Case Presentation: A 63-year-old man presented with fever for 1 week and bilateral leg pain. He was found to have bilateral deep vein thrombosis (DVT) and treated with heparin drip, then Eliquis, but fever and leukocytosis (14-20k/mm3) persisted. Extensive workup—computed tomography (CT) scans of his chest and abdomen/pelvis, magnetic resonance imaging of his spine, nuclear medicine bone scan, and tagged white blood cell scan—was negative for any etiology. Bone marrow biopsy and flow cytometry were negative for abnormal hematolymphoid cell populations, but he had hypercellular marrow with marked myeloid hyperplasia. Blood cultures remained negative; stool was positive for Blastocystis that was not likely pathogenic. He received levofloxacin, vancomycin, meropenem, and doxycycline with antifungal therapy (fluconazole). He was later found to have positive serology for Coxiella burnetii concerning for chronic Q fever. Further discussion revealed his history of frequent visits to a farm in India 1 year earlier where he had exposure to goats. He returned for transesophageal echocardiogram (TEE) that ruled out vegetations or valvular abnormalities. CT angiography of his chest, abdomen and pelvis were negative for mycotic aneurysm. He continued on doxycycline 100mg BID and moxifloxacin 400mg qday, and continues follow up with infectious disease.
Discussion: Q fever is caused by the bacterium C. burnetti, transmitted via inhalation of contaminated soil or animal waste (e.g., goats, sheep, cows). Mean incubation period is 20 days for acute Q fever but it can be asymptomatic. Q fever should be suspected in patients with prolonged fever with leukocytosis, thrombocytopenia, or elevated liver enzymes, though some have normal labs. Q fever can be diagnosed by serology or C. burnetti DNA PCR. Serology may be negative in the first 2 weeks of illness, so patients should be started on treatment prior to confirmatory serology results. Acute Q fever progresses to chronic Q fever in 1-5% of patients, usually several months or years after acute infection. Chronic Q fever has higher morbidity and can be fatal if untreated; patients have increased risk of endocarditis, aneurysms, and formation of granulomatous lesions in their liver, lungs, and bone marrow. A positive PCR or anti-phase I IgG antibody titer ≥1:800 (>1:1024 in the US) with endocarditis or proven vessel/prosthetic infection by imaging is diagnostic of chronic Q fever. TEE is the gold standard for screening, but due to small size of endocarditis, cardiac vegetation is visible in only 12% of patients. TEE should be repeat every 3-6 months for 2 years to evaluate for endocarditis. Treatment is usually doxycycline for 14 days; in cases of resistance or intolerance, minocycline, trimethoprim-sulfamethoxazole, or clarithromycin are reasonable alternatives. For Q fever endocarditis, therapy includes doxycycline and chloroquine for 18-24 months. Fluoroquinolones or rifampin can substitute for hydroxychloroquine in cases of intolerance or contraindication, although treatment can take >3 years.
Conclusions: Acute Q fever infection can be asymptomatic or mild, with no significant lab findings, which makes diagnosis difficult. Chronic Q fever occurs >6 months post exposure and can cause severe illness like endocarditis, aneurysms, or granulomatous lesions; positive PCR or anti-phase I IgG antibody >1:1024 with endocarditis or vessel/prosthetic infection on imaging is diagnostic of chronic Q fever.