Risk Factors and Outcomes of Nontuberculous Mycobacterial Disease among Rheumatoid Arthritis Patients: A Case-Control study in a TB Endemic Area

Tuberculosis (TB) and nontuberculous mycobacteria (NTM) are a major part of the clinical spectrum of mycobacterial diseases. Nontuberculous mycobacteria are widely distributed in the environment, and human infection is suspected to be acquired from environmental exposures1,2. Both TB and NTM disease have similar symptoms and pulmonary radiographic findings, in which makes these infections difficult to distinguish clinically2 and leads to the danger of NTM disease being neglected3. Diseases caused by NTM are being diagnosed with increasing frequency worldwide2, including in Taiwan4. In western developed countries, the incidence rate of TB is generally low and the burden of NTM infections far outstrips that of TB5. There is a high prevalence of TB in Taiwan (49.4 cases per 100,000 population in 2013), despite the extensive implementation of TB control measures and the mandatory Bacillus Calmette-Guerin vaccination6. A laboratory-based surveillance study indicated a trend toward a decrease of TB cases but a significant increase in NTM cases in Taiwan during the period between 2000 and 20124. Several NTM strains are resistant to many antibiotics, which makes treatment difficult2. Rheumatoid arthritis (RA) patients have a higher risk of mycobacterial diseases, which may be due to disease-related immune dysfunction or the immunosuppressive effects of therapeutic agents7,8,9. Biologics are increasingly used to treat RA patients and have been shown to decrease symptom severity and disability10. Increasing evidences have indicated that the incidence of NTM disease was significantly higher in RA patients who received anti-tumor necrosis factor (TNF) biologics therapy11,12. The prevalence of NTM disease in Asia is probably higher than that in western countries13,14. However, very few laboratory-based clinical and epidemiological studies have investigated the association of RA with NTM disease in Asia. Recently, we conducted a nationwide population-based retrospective cohort study and found an increased risk of developing TB and NTM disease in RA patients compared to the control cohort9. Furthermore, the risk of death in RA patients with mycobacterial infection was higher than that in patients without infection9. However, limitations of the previous study included a lack of laboratory results (e.g. NTM species distribution, antimicrobial resistance), information of lifestyle factors (e.g., smoking) or individual health status variables (e.g. BMI) associated with NTM infection and RA9. In addition, the association between anti-rheumatic medication and NTM disease occurrence in RA patients remains unclear. Therefore, we conducted a case-control study using laboratory-based data combined with medical records to analyze the epidemiology, predisposing factors and outcomes of NTM disease in RA patients admitted to one medical center in Taiwan during the period 2001–2014.