Fevers, Acute Hepatitis, and Hypercoagulability in an Immunocompetent Host

Abstract

Question: A 46-year-old man who worked as a garbage hauler was admitted to the hospital with an 8-day history of daily fevers and progressively worsening right upper quadrant pain. He had no prior health conditions and did not take any medications on a regular basis. He denied tobacco, alcohol, or recreational drug use. At presentation, his vital signs were as follows: temperature 39.0°C, heart rate 119 beats per minute, blood pressure 142/84 mm Hg, respiratory rate 20 breaths per minute, and oxygen saturation of 97% on room air. Physical examination revealed jaundice and right upper quadrant abdominal tenderness without rebound or guarding. Laboratory studies (reference range in parenthesis) showed hemoglobin 16.3 g/L (reference range, 13.2–16.6 g/L) , leukocytes 10,000/L (3400–10,000/L), neutrophils 8390/L (1560–6450/L), alanine aminotransferase 404 U/L (7–55 U/L), aspartate aminotransferase 307 U/L (8–48 U/L), alkaline phosphatase 251 U/L (40–129 U/L), total bilirubin 5.8 mg/dL (≤1.2 mg/dL), erythrocyte sedimentation rate 41 mm/h (1–22 mm/h), C-reactive protein 306.4 mg/L (0–8 mg/L), iron 23 μg/dL (50–150 μg/dL), and ferritin 10,173 μg/L (31–409 μg/L). Right upper quadrant ultrasound with liver Dopplers demonstrated a normal-appearing liver without biliary obstruction or vascular abnormalities. Computed tomography abdomen with intravenous contrast illustrated diffuse hepatic steatosis without intra- or extrahepatic biliary dilation and multiple wedge-shaped hypoenhancing areas in the spleen suggestive of infarcts (Figure A). Hepatitis A, B, and C serologies, antinuclear antibody, smooth muscle antibody, and antimitochondrial antibody were unremarkable. A fine-needle biopsy of the liver was performed with representative pathology images highlighted in Figure B. What is the most likely diagnosis? Look on page 55 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and images in GI. Liver biopsy revealed non-necrotizing granulomatous inflammation including fibrin ring granulomas and mild microvascular steatosis. Additional laboratory evaluation (reference range in parenthesis) revealed a positive Coxiella burnetii polymerase chain reaction on the liver biopsy with a serum Q fever phase II immunoglobulin (Ig)M level 1:2048 (<1:16), serum Q fever phase II IgG level 1:64 (<1:16), and negative phase I IgG and IgG, consistent with acute Q fever. On further questioning, he revealed that he hauled garbage from a sheep farm, a likely source of exposure to Coxiella burnetii. Given the splenic infarcts, a thrombophilia workup was pursued that showed serum antiphospholipid (aPL) antibody IgM level 108.9 MPL (<15 MPL) and serum aPL antibody IgG level 60.9 GPL (<15 GPL). He underwent a screening transesophageal echocardiogram that did not reveal any valvular abnormalities or vegetations. Doxycycline 100 mg twice daily and hydroxychloroquine 200 mg 3 times daily was initiated. At the time of last follow-up, he continued to experience fatigue, but fever resolved and right upper quadrant pain improved. Coxiella burnetii, the bacterium responsible for causing Q fever, is a ubiquitous zoonosis that infects humans who are exposed to contaminated aerosols from mammalian amniotic fluid or placenta.1Fournier P.E. Marrie T.J. Raoult D. Diagnosis of Q fever.J Clin Microbiol. 1998; 36: 1823-1834Crossref PubMed Google Scholar Patients with acute Q fever commonly present with acute hepatitis, seen in 46.3% of 1668 cases in one study.2Melenotte C. Protopopescu C. Million M. et al.clinical features and complications of Coxiella burnetii infections from the French National Reference Center for Q Fever.JAMA Netw Open. 2018; 1e181580Crossref Scopus (61) Google Scholar The characteristic pathology features from tissue infected with Coxiella burnetii is commonly described as “doughnut granulomas” which consist of dense fibrin rings surrounding a central lipid vacuole.1Fournier P.E. Marrie T.J. Raoult D. Diagnosis of Q fever.J Clin Microbiol. 1998; 36: 1823-1834Crossref PubMed Google Scholar Positive aPL antibodies are associated with a high risk of clinical complications in acute Q fever, including hepatitis, as seen in our patient, and pneumonia and acute endocarditis, which were not seen in our patient.2Melenotte C. Protopopescu C. Million M. et al.clinical features and complications of Coxiella burnetii infections from the French National Reference Center for Q Fever.JAMA Netw Open. 2018; 1e181580Crossref Scopus (61) Google Scholar The treatment for patients with acute Q fever with positive aPL antibodies and without evidence of acute Q fever endocarditis includes doxycycline plus hydroxychloroquine until aPL antibody levels normalize.3Anderson A. Bijlmer H. Fournier P.E. et al.Diagnosis and management of Q fever--United States, 2013: recommendations from CDC and the Q Fever Working Group.MMWR Recomm Rep. 2013; 62: 1-30PubMed Google Scholar