • Vibratory angioedema
  • Cholinergic urticaria
  • Contact urticaria

Can be mixed! Some tests have been suggested eg ice cube test (ice cube in a sealed plastic bag over the forearm for up to 10 min – wait for skin to rewarm), flannel test for aquagenic (wet towel for a few minutes on area of skin most affected).

Can be hormonal in girls, therefore cyclical (catamenial).

Differential

These things are considered to have different mechanisms:

  • Hereditary angioedema
  • Delayed food allergy eg alpha gal, or exercise induced
  • Atopic dermatitis
  • Chronic or recurrent infection (consider occult eg dental)
  • Erythema marginatum (as in rheumatic fever, but also a prodrome to HAE!)
  • Erythema multiforme
  • Drug reactions
  • Polymorphous light eruption
  • Thyroid disorders
  • Cutaneous mastocytosis
  • Systemic lupus erythematosus
  • Cryopyrin (autoinflammatory) disorders, typically with fever, arthralgia, eye inflammation eg Muckle Wells
  • Schnitzler syndrome – with monoclonal gammopathy
  • Gleich syndrome – with eosinophilia
  • Urticarial vasculitis (often spectacular, lasts more than 24 hours, bruising develops)
  • Autoimmune urticaria (caused by autoantibodies vs FC epsilon RI alpha, but antibodies do not correlate well with symptoms)
  • Mastocytosis and urticaria pigmentosa
  • Oestrogen, progesterone and pregnancy related dermatoses

And if everything else excluded, that leaves Chronic idiopathic urticaria.

Urticaria Activity Score available – wheals and itch over course of day, score 0-3. Moderate wheals are 20-50. Do for 7 sequential days and add up to give UAS7 score.

Diagnosis

Basophil histamine release assay and autologous serum skin tests suggested, 25% of all chronic urticaria patients are positive for one and/or other, but  50% are negative for both – so struggling for a diagnostic standard.

Essential:

  • FBC, CRP, ESR – CRP raised and eosinophils low in type IIb (mast cell-directed autoantibodies)
  • Total IgE – reduced in type IIb
  • Anti TPO antibody – high in type IIb (high ratio to total IgE)

After that, as indicated, eg:

  • ASOT
  • Immunoglobulin electrophoresis done in adults to look for paraprotein
  • H pylori – some have suggested eradication helps but BSACI come down against routine screening
  • TFTs, Functional autoantibodies eg Thyroid, ANA
  • Pseudoallergen (additives, flavourings, colourings) free diet for 3 weeks? BSACI not v keen
  • Tryptase – systemic mastocytosis? Not in BSACI guideline!
  • TTG – some case reports of association with coeliac disease
  • C3/4 – if suspected urticarial vasculitis, and if reduced, measurement of anti-C1q antibodies [BSACI urticaria guideline]. C4 low in HAE.
  • Cryoglobulins for cold induced
  • Biopsy – but for mastocytosis, bone marrow aspirate most sensitive!
  • Specific tests: ice cube, flannel, dermatographism, hot bath, exercise. 

Incidence of underlying cause varies regionally. And some of these things may simply be aggravating underlying spontaneous urticaria, rather than a cause as such!

Assess for co-morbidity – mental health, autoimmune disease, allergy.

Treatment

Identify triggers – drugs (esp NSAIDs), foods (high histamine, pseudoallergens?), stress, infection.

For acute, non-sedating antihistamines (H1 blockers), else steroids. Evidence for H2 blockers eg ranitidine very weak.

For chronic, continuous non-sedating AH effective in <50% of patients. No evidence that one antihistamine is better than any other. Guidelines recommend up to 4x updosing (studies support for cetirizine, fexofenadine, otherwise desloratadine, levocetirizine, rupatadine!). 

No evidence that using different H1 blockers at the same time has any advantage (moderate consensus only, however…)

Weak evidence for steroids! Suggests maximum 10 days. Similarly montelukast.

Omalizumab is second line for both spontaneous and inducible – monthly SC injections 300mg (not dependent on IgE, as is asthma dosing) every 4 weeks (safety data now from age 1). Increase dose or shorten interval if necessary (up to 600mg every 2 weeks). After that, ciclosporin.

Other treatments with limited evidence include doxepin, ranitidine, methotrexate, dapsone etc. 

Tranexamic acid for angioedema?

No evidence for thyroxine treatment if autoantibodies, if euthyroid.

Plasmapheresis and IVIG have been used…

Tolerance to triggers can be induced (rapidly in some cases, eg within days), but not usually v pleasant, and temporary only…

Note the high rate of anxiety, depression, somatising disorders (50%).

[EAACI/GA2LEN 2021]

Alpha 1 Antitrypsin deficiency

Gastro, General paediatrics, Genetics, Respiratory,

Similar incidence to CF in white populations. Protease inhibitor (PI), counteracts neutrophil elastase. Alleles include PiZ (defective), PiM (normal), PiNull (non functioning). Protein phenotype then described as Z, M, MZ, or None

  • Double Null – very high risk of COPD but no liver disease!
  • ZZ have high risk of COPD and liver disease.
  • SZ also seen, risk of COPD.

The risk of emphysema is increased in males, in asthma and especially in smokers.

PiMZ genotype does not appear to predispose to chronic liver disease (in case control study). On the other hand, patients with decompensated liver disease (of any cause) were significantly more likely to have PiMZ, and particularly in HCV or NAFLD PiMZ was associated with more severe liver disease and need for liver transplantation. Suggests that if you have some other cause for liver disease, PiMZ will do less well.

J Pediatr Gastroenterol Nutr. 2006 Jul;43 Suppl 1:S30-5. [pmid:16819398]

About 10% of children with Z phenotype have prolonged (obstructive) jaundice as babies, most have abnormal LFTs at some point in first year of life. Only 2% progress to liver failure requiring transplantation, however. Risk of hepatocellular carcinoma higher, not surprisingly.

Augmentation therapy with IV AAT approved by FDA, expensive. May slow decline in lung function but not great evidence yet. No intended to treat liver disease.

Screening is really only useful in aggressive smoking and alcohol advice. Non-alcoholic fatty liver disease seems to worsen other causes of liver disease so avoidance of obesity seems important too.

Necrotizing panniculitis associated with AAT deficiency, seems to respond rapidly to AAT treatment.

 

Ulcerative Colitis

Gastro, General paediatrics

About a third of IBD in kids, incidence stable unlike Crohn’s.

Associated with autoimmune disease especially sclerosing cholangitis.
80% kids have pancolitis (cf 20% adults), otherwise proctitis alone or
other local disease.

Acute Severe Colitis

“About saving lives, not saving colons”.

15% severe at presentation, 28% have at some point in childhood.

The first attack of colitis tends to be more severe and disease more
extensive in children than in adults. Many respond to conventional
medical therapy but 8-30% at 1 year will have undergone colectomy for
failed medical treatment (depending on disease severity).

Acute severe colitis is characterised by greater than 6 bloody stools
per day, abdominal tenderness, fever, anaemia, leucocytosis, and
hypoalbuminaemia. This is a typical presentation of ulcerative colitis
or may occur as an exacerbation, but the differential includes:

  • Infectious colitis eg Shigella, E. coli O157
  • Crohn’s colitis
  • pseudomembranous colitis
  • ischaemic colitis

Equivalent to PUCAI >65. Moderate colitis 35-60.  Day 3 PUCAI already predictive of future colectomy, second line therapy.

Clostridioides prev Clostridium difficile- less in kids than adults.  Intermittent shedding so multiple samples required.

CMV colitis – not always immunosuppressed.  But no evidence for treatment or prophylaxis…

1-1.5mg/kg max 60mg IVMP.  If toxic or colonic dilatation then NBM, antibiotics, surgical opinion.

Day 3 under 35 PUCAI can consider oral steroids (120% IV dose).  Over 45 refer tertiary centre, screen for second line therapy, start involving surgeons/stoma therapist, sigmoidoscopy (safer than full colonscopy), check HBV/HCV/TB for starting ANti TNF Rx.

Day 5 over 65 start second line (infliximab).  “Sponge, sieve, shark”.  Dose, timing?  Sponge soaks up Abs.  Shark is immune system removing Ab.  Sieve – leaking Ab?  Not much evidence yet!

No response at day 11 consider colectomy.

Alternative second Rx are ciclosporin, tacrolimus.

Toxic megacolon – pain, distension.  Signs less if already on steroids.  Amp, gent, metro.  40mm under 10, 56mm otherwise.

Thrombosis – recognized risk of stroke.  Consider 3+/12 treatment prophylaxis eg OCP, FH

No evidence for bowel rest!

Number of stools can be over estimated if very close episodes. Some may conceal or underestimate number/blood.

Investigations

  • FBC, coag
  • Group and save – consider Cross match esp if possibly for surgery
  • CRP, ESR
  • U&Es, LFTs, Ca – hypokalaemia can precipitate toxic megacolon
  • Blood culture, stool cultures, stool microscopy, C diff toxin
  • CMV serology if immunocompromised
  • AXR – toxic megacolon = 5.5cm+ dilatation

These also used for monitoring, in addition to PUCAI score, a clinical score:

  • abdominal pain (can be ignored or not),
  • rectal bleeding (some stools, most stools, more blood than stool),
  • stool consistency and frequency,
  • nocturnal stooling,
  • activity level (limitation or not).

Under 10 normal, 10-30 mild, 30-60 moderate.  Best averaged over 2 days unless rapidly changing clinically.

Endoscopy is not considered first line investigation given risk of
performation. Limited sigmoidoscopy may give useful information
however.

Management

  • Fluids and nutrition
  • Blood transfusion, esp if Hb<8 or <10 and symptomatic
  • Consider antibiotics (IV Cef and met) if high risk of infection or pre-surgery
  • Stop aminosalicylates until improving
  • Steroids – Hydrocortisone 10mg/kg in 4 divided doses, max 400mg/d else Methylprednisolone 1mg/kg, max 60mg. Do not delay pending microbiology!
  • TED stockings, LMWH
  • Surgical review

Joint medical/surgical care is appropriate. If surgery is likely to be
needed, a stoma nurse would be useful. PUCAI >45 on day 3 suggests
failure to respond (30-70%, depending on severity). Cyclosporin and
Infliximab are second line.

Maintenance

Azathioprine and 6MP are useful for maintenance, less useful acutely
given delayed onset of action. TPMT deficiency predicts myelotoxicity
(use lower doses). 6MP has less side effects (nausea, vomiting,
headache, fatigue). prob best for younger kids.

Sulphasal liquid, various granule products for older kids.

Mesalazine enemas good but low acceptability.

[Richard Hansen 2016]

Riley Day Familial dysautonomia

Cardiology, General paediatrics, Genetics, Neurology

Seen virtually exclusively in Ashkenazi Jews. Subtype of hereditary
sensory and autonomic neuropathy (cf HSMN).

From birth, absence of tears, poor tone and suck, blotchy skin rashes.
Insensitivity to pain can lead to accidental self mutilation. Speech,
motor development and growth all impaired, but intelligence normal.

Autonomic crises occur, triggered by physical or emotional stress –
sweating, high blood pressure, blotchy rash, vomiting.

Sexual history

Clinical, General paediatrics,

Explain why (cf nosiness), offer confidentiality

Fear of disappointment/disapproval, parent/authority figure, stigma, genital examination.

Closed questions – curiosity not judgement:

  • Who was it with?  How old is she/he (clarify!).  Regular partner or casual (cf one off, one night stand, other judgemental terms).
  • Did you use a condom?  Did you use contraception (not the same thing)?
  • Did you want to?
  • Did you enjoy it? (!)
  • Do you tend to have sex when you’ve been drinking alcohol

Primary C3 complement deficiency

General paediatrics, Immunology

C3 is the major complement component.  Associated with bacterial infections esp gram neg eg Meningococcus, Enterobacter, Haemophilus, E coli.  Gram pos infections also seen.  Some increase in autoimmune eg SLE but this is more well recognized with C1q, C2 and C4 def.

Secondary C3 def seen with nephritis (complement activation products in kidney), but also with hereditary factor I and H deficiency (cofactors in C3 product cleavage).

Immunodeficiency

General paediatrics, Immunology

Age of child and type of bugs found important.  SCID and severe DiGeorge can present in first few months of life (failure to thrive, chronic diarrhoea, recurrent viral infections, thrush). Antibody defects tend to present in later childhood; neutrophil problems in between (which goes to show how good your innate immunity is).

On average, a young infant will get 5-6 resp infections per year; if day care + older sibs that goes up to 12/yr.

ESID diagnostic protocol is not particularly simple but does help by starting with clinical presentations. [Clin Exp Immun 2006; 145:204]

  • Family history (including autoimmune disease eg SLE, arthritis, thyroid, vitiligo, endocrine glands)
  • PMH of 2 invasive, or 1 invasive plus many minor infections
  • Lymphopenia: at least 2.5 in baby or infant as rule of thumb.

Age of Presentation:

  • Under 6 months: SCID, T cell (DiGeorge, Chronic Mucocutaneous Candidiasis, Wiskott Aldrich)
  • 6 months to 5 yr: ataxia telangiectasia, antibody disorders
  • Over 5 yr: specific antibody, complement disorders

Typical bugs:

  • Bacteria – if gram positive or Haemophilus, think antibody or complement disorder (or SCID, of course). Plus:
    • Staphylococcus – phagocytic (eg Chronic granulomatous disease)
    • Meningococcus – properdin disorder
    • Pneumococcus – spleen, ectodermal dysplasia, IRAK4 deficiency
    • Enteric bacteria – phagocytic, SCID
    • Salmonella – cellular or phagocytic disorder
    • Listeria – SCID
  • Viruses – think cellular or SCID, esp CMV and other herpesviruses.
    • HSV – Ataxia Telangiectasia! Mollaret’s meningitis is recurrent chronic meningitis due probably to HSV
    • Enteroviruses – antibody disorder
    • Warts – DOCK8 (with eczema, also molluscum)
  • Fungus – which fungus helps you know what the problem is.
    • Aspergillus commonly seen in CGD, in fact CGD appears to be the only condition where lung aspergillus is seen, and A nidulans v specific for CGD).  Whereas candida rarely a problem in CGD unless neonate or heavy steroids for colitis! Rarely in SCID (other bugs out compete!). Having damaged lungs however can create potential for aspergillus infection in other immunodeficiencies eg Hyper IgE.
    • Candida on the other hand is often seen with SCID. Also autosomal dominant Hyper IgE syndrome (also eczema, pneumonia, skin abscesses), and then a range of conditions where it is the main feature:  IL 17 (recruits neutrophils) and IL 23 (pathway includes STAT3, AIRE, DOCK8, CARD9). CARD9 classically associated with CNS infection but now cases of invasive moulds. AIRE associated with autoimmunity viz APECED (see below).
    • Invasive fungal disease also seen in severe congenital neutropenia and Leucocyte Adhesion Disorders but they usually get severe bacterial infections first!  Functional assays can guide treatment eg IFN.
  • Cryptosporidium – CD40 ligand
  • Pneumocystis jiroveci – SCID, CD40 ligand, phagocyte disorders, ICF (= Immune dysfunction, Centromere instability, Facial dysmorphism; actually a humoral defect. Due to DNA methylation defect hence bizarre chromosomes).  Not just HIV!
  • Toxoplasma – SCID
  • Mycobacterium incl BCG – cellular and phagocytic disorders
    • IL12, IL23, IFNgamma, and STAT1 disorders – various defects identified, which explain about half of all atypical infections. But these defects have low penetrance, rarely disseminated BCG or TB. Multifocal mycobacterial osteomyelitis and granulomata seem to be particularly troublesome though in those with otherwise mild disease. Also susceptible to salmonella, listeria, CMV and other herpesviruses. NOT staph, aspergillus, burkholderia.
    • NEMO (NF Kappa beta Essential MOdulator) defects affect all manner of nuclear activating cytokines, so are not very organism specific; gram positives or negatives, PCP, CMV, mycobacteria all more likely. Strangely, aspergillus does not appear to be a major problem! Null alleles are lethal so always hypomorphic. X-linked, females sometimes affected if mosaic, so look for incontinentia pigmenti.
  • RSV – HIV!
  • Chronic recurrent multifocal osteomyelitis = a clinical diagnosis, inflammatory not infective! Self-limiting, rarely persistent bony abnormalities.

Other clinical problems:

  • Cardiac – Digeorge
  • Eosinophilia and eczema – Hyper IgE, IPEX, Wiskott Aldrich, DOCK8
  • inflammatory bowel disease – CGD, IPEX, CVID, CD40 ligand.
  • Rash in SCID (=GVHD)
  • Liver abscesses – 50% will have CGD in UK.
  • pneumatocoele – Hyper IgE
  • Absent thymus on CXR (pleurae appear to meet in middle) – DiGeorge, SCID
  • Bruising/bleeding – Wiskott Aldrich
  • Abnormal nails, hair, teeth (eg conical incisors), skin (erythroderma), sweat glands – Ectodermal dysplasia, or Cartilage-Hair (= immune osseous dysplasia, due to RNA processing defect, short limbed dwarfism, variable combined defect esp human herpesviruses. Predisposed to lymphoma). X-linked recessive anhidrotic type ectodermal dysplasia presents early in life, but NEMO defects found with abnormal teeth alone (see above). Often get surprisingly little inflammatory response with infections, at least milder ones.  Also APECED (just candida).
  • Coarse facies – Hyper IgE, esp extra/irregular teeth, ICF, but lots of other syndromes of course
  • Persistent vaccination nodule – CGD!
  • Albinism – Chediak Higashi (patches in retina or skin) and related. Incontinentia pigmenti suggests mosaicism, so girl may have X-linked disorder.
  • Late walking, unsteadiness, drooling – ATA (telangiectasia later, esp eye)
  • Diplegia/dysarthria – PNP def
  • Bird head – DNA repair defect (like Seckels, developmental delay)
  • Erythrophagocytosis/lymphoma/aplastic/persistent EBV – X linked lymphoproliferative disorder
  • Late cord detachment = neutrophil or leucocyte adhesion defect
  • Autoimmunity – CVID, CD40 ligand, APECED (ectodermal dystrophy, chronic mucocutaneous candidiasis), IPEX (enteropathy, x-linked)
  • Cytopenias – ALPS, DNA repair and autoimmunity in CD40 ligand.
  • Granulomas – CDG, CVID

History

Consanguinity.

Examination

Scars, nails, creases.

Tests

Always test for HIV!

IgG will be maternal in first 6 months of life.  IgM reaches adult levels in toddlerhood.  IgG in young childhood.  IgA only in adolescence – often low in young children, deficiency only diagnosed after age 4.  Immunoglobulin levels can be high in HIV, Digeorge, CGD.

IgG subsets are controversial – not great evidence that they are responsible for increased infections. High IgM can indicate a problem with class switching eg Hyper IgM syndrome.

Lymphocyte counts:

Total Lymph count (5th centile) Age
2.9 2-3/12
3.6 4-8/12
2.18 12-23/12
2.4 2-5yr
2 7+yr
(Comans, JPed 1997;130:388)

Functional abs – pneumo often worse response esp polysacch.

Subsets – EDTA, fresh, room temp (else CD4 drops – “fridge AIDS”).   CD3 are T cells, which then subdivide into CD4 and CD8 T-helper cells. CD19 and 21 are B cells, CD56 are NK cells. CD4 numbers should exceed CD8 – reversed ratio seen in HIV. A specific NK problem has been described with increased susceptibility to herpesviruses and papillomaviruses. Abnormal NK numbers also seen in Chediak-Higashi, CD40 ligand and NEMO (?).  Low CD4 seen in steroids, sepsis, Digeorge, CVID, Ataxia telangiectasia, Coeliac.

If subsets normal, look at proliferation studies (signalling problem rather than maturation problem).

A total hemolytic complement (CH50 or CH100) screening assay looks for defects in the complement pathway. AH50 or AH100 tests the alternative pathway. [C3/C4 are not enough!]

[Peds 11.127.810]

Pneumonia

General paediatrics, Respiratory, ,

NICE CG250 updated September 2025 to recommend 3 day antibiotic course for non-severe pneumonia in children without complications or underlying disease aged 3 months to 11yrs. Extend to 5 days if necessary. If penicillin allergic, offers 3 days clarithromycin (or 5 days Doxycycline for 12+). (Guideline includes adults so harder to use than BTS…)

NICE recommends co-amoxiclav first line for severe disease (based on oxygen requirement, clinical signs, poor feeding/intake etc).

SIGN/BTS pneumonia guideline last revised 2011 – microbiology bit more subtle now: yes, anything between 1/3 and 2/3 are viral, particularly under 2 years, and probably a third are mixed, but you still get pneumococcus and mycoplasma in infants.

Bugs

Strep pneumoniae (Pneumococcus) is the most common bacterial cause of pneumonia in childhood.

Pneumococcus causes about one-third of radiologically confirmed pneumonia in children aged <2 years.

PCV7 has dramatically decreased IPD due to vaccine serotypes in the UK, but a steady increase in vaccine serotype replacement is evident in the UK.

Group A streptococci and S aureus disease are more likely than pneumococcal to progress to ICU or empyema.

Overall, viruses account for 30-67% of CAP (community acquired pneumonia) cases in childhood and are more frequently identified in children aged <1 year than in those aged >2 years.

1/3 of cases of CAP (8-40%) represent a mixed infection.

Mycoplasma is not unusual in children aged 1-5 years.

Age is a good predictor of the likely pathogens:

  • Viruses alone are found as a cause in younger children in up to 50%.
  • In older children, when a bacterial cause is found, it is most commonly S pneumoniae followed by mycoplasma and chlamydial pneumonia

Wheeze used to be seen as excluding pneumonia, but now only comment is that it can be one of the clinical features of pneumonia, none of which is very specific.  Bacterial pneumonia should be considered in children when there is:

  • persistent or repetitive fever >38.5C, together with chest recession and a raised respiratory rate. [D].

Clinical presentation

Wheeze and chest pain can be symptoms of pneumonia. But none of the symptoms of pneumonia are very specific for pneumonia.

In children over 3yrs, history of difficulty breathing is an additional valuable symptom.

Consider bacterial pneumonia if recurrent/persistent fever >38.5 together with recession and tachypnoea.

  • Re-consultation (in the community) for persistent fever can suggest pneumonia
  • Reassess if pneumonia symptoms do not respond to treatment
  • Refer to hospital if sats <92%
  • Absent breath sounds with dull percussion suggest effusion, refer to hospital
  • Children with pneumonia in hospital should be reassessed if fever persists 48hr after starting treatment, or if there is increased work of breathing or agitation/distress
  • Microbiogical investigations for pneumonia include blood culture, NPA for PCR/IF, serology for resp viruses, Mycoplasma, Chlamydia, pleural fluid C+S/Pneumococcal antigen/PCR.

Investigations

CXR not useful in mild cases, certainly not necessary if admission not being considered. I would consider if hypoxia was disproportionate to degree of breathlessness (suggests collapse), suspicion of effusion (stony dullness on percussion) or pneumothorax.

CXR is not useful in establishing viral vs bacterial vs atypical aetiology!

Repeat CXR in convalescence is only required for persisting symptoms, lobar collapse or round pneumonia.

CRP etc not useful in establishing viral vs bacterial vs atypical aetiology!

Microbiological investigation not necessary routinely, but important if complications or ICU needed.

Antibiotics

Under 2yrs, mild lower resp tract symptoms are not usually due to pneumonia (esp if pneumococcal immunized) so do not need to be given antibiotics – but review if symptoms persist.

No longer age related antibiotic cut offs.

Amoxicillin is first choice, macrolide is an alternative (as is co-amox).  Macrolide should be added if poor response or if severe (D level recommendations though).

In influenza pneumonia (higher rate of staph), co-amoxiclav is recommended [D].  Similarly for measles.

Oral antibiotics equivalent to IV (if tolerated) even in severe disease (PIVOT trial, Nottingham).  But IV for complicated or signs of septicaemia.  Recommended IV antibiotics include amoxicillin, co-amoxiclav, cefuroxime, cefotaxime, ceftriaxone. Rationalize as able, change to oral when clear evidence of improvement.

CAP-IT trial

2021 trial in UK & Ireland – excluded under 6 months and under 6kg or severe underlying chronic condition. Excluded anybody already treated with beta lactam antibiotics for 48+ hrs or any other antibiotic for any duration.

Twice daily amoxicillin 35-50mg/kg/d for 3 days was equivalent to higher doses for 7 days. Longer course had 2 days less cough. [JAMA 2021]

Susan Lipsett et al from Boston suggest that most of these kids would probably have improved without antibiotics anyway – they discharged 80% of kids who fulfilled CAP-IT criteria but who had normal x-rays without antibiotics (!) and only 2% came back! [JAMA Open 2024]

Management

Strongly against NG tubes in severely ill esp infants.  Use smallest nostril if cannot be avoided

Use oxygen if sats <=92%

Monitor bloods daily if on IV fluids

Chest physio is NOT beneficial – at least, not routinely, potentially if focal collapse identified and slow to come out of oxygen.

If going home, advice on managing fever, preventing dehydration, identifying deterioration.

Follow up severe pneumonia, empyema and lung abscess until recovered completely and CXR near normal.