Enteric fever

General paediatrics, Infectious disease

Meaning typhoid and paratyphoid infection.

Typhus means smoke, refers to clouded consciousness characteristic of typhus and typhoid.

S. paratyphi treated the same but milder.

Pretty non-specific presentations – although called enteric, not striking vomiting/diarrhoea, in fact can be constipated…

Intracellular organism… Gall bladder and Peyer’s patches become focuses of infection (including chronic infection). Incubation period 10-14 days (up to 30!).

3 sets of blood cultures and stool cultures!

Typhoid Mary was Irish-American cook who was an asymptomatic carrier and caused at least 80 cases of typhoid in New York – her signature dish was peach ice cream… Asymptomatic carriage was not known about until her case investigated, she was told not to continue working as a cook but was not offered compensation. She was quarantined for 30 years of her life, the last 23 essentially in solitary confinement on an island off New York… Pretty harsh.

Clinical

Abdominal tenderness common. Rose spots (maculopapular, contain organisms!) hard to see in non-Caucasian. Less than 1 in 4 have them. Bradycardia with fever in first week. Hepatosplenomegaly in up to 50%. Nothing specific otherwise, but see complications below…

Complications

  • GI bleeding and perforation
  • Cholecystitis
  • Pancreatitis
  • Myocarditis/pericarditis
  • Osteomyelitis
  • Pneumonitis

Diagnosis

Culture from blood or bone marrow is gold standard. Stool culture could potentially pick up aysmptomatic carrier with another febrile illness… Low sensitivity anyway, esp first week.

Serological tests poor sensitivity/specificity (cross react with other Salmonella types).

Treatment

Always treat, even if well and only from stool (cf other salmonella types).

IV ceftriaxone if sepsis/shock, GI bleeding, intestinal perforation, encephalopathy, metastatic infection, total 10-14 days. Else azithromycin (loading dose 1g, 500mg daily 7 days; children 20mg/kg). [UK-PAS] For areas of high resistance and sepsis, Meropenem plus azithro [CDC Yellow Book].

Normal for fever to take 3-5 days to settle. After that, look for persistent locus and consider additional antibiotic. Fever can persist for 10 days with cefalosporins (low intracellular penetrance).

Drug resistance is a big problem. Fluoroquinolone resistance in most of Asia and sub-Saharan Africa. Oral third generation cephalosporins are also effective although inferior in RCTs.

Where nalidixic acid resistant, in vitro susceptibility to quinolones definitely reduced – use of maximum permitted doses and extending treatment course to 10-14 days will result in cure in >90% of cases — although the clinical response is slower.

Lots of data on quinolone use in children, but theoretical risks so Azithromycin preferred although response possibly slower.

[BIA guideline for England 2022]

PANDAS

General paediatrics, Neurology

=Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) – tics and obsessive-compulsive disorder that have an acute onset and relapsing course, related to streptococcal infection.

Swedo first reported 4 cases of acute onset/exacerbation (2 with evidence of strep), treated successfully with immunosuppression, in 1995. Term first suggested in 1998 by National Institute of Mental Health. Presumed to be causative of course, mediated by inflammation. Has ICD code (8E4A) and everything, but still in 2019 “substantial controversy regarding a role for inflammation in tics and OCD”.

Because many children with similar presentations did not have evidence of streptococcus, a broader category of PANS, paediatric acute onset neuropsychiatric syndrome, was created, which is agnostic to cause. But such a broad category, almost unhelpful.

Finding evidence of previous streptococcal infection is not hard, nor uncommon. Tics and OCD are relatively common too. Although evidence of basal ganglia antibodies, these are non-specific. Lots of neurological problems have acute onset, not least epilepsy. 2020 US study found 91.4% of PANDAS cases had at least 1 of 4 neuronal antibodies in the “Cunningham panel”, and most at least 2, cf 32% of normal controls. Levels dropped over time, as did symptoms. CaMKII (synaptic protein) activity higher too. The antibodies studied were:

  • Anti-dopamine receptor D1 (D1R) IgG
  • Anti-dopamine receptor D2 (D2R) IgG
  • Anti-lysoganglioside GM1 IgG
  • Anti-tubulin IgG

[Frontiers in Psychiatry, 24 June 2020 – US study, including Swedo – compares PANDAS with Tourettes and OCD]

In a study of 58 children tested with the Cunningham panel, antibody levels dropped over time, and corresponded well with improvement in symptoms (median 1 yr follow up). Nearly all had treatment, 40% had immune therapy (including IVIG, plasmapheresis and rituximab, but not steroids, curiously), antibiotics (about half) or psychotropics. Mental health symptoms did better than movement disorders. A group of patients who had negative initial tests were then positive on repeat testing. https://doi.org/10.1016/j.jneuroim.2019.577138

Cunningham panel has been criticised however.

Neuropsychiatric problems are well recognised in and after Sydenhams chorea so it is not without basis (but other organ systems involved, and good evidence for inflammation). Encephalitis lethargica is an encephalitic illness with parkinsonism, dyskinesias, and psychiatric disturbance as dominant features. It is assumed to be autoimmune. NMDA-R encephalitis is an encephalitis with dramatic psychiatric disturbance, dyskinesias, cognitive alteration, and seizures, associated with autoantibodies against NMDA-R (originally described in relation to ovarian cancer).

Movement disorders are also described associated with systemic lupus erythematosus and antiphospholipid syndrome.

Diagnosis

PANS –

  • I. Abrupt, dramatic onset of obsessive-compulsive disorder or severely restricted food intake
  • II. Concurrent presence of additional neuropsychiatric symptoms, (with similarly severe and acute onset), from at least two of the following seven categories:
    • 1. Anxiety
    • 2. Emotional lability and/or depression
    • 3. Irritability, aggression, and/or severely oppositional behaviours
    • 4. Behavioural (developmental) regression
    • 5. Deterioration in school performance (related to attention-deficit/hyperactivity disorder [ADHD]-like symptoms, memory deficits, cognitive changes)
    • 6. Sensory or motor abnormalities
    • 7. Somatic signs and symptoms, including sleep disturbances, enuresis, or urinary frequency
  • III. Symptoms are not better explained by a known neurologic or medical disorder, such as Sydenham’s chorea.

So typically very ill, and usually referred urgently to psychiatric services. NB part III – PANS is a “diagnosis of exclusion”. [Swedo, 2012]

Family history is interesting – mental health issues including tic disorders often run in families, but so do autoimmune conditions, and Sydenham’s chorea.

Kiki Chang’s clinical evaluation guideline defines chorea-like movements seen in PANS as “piano playing movements of fingers when arms extended and eyes closed”, which is very specific. Also states this is only valid over age 8?! But then distinguishes this from “full chorea” (not specified), which should prompt search for a different diagnosis.

For PANDAS, specifies history of scarlatiniform rash, impetigo but also perianal/perivulval dermatitis. ASOT should show rise of at least 58% over 4-8 weeks, or else a single reading more than double the upper limit of normal.

Role of Cunningham panel (discussed above) stated as “useful ancillary information” for PANDAS, but unclear role in PANS.

[Chang 2015]

PANDAS Network recommends the following tests, besides usual inflammatory markers:

  • Vit D, B 12
  • ANA
  • Mycoplasma IgA/M
  • Lyme, EBV, Coxsackie, HHV-6 titres

Treatment

Lack of controlled treatment trial with more than 50 patients.

2 studies looking at exacerbations and throat cultures in Acute onset and non acute onset, non relapsing tics/OCD.  V similar patterns of exacerbations and no obvious link to strep infection.

Controlled trials of antibiotics in PANDAS have not provided strong evidence. Large symptom improvements reported in placebo arm too, for example. No evidence for tonsillectomy. 2016 controlled trial of IVIG showed no benefit (n=35, doi: 10.1016/j.jaac.2016.06.017).

Groups often self selected so at risk of bias. No evidence for 4/52 azithromycin in PANS. 

2017 PANS/PANDAS guidelines (PANS/PANDAS Consortium) are not based on high impact journal research, mostly expert opinion.  Table 1 lists “treatment approaches” but in the foot notes it states “this is not a definitive treatment algorithm; rather, it is a framework to aid in clinical decision making. Before initiating any of the therapies, clinicians must consider the risk/benefit ratio for their individual patients and provide careful/informed counseling about risk of side effects”.

Parental anxiety can be increased by the theory that “the brain is under inflammatory attack” which also fuels demands for treatment.

Is PANS/PANDAS diagnosis more acceptable than idiopathic psychiatric problem? Perverse incentives to diagnose, investigate and treat, of course.  Vaccines get blamed…

Useful perhaps that more research into inflammation getting done, even if putative triggers still unclear. Still v rare however to see high profile research in psychiatric conditions related to inflammation.

Just as interesting to research effect of parental anxiety and expectations on pattern of exacerbations and prognosis. 

[Donald Gilbert, J Child Neurology 2019]

BPNA statement

In response to increasing demands for PANDAS services, the British Paediatric Neurology Association published a consensus statement (2021) that was then criticised by PANDAS groups. The statement does not recommend the use of antibiotics, steroids or IVIG “as they have an insufficient evidence base to say the potential benefits outweigh the risks”, and “their usage could divert the focus away from effective symptom-directed treatments”. When the BPNA then conducted a priority setting exercise, PANDAS came in at number 8. There is now a BPNA PANDAS working group. The latest statement highlights that –

  • all children presenting with acute onset neuropsychiatric symptoms should receive a full medical evaluation.
  • referrals from primary care should not be rejected on the basis that a MDT service may not currently be in place, nor on the basis that there are limited RCTs applicable to PANS or PANDAS.
  • [use] proficiency and judgment, acquired through clinical experience and clinical practice .
  • note existing international peer-reviewed and published treatment guidelines; discuss with regional and tertiary services.

Vaccine allergy

Allergy, General paediatrics, Immunology

The most common adverse events of vaccines are fever, local pain or irritation, and local redness or swelling, which are not signs of allergy

With live vaccines, adverse effects can be delayed until 7 to 21 days after immunization; this includes vaccine-induced delayed-onset urticaria, which is commonly mistaken for allergy.

Assessment and allergy-focused clinical history

  • Testing appropriate for all, whether anaphylaxis, mild symptoms, unknown history or family history.
  • Gold standard is an oral challenge with a therapeutic dose of amoxicillin, 1hr observation, then 5 day course at home to ensure no delayed reaction.
  • Low risk individuals, where IgE mediated reaction unlikely, can go direct to challenge without testing.
  • Puncture and intradermal skin testing is recommended where reaction was within last 12 months, or there were respiratory symptoms. 
  • Skin testing using only penicilloyl-polylysine, with at least 5 mm of wheal and flare greater than wheal as the criteria for a positive test result, is now sufficient to rule out a high risk of having anaphylaxis during a confirmatory oral amoxicillin challenge

Egg is used in the manufacture of a number of vaccines. Whether this is clinically significant or not depends on the vaccine and the severity of the allergy:

  • MMR – only contraindication is anaphylaxis to MMR or other constituent of MMR vaccine
  • Influenza – (live nasal or inactivated injectable) patients with “severe anaphylaxis” (ie requiring intensive care) should be vaccinated in hospital.
  • Varicella, Rabies – no contraindication for egg allergy
  • Yellow fever – discuss with specialist if egg allergy

Gelatine (derived from pork or beef) can be a cause of allergic reactions esp MMR, Varicella, Japanese encephalitis. Allergy would usually be established from history of food reactions eg gummy/jelly sweets, marshmallows.

Latex – can be present in syringe or bung. See Latex allergy.

Despite these potential causes of allergy, immunisation can often be achieved through graded administration.

Some reports of persistent itchy nodules at injection site due to aluminium delayed hypersensitivity.

https://www.annallergy.org/article/S1081-1206(18)30627-6/fulltext#/article/S1081-1206(18)31201-8/abstract

Thrombosis

General paediatrics, Haem/Oncology

The basic coagulation screen is PT, APTT and Fibrinogen.

  • PT – liver disease, warfarin, DIC
  • APTT – haemophilia, heparin, DIC, anticoagulant eg lupus anticoagulant
  • Fibrinogen – congenital hypofibrinogenaemia, DIC

A prolonged APTT which corrects (at least partially) on mixing with normal plasma is deficient in clotting factors. If correction is not possible, then must be an anticoagulant.

The more advanced coagulation tests are:

  • Diluted Russel Viper Venom Time (DRVVT)
  • Kaolin Clotting Time (KCT)

Basic thrombophilia screen is:

  • Protein C/S
  • Anti-thrombin III
  • Prothrombin mutations
  • Factor V Leiden mutation
  • Homocysteine

Protein C and S can be transiently low with acute thrombosis. Levels also affected by warfarin but not by LMWH.

Factor V Leiden

Most common inherited thromophilia in Europe. Co factor for factor X. Autosomal dominant so variable penetrance. Rare in East Asian and African.

Anti-Phospholipid Syndrome

Antiphospholipid antibodies are a mixed bag:

  • Lupus anticoagulant – total misnomer, as it is PRO-thrombotic and only occasionally associated with lupus! Anticoagulant only in vitro. Overall, found in 1-5% of normal population, though in low titre, usually IgM and transient. Persistent positivity is strongly associated with venous thrombosis and stroke and fetal loss.
  • Anticardiolipin is more associated with pregnancy morbidity than with thrombosis, and is less predictive than LA.
  • Anti beta2 glycoprotein 1 (beta2Gp1) antibodies are less well established as an independent risk factor but are cumulative with the other 2.

An autoimmune disorder of recurrent thrombosis and pregnancy loss! Migraine, livedo, raynauds, unexplained persistent thrombocytopenia can be clues. Not well defined in children, usually heralds SLE and is probably much the same thing.

There is no one antiphospholipid syndrome, despite the name! All have persistent antiphospholipid antibodies (of one sort or another) plus 1 or more clinical criteria:

  1. thrombosis
  2. pregnancy related morbidity:
    • unexplained IUD beyond 10/40 with normal morphology
    • preterm (<34/40) due to pre-eclampsia/placental insuff
    • 3+ unexplained consecutive miscarriages

For lab, must test positive on 2 occasions, 12+/52 apart. Testing is affected by warfarin and heparin.

Antiphospholipid syndrome occurs in isolation in more than 50%. 30% of SLE patients get it. A catastrophic clinical presentation can occur with multiorgan involvement (pulmonary haemorrhage, ARDS, cerebral/adrenal infarction, Budd-Chiari), microangiopathic thrombocytopenia, haemolysis similar to TTP/HUS/DIC (Rx anticoagulation, high dose steroids, plasma exchange, IVIG).

Acute treatment is with IV or subcut heparin, followed by warfarin (target INR 2-3). Aspirin may be added if problematic. Hydroxychloroquine should probably always be used. Avoid smoking, oestrogens, cocaine… Plasma exchange and Rituximab may be used in life-threatening cases.

The antibodies act by inducing adhesion molecules from endothelial cells, upregulating tissue factor, activating platelets and the complement cascade generally.  [Current Opinion in Hematology. 13(5):366-75, 2006]

[BMJ 2010:340;1125]

Von Willebrand disease

General paediatrics, Haem/Oncology

Presents with mucous membrane bleeding (eg epistaxis, ecchymoses, menorrhagia, and excessive bleeding with surgical or other invasive procedures esp post adenotonsillectomy). Not usually petechiae (more commonly associated with platelet function defects) but may be seen esp if aspirin/NSAID has been taken. Not usually haematomas (more characteristic of hemophilia) but may be seen if severe vWD. Menorrhagia is a frequent presentation in women.

vWD has been reported in association with hemorrhagic telangiectasia (Osler-Weber-Rendu) syndrome; so consider telangiectasias contributing eg recurrent epistaxis or gastrointestinal bleeding.

Diagnosis may be missed esp in mild vWD, because vWF levels are influenced by factors such as age, inflammation, stress, pregnancy, hormonal cycles, hypo- or hyperthyroidism, and various medications. Hence stress and inflammation due to illness (eg ruptured appendix) may reduce symptoms, whereas minor surgery in the nonstressed patient may be associated with severe bleeding! Family history should be positive, as VWD is mostly inherited in autosomal dominant fashion.

Although men and women are affected equally, women may be recognized more often because of menorrhagia and excessive bleeding with childbirth.

vWF binds platelets in plug formation. It is also a carrier for Factor VIII – without it factor VIII is lost from the circulation. Subtypes:

  • Type 1 is the commonest and the mildest – simple deficiency.
  • Type 2 is mutant vWF, so doesn’t work well. Type 2B binds platelets spontaneously leading to thrombocytopenia.
  • Type 3 is total absence, factor VIII usually low (3-5% of normal) – severe, very rare (usually autosomal recessive).

Diagnosis

Bleeding time is not particularly sensitive or specific. Prothrombin time is normal. APTT may be prolonged, depending on the impact on factor VIII. Specifc vWF antigen/activity tests (Ristocetin stimulates platelet aggregation in presence of vWF) available.

Treatment

Desmopressin (DDAVP) is available in IV form and concentrated intranasal form (not the same as used for enuresis and diabetes insipidus!).

  • IV desmopressin = 0.3 mcg/kg in 25-50 mL normal saline over 30 minutes.
  • Intranasal desmopressin = 150 mcg (one puff) for under 50 kg and 300 mcg (two puffs) for those over 50 kg.
  • Side effects are minimal and include facial flushing, headache, or mild increases in pulse rate or blood pressure that resolve when the infusion is slowed or discontinued. Rare cases of seizures and central nervous system injury that are associated with hyponatremia have been reported.
  • In type 2B desmopressin may worsen platelet count.

Several vWF concentrates are available, with different ratios of vWF to Factor VIII – used to cover surgery. Maximal increase in VWF/FVIII occurs at 30 to 60 minutes, so time the infusion as close as possible to the surgical procedure. The response time varies between individuals and tachyphylaxis (ie reduction in effect) may occur with repeated doses of desmopressin. A trial to establish effectiveness (judged by vWF:RCo (Ristocetin) level) may be helpful.

For major surgery, give concentrate every 12 to 24 hours for 2 to 3 days to achieve levels of VWF greater than 40%. In patients who have decreased baseline VWF:RCo, levels should be measured daily and extra doses concentrate should be administered if tachyphylaxis occurs. In patients in whom FVIII:C levels also are decreased, FVIII:C should be monitored and maintained at a hemostatic level as recommended for hemophilia A. In Type 2B give platelets if low count.

Antifibrinolytics eg tranexamic acid are useful esp for oral/nasal mucosal bleeding. Can even be used topically (mouthwash).

Alagille Syndrome

Cardiology, Congenital, Gastro, General paediatrics, Neonatology

Autosomal dominant condition (70% sporadic) with characteristic facies, biliary hypoplasia, vertebral and cardiac abnormalities. JAG1 gene.

Paucity of intrahepatic bile ducts so typically prolonged jaundice, but depending on how many ducts, may not be obvious in first few months. Jaundice gradually improves, but only minority clear completely. 30% progress to cirrhosis.

Posterior embryotoxon (white ring at periphery of cornea) is a clue, but seen in 10% of normal population so not specific.

Cardiac includes pulmonary stenosis, Tetralogy of Fallot.

Facies: broad forehead, triangular face, deepset eyes, long nose with bulbous tip.

Butterfly vertebrae characteristic (asymptomatic – see on chest x-ray).

Other:

  • Renal Tubular Acidosis, renal cysts
  • Growth failure
  • Pancreatic insufficiency

Fruit allergy

Allergy, General paediatrics, Immunology

A range of possibilities!

  • Isolated type 1 allergy
  • Multiple type 1 fruit allergies – usually to similar fruit but also some common co-sensitivities eg banana/melon/avocado/chestnut/latex group
  • Oral allergy syndrome (pollen food syndrome) – esp peach and related stoned fruit, cross reactivity with pollen (so hay fever), sometimes nuts too. Various patterns depending on allergen family.
  • Salicylate intolerance (so not allergy) esp cherries, raw tomato, pineapple juice
  • Histamine-releasing foods (wine famously, otherwise strawberry, papaya, kiwi and pineapple)
  • Naturally occurring serotonin (tomato again, banana) and tryptamine (tomato again, plum) cause allergy like symptoms [EAACI 2023]

Berry allergy

Some evidence of cross reactivity between raspberry and strawberry but there’s not much evidence to suggest cross reactivity with other berries.  There’s a theoretical link with blackberry, and other things in the same family (Rosaceae – massive group of fruit including apples, peach, pear, apricot, cherry).

Only one report of blueberry allergy ever!

Found one paper that said tree nuts, celery and parsley might also be related to berries, but again I think theoretical.

Pineapple allergy

Can be part of pollen food syndrome (due to profilin allergy) so mostly oral symptoms, hay fever, cross reactivity with other fruits as well as nuts.

Might be salicylates as above rather than allergy.

But can also be allergy to bromelain (similar to papain), with potential for anaphylaxis.

Sometimes associated with latex-fruit syndrome and ficus-fruit syndrome (all tropical, not latex – kiwi, papaya, avocado, banana).

Melon allergy

Can be part of banana/latex group, but also cucurbitae – watermelon, cucumber, courgette, pumpkin.

Juvenile Myoclonic Epilepsy

General paediatrics, Neurology

Common form of childhood epilepsy. cf juvenile absence epilepsy.

One or more of:

  1. Myoclonic jerks on waking and first hour of day, esp if tired
  2. Absences (typical) in about half
  3. Tonic-clonic, on waking and first hour of day, esp if tired
  • Precipitated by alcohol, arousal!
  • Mid teens, hence alcohol/arousal…
  • 3-6 Hz spike and wave seen on EEG.
  • Often photosensitive (40%), unlike Juvenile absence epilepsy.
  • Very sensitive to valproate. Else lamotrigine, levetiracetam.
  • Usually life long, despite the name.

Juvenile absence epilepsy

General paediatrics, Neurology

Quite different from childhood absence epilepsy! Less nice.

  • Rare
  • Onset 9-12 years but occasionally younger.
  • Non-remitting, despite the name
  • Longer absences eg 45 seconds, more frequent
  • Automatisms (eg eye flickering, lip smacking), may be able to continue some automatic activities during absence
  • Occasional tonic clonic seizures, myoclonic jerks despite the name! But much less commonly seen than in juvenile myoclonic epilepsy (JME).
  • Not photosensitive cf JME.
  • Treat with valproate, ethosuximide (unless tonic clonic seizures), or lamotrigine.

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]