Coxiella burnetii endocarditis as a possible cause of ANCA-associated vasculitis

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Sir, Coxiella burnetii, the bacterium responsible for Q fever, is known for its vascular tropism. Its triggering role in autoimmune disorders is supported by the presence of autoantibodies in two-thirds of infected patients [1]. Anticardiolipin antibodies, ANCAs, ANAs, anti-dsDNA and anti-parietal cell antibodies are the most frequently observed [2]. We report a case of autoimmune vasculitis in a context of persistent C. burnetii infection.

A 73-year-old man presented to the infectious disease ward with a 3-month history of fever, myalgia, arthralgia of large and medium joints, and asthenia. He lived in a rural area surrounded by sheep farms. He had no respiratory symptoms, heart murmur or joint effusion. Blood tests revealed mild inflammatory syndrome (CRP 36 mg/l); liver function tests were normal. Coxiella burnetii serology was positive in immunofluorescence assay (phase I IgG 1:1024, IgM 1:512 and phase II IgG >1:2048, IgM 1:512, elevated levels of phase I IgG suggesting chronic Q fever [3]), whereas C. burnetii PCR was negative on plasma. Transthoracic echocardiography showed moderate aortic insufficiency that did not exist on a previous examination. The diagnosis of possible C. burnetii persistent endocarditis was established, and a treatment with doxycycline and HCQ was initiated for a planned duration of 18 months, according to recommendations [3, 4]. Indeed, HCQ increases phagolysome pH, thereby increasing doxycycline intracellular antibacterial activity, which explains the synergy between these two drugs [5]. Fever disappeared within 2 weeks, but the patient reported a worsening of myalgia and arthralgia, without joint swelling. In the same time, creatininaemia increased from 90 µmol/l at baseline to 130 μmol/l, and urine analysis showed a significant glomerular proteinuria (0.7 g/24 h) without microscopic haematuria. Immunoassays revealed c-ANCA, with specificity against PR3 demonstrated by indirect immunofluorescence (ANCA titer 1/50), multiplexing Bioplex BioRad (6.3 IA, with a threshold of positivity >0.2), ELISA (3.05, positivity threshold >2), fluoroenzymology (15 U/ml, positivity threshold >3.0) and immunodot assays. He had no rhinosinusal involvement, no peripheral neuropathy and no pulmonary parenchymal abnormality on CT scan. Renal biopsy demonstrated a pauci-immune extracapillary crescentic glomerulonephritis (Fig. 1), confirming the diagnosis of ANCA-associated vasculitis with articular and renal involvement. Induction treatment with prednisone and cycles of CYC followed by maintenance treatment with rituximab stabilized the renal function and allowed a complete regression of arthralgia and myalgia. The treatment of Q fever was continued in parallel with the treatment of ANCA-associated vasculitis.