Category Archives: Gastro

Fatty liver/MASLD

Gastro, General paediatrics

Not v uncommon in obese children/adults, which is logical. But non-alcoholic fatty liver disease (97% of which is Metabolic dysfunction associated steatotic liver disease (MASLD)) may progress to steatofibrosis, non-alcoholic steatohepatitis (NASH), cirrhosis, liver failure and hepatocellular carcinoma. It is now the most common cause of liver disease in adolescents and amongst the top three indications for liver transplantation in adults.

Data from 2020 in US found prevalence of 20% for obesity and MASLD among 12-17yr olds, with about 70% of obese adolescents affected by MASLD. More common in boys, particularly among Mexican American adolescents. Adolescents with MASLD had significantly higher triglyceride levels and alanine transaminase (ALT) levels, along with lower high-density lipoprotein (HDL) cholesterol. Insufficient physical activity and poor diet quality were key risk factors, not surprisingly. 

And not all cases are obese.

Alcoholic fatty liver disease is a different thing – depends on type of beverage, genetic risk factors, drinking pattern, duration of exposure etc so unpredictable. 

Particularly likely to progress when co-exists with metabolic syndrome (obesity esp high waist circumference, high blood pressure, high insulin resistance, high lipids).  Some polymorphisms also contribute higher risk of progressive disease.  So family history important too.

Some drugs can contribute, including methotrexate, steroids, valproate.

On examination, look for acanthosis nigricans (marker of insulin resistance) as well as signs of chronic liver disease. Hepatomegaly suggests an alternative diagnosis.

Investigations

Essentially to assess co-morbidity and exclude other causes:

  • Fasting serum glucose/ insulin.
  • HOMA-IR (fasting glucose x fasting insulin/ 22.5)
  • HbA1c measurement
  • Renal function tests
  • Vitamin D level
  • Assessment of liver function and screening for other causes of raised transaminases/ steatosis
    • First Line Investigations: ALT, AST, ALP, GGT, Split bilirubin, FBC, Coagulation screen, Albumin, Fasting lipid profile, Immunogloblins and complement levels, Autoimmune profile including ANCA, Anti-transglutaminase antibodies, Thyroid function tests, A1AT level and phenotype, Copper and caeruloplasmin, Plasma free fatty acids, amino acids, organic acids, uric acid, acylcarnitines, and lactate, Hepatitis A, B, C and E serology
    • Second line investigations: If raised triglyceride level consider Lysosomal acid lipase, 24-hour urine copper collection, ophthalmic examination and/ or genetic testing for Wilson’s disease. If organomegaly/ raised uric acid/ raised lactate or a history of hypoglycaemia consider genetic testing for glycogen storage disease

So pretty much as for viral or autoimmune hepatitis.

Non-invasive measures of fibrosis available in some centres.

Reasons to refer to liver unit

  • Age < 10yr
  • Evidence of alternative cause for steatosis detected through screening investigations
  • Presence of metabolic syndrome, type 2 diabetes mellitus, and/ or hyperlipidaemia
  • Increased AST/ALT ratio (>1) and/or a raised AST/ ALT (≥80IU/L)
  • Raised serum level of GGT
  • Child has panhypopituitarism
  • Raised non-invasive marker of fibrosis measurement
  • Presence of hepatomegaly/splenomegaly
  • Thrombocytopenia
  • Jaundice
  • Synthetic dysfunction (raised PT or low albumin level)

  [Caroline says only if double normal)

Patient information leaflets and guidance for NAFLD are available via the Children’s Liver Disease Foundation at https://www.childliverdisease.org

[BSPGHAN 2020 guideline]

Dyschezia

Common, Gastro, General paediatrics, OPD

Baby strains and cries to pass stool but it comes out soft or not at all.  Functional gastrointestinal disorder thought to occur in 0.9 – 5% of infants under 6 months (Rome IV criteria).

Due to poor co-ordination of pelvic floor muscles with increased intra-abdominal pressure generated during stooling. Seen in babies up to 9 months.

Studies have reported symptoms of discomfort around passing normal stool in up to 18% of babies, not all of these children will strictly meet the diagnostic criteria for dyschezia.

Differentiating from true constipation etc requires a clinical history and a normal clinical examination, with the key difference being that the stool is not hard in dyschezia.

No medication (or any form of rectal stimulation) required, can be expected to resolve spontaneously.

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

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.

 

E. coli O157

Gastro, General paediatrics, Infectious disease, Microbiology, Renal

Notorious STEC/VTEC producing strain of E coli. STEC is shigella toxigenic E coli, VTEC is verocytotoxin toxigenic E coli (same thing).

Cause of potentially fatal Haemolytic uraemic syndrome. But other strains also recognised.

1996 Lanarkshire outbreak, traced back to meat pies from John Barr’s butcher’s in Wishaw.  21 deaths, 512 cases of HUS, esp Wishaw Parish Church Hall luncheon and a local pub birthday party. At the time it was the most deadly food related disease outbreak in world history.  As of 2023 it is still the 6th most deadly food related outbreak in history, and still the worst death toll from O157.

A sad claim to fame for the town.  John Barr was eventually fined £2500.

Emerged in late 80s, rates in Scotland have always been highest in UK until Northern Ireland outbreak with 140 cases in 2012. Odd because England has a lot more cows…

Scotland is said to have 2nd highest incidence globally, although not great data from many places, high regional variability, under-reporting…  Canada and Iran worse?

At the same time as the Lanarkshire outbreak, there was an outbreak in Sakai city, Japan – 12 000 cases of infection, mostly primary school kids.  121 developed HUS, 3 died.  Traced to white radish sprouts.

The most serious outbreak was in 2011, Northern Germany. O104 strain however, enteroaggregative plus toxin. 800 cases HUS (90% adults), 53 deaths.  Traced to organic fenugreek sprouts, although Spanish cucumbers blamed initially, exports dropped £120 million per week until consumer confidence returned.

In 2024, there was a UK wide outbreak of O145 related STEC, with 293 cases and 11 HUS cases. There were 2 deaths. Traced back to salad leaves in pre-packed sandwiches, although never proven.

Ratio of unreported human VTEC O157 infection to reports to national surveillance is estimated at 7.4 to 1.

Cows

E coli O157 is now commonly found in cattle, but causes no clinical effect, therefore no incentive for farmers to control. Supershedders are recognized, with one such cow able to contaminate a huge proportion of other animals’ hides.   Current FSA research project underway.  A vaccine has been developed.

Sheep have also been found to carry it…  Likely cause of outbreaks related to “Tough Mudder” events.

Pathology

Lots of acronyms!

  • EHEC = Enterohaemorrhagic E coli
  • O157:H7 = serotype
  • STEC = Shiga toxin producing E coli, same as VTEC (verocytotoxin)
  • STX1/2 genes (same as VTX) code for this toxin.
  • D+/- = Diarrhoeal illness associated (or not)
  • HUS – Haemolytic uraemic syndrome

More than 400 O:H serotypes – 6 account for most HUS.

Other genes are also relevant for virulence eg Intimin (an adherence factor, coded for by eae gene).

Diagnosis

  • Stool culture – should be collected and processed urgently.  State if bloody diarrhoea present and/or suspicion of STEC infection. Routinely tested for the presence of E. coli O157 at local laboratory, which takes 24-48 hours from sample receipt, but will miss non-O157 types. If positive, isolates are referred to SERL for confirmation of identity and typing.
  • PCR stool testing – if stool culture negative, and clearly bloody (or clinical info suggests likely STEC), then Scottish (SNERL) guidance is to send stool for PCR at the Scottish E. coli O157/ STEC Reference Laboratory (SERL), which detects both E. coli O157 and non-O157 STEC.
  • Serum serology – is used for suspected cases where culture/PCR negative.
  • Rectal swabs – may be submitted directly to SERL from cases of HUS who are unable to produce a stool sample.

Do not delay appropriate clinical and public health management while awaiting reference laboratory results.

Regarding laboratory processes:

  • Rapid referral of samples from diagnostic laboratories to SERL is important to improve the probability of culture confirmation.
  • Positive PCR results will be telephoned immediately to the referring diagnostic laboratory and culture results will follow.
  • The local diagnostic laboratory will inform the clinical team and the local public health team of positive PCR and culture results.
  • PCR (stool) may become available to local diagnostic laboratory, removing need for samples to be referred to SERL . However, if a patient presenting with HUS or acute bloody diarrhoea tests negative by local PCR and is causing clinical concern, please discuss referral of stools for further testing with SERL.

Constipation

Common, Gastro, General paediatrics, OPD, Psychology

Consider constipation if:

  • episodes of faecal incontinence (stains or smears in pants, potentially larger accidents),
  • retentive posturing (standing or sitting with their legs straight and stiff or crossed legs, some will sit on their own heel),
  • occasional massive but soft stools that virtually obstruct toilet.

Not just hard painful infrequent stools! Beware also dyschezia, where baby appears to strain at stool but not actually hard/large.

In a population-based prospective birth cohort, where dietary types were extracted from questionnaire, adherence to a ‘Western-like’ dietary pattern was associated with a higher prevalence of constipation up to 48 months [aOR 1.39; 1.02-1.87], which was not mediated by overweight or sedentary behaviour. Adherence to a ‘Health Conscious’ dietary pattern was only associated at short term, with a lower prevalence of constipation at 24 months (aOR; 0.65; 0.44-0.96). This suggests that specific dietary patterns in early childhood could be associated with higher or lower risks for constipation, but these effects are time-dependent. [Maternal & Child Nutrition. 9(4):511-23, 2013 PMID: 22288911]

Straining is not a criteria, in NICE, interestingly, although it is in Rome III criteria!

Red flags:

  • multiple anal fissures,
  • gross abdo distension,
  • tenderness with guarding,
  • abnormal lumbosacral or lower limb findings,
  • failure to thrive
  • ribbon like stools (?anal stenosis)
  • etc

“Do not use dietary interventions alone as first-line treatment for idiopathic constipation” – because no evidence that it helps! But yes, adequate hydration and fibre important (whole grains, fruit/veg, pulses).

NICE recommends Movicol/Laxido (macrogol) as first line, combining with a stimulant (picosulfate, biscodyl, senna) as second line. If macrogol not tolerated, use stimulant +/- softener (lactulose, docusate).

Warn that pain and soiling gets worse before getting better!

Review of adherence and dose important.

Toilet training eg diary, reward system, regular post prandial sitting 5 mins +/- feet on hard surface eg stool.

“Poo should be as soft as toothpaste and should come out like a snake” (Snakes and ladders booklet, Kidney Kids Scotland). Tell your teacher if no toilet paper/soap or broken seat/locks etc.

Soiling

Typically, episodes of soiling (large and small) are due to overflow of liquid stool past a large impacted stool in the rectum.  The child is unable to control, due to the distortion of the rectum.

However, children often try to deny being aware of soiling, despite the obvious smell or discomfort – this is simply a coping method, and normal sensation is usually easy to demonstrate.

The diagnosis is easier in the presence of a large suprapubic mass, or a rectal mass on digital examination.  Some children however soil for attention, without any bowel or rectal disorder.

The presence or implication of a large rectal mass requires disimpaction – an escalating regimen of a paediatric formulation of macrogol (Laxido or Cosmocol are cheaper than Movicol) as per NICE guideline 99 (doses and licensing may differ from product literature):

  • Child under 1 year: ½-1 sachet daily (non-BNFC recommended dose)
  • Child 1-5 years: 2 sachets on 1st day, then 4 sachets daily for 2 days, then 6 sachets daily for 2 days, then 8 sachets daily (non-BNFC recommended dose)
  • Child 5-12 years: 4 sachets on 1st day, then increased in steps of 2 sachets daily to maximum of 12 sachets daily (non-BNFC recommended dose)
  • If macrogol not tolerated, use stimulant laxative eg picosulfate +/- lactulose

If no progress after 2 weeks add stimulant laxative eg senna, picosulfate, bisacodyl, docusate.

Enemas eg citrate can prevent megarectum where prolonged medical treatment fails.

Polyethylene glycol licensed for distal intestinal obstruction!?

Maintenance

I suggest half disimpaction dose for maintenance.

Preferred treatment is paediatric formulation of macrogol (Laxido or Cosmocol are cheaper than Movicol) as per NICE guideline 99 (doses and licensing may differ from product literature).

  • Child under 1 year: ½–1 sachet daily (non-BNFC recommended dose)
  • Child 1–6 years: 1 sachet daily; adjust dose to produce regular soft stools (maximum 4 sachets daily) (for children under 2, non-BNFC recommended dose)
  • Child 6–12 years: 2 sachets daily; adjust dose to produce regular soft stools (maximum 4 sachets daily)
  • If macrogol not tolerated, use a stimulant laxative eg sodium picosulfate (5mg/5ml, NICE recommended doses):
    • Child 1 month to 4 years: 2.5–10 mg once a day
    • Child/young person 4–18 years: 2.5–20 mg once a day
    • Add lactulose or docusate if stools hard

For babies, Senna and lactulose from age 1/12.

At least 3/12 of maintenance before weaning if disimpaction required initially.

I always highlight that laxative use does not induce dependency, rather, that chronic constipation is unlikely to improve without adequate treatment.

Review regularly – symptoms, toileting, taking medication.

Continue maintenance treatment until regular bowel habit established for at least a few weeks or until toilet trained. Do not stop dose abruptly.

General advice re balanced diet including fruit, vegetables, high-fibre bread/breakfast cereals, baked beans, regular toileting, exercise, sufficient fluid intake (1000-1400ml age 4-8yrs, 1200–2100ml age 9–13yrs).

Involve Health Visitor in pre-school group.

Consider trial of milk exclusion (to rule out cow’s milk protein allergy if intractable (ESPGHAN 2023).   Coeliac disease, hypothyroidism, cystic fibrosis, Hirschsprung’s disease and hypercalcaemia also come into the differential.

Surgery

Rectal biopsy indicated if delayed meconium at birth (ie >48hrs), Downs, enterocolitic episodes.

Anal fissures have high spontaneous healing rate with medical treatment.

Manual evacuation under GA may be required if resistant. No benefit on RCT for anal dilatation. Small RCT found botox as good as internal sphincter myectomy for refractory constipation.

Appendicostomy or caecostomy antegrade colonic enema (where bowel irrigated using catheter) has a role in refractory cases after age 6yrs. QOL, continence improve but appreciable morbidity.

Relapses more common in boys, under age 4, background of psychosocial or behavioural probs, encopresis. 1/3 of post pubertal children continue to have severe problems.  See also parenting and constipation.

Parent information

ERIC website – www.eric.org.uk

[NICE clinical guideline 99 – constipation in children and young people (Published 2010)]

[BMJ 2012]

Gilbert’s syndrome

Common, Gastro, General paediatrics, OPD

Gilbert’s syndrome is an hereditary, chronic/episodic, mild unconjugated hyperbilirubinemia.  Due to impaired hepatic bilirubin clearance (glucuronyltransferase deficiency).  Otherwise liver function is normal.

It does not cause chronic liver disease. Non pruritic.  Jaundice may be provoked by fasting, surgery, dehydration, alcohol ingestion, infectious illnesses, heavy physical exertion, and lack of sleep.  Symptoms eg tiredness are due to exacerbating condition, not high bilirubin!

Common, 2–10% of the general population, many undiagnosed. At least 30% of people with Gilbert’s syndrome never develop symptoms.

Gilbert’s syndrome can be diagnosed when the person has:

  • Unconjugated hyperbilirubinemia (on at least 2 occasions, and not progressing).  Conj bilirubin may be sl high but always less than 20% of total.
  • Bilirubin is less than 3x upper limit of normal (approx 60).
  • No evidence of haemolysis (normal full blood count, reticulocyte count, blood film, Coombs’ test, haptoglobin level, and lactate dehydrogenase level).
  • Normal liver enzyme levels.
  • No clinical evidence of liver disease.
  • Commonly homozygous for allele 7.

Differential is Crigler Najjar type 2 – can cause persistent jaundice in childhood (cf type 1 = severe jaundice in first few days of life).

No treatment is required.

Some drugs should be used with caution in people with Gilbert’s syndrome:

  • Atazanavir and indinavir.
  • Gemfibrozil.
  • Irinotecan.
  • Statins when combined with gemfibrozil.

[NICE clinical knowledge summary]

Parent/family information at https://childliverdisease.org/liver-information/childhood-liver-conditions/gilberts-syndrome/

Clostridium difficile

Gastro, Infectious disease

Classically causes pseudomembranous colitis.  A soil anaerobe, spore producing.

In children, most will have had antibiotics within past 4-12 weeks, other risk factors are past and/or prolonged hospitalization.  Many comorbid conditions associated esp cancer, inflammatory bowel disease. Clindamycin was classically the antibiotic most associated but any will do.

There may be fever and abdominal pain.  Colitis can mimic (or exacerbate) IBD.  Severe infection unusual.  Markers established in adults for severe infection resulting in colectomy or transfer to ICU have not been shown to correlate in kids.

“Pseudomembranes” are a non-specific endoscopy finding.  Not always tested for automatically by lab, you may need to specify. Toxin test (not 100% sensitive).

Current Opinion in Pediatrics. 26(5):568-72, 2014 Oct. PMID 25032717

Coeliac disease

Gastro, General paediatrics

Autoimmune process triggered by gluten, distinct from type 1 IgE mediated wheat allergy –  leads to subtotal villous atrophy in terminal ileum. Multifactorial, genetics important – at least 90% positive for DQA1*05 and DQB1*02 alleles that code (confusingly) for DQ2 and/or the DQB1*03:02 allele that codes for DQ8 molecules.  The risk of having coeliac disease without these variants is less than 0.1% so good negative predictive value, but very little positive predictive value – you may not have it now, but you may well get it in the future.

1 in 200, mostly undiagnosed/adult, decreasing in children. More girls than boys, 10% risk to 1st degree relatives.

Randomized trial of early introduction of gluten (4 months, rather than UK recommended 6 months) in 1300 babies found not a single case of coeliac disease at age 3, cf 7 cases in later introduction group (JAMA Ped 2020) – similar result for egg/peanut allergy (same EAT study).

Signs

Become less convincing the older you are! Can present even in infancy, although diagnosis may be delayed for a year or more.

Consider in patients with:

  • Chronic or intermittent diarrhea
  • Chronic constipation not responding to usual treatment
  • Chronic abdominal pain
  • Distended abdomen
  • Recurrent nausea, recurrent vomiting

Should also be considered for these extra-intestinal symptoms:

  • Weight loss, failure-to-thrive, stunted growth/ short stature
  • Delayed puberty, amenorrhea
  • Irritability, chronic fatigue
  • Neuropathy
  • Arthritis/arthralgia
  • Chronic iron-deficiency anaemia
  • Decreased bone mineralization (osteopenia/osteoporosis), repetitive fractures
  • Recurrent aphthous stomatitis
  • Dermatitis herpetiformis–type rash
  • Dental enamel defects
  • Abnormal liver biochemistry

And consider for these specific situations:

  • First-degree relatives with CD
  • Autoimmune conditions: T1DM, thyroid disease, liver disease
  • Down syndrome, Turner syndrome
  • William’s-Beuren syndrome
  • IgA deficiency

[ESPGHAN guidelines 2020]

Diagnosis

Biopsy is no longer essential for diagnosis in children with high serum IgA class antibody concentration against transglutaminase 2 values (10 times the upper limit of normal) with appropriate tests and positive endomysial antibodies (EMA-IgA) in a second serum sample, even in absence of symptoms. Shared decision making with parents recommended.

Children with positive IgA class antibodies but under 10x ULN should have biopsy.

Beware IgA deficiency (associated with coeliac disease, which gives false negatives for IgA TTG – our lab can see this when they do the test, so no need to request total). Also good to check FBC, ferritin, folate, LFTs, Calcium, prothrombin time.

“HLA typing is not required in patients with positive TGA-IgA, if they qualify for CD diagnosis with
biopsies or if they have high serum TGA-IgA (>=10x ULN) and EMA-IgA positivity. If a patient tests negative for HLA DQ2 and DQ8, the risk of CD is very low, while a positive result does not
confirm the diagnosis.”

“Recent studies suggest that the no-biopsy approach to diagnose CD can be applied in asymptomatic children. In asymptomatic children, however, the PPV of high TGA-IgA >=10x ULN may be
lower than in symptomatic children, which needs to be considered during the decision-making process”

  • Positive tTG alone is insufficient for diagnosis, and should not be a reason for gluten free diet.
  • If tTG is high but less than 10x upper limit, then proceed to duodenal biopsy.
  • If tTG more than 10x upper limit of normal, alternative to biopsy is to check IgA EMA and do HLA DQ2/8 screening. If BOTH positive, diagnosis is confirmed. If EMA not available, a second strongly positive tTG is an acceptable alternative (but save serum for EMA testing at future date).
  • If IgA deficient, use IgG tTG or EMA, but less specific so low threshold for biopsy.

Note that antibodies may be false negative if the diet is low in gluten at the time of testing. So normalize gluten intake (at least 2 meals per day, for at least 6 weeks) but discuss with specialist if clinical condition so poor that treatment cannot be safely delayed.

False positives also occur, so diagnosis must be confirmed by endoscopy (or another diagnosis may become apparent). Endoscopy for high risk symptoms (diarrhoea, wt loss, anaemia) and serology is 100% sensitive for coeliac. But a proportion with high risk symptoms and positive serology do NOT have positive biopsies! Cause? Perhaps atypical disease (ie no GI symptoms) is actually more common than typical! Consider the incidences of anaemia, infertility, short stature, unfavourable pregnancy outcomes…

Screening

Coeliac disease is associated with other conditions, which may justify screening:

  • Type 1 diabetes (8%)
  • IgA deficiency (up to 7%)
  • Downs, Williams and Turners syndromes!
  • Autoimmune thyroiditis
  • Autoimmune liver disease
  • Unexplained abnormal LFTs
  • Relatives of coeliac disease patient (10% in 1st degree relative)

Before testing, discuss relative risks of untreated coeliac disease (osteoporosis, infertility, small bower cancer), and the need for biopsy and gluten free diet if tests are positive. Then test:

BSPGHAN say check HLA DQ status and IgA tTG.  NICE says do not use HLA DQ2/8 in non-specialist settings, but consider if not proceeding to biopsy or those on low gluten.

  • If HLA DQ2/8 neg, then v unlikely.
  • If DQ pos but tTG neg, then unlikely (unless IgA deficient or on low gluten diet). Still potential to get disease later in life, so test again in 3yrs or if symptomatic.
  • If DQ/tTG pos but tTG less than 3x upper limit of normal, then do IgA endomysial antibody (EMA) and proceed to biopsy if positive. If EMA negative, continue to monitor.
  • If DQ pos and tTG higher than 3x, biopsy. (Although option is given to retest in 3-6 months)
  • If IgA deficient (<0.07mg/L), consider using IgG EMA, deamidated gliadin peptide (DGP), or tTG
  • Have a low threshold for retesting if signs/symptoms consistent!

Biopsy

Villous atrophy on biopsy (do 4) is characteristic. Marsh grading system: infiltrative changes with crypt hyperplasia is compatible, positive serology strengthens diagnosis. If diagnosis still uncertain, consider HLA testing as above, repeat biopsy after increasing gluten intake or else go the other way, and biopsy after gluten free diet!

Biopsy if gluten excluded and persistent high titres at 12 months or persistent symptoms.  Serological tests alone not adequate to determine if gluten has been excluded!

Treatment

The benefits of treatment, in symptomatic children are:

  • resolution of symptoms,
  • reversal of bone demineralisation,
  • Resolution of micronutrient deficiencies and probably better height gain
  • less delayed puberty, menstrual problems, subfertility, spontaneous abortions and LBW babies
  • decreased risk of some intestinal cancers, to normal levels (T cell lymphoma, Ca oes/pharynx).  T cell lymphoma risk falls to baseline after 10 years gluten free diet
  • Possible prevention of associated autoimmune conditions (evidence conflicting) – see below

In asymptomatic patients, there are no long term studies as yet to show benefits so need to discuss with family.

Diet

Food labelling allows up to 200ppm gluten in gluten-free foods: some people may be sensitive at lower levels than this (at least, their mucosa may be sensitive – they may remain asymptomatic). Gluten free foods are available on prescription.

Oats are safe for 95% of patients (besides contamination issues and the above food labelling problem). Ideally exclude initially and consider reintroduction (products marked gluten free) when well eg at 1yr; normalization of tTG and continued low titres reassuring!  NICE says can be included at ANY stage, but review immunological/clinical/histological response.

Most coeliac patients can tolerate wheat starch and malt extract but not all.

Follow up

If compliant on diet, antibodies should go negative within a year. The mild transaminitis commonly seen at diagnosis should resolve – if not, and on diet, then consider Autoimmune Hepatitis. Complete mucosal recovery can take years.

Monitor symptoms, growth, puberty, antibodies (eg 6 monthly, then 12-24 monthly). Poor clinical response = poor compliance! TTG, FBC, Ca/Phos/ALP, Ferritin, Vit B12, folate, Vit D, PTH, TFTs.

Consider bone scan – see osteoporosis

Discuss oats, as above.

Pneumococcal vaccine recommended.

Transition

Understanding of diagnosis, antibodies.

  • Encourage maturation of communication and decision-making skills.
  • Allow patients to take responsibility for medical self-management.
  • Help the patient develop healthy habits and self-care skills that encourage autonomy eg smoking, exercise, alcohol/drugs
  • Education and counselling re: gluten-free diet (food on prescription, nutritional completeness, healthy weight) and consequences of non-adherence.
  • Recognition and treatment of psychological/emotional issues eg : discouragement, feeling overwhelmed, anxiety about the future and complications such as depression and eating disorders.
  • Familiarize young person with healthcare system

For those patients with significant pubertal delay, paediatric provider may be better suited to provide guidance until transition to an adult provider at the completion of puberty.

Topics for discussion –

  • How there can be a long interval between gluten exposure and the return of symptomatic disease.
  • How coeliac disease can interfere with school, education and work (eg military service)
  • Sexuality and fertility (women with untreated CD are more likely to suffer an adverse pregnancy outcome) – lifetime fertility however is similar in individuals with and without coeliac
  • Adolescents report lower adherence than younger children, esp at social events. Dietary non-adherence is associated with poorer QoL and increased physical symptoms. Most young people with CD think that avoiding cancer is the most important reason to adhere to diet, but the risk for cancer is much lower than previously presumed, so osteoporosis and adverse pregnancy outcome may be bigger issues.
  • Risk of passing it on to children.
  • Associations with diabetes, thyroid disease, autoimmune liver disease.

Primary care may be a suitable care provider.

[Prague consensus, Ludvigsson Gut 2016;65:1242-1251.]

Coeliac UK support group

Hepatitis B

Gastro, General paediatrics, Infectious disease

Highly infectious blood borne virus. A single contaminated needle stick injury carries a significant risk of transmission. In endemic areas, significant rates of postnatal infection in children, presumably from minor trauma.

Acute infection develops over 1-6 weeks and can be fulminant. Symptoms are non-specific fever, lethargy, abdo pain.  15% have serum sickness type  symptoms in pre-icteric phase viz fever, arthralgia, urticaria. Jaundice then develops.   Various antigens, which may or may not clear as antibodies produced, used to diagnose, judge stage of infection, and infectivity.

  • HBsAg – shows Acute or chronic hepatitis B infection. Can be negative in acute fulminant disease.
  • Anti HBs (or Anti HBs) – Immunity to hepatitis B, postinfective (only 6% of patients) or with active or passive immunization
  • Anti HBc IgM – first antibody to appear, even before HBsAg.  High titer: acute hepatitis; Low titer: chronic infection
  • Anti HBc IgG – Past exposure to hepatitis B, or maternal antibody crossing placenta in young infants
  • HBeAg – highly infectious.  Without treatment, 85% of children clear HBe.
  • anti HBe – not immune, but low infectivity. Do not develop chronic hepatitis; but low risk of hepatocellular carcinoma persists.

NB there may be an interval following the disappearance of a hep B antigen before its antibody becomes detectable.

For acute hepatitis, no specific treatment is required, just supportive. If fulminant, some people use antivirals, but basically the issue is whether you need to transplant – see below.

Carrier rate (ie chronic infection, = HBsAg pos for 6/12, and hence potential for serious sequelae) is higher in males and greatest in those infected in first 3 years of life.  Also higher in those with mild symptoms viz anicteric with minimal elevation of transaminases.

Some carriers will be inactive with anti-HBe, low levels of DNA (<100 000 copies on PCR) and normal transaminases. Liver disease progresses very slowly if at all, although hepatocellular carcinoma risk is still higher than normal (but much less than in HbeAg positive). Monitor LFTs every 6-12 months.

In active chronic infection, DNA levels are high indicating active replication, transaminases are 2x the upper limit of normal or higher, and biopsy will show stage 4 histological activity or more. HBeAg is usually positive although some mutants will be negative. Adults with chronic hep B have 20% cirrhosis rate after 10 years and 37% after 15 years. Alcohol intake is an independent factor. Hepatocellular Ca rate is about half that.

When to biopsy is tricky, partly because the clinical course is unpredictable but also because treatment is ineffective. Transaminases can be raised transiently, so repeat after 1-3 months. Histological cirrhosis has a poor prognosis. With treatment, 32% of patients with chronic disease clear HBeAg cf 11% of untreated (metanalysis). There is no benefit in patients with normal LFTs.

Do USS and alpha fetoprotein every 2 years as screening for hepatocellular Ca for both inactive carriers and chronically infected.

Other management points –

  • immunisation of household contacts
  • vaccination against hepatitis A (in low prevalence areas)
  • avoiding alcohol
  • safe sexual practices
  • weight reduction
  • Careers advice
  • Immunosuppressive drugs may activate hepatitis B infection. Equally, immunosuppressed children may have hepatitis B infection without serological evidence – so do PCR.

Treatment

For acute, no specific treatment, just supportive. If fulminant, look for co-infections that may have precipitated episode. Main issue is whether transplant required, although American Association for study of liver diseases recommends using antivirals in adults: no great evidence but seem reasonably safe, and reduces risk of re-infection of grafted liver after transplant (pretty inevitable – HBIg post transplant also delays infection but resistant mutants come through). Lamivudine or telbivudine suggested when the anticipated duration of treatment is short; otherwise, entecavir is preferred. Treat until HBsAg cleared or indefinitely in transplants. Interferon is contraindiated.

For chronic infection:

  • Pegylated IFN alpha (5 million units a day or 10 MU thrice SC for 48 weeks) both antiviral and immunomodulatory activity.

Other issues:

  • Co-infection with HCV has a poorer prognosis even though DNA levels may be less; treatment should be considered at 1000+ copies.
  • In decompensated cirrhosis, transplantation is the only definitely effective option. Lamivudine may help (historical controls). IFN increases complications.