Mostly diagnosed in neonatal period, classically with delayed passage of meconium, but potentially with enterocolitis: usually diarrhoea ?fever ?constipation! (but explosive diarrhoea on rectal). Initial management is rectal washouts to decompress (else colostomy).
Diagnosis by rectal biopsy - shows aganglionosis. If presents later then there is always a history from birth - but never soiling! Enterocolitis still occurs post Hirschsprung pull through repair - presumably residual intestinal neuronal dysplasia.
4 male:1 female. Maternal history is more significant than paternal! NB Associated with TOF, other abnormalities.
1st week to 5 months, but usually after 3 weeks. Olive 2 cm felt RUQ, from left side, after vomit. Differential diagnosis = CAH, inborn error
1 in 200, mostly undiagnosed/adult, decreasing in children. More girls than boys, 10% risk to 1st degree relatives.
Signs:
Should be considered in patients with symptoms of irritable bowel syndrome, iron deficiency anemia, unexplained arthritis, and even chronic elevations of aminotransferases . (Curr Op Peds 16(5); 2004)
AEA 100% specific, 85% sensitive. AGA is added for dubious negatives. Tissue Transglutaminase antibodies are a new screening test. If compliant on diet, antibodies should go negative within a year. The negative predictive value of anti-Endomysial Ab assessment in children suspected of coeliac disease is high but under 90%. Archives of Disease in Childhood 2005;90:41-42
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…
IgA deficiency is associated with coeliac disease and gives false negatives unless IgG antibodies looked for especially.
The mild transaminitis commonly seen at diagnosis should resolve - if not, and on diet, then consider Autoimmune Hepatitis (see below).
Complete mucosal recovery can take years. Poor clinical response = poor compliance! Coeliac society allows moderate oats - no proven harm from oats in diet, for at least 12 months, but often contaminated with wheat! Risk of T cell lymphoma, Ca oes/pharynx.
Low threshold for suspicion of VTEC eg O157, given importance of infection control and potential role for early volume expansion in preventing HUS. Consider risk factors eg farm/farm animal contact, possible contamination of food. Absence of fever at presentation is the rule (though often reported) cf other infectious causes. Monitor urine output and check FBC, film, U&Es, LDH, CRP
Bloody diarrhoea is presenting symptom in 75% of UC and 25% of Crohns. If persistent for more than 7 days, esp where associated with weight loss, poor growth, clubbing, systemic features (fever, erythema nodosum), or oral/perianal lesions then refer to gastroenterology.
Severe bloody diarrhoea (viz more than 5x per day) requires urgent referral - associated with increased risk of non-response to medical treatment, progression to toxic megacolon and colonic perforation. IV steroids or ciclosporin may be effective else emergency colectomy sometimes needed. Hb and platelet count have a sensitivity of 92% and NPV of 93% for UC when 1 or both is abnormal; but in mild disease, 19% have normal inflammatory markers.
Cochrane says Salmonella should not be treated with antibiotics and may prolong carriage. Reserved for suspected bacteraemia, or impaired immunity. Shigella on the other hand should get antibiotics unless mild (says BNFc). Campylobacter can be treated with antibiotics if severe.
CMPI is a possible diagnosis in infants. Chronic bloody diarrhoea is even seen in breastfed (?maternal antigens!). In a series of 40 infants (23% had eosinophilic infiltration), cow's milk elimination and re-challenge supported the diagnosis in only 18% (were they the ones with eosinophils? no full text). Usually such bleeding is intermittent, lasts a month or 2, goes away spontaneously, and cow's milk elimination did not affect duration!
Necrotizing enterocolitis (NEC) - abdo distension, bilious vomiting, signs of septicaemia - can develop up to 10 weeks of age. Up to 10% of cases occur in full term neonates, where onset is usually in the 1st week of life.
Hirschsprungs - more than 90% have delayed meconium beyond 24 hours. 25% present with enterocolitis rather than constipation. 80% present in 1st year of life.
Solitary rectal ulcer syndrome - seen on endoscopy, several centimetres above anal canal, presumably due to mucosal prolapse.
Murphy, BMJ 2008; 336:1010
Disease of N America, Europe. Strong geographic & genetic influences. Cause is presumably exaggerated immune response to bacterial antigens: note that ileal diversion cures, whereas infection triggers exacerbations. Incidence has doubled over 20 years.
Risk factors:
Presents with abdo pain, diarrhoea (esp bloody diarrhoea), poor weight gain or weight loss, delayed puberty, oral/anal lesions. Other findings at presentation may include clubbing, arthritis, uveitis, erythema nodosum.
Crohns outnumbers UC 2.5:1 in kids. 8 gene regions identified which increase susceptibility and are predict phenotype (eg ileal disease, inflammatory markers, need for surgery).
Mouth to anus, discontinuous, transmural, granulomas (few crypt abscesses), males predominate 2:1 in childood (but opposite in adults).
Dalziel described chronic enteritis in BMJ 1913 before Crohn!
Perianal lesions (fissure, skin tag, abscess, fistula) often asymptomatic in Crohns so often missed in primary care.
Investigations - Porto criteria for diagnosis. High platelets are suspicious; together with anaemia has 90% PPV for IBD. PMID:15990620 JPGN 2005;41:1-7
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.
Induction and Remission model favoured. Depends on severity and location.
European Guidelines for adults at Gut 2006;55(Supplement 1):i16-i35.
For mild ileal disease, no treatment is an option, and a proportion do go into remission spontaneously. Otherwise, steroids are used (but do not prevent relapse). Budesonide has low systemic bioavailability so has less side effects than prednisolone, but is a little less effective so for moderate disease use prednisolone or systemic steroids. Antibiotics are added for septic complications eg fever, local tenderness, abscess on scan.
Meta-analysis in 2004 found that 5-ASA doesn't work much better than placebo.
In severe disease, Azathioprine/mercaptopurine has steroid sparing effect but usually reserved for relapses. If azathioprine is not tolerated then methotrexate is an alternative. Infliximab is usually reserved for resistant cases, although it can prevent the need for surgery so has a role where early surgery is not thought appropriate. There is also some evidence in adults that step-down treatment after azathioprine and infliximab showed better relapse rates than step-up treatment (sequential after steroids). Selecting poor prognosis patients for these more intensive induction/maintenance treatments seems sensible.
Sulphasalazine is used for mild colonic disease. Topical 5-ASA (Asacol enema) can be considered for distal(left sided) colonic disease but has not been subjected to a RCT. Budesonide is ineffective in colonic disease so most patients need prednisolone or IV steroids. Metronidazole alone can work but there is a high incidence of side effects. Again, azathioprine is good for relapses, and infliximab can prevent the need for surgery early on. Many patients will need surgery at some point.
Since inflammatory and nutritional consequences are significant, early immunomodulation is a good idea (including methotrexate), as is early nutritional support. Nutritional support can be considered primary treatment in mild cases.
Proton pump inhibitors for oesophageal/gastoduodenal disease. Antibiotics (metronidazole, ciprofloxacin) are used for perineal disease and bacterial overgrowth but side effects common and there is anxiety about long term use.
Nutritional therapy only relevant to Crohns. First line for both small & large bowel disease. PEG offered if anorexic and NGT unsuccessful. Exclusive 8/52. Polymeric feeds esp Modulen more palatable, lower osmo, cheaper but cow's milk based cf elemental. Works by ?bowel rest ?immune modulation? No side effects but diarrhoea may not settle for 1-2/52.
Risk factors for major resection are:
For maintenance, 6-mercaptopurine gives a 18 month relapse rate of 9% (vs 47% in controls). Used for relapses. Side effects are myelosuppression, hepatitis, pancreatitis, flu-like illness. Role of thiopurine genotype testing or levels is unclear. Ciclosporin helps both. Methotrexate not useful in UC, but can be used where intolerant of thiopurines. ?infliximab ?leucopheresis.
Infliximab (=anti TNF Ab) IV infusion for Crohn's esp steroid resistant, refractory fistulas. SE 10% but mild. High response rate, but doesn't
Acid gastro-oesophageal reflux disease and/or histological oesophagitis are frequently diagnosed in irritable infants. There was no relation between symptoms and abnormal pH metry or oesophagitis; however, the reflux index does not accurately predict oesophagitis and normal histology does not accurately exclude acid gastro-oesophageal reflux disease! So treat empirically and review.
Eosinophilic esophagitis (EE) is an isolated, eosinophilic inflammation of the esophagus. Causes vomiting and abdo pain. Due to food allergy, it can eventually lead to stricture formation requiring elemental feeding. However it is not IgE mediated so identification of allergen is difficult. The incidence of EE is rising. (Curr Op Peds 16(5); 2004)
Helicobacter pylori is associated with social class, and is present in up to 25% of normal children ie can be commensal. Diagnosis by 13C-urea-breath-test (UBT), else stool antigen test (HpSA): 91-93% sens and specific. Antibodies are less closely associated with disease, and persist for months after eradication, so serology is generally unhelpful.
Pneumonia rate in adults doubled if on acid suppression therapy (Netherlands).
Sequential triple therapy for 10 days is better than regular triple therapy (PPI, clarithro, amox). Give just amoxicillin and the PPI for 5 days, then swith to the other antibiotics for the next 5 days.
A paroxysmal, especially severe, recurrent vomiting disorder of unknown etiology. Based on epidemiologic surveys, CVS can no longer be considered a rare disorder; it may be second only to gastroesophageal (GE) reflux disease as a cause of recurrent vomiting in children. It affects not only children but also adults.
Affected girls slightly outnumber boys, as in migraine. CVS affects children of all races and ethnicities but disproportionately whites. The median age of onset was 4.8 years in children under 18 years. Delay to diagnosis is typically 2.7 years in children (representing approximately 20 episodes). Thus far, the median age of resolution of vomiting episodes has been 10.0 years, but this will move upward as the cohort ages. As vomiting resolves, 28% have concomitantly developed migraine headaches.
Despite the fact that children are ill less than 10% of the time, there was substantial academic and medical morbidity in terms of school absence, IV rehydration, emergency department visits, hospital stays, testing.
The hallmark clinical feature used in diagnosis is severe, recurring, discrete, stereotypical, and episodes of vomiting. Children with more than three episodes of recurrent vomiting can be split into cyclic and chronic. The cyclic group have a high intensity (12.6 peak emeses/hour), low frequency (1.5 episodes/month) pattern whereas the chronic group have a low intensity, high frequency, daily pattern (1.9 peak emeses/hour with 36.6 episodes/month). The cutoff for the cyclic pattern lies at greater than or equal to four vomits per hour and less than or equal to two episodes per week, and is very sensitive and specific where other diagnoses have been excluded.
Vomiting pattern points to different diagnoses: outside the gastrointestinal (GI) tract in those with the cyclic pattern, and inside the GI tract in those with the chronic pattern of recurrent vomiting. Those with the cyclic pattern primarily had extra-intestinal disorders—neurologic (esp abdominal migraine), renal, metabolic, and endocrine. In contrast, those with the chronic pattern predominantly had GI disorders (eg peptic esophagitis).
There is a short prodromal phase before the onset of vomiting lasting a median of 1.5 hours with nonspecific signs including pallor, lethargy, anorexia, and nausea. The episode itself is defined by a median of 15 total emeses and a duration of 24 hours. Episodes may lengthen with age. The vomit may be projectile (48%) containing bile (81%) and blood (34%). An OGD typically confirms secondary esophagitis and prolapse gastropathy from herniation of the gastric mucosa through the lower esophageal sphincter. The recovery phase, from the last emesis to the turning point of being able to retain liquids and food and resume play, is a remarkably brief 6 hours, often typified by sleep. Some parents note such an instantaneous transition from misery to playfulness that they describe it as "turning off a switch".
Other features:
The most difficult differential diagnosis to delineate is between an acute episode of CVS and viral gastroenteritis. Affected children are qualitatively and quantitatively sicker - there is a 75-fold higher rate of IV rehydration than in rotavirus gastroenteritis. Profound lethargy and inability to walk, talk, or interact may simulate semi-coma and concerns about the presence of shock, meningitis, or toxic ingestion. Finally, abdominal pain can be of sufficient severity to mimic an acute abdomen.
Of those who present with the cyclic vomiting pattern, 12% turn out to have a surgically-correctable lesion or metabolic disorder not idiopathic cyclic vomiting syndrome. The most potentially devastating of these is malrotation with intermittent volvulus which, if unrecognized, can result in small intestinal resection. If episodic right upper quadrant pain and vomiting recurs post-operatively a sphincterotomy may help.
First, the most common surgical disorders are best detected by small bowel radiography and abdominal ultrasound or CT. Second, laboratory screening for metabolic, endocrine, hepatobiliary, and pancreatic disorders is optimally performed during the episode to maximize the chance of detecting an intermittently symptomatic disorder (eg, disorder of fatty acid oxidation).
Various studies have found a high rate of improvement (75%) in response to anti-migraine therapy. Eighty percent of those with CVS could also be co-classified as abdominal migraine (based on the presence of concomitant abdominal pain), and 54% of those with abdominal migraine could also be co-diagnosed with CVS (based on the presence of concomitant vomiting). There is new evidence that these disorders share similarities in autonomic nervous system function with a predominance of sympathetic adrenergic over parasympathetic cholinergic tone.
The authors calculated that, based on the high potential cost of a missed mid-gut volvulus and high response rates to anti-migraine prophylaxis, a 2-month empiric trial of anti-migraine prophylaxis after an initial small bowel contrast study was the most cost-effective approach.
Among anti-migraine agents, the authors found low dose amitriptyline (54%) and propranolol (50%) to be more effective than cyproheptadine (39%). Anderson, et al reported high resolution rates for phenobarbital and and erythromycin. In adults, low dose tricyclic antidepressants—amitriptyline, doxepin, and nortriptyline—have been useful.
Both anti-migraine and anti-emetic agents have been used as abortive medications. Sumatriptan, a 5HT1B/1D agonist, used off label has a 46% efficacy rate in the authors' experience when administered by either the intranasal or subcutaneous route. Unfortunately there are no pharmacokinetic studies to guide dosing in children. The switch to the nasal form has significantly reduced the unpleasant burning sensation in the chest and neck commonly experienced with subcutaneous injection.
Ondansetron (5HT3 antagonist) is the mainstay of anti-emetic therapy at higher doses of, 0.3 to 0.4 mg/kg every 6 hours and is rendered more effective in severe episodes by use of a benzodiazepine (lorazepam) as an adjunctive anti-nausea agent. It can be reconstituted as a suppository and is anecdotally said to be effective.
Tachykinin (NK1) receptor antagonists, have just been released for use in adults with chemotherapy-induced emesis, appear more potent on the late phase emesis. Corticotropin-releasing factor R1 antagonists currently in development could theoretically ablate the vomiting by blocking the vagally-mediated action of CRF.
Fluids alone help perhaps by terminating the ketosis in addition to intravascular replenishment. Because these children are hyperesthetic, a quiet, dark private room with minimal stimulation is key. By patient report, sleep generally provides the only respite from the intractable nausea and may in fact initiate the recovery phase. It is worth noting that phenothiazine anti-emetics (eg, promethazine and prochlorphenazine) are ineffective in CVS. Opiates may exacerbate vomiting.
Cyclic Vomiting Syndrome Association
To describe CVS as having a migraine mechanism is like exchanging one black box for a gray one. At its mechanistic core is regional post-synaptic neuronal hyperexcitability that when enhanced by several factors—membrane channelopathies, cellular energy deficits, and hormonal state—may result in episodic depolarization in the brain.
Gastroenterology Clinics of N America; 32 (3) 2003
Mostly caused by Clostridium difficile. Spores survive for months and are resistant to commonly used disinfectants. Rare in kids (although diarrhoea common) except neonates and CF patients. Risk factors are hospitalisation and antibiotic therapy esp beta lactams and clindamycin, but most are associated except for vanc, metronidazole and aminoglycosides. Asymptomatic stool carriage occurs so look for toxin. Necrotic ulcers form, then membrane of fibrin and leucocyte debris. Presentation can vary from simple gastroenteritis through dysentery (disproportionate amount of blood is a clue) to toxic megacolon with perforation. Intramural gas seen in NEC, immunocompromised children with rota/adeno, C. diff, CMV. Presumably combination of mucosal injury by infection or systemic disease/drugs, increased luminal pressure (eg coughing, lots of chronic resp adult cases), bacterial gas production. Differential is other infective diarrhoea, Hirschsprung's. Treat with oral metronidazole 35mg/kg/d (cheaper, less likely to induce resistance but occasionally C. diff resistant), oral vancomycin 40 mg/kg/d if severe (if IV required, metronidazole gives better colonic levels, failure reported with IV vanc). High flow O2 works. Relapse common, use same treatment! Avoid beta lactams. For multiple relapses, cholestyramine has been used, no other preventive strategies have been shown to be effective.
Complex hormonal/metabolic problems associated with refeeding. Associated with prolonged hospital admission, esp intensive care, poor nutritional status (including anorexia). Deaths have occurred due to complications.
Diagnosis - hypophosphataemia below 0.65mmol/l after the onset of enteral refeeding. Severe is below 0.3. Can develop within hours; highest risk during first week.
NICE guideline 2006 for prevention/treatment.
Prevention:
Beware tachycardia; may be due to fluid shifts or associated infection as well as cardiac dysfunction due to hypophosphataemia/kalaemia.
Clinical Nutrition. 21(6):515-20, 2002 Dec.
Associated with bile salt degradation.
Post exposure prophylaxis for hepatitis A with hepatitis A vaccine reduces secondary infection rate from 13% to 2.8% (NNT=18).
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. Without treatment, 85% of children clear HBe, only 6% lose HbsAg. Hepatitis relapse is sometimes seen after loss of HBeAg , some of which is due to HBe minus mutants. Carrier rate (and frequency of serious sequelae) is higher in males than in females; greatest in those infected in early infancy or by 3 years of age; higher in those with anicteric hepatitis with minimal elevation of the transaminases.
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.
In chronic infection (HBsAg pos for 6/12), some will be inactive carriers 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 -
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:
Other issues:
HBV immunization lasts at least 15 yrs, protection even when anti-HBs undetectable so probably life long. Usually boosted if anti-HBs titer falls below 100 IU/l. UK is one of a few developed countries that do not have universal immunization. Cost effective even in low income countries with intermediate endemicity. Instead of the UK recommended dose of 20 g doses as low as 2 g given intradermally or intramuscularly are almost as efficacious (Milne et al 1987).
Post-exposure prophylaxis: people who have not been immunised (or are only partially immunised) and are exposed to hepatitis B (through needlestick injury, splashing, or sexual exposure to partners infected with hepatitis B virus) should receive HBIg (0.04-0.07 ml/kg) as soon after exposure as possible, preferably within 48 hrs, and certainly within 7 days. Active vaccination should be started simultaneously, with the first dose given at a site different from that for HBIg; an accelerated four dose immunisation schedule (0, 1, 2, and 12 months) is preferred in this setting. See Green Book. Markers including HBsAg may well appear, but should disappear by 1 year if prophylaxis successful.
BMJ 329(7474), 6 November 2004, pp 1080-1086
Hep B should be available globally, says WHO since 1997. Hexavalent vaccine available. But would still miss immigrants so targeted neonatal screening still needed. Adolescent HPV programme could also be co-opted.
Similar to, but far less infectious than Hepatitis B. Asymptomatic for many years, it eventually leads to cirrhosis and hepatocellular carcinoma, but since it hasn't been around that long, the prognosis for infected children is very uncertain. It is particularly important among intravenous drug users, with over 70% of users positive in Glasgow, and about 53% across England and Wales.
Blood borne (ie blood products, needlestick) and vertical transmission.
Can cause an acute hepatitis with fever and jaundice, but pretty rare - most cases only diagnosed after an incidental finding of deranged LFTs or on screening. Infection may be cleared spontaneously (sometimes even antibody is lost, eventually), but most go on to have chronic infection. Years may go by before there is progression to cirrhosis or hepatocellular carcinoma.
Blood tests will differentiate:
LFTs and USS appearances are poorly predictive of liver fibrosis, and can only really differentiate mild disease from cirrhosis. So liver biopsy may be required to establish severity, especially when treatment is being considered. Treatment of infected children <2 years of age has not been pursued to date, so that liver biopsy is postponed until that age. Rosie considers biopsy if unwell or rising LFTs or ALT >2x upper limit of normal, or if family keen for treatment. Viral load is not useful. USS not useful - cancer is not a risk until cirrhosis has occurred.
The risk of progression to cancer or cirrhosis has not been quantified in children. In adults, men have a higher risk, moderate or higher alcohol intakes, smoking and HIV or HBV coinfection all increase risk. Genotype, surprisingly, does not appear to make a difference.
By 13 years after infection, most had an ALT 1-3x upper limit of normal; 12% had significant fibrosis. Fibrosis on biopsy correlates with age at infection and gamma-GT. Serum ALT correlated with inflammation on biopsy unless complicated by comorbidity, but prob not very useful. J Pediatrics 2007, 150: 168-174 [17236895].
No paediatric studies comparing treated with untreated children. Aims are to decrease ALT, clear HCV RNA and improve liver histology. Endpoint is not cure but sustained virologic response (SVR) = PCR negative at 6 months. Patients who improve but do not achieve SVR are called nonsustained responders. SVR is associated with:
Treatment is with combination Interferon (IFN) alpha 3 times/week, and daily oral ribavirin, for 12 months. Achieves in adults SVR rates of 10-41%. Pegylated (peg) IFN is given once a week and is more efficacious (56% SVR in combination therapy), with a similar side effect profile.
IFN inhibits viral replication, increases maturation of cytotoxic T cells and promotes NK cell activity. The exact mechanism of action of ribavirin is unclear.
8 published pediatric studies with IFN only, mostly uncontrolled, n=172. Doses and study designs varied widely. 40% of patients had a SVR 6 months after treatment. Nearly all experienced the side effect of an influenza-like syndrome, and many had alopecia, leukopenia and thrombocytopenia. Hypo/hyperthyroidism reported. Suoglu et al reported the only pediatric combination therapy study (IFN-[alpha] plus ribavirin for 12 months). In this study, adding ribavirin to IFN was associated with higher end-of-treatment response (30% vs 50%) and higher SVR (30% vs 41.7%).
Contraindications to IFN eg decompensated cirrhosis, drug/alcohol use etc are rare in children. Contraindications for ribavirin include renal failure, anemia, hemoglobinopathies and severe heart disease.
Pediatric Infectious Disease Journal. 23(3):257-258, March 2004.
There is currently no vaccine for HCV. Early treatment of new infections where spontaneous clearance does not take place has been validated, but is not yet standard practice.
History: maternal, immunisations, transfusions, outdoor activities, pets, holidays, drugs, tattoos.
Look for signs of liver failure (below), lymphadenopathy, eyes (Wilsons - best with slit lamp), tattoos.
Consider:
So do:
Broad spectrum antibiotics usually added in. Some suggest N-acetyl cysteine even without Paracetamol ingestion (Gastroenterology. 2009 Sep;137(3):856-64).
Transplant: bilirubin >150, hypoalbuminaemia, failing nutrition.
Associated with cirrhosis. Severe deficiency (phenotype Pi ZZ) also liable to develop emphysema, especially in smokers.
Partial deficiency can occur (phenotypes Pi MS and MZ - normal is Pi MM). PiMZ genotype does not appear to predispose to chronic liver disease (in case control study). On the other hand, patients with decompensated LD (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]
= hepatolenticular degeneration. Autosomal recessive condition with copper accumulation due to impairment of biliary excretion. Leads to cirrhosis, via a stage indistinguishable from chronic active hepatitis, plus neurological disease. Caused by mutations of the ATP7B gene that codes for a copper transporting ATPase - over 300 mutations known, varying geographically.
Usually presents in late teens but has been described as young as 3yrs. Neurological presentation tends to be older (by 5 years) although they usually have subclinical liver disease. Hepatic disease varies from elevated aminotransferases, through chronic liver disease to fulminant hepatic failure (often with Coombs negative haemolytic anaemia), about 5% of presentations.
Basal ganglia involvement leads to movement disorders viz:
Other neurological signs are:
It can also cause:
Can be tricky given multisystem disorder and limited sensitivity/specificity of tests. Heterozygotes may also have borderline results. If typical presentation then diagnosis can be made on basis of:
May require extensive tests of copper metabolism especially with severe hepatic presentation, where up to 50% can have normal ceruloplasmin (an acute phase reactant) eg
In fulminant hepatic failure the following features may suggest diagnosis:
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 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 clinically but probably more jaundice and cirrhosis with less impairment in synthesis. Seronegative hepatitis has been described but v rare. Raised immunoglobulins are a clue (but not specific - also seen in Wilson's disease); other causes should be excluded too. Interface hepatitis on biopsy. Treat with steroids, azathioprine when improving, else mycophenylate. Unlikely to outgrow.
Nearly half of kids with confirmed appendicitis had atypical features eg lack of percussive tenderness/guarding/nausea. WCC less than 10 and neuts less than 7.5 are strongest negative predictors in atypical cases.
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