Red flag symptoms: Jaundice

The red flag symptoms associated with serious causes of jaundice, with advice on distinguishing jaundice from pseudo-jaundice, identifying malignant or genetic causes, initial investigations and when to refer.

Red flag symptoms

  • Abdominal pain
  • Palpable gallbladder
  • Weight loss
  • Fever
  • Encephalopathy
  • Evidence of bleeding from GI tract
  • Coagulopathy

Jaundice is the result of bilirubin accumulation and deposition in the skin, sclerae and mucous membranes. It may be clinically appreciable with bilirubin >51 micromol/L. The upper limit of normal bilirubin is 20 micromol/L.

Jaundice may be due to pre-, intra- and extra-hepatic causes. It is important to distinguish jaundice from pseudo-jaundice, which may often be caused by carotenaemia. The difference is that the sclerae are spared in carotenaemia.

Possible causes
  • Malignant - carcinoma of the head of the pancreas, cholangiocarcinoma
  • Primary sclerosing cholangitis
  • Primary biliary cirrhosis
  • Biliary structure
  • Haemolytic anaemia
  • Choledocholithiasis
  • Genetic: hereditary haemochromatosis, Gilbert’s syndrome
  • Viral hepatitis
  • Alcoholic liver disease
  • Drug-induced hyperbilirubinaemia

Malignant causes

Malignant causes of obstructive jaundice include hepatocellular carcinoma, carcinoma of the head of the pancreas and cholangiocarcinoma.

The latter is usually an adenocarcinoma that may arise from the intra- or extra-hepatic biliary epithelium.

Up to 6% of patients with ulcerative colitis can develop primary sclerosing cholangitis, which may result in jaundice; they are at increased risk of cholangiocarcinoma. Choledochal cysts may also be associated with increased risk of cholangiocarcinoma.

Anaemias, genetic causes

Hereditary haemolytic anaemias, such as hereditary spherocytosis and sickle cell anaemia, are a cause of jaundice. Massive haemolysis in the acute setting may also cause jaundice. Genetic causes include hereditary haemochromatosis, alpha-1 antitrypsin deficiency and Gilbert's syndrome.

Gallstones

Choledocholithiasis is a benign cause of obstructive jaundice and may be due to the formation of stones in the common bile duct or stones passing into the common bile duct via the cystic duct.

As well as causing jaundice, gallstones may produce abdominal pain, cholangitis and pancreatitis. Fever, jaundice and right upper quadrant abdominal pain may be indicative of cholangitis (Charcot's triad).

Surgery to the biliary tract may result in stricture formation, which may cause obstructive jaundice.

Alcohol and medication

Primary biliary cirrhosis may result in liver fibrosis and is associated with the presence of antimitochondrial antibodies.

Viral hepatitis and alcoholic liver disease may cause jaundice, so risk factors should be considered when eliciting the history.

Paracetamol overdose, use of highly active antiretroviral therapy (HAART) for HIV and some antibiotics may cause drug-induced hyperbilirubinaemia.

A careful history and examination are important in elucidating the underlying cause of jaundice.

Key questions

  • When did the patient notice they were becoming jaundiced?
  • Was the onset acute?
  • Is dark urine reported? This is indicative of hyperbilirubinaemia
  • What is the colour of the patient’s stools?
  • Is pregnancy a possibility? Mild jaundice may accompany cholestasis of pregnancy
  • Elicit the family history - a hereditary liver disorder may be identified
  • Ask about sexual history, IV drug use, alcohol misuse and travel history (risk factors for hepatitis)
  • Ask about systemic features such as weight loss, fevers, arthralgia, rash and vomiting

Past medical history may reveal the underlying cause, for example, if there is a history of liver cirrhosis, previous biliary tract surgery, or an underlying condition resulting in excessive haemolysis, such as sickle cell disease, inflammatory bowel disease or HIV. The drug history may reveal a potential cause of jaundice.

Examination

General examination may reveal cachexia and/or the patient may look unwell. Bruising or petechiae, palmar erythema, muscle wasting, asterixis and/or gynaecomastia may be seen. Observations should be made. Review of systems should include fever, malaise and joint pain.

Assess for the presence of abdominal pain, steatorrhoea, pruritus, pale stools, nausea and vomiting and weight loss. Easy bruising and melaena may suggest a coagulopathy.

Abdominal examination should include palpation and percussion of the liver and spleen, and a digital rectal examination. The patient may have ascites or collateral blood vessels. It is worth noting that if the gall bladder is enlarged in the presence of jaundice, a carcinoma of the head of the pancreas is more likely to be responsible than a common bile duct stone (Courvoisier's law).

Right heart failure may be a cause of liver dysfunction, so cardiovascular examination is important. A pleural effusion may be detected. Neurological examination may be relevant.

Investigations

Initial investigations include blood tests, such as FBC, coagulation screen and LFTs, as well as measurement of direct and indirect bilirubin. Iron studies may be necessary.

Elevated bilirubin, alkaline phosphatase and gamma-glutamyltransferase may suggest cholestasis. This is in contrast with elevated bilirubin, AST and ALT, which may be more suggestive of a hepatocellular cause of jaundice. It may be necessary to exclude autoimmune hepatitis, as well as viral hepatitis.

If liver function tests show a non-obstructive pattern, a full liver screen may include a viral hepatitis screen, immunoglobulins, autoantibodies, ferritin, alpha 1-antitrypsin, alpha fetoprotein and caeruloplasmin.

Biliary obstruction secondary to a benign cause is more likely in those with jaundice and acute abdominal pain, in contrast to those with symptoms such as weight loss. In the former, ultrasonography may be considered in primary care, depending on the severity of the case.

The British Society of Gastroenterology advises acute admission if jaundice is accompanied with a patient that is acutely unwell, has a fever, signs of encephalopathy, symptoms and signs of cholangitis, dehydration, coagulopathy or if bilirubin is >100micromol/l. Confusion and melaena may also prompt same-day referral.

Urgent (two-week) referral is warranted if malignant biliary obstruction is suspected. NICE guidance advises urgent referral for pancreatic cancer in those aged 40 and above presenting with jaundice. Urgent direct access CT scan may be considered to assess for pancreatic malignancy in those aged 60 and over, presenting with weight loss and bowel symptoms, back or abdominal pain or new-onset diabetes.

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  • Dr Kochhar is a GP in Bexhill, East Sussex

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