Background The Netherlands faced a large Q fever outbreak from 2007-2010, during which many individuals have been infected with Coxiella burnetii, the intracellular bacterium causing Q fever. Initial infection is often asymptomatic. Chronic Q fever, which develops in a minority of infected individuals (1-5%), presents months to years after primary infection, mostly as endocarditis or vascular infection. Immunosuppression, although not clearly defined, is a stated risk factor for chronic Q fever. Anti-TNF therapy is associated with increased risk of intracellular infections.
Objectives To examine whether rheumatoid arthritis (RA) patients on anti-TNF therapy are at increased risk of development of chronic Q fever, compared to TNF-naive RA patients using disease modifying drugs (DMARDs).
Methods RA patients, living in Q fever epidemic areas, were identified in rheumatology outpatient clinics in participating hospitals. We selected a cohort of patients on anti-TNF therapy (infliximab, etanercept, adalimumab) for at least three months during the epidemic and a cohort TNF-naive patients who were using DMARDs during the same period. Participants were screened for anti-C. burnetii antibodies, measuring IgG against C. burnetii phase I and II in serum. Patients with phase I and/or II IgG titres ≥1:32 were defined as seropositive, indicating previous exposure to C. burnetii. All seropositive individuals were referred for follow-up to the department of internal medicine. Chronic Q fever was diagnosed according to the Dutch guideline on chronic Q fever diagnostics,1 by a team of medical specialists.
Results From December 2011 to July 2012, 361 patients on anti-TNF therapy and 398 TNF-naive patients participated. The anti-TNF treated patients more frequently used systemic prednisone (at least three months during the epidemic) (P < 0.001). Of patients on anti-TNF therapy, 60/361 (16.6%) were seropositive, compared to 56/398 (14.1%) of TNF-naive patients (P=0.35). Overall, 10/116 (8.6%) seropositive patients were diagnosed with chronic Q fever, of which 7/60 (11.7%) patients on anti-TNF therapy compared to 3/56 (5.4%) TNF-naive patients (P=0.33). Univariate analysis in seropositive patients identified higher age, the use of systemic prednisone, valvulopathy/prosthetic valve and aneurysm/vascular prosthesis as significant risk factors for chronic Q fever.
Conclusions We did not find a significantly higher prevalence of chronic Q fever in patients on anti-TNF therapy compared to TNF-naive patients in this population. Nevertheless, the prevalence of chronic Q fever in seropositive RA patients, either on anti-TNF therapy or DMARD therapy, was substantially higher (8.6%) than reported in non-selected infected individuals (1-5%), suggesting that RA and anti-rheumatic treatment are a risk factor for development of chronic Q fever. Specifically, the use of systemic prednisone was identified as a risk factor in this population.
Wegdam-Blans MC, Kampschreur LM, Delsing CE, et al. Chronic Q fever: review of the literature and a proposal of new diagnostic criteria. J Infect 2012; 64(3): 247-59.
Acknowledgements Investigators initiated study funded by Pfizer. This work was also supported by The Netherlands Organisation for Health Research and Development [grant number 205520002 to T.Schoffelen]
Disclosure of Interest None Declared