A 42-year-old man comes to the office for a routine medical evaluation. He has no known medical conditions but has not seen a health care provider in many years. The patient has had an intermittent, nonproductive cough and otherwise feels well. He takes no medications, drinks alcohol occasionally, and does not use tobacco or illicit drugs. Vital signs are within normal limits. Physical examination shows no scleral icterus or mucosal pallor. The lungs are clear on auscultation and heart sounds are normal. The liver edge is palpable 3 cm below the right costal margin, and the spleen tip is palpable below the left costal margin. There is no skin rash or extremity edema. Laboratory results are as follows: Chest x-ray shows mediastinal fullness and bilateral reticulonodular opacities, mostly involving the upper lungs. Which of the following is the most likely underlying cause of this patient's liver disease?

Question

A 42-year-old man comes to the office for a routine medical evaluation.  He has no known medical conditions but has not seen a health care provider in many years.  The patient has had an intermittent, nonproductive cough and otherwise feels well.  He takes no medications, drinks alcohol occasionally, and does not use tobacco or illicit drugs.  Vital signs are within normal limits.  Physical examination shows no scleral icterus or mucosal pallor.  The lungs are clear on auscultation and heart sounds are normal.  The liver edge is palpable 3 cm below the right costal margin, and the spleen tip is palpable below the left costal margin.  There is no skin rash or extremity edema.  Laboratory results are as follows:  Chest x-ray shows mediastinal fullness and bilateral reticulonodular opacities, mostly involving the upper lungs.  Which of the following is the most likely underlying cause of this patient's liver disease?

Quizplus · Accepted Answer

11ec25c8_d404_9620_bc81_49be93c36608_MD0003_00 This relatively asymptomatic man has hepatosplenomegaly and liver function tests (LFTs) showing mixed cholestatic and hepatocellular abnormalities. Given his associated hypercalcemia and hilar lymphadenopathy (suggested by radiographic findings), this presentation is consistent with extrapulmonary sarcoidosis. Sarcoidosis is a multisystemic, inflammatory granulomatous disease. Asymptomatic liver involvement (eg, abnormal LFTs, hepatomegaly) is common (~65%). Patchy infiltration by noncaseating granulomas can cause cholestatic (eg, mild alkaline phosphatase elevation) followed by hepatocellular (eg, mild aminotransferase elevations) changes. Reticuloendothelial granulomatous infiltration can also cause splenomegaly. Other common sarcoidosis findings seen in this patient include lung involvement (>90%), with radiographs showing evidence of hilar lymphadenopathy (eg, described as upper lobe reticulonodular opacities, diffuse or nodular parenchymal infiltrates), and hypercalcemia (due to vitamin D conversion by macrophages in granulomas). upper lobe reticulonodular opacities Biopsy of the most accessible lesion (eg, liver, enlarged lymph node) can establish the diagnosis. (Choice A) Excessive iron accumulation from hereditary hemochromatosis, which commonly affects middle-aged men, can cause infiltrative liver disease, resulting in hepatosplenomegaly and transaminase elevations (primary hepatocellular pattern). However, lung involvement and hypercalcemia would not be expected. (Choice B) Amyloidosis, a multisystem condition characterized by insoluble fibril deposition, can affect the liver, causing hepatomegaly and elevated alkaline phosphatase. However, this patient lacks other associated findings of amyloidosis, such as easy bruising and bleeding, peripheral edema (nephrotic syndrome), or anemia. In addition, hypercalcemia would not be expected. (Choice C) Hepatosplenomegaly and elevated alkaline phosphatase (primary cholestatic pattern) can be seen in patients with primary biliary cholangitis (PBC), a condition involving T-lymphocyte-mediated bile duct destruction. However, jaundice (eg, scleral icterus) is common, lung involvement is not seen, and >90% of patients with PBC are women. (Choice D) Alpha-1 antitrypsin deficiency can cause early-onset lung emphysema, liver cirrhosis, and panniculitis. Elevated transaminases and cough can be presenting symptoms. However, chest imaging characteristically shows changes (eg, bullae) at lung bases, rather than the upper lobe opacities seen in this patient, LFTs typically show a primary hepatocellular pattern, and hypercalcemia would not be expected. Educational objective: Sarcoidosis is characterized by multisystem inflammatory noncaseating granuloma formation. Subclinical (asymptomatic) hepatic involvement is common, and liver function tests demonstrate a mixed cholestatic and hepatocellular pattern. References: Hepatic sarcoidosis presenting as portal hypertension and liver cirrhosis: case report and review of the literature. (http://www.ncbi.nlm.nih.gov/pubmed/22679408) Course of asymptomatic liver involvement in sarcoidosis: role of therapy in selected cases. (http://www.ncbi.nlm.nih.gov/pubmed/9186992) Gastrointestinal and hepatic manifestations of sarcoidosis. (http://www.ncbi.nlm.nih.gov/pubmed/18853979)

A 42-Year-Old Man Comes to the Office for a Routine