Clerking jaundice

The diagnosis of jaundice is usually straightforward to establish based on history and observation of yellow discoloration of the sclerae, skin, and mucous membranes. Yellowness due to carotenaemia does not involve the sclerae. In clerking jaundice, the following approach may be applied:

History

Greet the patient and establish rapport.

Obtain the biodata.

Characterise the jaundice with attention paid to:

  • Onset and Severity: the deepness of the yellow discolouration and how rapidly it developed to its current severity.
  • The presence or absence of a greenish tinge to the yellowness: a greenish tinge points to an obstructive cause.
  • Associated symptoms: itching, pale stool, dark urine, neurological deficits.

More specific questions may then be asked as follows based on the likely differentials generated from the above:

  • Alcoholic liver disease: 

5 to 10 years of alcohol abuse, abdominal pain, pruritus, generalised malaise, weight loss, fatigue, anorexia, cachexia, pale stool, dark urine, melaena, or haematemesis

  • Choledocholithiasis:

fever, RUQ pain, aggravated by meals

  • Hepatitis E:

may be hx of risk factors (e.g., travel to Southeast Asia, northern and central Africa, India, and Central America), exposure to pigs or undercooked pork; more common in middle-aged/older men; anorexia, nausea and vomiting, diarrhoea, abdominal pain, pruritus, myalgia, neurological symptoms (5% of patients); pregnancy is associated with more florid disease; patients with pre-exsiting liver disease have a high risk of decompensation and a 70% mortality

  • Hepatitis A:

may be hx of risk factors (e.g., travel to endemic part of the world, close contact with known infected person, known food-borne outbreak), anorexia, nausea, vomiting, diarrhoea, abdominal pain, weight loss

  • Hepatitis B:

may be hx of risk factor (e.g., travel to endemic part of the world, high-risk sexual hx, intravenous drug use), may have minimal or no symptoms, may have lethargy, nausea, vomiting, abdominal pain; acute presentation (uncommon): worsening jaundice and lethargy, confusion; chronic infection with late complications: pruritus, abdominal swelling, haematemesis, melaena, confusion, lethargy, weight loss, weakness, bruising

  • Hepatitis C:

may be hx of risk factors, (e.g., intravenous drug use, blood transfusion before 1992 in the US, high-risk sexual hx); acute infection: usually asymptomatic, may be fatigue, jaundice; chronic infection: may be asymptomatic, but possible symptoms related to cirrhosis and its complications, such as pruritus, abdominal swelling, haematemesis, melaena, confusion, lethargy, weight loss, weakness, bruising

  • Non-alcoholic steatohepatitis:

often asymptomatic, obesity, diabetes, hypertension, high triglyceride level, low HDL cholesterol, fatigue, malaise, dull ache in RUQ, pruritus

  • Drug-induced direct hyperbilirubinaemia:

paracetamol overuse or overdose, use of highly active antiretroviral therapy (HAART) for HIV, isoniazid, ethambutol, amiodarone, NSAIDs, herbal preparations (kava, ma-huang, comfrey, black cohosh, cascara), antibiotics (especially amoxicillin-clavulanate, gentamicin, erythromycin, novobiocin, rifampin), calcium-channel blockers, ACE inhibitors, chlorpromazine, halothane, oestrogenic or anabolic steroids, statins, oral contraceptives, ascorbic acid, theophylline, methyldopa, phenelzine, isoproterenol, aminophenol, epinephrine (adrenaline), RUQ pain, pruritus, generalised malaise, weight loss, fatigue, anorexia, pale stool, dark urine

  • Ascending cholangitis:

chills, pain, pale stools, dark urine, pruritus, generalised malaise, weight loss, fatigue, anorexia

  • Autoimmune hepatitis:

fatigue, abdominal pain, arthralgias, pruritus, nausea and vomiting, pale stool, dark urine; may have associated haemolytic anaemia, thyroiditis, ulcerative colitis, diabetes, and/or Sjogren’s syndrome

  • Pancreatic carcinoma:

often asymptomatic until late disease, depression, weight loss, early satiety, new-onset diabetes, abdominal pain, pruritus, generalised malaise, fatigue, anorexia, pale stool, dark urine

  • Haemochromatosis: 

usually asymptomatic or found after screening in patients with a positive FHx, jaundice occurs in decompensated disease with established cirrhosis; rarely patients present with symptoms of diabetes

  • Pregnancy:

pregnant or recently delivered, pruritus, hyperemesis gravidarum (first trimester), HELLP syndrome (haemolysis, elevated liver enzymes, low platelets) in second and third trimesters and post-partum, abdominal pain, pruritus, generalised malaise, weight loss, fatigue, anorexia, pale stool, dark urine

  • Post-operative stricture:

gallbladder or bile duct surgery, abdominal pain, pruritus, fatigue, anorexia, pale stool, dark urine

  • Drug-induced indirect hyperbilirubinaemia:

paracetamol overuse or overdose, use of highly active antiretroviral therapy (HAART) for HIV, isoniazid, ethambutol, amiodarone, NSAIDs, herbal preparations (kava, ma-huang, comfrey, black cohosh, cascara), antibiotics (especially amoxicillin-clavulanate, erythromycin, gentamicin, novobiocin, rifampin), calcium-channel blockers, ACE inhibitors, chlorpromazine, halothane, oestrogenic or anabolic steroids, statins, oral contraceptives, ascorbic acid, theophylline, methyldopa, phenelzine, isoproterenol, aminophenol, epinephrine (adrenaline), RUQ pain, pruritus, generalised malaise, weight loss, fatigue, anorexia, pale stool, dark urine

  • Haemolytic anaemia:

fever or chills, FHx of haemolytic disorders, abdominal pain, pruritus, generalised malaise, weight loss, fatigue, anorexia, dark urine

  • Gilbert’s syndrome:

young adult age, more common in males, often asymptomatic or non-specific symptoms (abdominal cramps, fatigue, malaise)

  • Hepatitis D:

may be hx of risk factors (e.g., infection with hepatitis B virus, high-risk sexual hx, intravenous drug use), minimal or no symptoms; acute presentation (uncommon): jaundice, lethargy, confusion; chronic infection with late complications: itching, abdominal swelling, haematemesis, melaena, confusion, lethargy, weight loss, weakness, bruising

  • IgG4 cholangiopathy: 

epigastric and abdominal pain, jaundice, weight loss; typically men aged 50 to 60 years; may give history of new onset diabetes mellitus or diarrhoea associated with pancreatic insufficiency

  • Cholangiocarcinoma:

pruritus, generalised malaise, weight loss, fatigue, anorexia, pale stool, dark urine

  • Primary biliary cirrhosis:

female, pruritus, fatigue, abdominal pain, generalised malaise, weight loss, anorexia, pale stool, dark urine, keratoconjunctivitis, xerostomia

  • Primary sclerosing cholangitis: 

often asymptomatic, hx of ulcerative colitis or Crohn’s disease may be present; chills, night sweats, abdominal pain suggest infection; pruritus, generalised malaise, weight loss, fatigue, anorexia, pale stool, dark urine

  • Wilson’s disease:

adolescence and early adulthood onset, tremor, clumsy gait, slurred speech, abdominal pain, pruritus, generalised malaise and weakness, weight loss, anorexia, pale stool, dark urine, irritability, depression, dementia, psychosis, easy bruising

  • Alpha-1 antitrypsin deficiency:

FHx of liver disease, abdominal pain, pruritus, generalised malaise, weight loss, fatigue, anorexia, pale stool, dark urine, emphysema

  • Parasitic infections:

travel to endemic areas, abdominal pain, pruritus, generalised malaise, weight loss, fatigue, anorexia, pale stool, dark urine

  • AIDS cholangiopathy:

abdominal pain, pruritus, generalised malaise, weight loss, fatigue, anorexia, pale stool, dark urine, high-risk sexual activity (many partners, unprotected intercourse, intercourse with HIV-infected), HIV-positive, diarrhoea

  • Crigler-Najjar syndrome, types 1 and 2:

severe jaundice within first few days after birth (type 1), abdominal pain, pruritus, generalised malaise, weight loss, fatigue, anorexia, pale stool (normal in type 1), dark urine.

The past medical history should include specific questioning identifying inflammatory bowel disease, pancreatic disorders, history of blood transfusions, anaemia, or the presence of an inherited haemoglobinopathy such as thalassaemia or sickle cell disease.

Past surgical history should focus on procedures involving the hepatobiliary tract and the pancreas.

Family history should inquire about symptoms of inherited anaemias, haemoglobinopathies, and liver disorders.

Drug and allergy history reviews both current and recent past prescription and OTC medication and herbal supplement use.

Examination

General physical examination

  • Determine whether the patient is acutely of chronically ill-looking: The features of chronic illness include fluffy hairs, sunken eyes and muscle wasting.
  • Examine the jaundice to determine the severity and the presence of absence of a greenish tinge.
  • Check for pallor, dehydration, digital clubbing and edema. 
  • In those with known or presumed liver disease, a careful skin examination may reveal track marks on the extremities, evidence of ecchymosis or petechiae, and, in some, the presence of spider angioma and palmar erythema. Muscle wasting may be present in patients with chronic liver disease. The presence of parotid gland enlargement, gynaecomastia, and a Dupuytren’s contracture is highly suggestive of chronic alcohol abuse.

Abdominal examination

  • Inspect for abdominal enlargement, distended abdominal veins and collateral veins (caput medusae).
  • Palpate and percuss for liver enlargement and pain, noting the nature of the edge and the nodularity of the surface. An enlarged spleen may also be palpable. The presence or absence of a palpable gallbladder should be noted as well.

Nervous system examination

Confusion or frank somnolence on continued questioning, asterixis, or altered deep tendon reflexes may be indicative of hepatic encephalopathy.

Chest examination

  • Lung examination may reveal evidence of pleural effusion (hepatic hydrothorax).
  • Cardiovascular examination may point towards liver dysfunction due to congestion from right heart failure. 

Specific examination findings for each of the differentials above are as follows:

  • Alcoholic liver disease: 

parotid gland enlargement, Dupuytren’s contracture, generalised wasting, gynaecomastia, altered sensorium, asterixis or altered deep tendon reflexes, track marks (if concomitant drug use), ecchymosis or petechiae, spider angioma, thenar eminence loss, palmar erythema, caput medusa, ascites, hepatosplenomegaly or small liver, pleural effusion, right heart failure, positive rectal examination (blood)

  • Choledocholithiasis:

RUQ abdominal tenderness, fever

  • Hepatitis E:

may be normal; abdominal tenderness, tender hepatosplenomegaly, lymphadenopathy, jaundice, ascites, signs of encephalopathy (e.g., memory, attention, and concentration deficits, confusion, asterixis, nystagmus, clonus, rigidity, coma)

  • Hepatitis A:

abdominal tenderness, tender hepatosplenomegaly, lymphadenopathy, jaundice; fulminant infection: worsening jaundice, ascites, signs of encephalopathy (e.g., memory, attention, and concentration deficits, confusion, asterixis, nystagmus, clonus, rigidity, coma)

  • Hepatitis B:

acute infection: usually normal, but may have jaundice, tender hepatomegaly, and if severe: signs of encephalopathy (e.g., memory, attention, and concentration deficits, confusion, asterixis, nystagmus, clonus, rigidity, coma); chronic infection: may have jaundice, muscle wasting, gynaecomastia, palmar erythema, spider angiomata, petechiae, ascites, distended abdominal veins, hepatosplenomegaly, signs of encephalopathy

  • Hepatitis C:

early disease: normal exam; late disease with chronic infection: may be jaundice, muscle wasting, gynaecomastia, palmar erythema, spider angiomata, petechiae, ascites, distended abdominal veins, hepatosplenomegaly, signs of encephalopathy (e.g., memory, attention, and concentration deficits, confusion, asterixis, nystagmus, clonus, rigidity, coma)

  • Non-alcoholic steatohepatitis:

advanced disease: hepatosplenomegaly, ascites, spider angioma, oesophageal or intestinal varices

  • Drug-induced direct hyperbilirubinaemia:

tender hepatosplenomegaly, lymphadenopathy

  • Ascending cholangitis:

Charcot’s triad: fever, RUQ tenderness, jaundice

  • Autoimmune hepatitis:

advanced disease: ascites, hepatomegaly, cirrhosis, spider angioma, mental confusion

  • Pancreatic carcinoma:

positive Courvoisier’s sign, palpable gallbladder, ill-appearing, cachectic

  • Haemochromatosis: 

usually normal; gynaecomastia, ascites, altered sensorium, cachectic; in decompensated disease signs of chronic liver disease plus associated arthropathy

  • Pregnancy:

elevated BP (pre-eclampsia and eclampsia), tender hepatomegaly, splenomegaly, lymphadenopathy

  • Post-operative stricture:

often normal examination

  • Drug-induced indirect hyperbilirubinaemia:

tender hepatosplenomegaly, lymphadenopathy

  • Haemolytic anaemia:

new onset of pallor, splenomegaly

  • Gilbert’s syndrome:

normal other than icterus

  • Hepatitis D:

usually normal, but if severe acute infection may be jaundice, tender hepatomegaly, signs of encephalopathy (e.g., memory, attention, and concentration deficits, confusion, asterixis, nystagmus, clonus, rigidity, coma); chronic, late infection: may be jaundice, muscle wasting, gynaecomastia, palmar erythema, spider angiomata, petechiae, ascites, distended abdominal veins, hepatosplenomegaly, signs of encephalopathy

  • IgG4 cholangiopathy: 

epigastric tenderness, jaundice; may have lymphadenopathy, bibasal crepitation related to multisystemic manifestation

  • Cholangiocarcinoma:

usually normal; cachectic

  • Primary biliary cirrhosis:

xanthelasma, hepatosplenomegaly, RUQ pain, fatty subcutaneous deposits

  • Primary sclerosing cholangitis: 

usually normal, skin excoriations may be present

  • Wilson’s disease:

Kayser-Fleischer rings, parkinsonian-like tremor, rigidity, clumsy gait, poor balance, impaired co-ordination, abnormal postures, repetitive movements, bradykinesia (tongue, lips, and jaw), dysarthria, dysphonia (hoarse voice), inappropriate and uncontrollable grinning (risus sardonicus), drooling, generalised wasting, gynaecomastia, ascites, altered sensorium, hepatosplenomegaly, hypermelanotic pigmentation, bruises

  • Alpha-1 antitrypsin deficiency:

necrotising panniculitis, generalised wasting, gynaecomastia, ascites, altered sensorium, cachectic, ill-appearing

  • Parasitic infections:

cachexia, muscle wasting, tender abdomen, hepatomegaly

  • AIDS cholangiopathy:

cachexia, RUQ and epigastric pain, fever

  • Crigler-Najjar syndrome, types 1 and 2:

kernicterus (type 1), encephalopathy (type 1, rare in type 2), oculomotor palsy

Laboratory tests

Initial laboratory testing for all patients should include LFTs showing total and direct (conjugated) bilirubin levels, prothrombin time (PT) and INR, and FBC. A low platelet count is suggestive of portal hypertension or alcohol abuse. Anaemia is a prominent feature in liver disease patients, prompting iron studies. An increased PT and INR when coupled with a low albumin is indicative of synthetic liver dysfunction and suggestive of cirrhosis or acute liver failure.

Two patterns of liver function derangement have been described: cholestatic or hepatocellular. The cholestatic pattern consists of predominant elevation of direct bilirubin, Alk phos, and gamma-GT, and the hepatocellular pattern consists of elevations of indirect bilirubin, AST, and ALT. These patterns are however, non-specific and can significantly overlap.

For specific cases additional tests are needed.