Q fever is a systemic zoonotic infection caused by Coxiella burnetii, a pleomorphic intracellular bacterium. Diagnosing Q fever can be challenging due to its nonspecific and variable clinical presentation, making it crucial to identify risk factors. Clinical presentation is usually a flu-like illness of varying severity.^[1]

A 28-year-old telecommunication technician working in a rural area was admitted to the emergency department with a two-week history of persistent fever, myalgia, fatigue, and headache. He had no significant past medical history, no allergy history, recent flights, tea or mushroom consumption, hepatotoxic substance use, or regular medication. He had hepatosplenomegaly, jaundice, and a fever (tympanic temperature of 38.8°C) at the physical examination. Laboratory investigation showed elevation of white blood cell count (12600/mm ³ (normal range 4000–10000/mm ³) , with 51.2% neutrophils; sedimentation rate of 100 mm/1 h (normal range <15 mm/1 h), C reactive protein of 18 mg/dL (normal range <0.5 mg/dL), hemolytic anemia (Hgb of 10.6 g/dL, normal range 13.6–18 g/dL); 3.2% of reticulocytes (normal range 0.5–2.5%); unconjugated hyperbilirubinemia with a total bilirubin count of 2.3 mg/dL (normal range 0.2–1.2 mg/dL), indirect bilirubin of 1.3 mg/dL (normal range 0.0–0.6 mg/dL), direct bilirubin of 1.0 mg/dL (normal range 0.0–0.5 mg/dL); LDH of 446 U/L (normal range 125–220 U/L); haptoglobin 132 mg/dL (normal range 14–258 mg/dL); INR 1.5; prothrombin time of 16.6 s (normal range 9.3–13.0 s); partial thromboplastin time test of 63 s (normal range 25.1–36.5 s); fibrinogen 406 mg/dL (normal range 200–393 mg/dL) and hepatic tests alterations: GOT 110 U/L (normal range 5–34 U/L), and GPT 401 U/L (normal range 0–55 U/L); alkaline phosphatase 198 U/L (normal range 40–150 U/L); GGT 101 U/L (normal range 12–64 U/L). The direct antiglobulin test with poly-specific Coombs reagent was negative. Results of tests for lupus erythematosus-related phenomena and antibodies to nuclear components and DNA were negative. The peripheral blood smear showed some atypical lymphocytes with hyperbasophilic cytoplasm and slight anisochromia, and the myeloid aspiration was normal. Both abdominal ultrasound and abdominal computerized tomography confirmed liver and spleen enlargement. Viral serologies showed past B19 parvovirus and Epstein-Barr infections and were negative for human immunodeficiency virus, hepatitis A, B, and C, and cytomegalovirus. Microscopic examination of blood films didn’t find any signs of plasmodia. Blood and urine cultures did not reveal bacterial pathogens, and transthoracic echocardiography did not reveal any signs of endocarditis. Thoracic computerized tomography showed lung parenchyma with preserved characteristics, without any alteration, namely nodules, infiltrates, or adenopathies. Other infections were excluded by urinary antigen tests, such as Streptococcus pneumoniae and Legionella pneumophila, and by serology, such as Salmonella typhi, leptospirosis, Borrelia burgdorferi, and Rickettsia conorii, and the interferon-gamma release assay (IGRA) for tuberculosis was also negative. The patient started empirical antibiotic therapy with IV ceftriaxone with no response, maintaining fever. The result of Coxiella burnetii serologies was suggestive of acute Q fever, showing higher titers of IgG phase II (>1/4096) compared with phase I (1/2048) and higher titers of IgM phase II (>1/4096) compared with phase I (1/4096). A bone marrow biopsy revealed multiple granulomas with a central lipidic vacuole, a “doughnut” or “fibrin ring” granuloma (Fig. 1) that can be found in Q fever. Doxycycline was started according to the suspicion of zoonosis, resulting in clinical improvement with apyrexia since the 7th day of antibiotics and with normalization of inflammatory parameters. Serologies were repeated four weeks later (IgG phase II 1/8192; IgG phase I 1/4096; IgM phase II 1/8192; IgM phase I 1/4096) and after 12 weeks (IgG phase II 1/8192; IgG phase I 1/4096; IgM phase II 1/4096; IgM phase I 1/4096), showing a chronicity development, with no clinical manifestations.

This is a case report of an unusual presentation of Q fever, characterized by acute hemolytic anemia, which is not commonly associated with the disease, while bone marrow involvement is not surprising due to the systemic nature of Coxiella burnetii infection.^[2] The presence of doughnut granulomas in bone marrow biopsy serves as an important diagnostic clue. However, these granulomas are not specific to Q fever and have also been observed in infections like CMV, Epstein-Barr virus, Brucella, Salmonella, and Leishmaniasis, as well as in conditions such as Hodgkin and non-Hodgkin lymphomas and various immune disorders.^{[2, 3]} This case emphasizes the need for clinicians to recognize atypical presentations of Q fever, particularly in patients with potential zoonotic exposure. Various mechanisms are responsible for hemolytic anemia in the course of an infection, including direct invasion of red blood cells by the pathogen, toxin production, mechanical effects, and immune-mediated hemolysis. Features of hemolytic anemia, such as a high reticulocyte count with a negative Coombs test, suggest that hemolytic anemia is more related to direct invasion of red blood cells and mechanical effects. Despite the rarity of hemolytic anemia as a complication of Q fever, bone marrow involvement signifies the systemic nature of the infection. This underscores the importance of including Q fever in the differential diagnosis when facing unexplained systemic or hematologic abnormalities, especially in individuals with potential exposure to animals or environments where zoonotic pathogens are prevalent.

MC, LB, and MR were responsible for preparing the manuscript and literature review and approving the final version. RMF and TV were responsible for revising the manuscript and approving the final version.

The authors have no funding to report.

The authors have declared that no competing interests exist.