Approach to jaundice in a 5 year old child

Dr. Venkatesh

1st year PG in Pediatrics

SVRRGGH

objectives

• To know how to evaluate a child with jaundice.

• To familiarise with various causes of jaundice in children.

• To recognise Red flag signs suggesting serious liver dysfunction in a child.

• Jaundice is a condition characterised by yellowish discoloration of sclera, skin, mucus membranes due to increased circulating bilirubin usually more than 2.5mg/dl in children

• Conditions mistaken for jaundice

Carotenemia

Lycopenamia

Rani is 5 year old girl is brought by parents with complaints of jaundice.

• What other questions are important to ask the patient and family?

• What tests would be useful to diagnose the child?

• Is patient vitals stable ,resuscitate if needed and maintain hydration status.

• Red flag signs suggesting serious liver dysfunction include altered mental status, coagulopathy , hypoglycemia, ascites, gastrointestinal bleeding. If present they should be managed in intensive care.

Jaundice

History—associated symptomsrisk factorsexposurespast medical historyfamily history

Physical examination

Findings suggesting specific diagnosis

no yes

Fractionation of bilirubin Confirmatory diagnostic studies

Fractionation of bilirubin

Conjugated <20% of total<2 mg/dL

Conjugated >20% of total>2 mg/dL

Diagnosis = UNCONJUGATED HYPERBILIRUBINEMIA

Diagnosis = CONJUGATED HYPERBILIRUBINEMIA

CBC Reticulocyte count Coombs test PT/PTTEvaluate smear

PTAlbuminGlucoseALT, ASTAlkaline phosphatase, GGT

Diagnosis = UNCONJUGATED HYPERBILIRUBINEMIA

Normal reticulocyte count Elevated reticulocyte count

Look for evidence of:1. Infection 2. Congestive heart failure .

None found

Familial disorders Gilbert syndrome Crigler-Najjartype II syndrome

Consider:1. Autoimmune hemolytic anemia2. Drug-induced hemolytic anemia3. Paroxysmal nocturnal hemoglobinuria4. Erythrocyte membrane defect5. Erythrocyte enzyme defect6. DIC7. Transfusion reaction8. Hemolytic uremic syndrome9. Hemoglobinopathy

Diagnosis = CONJUGATED HYPERBILIRUBINEMIA

Markedly ALT, ASTMildly alkaline phosphatase

1. Infection (viral serology)HAV IgM,HbsAg,anti-HBc,EBV2. Wilson diseaseserum ceruloplasmin,urine copperliver biopsy3. Drugs or toxins4. Autoimmune hepatitisautoantibodies (ANA, ASMA, anti-LKM)serum globulinliver biopsy

Looking for evidence of:

Alkaline phosphatase>3 times normalMildly ALT, AST

Obstructive process

UltrasonographyMRCP, ERCP, or PTC

Definitive diagnosis

yes

Specific treatment

no

Approach to jaundice in 5 year old child

• History

• Clinical examination

• Investigations

• Classifiy the type of jaundice

• diagnosis

history

Jaundice:• Age of onset• Duration(acute/chronic/acute on chronic)• Colour of urine

normal : unconjugatedhigh colour: hepatocellular / cholestatic jaundice

• colour of stoolpale :cholestaticNormal: hepatocellular

• Any bleeding manifestations

h/o fever• Duration• Fever without chills and rigors

Viral hepatitis, drug induced heptitis• Fever with chills and rigors

Cholangitis, weils disease,malarial hepatitis,liver abcess

• h/o intake of aspirin.h/o abdominal painright hypochondrial pain with feverConsider hepatitis,cholangitis,cholecystitis liver

abscess

h/o anorexia and fatigueConsider

hepatitis(early feature though nonspecific)possibility of metabolic liver diseaseh/o pallor, recurrent blood transfusions.h/o bleeding tendencyh/o abdominal distension

Diffuse /Upper abdomenh/o rash, arthralgia, arthritis

Consider infective/autoimmune (especially in girl child)

h/o recent blood transfusionsh/o recent travel/outbreak in their locality

H/o poor weight gainh/o reccurent vomitings,abnormal odourh/o developmental delay, seizures, poor vision,abnormal behaviour.

Past historyh/o jaundice in the pasth/o neonatal jaundice, if phototherapy givenh/o recurrent blood tranfusionsh/o needle pricks,tatooing,ear boringh/o recurrent diarrhea,respiratory tract infectionsh/o any abdominal surgeries Perinatal history:TORCH infections, IUGR, h/o umblical

catherisation.

metabolic

Family history

• Positive clue to genetic or metabolic disoder

• h/o thyroid disease, rheumatoid group of diseases early liver failure suggest autoimmune

• h/o consanguinity: possibility of metabolic disease

• h/o viral hepatitis in family member or sibling

• h/o sibling death due to jaundice or neuropsychiatric illness

• h/o pallor + recurrent blood transfusions

• h/o abdominal surgeries

• Sociocultural practices: cooking vessels

• Familial jaundice

Drug history

Antituberculous drugs

Anticonvulsants

Antipsychotics

Paracetamol

Toxins/native medicines.

General examination

• Level of conciousness and behaviour(alert/drowsy/stupor/coma)

• odour : fetor hepaticus

• vitals pulse ,RR, temperature , BP

• Pallor,icterus,clubbing, cyanosis, rash lymphadenopathy,pedal edema.

• Anthropometry

head circumference(microcephaly)

malnutrition,growth retardation

Ocular signs

Subconjunctival hemorrhage: weils disease, acute paracetamolpoisoning

KF ring ,sunflower cataract:wilsons disease

Oil drop cataract :galactosemia

Bitot spots: cholestatic jaundice

Posterior embryotoxon: Watson Alagillesyndrome

Chorioretinitis: autoimmune, TORCH infections

Oral cavity

Oral thrush

Fetor hepaticus

Nail changes

Clubbing

Leukonychia

Blue lunulae:wilsons disease

Shining nails: cholestatic jaundice

Skin changes

ecchymosis: hepatocellular failure, hypersplenism

hyperpigmentation:wilsons disease,cirrhosis

Vitiligo: consider autoimmune disorder

Palmar erythema,spider nevi:chronic liver dis.

Scratch marks,shiny nails :cholestatic jaundice

Dysmorphic features: Alagellisyndrome,cretinism

Systemic examination

• Examination of abdomenAbdominal distension,AscitesRight hypochondrial tenderness(viral hepatitis,right

heart failure,abscess,malignancy,cholangitis)Hepatomegaly :consistency and character of liver

edge. splenomegaly, Caput medusaeArterial bruit, venous hums and bowelsounds

• Respriratory system

Pleural effusion

Emphysematous lungs : alpha 1 antitrypsin deficiency. cystic fibrosis

• CVS: to rule out congenital heart disease

• CNS: level of conciousness, mental retardation, abnormal behaviour.

Abnormal neurologic findings,including tremor, fine motor incoordination, clumsy gait, and choreiform

movements, suggest Wilson disease.

Investigations

Complete hemogram & peripheral smear, hematological tests

• leukopenia,smear showing atypical lymphocytes(viriocytes)-viral hepatitis

• Leucocytosis with striking neutropilia with very high ESR in weils disease and cholangitis

• Target cells-cholestatic jaundice,spurr cells in chronic liver disease

• If hemolytic jaundice is suspected then smear,reticulocyte count are done

• Thrombocytopenia is typically seen in portal hypertension & hyperspleenism

• Coagulation profile

Serum bilirubin: if direct bilirubin more than 20%of total bilirubin – direct hyperbilirubinemia(cholestatic jaundice either intrahepatic or extrahepatic etiology)

• Hemolytic jaundice total bilirubin usually doesn’t exceed 5mg/dl

Levels of Serum aminotransferasesand their common etiologies

Symptomatic children with levels > 1000IU/L

•Acute viral hepatitis•Reyes syndrome•Autoimmune hepatitis•Ischaemic injury•Drug induced

•Serum aminotransferases levels : tests to detect liver cell injury

Symptomatic children with levels<1000IU/L

•Chronic heptitis•Infections like leptospirosis,dengue,malaria•Storage disorders like Gaucher’s disease•Inborn errorsof metabolism•Celiac disease

Asymptomatic children with levels<1000IU/L

•Non-alcoholic fatty liver disease(NAFLD)•Wilsons disease•Alpha 1-antitrypsin deficiency•Chronic hepatitis B,C

• Serum alkaline phosphatase: elevated in choleststic jaundice (intrahepatic or extrahepatic)

Normal range in 5 year old child:110-460 U/L

• Gamma glutamyl transpeptidse: elevated in choleststic jaundice.

Normal range in 5 year old child:5-55U/L

• Both ALP and GGT cannot differtiate intra-hepatic cholestasis from extrahepatic cholestasis

• High ALP ,low to normal GGT is seen in PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS

• Serum albumin, PT, APTT

• Blood urea,serum creatine and electrolytes

• Serological tests : HbsAg, HCV

• Ultrasound abdomen

• CT abdomen detects tumors,cysts,abscess,fatty liver,gall stones

• Cholescintigraphy

• Liver biopsy: to diagnose inborn errors of metabolism,storage disorders, indianchildhood cirrhosis,wilsons disease.

Classification of jaundice

jaundice

Hemolytic jaundice

Hepatocellularjaundice

Cholestaticjaundice

Hemolytic jaundice

• Anemia /pallor• Mild jaundice• Abdominal pain is uncommon feature • Splenomegaly with or without hepatomegaly• Stools yellow, urine variable colour• Hemolytic facies +/-• Positive family history +/-• Reticulocytosis +/-• Smear evidence of hemolysis• Indirect hyperbilirubinemia• AST,ALT - normal

Hepatocellular jaundice

• Jaundice

• High coloured urine

• Pale stools +/-

• GI symptoms: anorexia, vomiting ,abdominal pain

• Hepatomegaly with or without splenomegaly

• Bleeding tendency

Hepatocellular jaundice

infection

Drugs/toxins

metabolic

autoimmune

viral Non viral

Cholestatic jaundice

• Usually deep jaundice• Very pale stools• High coloured urine• Intense pruritis(scratch marks)• Xanthomas (chronic cholestasis)• Fat malabsorption• bleeding tendency

Cholestatic jaundice

Hepatocellularcholestasis

Obstructivecholestasis

Stepwise approach

• Step 1:To assess if the jaundice is hemolytic in origin or heptic in origin.

• Step2: To decide if the hepatic cause of jaundice is secondary to hepatocellulardysfunction or defect in bile flow

• step 3:Is it a chronic liver disease?

• Step4:is it compensated, decompensated or acute fulminant?

Viral hepatitis-HepatocellularHepatotropic viruses Non hepatotropic viruses

Acute:HAV,HEVChronic:HBV,HCV

HSV,EBV,CMV,enterovirus,adenovirus

Cause more isolatedliver injury thannon-hepatotropic virus

Cause hepatitis as a part of multisystem disease

•Signs and symptoms of hepatitis are mild to severe.•Extrahepatic manifestations unusal.•Transaminases can be as high as thousands during acute stage

•Signs and symptoms of hepatitis is mild.•Extrahepatic manifestations like rash,lymphadenopathy,neurological disease more common•transminases increse moderately

Non viral heptitis – when to consider

• Significant fever

• Extrahepatic manifestations-nephritis, anemia, diarrhea, rash are prominent.

• AST/ALT –elevation in hundreds.

• Causes: malaria, leptospirosis,typhoid fever, liver abscess (jaundice uncommon)

Drug induced or toxin induced heptatitis

• Clinical manifestations can be mild & nonspecific or severe in form of fever, rash, malaise

• Mild elevations of transaminases are very common,usually resolve sponteneously even on continuation of the drug .

• A 2-3 fold increase of transaminses or presence of jaundice indicates significant liver injury , which needs immediate discontinution of the drug.

• So children on hepatotoxic drug need to be on close followup

Metabolic disorder –when to cosider• No clear identifiable cause• Positive family history• Child with abnormal phenotype like dysmorphism or

short stature• Growth retardation• Recurrent vomiting• Associated neurological abnrmality like- developmental

delay, hypotonia, seizures, neurodegenration• Associated cardiac disease• Abnormal odour• Presence of cataract , rickets• Presence of large organomegaly• Presence of hypoglycemia, metabolic acidosis,

hyperammonia

Autoimmune hepatitis• Considered in any child with non-viral or non-drug induced hepatitis• Girls with hepatitis(girls more commonly involved)• Older children (though young children can be affected)• Extrahepatic manifestations• Features of chronic liver disease where

viral,toxic,metabolic causes have been ruled out• Prominent elevation of transaminases and not alkaline

phosphatase.• Elevated gammaglobulin level• Presence of autoantibodies:ANA,anti LKM

antibody,anti soluble liver antigen, anti smooth muscle antibody,anti mitochondrial antibody. Liver biopsy needed in these children

Cholestatic jaundice

• Direct hyperbilirubinemia,elevated ALP and GGT, intense pruritis, hypercholestrolemia and xanthomaswith evidence of fat malabsorption.

• Presence of significant pain with or without mass points towards obstructive cause of cholestasis

• High ALP ,low to normal GGT consider PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS

• Child presenting with cholestasis needs to be subjected to imaging studies like ultrasound and CT of abdomen,cholangiography.

• Radionuclear scans like HIDA are useful to differentiate hepatocellular cholestasis from obstructive cholestasis.

Is it chronic liver disease

Features of chronic liver diease:• Firm/hard hepatomegaly• Splenomegaly/varices(portal hypertension)• Ascites• Clubbing• Malnutrition• Spider angioma• Palmer erythema• White nails

Is it decompensated liver disese

Signs of decompensation include:

• Worsening jaundice in the background of shrinking liver

• Bleeding tendency

• Encephalopathy-altered sleep pattern, behavioural abnormality, coma

• Worsening edema and ascites

Causes of jaundice • Hepatocellular jaundice

Infectious hepatitis

Viral

• Hepatotropic virus A ,B ,C ,D,E

• Non hepatotropic virus: HSV,EBV,CMV,enterovirus,adenovirus

Bacterial

• Typhoid,brucellosis, disseminated TB, E.coli septicemia

Spirochaetal

• Weils disease

Protozoal

• Malaria,kala azar,schistosomiasis

Hepatocellular jaundice-causesDrugsAntituberculous drugsAnticonvulsantsAntipsychoticsParacetamolToxins• Aflatoxins• Mushroom poisoning• Vinyl chloride,carbon tetrachloride• Benzene derivatives• 4,4-diamino diphenyl methane(epping jaundice)

Heptocellular jaundice causesMetabolic causes• Wilsons disease• Galactosemia• Glycogen storage disorders• Tyrosinemia• Urea cycle disorders• Gauchers and Niemann pick disease• Indian childhood cirrhosis• Hemochromatosis• Crigler najjar, Gilbert, Dubin Johnson and Rotor

syndrome• Alpha 1 antitrypsin defiency

Cholestatic jaundice causes

Obstructive cholestasis• Choledochal cyst• Gall stones• cholangitis• Alagille syndrome.

Hepatocellular cholestasis• HAV,HEV hepatitis• Drug induced hepatitis• Metabolic –galactosemia• Progressive familial intrahepatic cholestasis

Management

• Focus on treating underlying cause, optimisation of hydration,nutrition and controlling pruritis

• Diet high in medium chain triglycerides should be used to promote growth in children with chronic cholestasis.

• Supplementation of fat soluble vitamins is essential

• Agents shown to reduce pruritis :

Cholestyramine(bile acid binding agent),

Ursodeoxycholic acid(cholerectic agent),

phenobarbitone, opioid antagonists, rifmpicin(may cause toxic hepatitis)

Pearls• Acute viral hepatitis due to HAV or HEV continues to

be most common cause of acute hepatitis in childhood.

• Drug induced hepatitis should always be considered in a child with exposure to drugs.

• Metabolic disorders and autoimmune disorders should be considered when the diagnosis of heptaitis is unclear.

• Transaminases can be in thousands in

acute viral hepatitis, drug/toxic hepatitis, ischemic hepatitis as seen in child with shock.

• Children presenting with features of cholestasis need imaging studies to rule out obstructive causes.

REFERENCES:

• IAP pediatric gastroenterology 2 ed.

• Indian journal of practical Pediatrics IJPP SERIES-4,2011.

• NELSON textbook of Pediatrics,19 ed.

• Pediatric Decision Making Strategies 2 ed.

• Practical strategies in Pediatric diagnosis and therapy,2ed.