Dr. Amdekar discusses the approach for 8 different cases of jaundice which prove that physical examination, thorough history taking, and ordering the right tests can be powerful tools in arriving at the right clinical diagnosis, precluding the need for unwarranted investigations.

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History alone can diagnose probable disorder. Physical examination nearly can confirm diagnosis. General appearance – sick or not sick, enlarged liver and/or spleen, other signs of liver disease such as oedema or ascites, and significant pallor offer clues to diagnosis. Thus, history and physical examination can help order specific tests to confirm diagnosis and avoid the battery of tests that may not be necessary.

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Case based discussions in jaundice

Case 1

An 8-year old child presented with moderate degree of fever for 2 days followed by high fever over the next 3 days without any other symptoms. On day 5, the mother noticed high-coloured urine and mild icterus.

Onset of moderate fever followed by high-degree fever suggests bacteremic infection that has not localised so far until day 5. Non-localising bacteremic infection typically is typhoid fever. Now that child has developed jaundice, it is mostly a complication of typhoid fever.

Viral A hepatitis classically starts with prodrome of nausea, vomiting and anorexia followed in a day or two by jaundice. Therefore, this is not viral hepatitis. Had it been an irregular pattern of fever, one may have considered malarial hepatitis.

Physical examination showed sick-looking, febrile child with mild icterus, tumid abdomen, liver 3F+, span of 9 cms, and spleen just palpable. CBC showed Hb 11 Gm%, WBC 3000, P 30, L 60, M10, E0, pl 80000, total bilirubin 4.3 mg% direct 3.4 mg%, SGPT 170, SGOT 250, and Alk phos- normal.

The CBC is typical of typhoid fever – leukopenia, lymphocytosis, monocytosis, thrombocytopenia. SGOT > SGPT indicates systemic extra-hepatic infection with secondary liver involvement and not primary liver disease. Blood culture grew S.typhi.

Diagnosis – Typhoid fever with hepatitis

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Case 2

A 6-year old child’s mother noticed a yellow tinge in his eyes. The child otherwise, was quite normal without any complaints. On direct questioning, it was informed that urine color was normal.

Normal urine color rules out hepatocyte and biliary disease. It may be haemolytic jaundice but pallor was not been noticed. Physical examination showed mild icterus but no pallor or hepatosplenomegaly. Growth and nutrition were normal. It rules out haemolytic jaundice.

This is a normal child with mild, unconjugated (indirect) bilirubinemia. It suggests enzyme deficiency – Gilbert disease. Diagnosis may be confirmed by liver biopsy but it is not indicated, as the clinical diagnosis stands to be benign disease, so invasive investigation may be avoided. This is a specific enzyme deficiency but all other liver functions are normal. It is a benign condition and the child will lead normal life without any problem but with jaundice.

Diagnosis – Gilbert disease.

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Case 3

An 8-year old child was noticed to have yellow eyes while he was getting ready to go to school. As he was fine, he insisted on going to school. On his return, his doctor diagnosed it as viral A hepatitis and suggested no specific treatment. Viral A hepatitis presents with a prodrome of nausea, vomiting and severe anorexia before developing jaundice and the child does feel weak. So it is most unlikely to be viral A hepatitis.

At this point we need to follow closely. Next morning when he got up to brush teeth, he suddenly fainted and the mother noticed severe jaundice. He was rushed to the hospital. It is evident that this child had developed fulminant liver disease that had worsened just over a day. Sudden fainting may suggest severe anaemia or syncope. So this child seems to be suffering from acutely worsening liver disease with or without anaemia.

Physical examination showed sick child, deep yellow, severely pale, liver 5F+ firm, spleen not palpable, no ascites. This child has a combination of acutely worsening jaundice with severe anaemia. This is not haemolytic jaundice as there is no splenomegaly and jaundice has been very severe. Sudden onset of any symptoms may be either immune-mediated or metabolic.

Autoimmune haemolytic anaemia and autoimmune hepatitis don’t go together and a child in either of these two conditions is not very sick. So this may be metabolic disorder.

The most common metabolic liver disorder in children >5 years of age is Wilson’s disease. It was confirmed by low serum ceruloplasmin. Wilson’s disease is treated with chelating agents such as D-penicillamine or triantene. This child had developed acute fulminant liver disease and so had no time for drugs to act. He underwent acute liver transplant and survived.

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Case 4

An 8-year old child presented with high fever, severe bodyache and headache over 4 days. Fever would respond poorly to paracetamol and he would look sick throughout the illness. His bodyache was so severe that he could not walk because of the pain. On day 6, he developed high-coloured urine and jaundice.

Analysing these symptoms- fever before onset of jaundice is common in viral infections, malaria and also typhoid or any other severe bacterial infection. Severe bodyache – myalgia – to an extent of inability to walk is an unusual feature in this child. Typical viral infection would often present as cold and cough and usually settle within 3-4 days. Malaria presents generally with erratic fever pattern and typhoid typically starts with moderate degree of fever that rises over a few days. Hence, it may be evolving bacterial infection that has not yet produced any localising symptom. Such infections include bacterial endocarditis, leptospirosis, rickettsia, or brucellosis. Development of jaundice suggests hepatic complication of extra-hepatic disease and leptospirosis is one of such diseases presenting with liver and kidney affection.

Physical examination showed sick-looking child, highly febrile with congested eyes, oral mucosa and throat, icterus+, liver 3F+, soft, not tender, and spleen not palpable. Other systems appeared normal. As mentioned above, jaundice developing after high fever with severe myalgia and headache favours diagnosis of leptospirosis. One may have to look for involvement of other organs, if not clinically visible, by relevant laboratory tests.

Investigations showed Hb 9 Gm%, WBC 18000, P 72, L 25, M 3, E 0, Pl 2.5, Serum bilirubin total 4 mg%, Direct 3.2 mg%, SGPT 250, SGOT 375, Alk Phos 85, Serun proteins 5.7 Gm%, Alb 3.4 Gm%, and serum creatinine 1.8 mg% Laboratory tests demonstrate neutrophilic leukocytosis favouring acute infection, conjugated bilirubinemia with increased enzymes suggestive of hepatocyte disease. High serum creatinine indicates nephritis.

Diagnosis – leptospirosis with liver and kidney involvement.

Diagnosis can be confirmed with IgM antibody to Leptospira. Amoxycillin or Doxycycline are drugs of choice. Leptospirosis presents with high fever with severe myalgia and congested mucosa, and a few patients develop immune-mediated complications affecting the liver and kidneys commonly. Other organs may also be involved.

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Case 5

A one-month old infant presented with jaundice that started on day 3 of life and was considered to be physiological jaundice that would settle down by itself. However, it persisted over the next 4 weeks and hence, the child was brought to a doctor. The infant was born from normal delivery and had been on exclusive breast feeds. He had gained 1 kg of weight in the last one month and was happy despite the jaundice. Urine colour was normal.

Normal urine colour rules out conjugated bilirubinemia and hence hepatocyte and biliary tract diseases are unlikely. It may be haemolytic jaundice but pallor would have been a major complaint and that was not so in this infant. Thus, it is unconjugated bilirubinemia but without haemolysis. It could be an enzyme deficiency such Criggler-Najjar syndrome that presents with severe jaundice or Gilber syndrome that presents with mild jaundice but often noticed later in childhood.

Physical examination was normal. Serum bilirubin was 3.2 mg%, direct 0.4 mg%. Other tests were normal. Because enzyme deficiency disorder such as Criggler-Najjar syndrome would have presented with severe jaundice at this age and Gilbert would have presented later, both these conditions are unlikely.

By exclusion, we need to look at other causes. Other causes of such jaundice are breast milk jaundice or breast feeding jaundice. Breast feeding jaundice is due to inadequate breast milk intake resulting in decrease in enterohepatic circulation. Such an infant would not gain adequate weight. Breast milk jaundice is due to a chemical substance present in breast milk that leads to jaundice that is self-limiting. As this infant had grown well, breast milk jaundice is the diagnosis.

There is no need to stop breast feeding as in spite of continuing breast milk, jaundice is known to disappear over the next few weeks. One may prove diagnosis of breast milk jaundice by withdrawing breast milk for few days and demonstrating clearing of jaundice. However, it is not necessary as transient withdrawal may disrupt breast milk secretions. Besides, the mother gets the wrong impression that her breast milk is not suiting the infant.

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Case 6

A one-month old infant presented with jaundice since day 3 of life and it was considered to be physiological jaundice. However, jaundice persisted over the next four weeks. Urine colour was normal. The infant was born full term via normal delivery with birth weight of 2.5 kg, and was on exclusive breast feeds. The mother complained about lethargy as baby would not cry for a feed and had to be coaxed to feed.

Jaundice with normal urine colour suggests unconjugated bilirubinemia. It is unlikely to be haemolytic jaundice as pallor would have been a major symptom. So it is likely to be non-haemolytic jaundice. Infant with an enzyme deficiency would not have been lethargic unless jaundice began increasing quickly. In which case, it would have resulted in convulsions or refusal of feeds. So, we need to think beyond common causes. This infant was lethargic, and that may suggest brain involvement that is likely to be a slowly-evolving disease as there are no acute symptoms of brain disease such as convulsions or refusal of feeds.

Physical examination showed lethargic infant, weight 3.4 kg, length 49 cms, head circumference 36 cm, no pallor, no hepatosplenomegaly, and no other abnormality. This infant had gained weight well but his length was short for his age. This suggests delayed bone growth characteristic of congenital hypothyroidism. Lethargy is another typical feature of hypothyroidism.

Diagnosis can be confirmed by serum T3, T4, and TSH levels. Bone age as estimated on the X-ray by special charts (Grulich-Pyle chart) would show delayed bone development. Treatment with thyroid hormone supplement would be necessary for life. It is important to diagnose congenital hypothyroidism right at birth to avoid permanent brain damage. It is ideal to order TSH level on cord blood on every infant at birth to suspect hypothyroidism even before symptoms develop. Prevalence of congenital hypothyroidism is one in 3,500 live births and so, quite high to justify routine screening for hypothyroidism at birth.

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Case 7

An 8-year old child presented with fever for two days followed by jaundice. Urine colour was normal. The child had been healthy without any prior illness. Jaundice with normal urine colour is due to unconjugated bilirubin. So this is likely to be either haemolytic jaundice or due to enzyme deficiency. Enzyme deficiency is not triggered by fever but haemolysis may and so it may be acute haemolytic jaundice. Presence of pallor may favour haemolysis and absence of pallor enzyme deficiency.

Physical examination showed a healthy child, well-grown, pallor++ with mild icterus, liver 1F +, soft, spleen 2F +, and no other abnormality. Pallor with splenomegaly suggests haemolysis and so this is haemolytic jaundice. As onset of this illness was with fever, it is likely to be acquired autoimmune haemolytic anemia and jaundice.

Investigations showed Hb 8 Gm%, normal total and differential WBC and platelets, serum bilirubin 3 mg% with direct 0.4 mg%. This confirms anaemia with unconjugated bilirubinemia. Coomb’s test may be positive indicating antibody related haemolysis. This condition may be self-limiting and if not, needs to be treated with steroids and if necessary packed cell transfusion. Blood transfusion may itself aggravate further antibody destruction and should be reserved only if there are no other alternatives. In such a case, there has to be proper match between the donor’s and recipient's rare blood groups.

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Case 8

An 8-year old child presented with jaundice and abdominal distension lasting a week. On direct questioning, he was not well over the previous 6 months. He had poor appetite, loose stools at times, reported feeling weak and had lost 2 kg weight. This suggests chronic progressive illness.

Prior to developing jaundice and abdominal distension, his past history would have made us search for chronic evolving disease. As the only localising symptom of loose stools relate to the gastrointestinal tract, one would think of GI disease. However, loose stools were not frequent and there were no other symptoms of GI disturbances such as vomiting, flatulence, or abdominal pain. Such a disturbance may denote indigestion which may be due to liver, gall bladder, or pancreatic disorders. Gall bladder or pancreatic disorders would present with pain. Absence of pain in this child may therefore suggest evolving liver disease.

It is now evident as he had developed jaundice and abdominal distension. Abdominal distension noticed over just a week suggests ascites and in ascites in chronic liver disease indicates decompensation with portal hypertension. Physical examination showed weight 16 kg, height 110 cms, icterus +, liver 4F +,firm, liver span 10 cms, spleen 3 F+, firm, ascites +, and other systems normal Investigations showed Hb 10 Gm%, serum bilirubin 5.2 mg Direct 4.1 mg%, SGPT 100, SGOT 60, serum proteins 4.2 Gm%, Albumen 2.3 Gm%, INR 1.8.

Laboratory tests prove chronic liver disease (low serum albumen) recently decompensated (bilirubinemia with mild raised enzymes but raised INR). Diagnosis – decompensated chronic liver disease – cirrhosis.

It can be confirmed by liver biopsy that may be dangerous at this stage with liver beginning to fail. It may not offer much more information and so may be deferred. Aetiology may not be apparent with liver biopsy. Treatment is symptomatic.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.