Clinical Pearls & Morning Reports
Granulomas are found in 1 to 2% of liver biopsies that are performed to investigate hepatic injury of unclear cause. Granulomatous changes arise in infectious, autoimmune, malignant, drug-induced, or idiopathic hepatopathies. The histologic features of the granuloma (e.g., necrotizing, suppurative, or epithelioid without necrosis) can suggest a diagnosis but are not pathognomonic. Read the Clinical Problem-Solving article on this topic.
Q: What are some of the infectious causes of granulomatous hepatitis?
A: Granulomatous hepatitis, particularly in association with necrotizing granulomas, raises suspicion of an infectious cause (although noninfectious causes may also, less commonly, be associated with necrotizing granulomas). Disseminated fungal and mycobacterial infections account for the majority of cases of infectious granulomatous hepatitis. Infections that are less frequently associated with hepatic granulomas, particularly infections involving some suppuration, include Francisella tularensis infection, yersiniosis, actinomycosis, Bartonella henselae infection, and brucellosis. Viral infections (e.g., infection with cytomegalovirus [CMV] or Epstein–Barr virus [EBV]) can also appear with a granulomatous pattern of liver injury.
Q: What are fibrin-ring granulomas?
A: Fibrin-ring granulomas are characterized by granulomatous inflammation with a central fat vacuole and surrounding ring of fibrin. They are suggestive but not pathognomonic of Q fever; in one series, 10 of 23 patients (43%) with fibrin-ring granulomas were shown to have this infection. Fibrin-ring granulomas have also been described in visceral leishmaniasis, toxoplasmosis, EBV hepatitis, and allopurinol hypersensitivity.
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Figure 1. (10.1056/NEJMcps1609391/F1) Liver-Biopsy Specimen.
A: Q fever is a worldwide zoonotic disease that is caused by the intracellular bacterium Coxiella burnetii. Infection begins with the inhalation of spores that originate in infected cattle, sheep, and goats. In the United States, states with the highest incidence include Utah, Oregon, and Nebraska. Q fever has also been reported in California and Texas. The typical incubation period is 2 to 3 weeks. The spores can survive for extended periods and can be carried by wind over long distances, occasionally farther than 10 miles. This durability and transmissibility may explain why 60% of patients with Q fever have had no known contact with livestock.
A: Most people remain asymptomatic after C. burnetii exposure and subsequent seroconversion. Acute Q fever is characterized by high temperatures, headache, pneumonia, and hepatitis. Myocarditis and meningoencephalitis are rare complications. The majority of acute infections resolve within 2 to 3 weeks, even without treatment. Persistent localized disease (formerly known as chronic Q fever) develops months after initial exposure and may follow acute symptomatic Q fever or asymptomatic infection. It occurs in less than 5% of patients; immunocompromised patients and pregnant patients are at highest risk. Endovascular infection, commonly endocarditis on the left side of the heart, is the most frequent manifestation, followed by osteomyelitis and chronic hepatitis. Serologic testing is the mainstay of diagnosis for both acute and chronic persistent localized disease. Doxycycline is the antibiotic of choice in nonpregnant adults without endocarditis.