What is the diagnosis for a 42-year-old male patient presenting with nausea, pruritus (itchy skin) on the trunk and arms, dysgeusia (metallic taste), dark urine, flank pain, fatigue, hard and pale stools, and jaundice (yellowish sclera), who recently discontinued doxycycline (Vibramycin) and ibuprofen (Advil)?

From the Guidelines

The patient's symptoms are most likely due to drug-induced liver injury (DILI) or viral hepatitis, and I recommend continuing to hold both doxycycline and ibuprofen, ensuring adequate hydration, and monitoring liver function tests closely. The constellation of symptoms including nausea, pruritus on trunk and arms, metallic taste, dark urine, flank pain, fatigue, pale/hard stools, and scleral icterus strongly suggests hepatobiliary dysfunction. The recent use of doxycycline and ibuprofen is significant as both medications can cause hepatotoxicity, with doxycycline causing idiosyncratic liver injury and ibuprofen causing dose-dependent hepatotoxicity 1. The ordered laboratory tests (CBC, CMP, urinalysis, hepatitis panels, and liver/kidney function tests) are appropriate to differentiate between medication-induced liver injury and viral hepatitis. If DILI is confirmed, symptoms typically improve within days to weeks after discontinuation of the offending agents, though complete resolution of laboratory abnormalities may take longer. For the management of cholestatic pruritus, I recommend using bezafibrate as the first-line pharmacological treatment, as it has been shown to be effective in alleviating moderate to severe itch in people with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) treated with ursodeoxycholic acid (UDCA) 1. Rifampicin may also be considered as a second-line treatment, but it may induce drug-induced hepatitis after 4-12 weeks in up to 12% of cholestatic patients, and regular monitoring is necessary 1. The patient should be advised to avoid alcohol and other potentially hepatotoxic substances, and considering gastroenterology consultation if laboratory results confirm significant hepatic dysfunction. In extreme situations, temporary relief has been obtained with plasmapheresis or albumin exchange, and liver transplantation for cholestatic pruritus is highly effective in terms of rapid reduction in pruritus severity 1. It is essential to note that the management of cholestatic pruritus is an area of active research, and new therapies are likely to emerge in the near future, but need evaluation in a clinical setting. The use of antihistamines, ondansetron, and phenobarbital is not recommended for reasons of lack of efficacy, limited efficacy, and excessive side-effect profile, respectively 1. In addition to pharmacological treatment, general recommendations for patients suffering from cholestasis-associated pruritus include using emollients to prevent dryness of skin, avoiding hot baths or showers, using cooling gels for affected skin areas, or keeping nails shortened 1.

From the Research

Patient Symptoms and Potential Diagnosis

• The patient presents with multiple complaints, including nausea, itchy skin on the trunk and arms, a metallic taste in his mouth, dark urine, and flank pain.
• The patient also reports feeling worn out, having hard and pale stools, and yellowish sclera.
• These symptoms could be indicative of a liver or bile duct disorder, such as primary biliary cirrhosis or primary sclerosing cholangitis, as suggested by studies 2, 3, 4.
• The patient's decision to stop taking doxycycline and ibuprofen may be relevant, as these medications can affect liver function.

Laboratory Tests and Diagnosis

• The ordered laboratory tests, including CBC, CMP, urinalysis, Hep C, Hep A, Hep B, kidney function, and liver panel labs, will help to determine the underlying cause of the patient's symptoms.
• The results of these tests may indicate the presence of a liver or bile duct disorder, and guide further treatment, as discussed in studies 5, 6.
• The diagnosis of primary sclerosing cholangitis, for example, requires a cholestatic liver enzyme profile, characteristic bile duct changes on imaging, and the exclusion of secondary causes of sclerosing cholangitis, as outlined in study 6.

Treatment Options and Management

• If the patient is diagnosed with a liver or bile duct disorder, treatment options may include ursodeoxycholic acid (UDCA), as discussed in studies 2, 3, 4.
• UDCA has been shown to improve serum liver chemistries, delay disease progression, and prolong transplant-free survival in patients with primary biliary cirrhosis and primary sclerosing cholangitis.
• The management of symptoms in cirrhosis, including pruritus, muscle cramping, and fatigue, is also an important consideration, as discussed in study 5.