Acute and probable chronic Q fever during anti-TNFα and anti B-cell immunotherapy: a case report

Abstract

Background: Q fever is caused by the intracellular bacterium Coxiella burnetii. Initial infection can present as acute Q fever, while a minority of infected individuals develops chronic Q fever endocarditis or vascular infection months to years after initial infection. Serology is an important diagnostic tool for both acute and chronic Q fever. However, since immunosuppressive drugs may hamper the humoral immune response, diagnosis of Q fever might be blurred when these drugs are used.

Case presentation: A 71-year-old Caucasian male was diagnosed with symptomatic acute Q fever (based on positive C. burnetii PCR followed by seroconversion) while using anti-tumor necrosis factor-α (anti-TNFα) drugs for rheumatoid arthritis (RA). He was treated for two weeks with moxifloxacin. After 24 months of follow-up, the diagnosis of probable chronic Q fever was established based on increasing anti-C. burnetii phase I IgG antibody titres in a immunocompromised patient combined with clinical suspicion of endocarditis. At the time of chronic Q fever diagnosis, he had been treated with anti B-cell therapy for 16 months. Antibiotic therapy consisting of 1.5 years doxycycline and hydroxychloroquine was started and successfully completed and no signs of relapse were seen after more than one year of follow-up.

Conclusion: The use of anti-TNFα agents for RA in the acute phase of Q fever did not hamper the C. burnetii-specific serological response as measured by immunofluorescence assay. However, in the presented case, an intact humoral response did not prevent progression to probable chronic C. burnetii infection, most likely because essential cellular immune responses were suppressed during the acute phase of the infection. Despite the start of anti-B-cell therapy with rituximab after the acute Q fever episode, an increase in anti-C. burnetii phase I IgG antibodies was observed, supporting the notion that C. burnetii specific CD20-negative memory B-cells are responsible for this rise in antibody titres.

Figure 1

Q fever serology during follow-up after acute Q fever in a patient with anti-rheumatic drugs. Serological titres of anti-Coxiella burnetii phase I and phase II IgG (as measured by immunofluorescence assay) during follow-up after acute Q fever (t = 0) of a patient using subsequently etanercept, adalimumab and rituximab as biological disease-modifying anti-rheumatic drugs. Rituximab was given with 7 months intervals, each time two dosages with two weeks interval. At t = 24 the diagnosis probable chronic Q fever was established followed by anti-microbial treatment with doxycycline and hydroxychloroquine for 1.5 years.