Asymptomatic carriage of Pneumocystis jiroveci in elderly patients with rheumatoid arthritis in Japan: a possible association between colonization and development of Pneumocystis jiroveci pneumonia during low-dose MTX therapy

Low-dose methotrexate (MTX) has been used effectively for rheumatoid arthritis (RA) because of its favorable risk-benefit ratio. One of the recent concerns arising from this therapy is a possible increase in the rate of opportunistic infections, particularly Pneumocystis jiroveci pneumonia (PCP). In this study, we report two cases of PCP occurring during low-dose methotrexate therapy for RA and review 13 additional cases from the literature on Japanese patients with RA. The average age of these patients was 67.7 years, and most were over the age of 60. MTX-associated PCP appears to occur more frequently in elderly individuals in Japan. To identify individuals with a high risk of PCP, we performed a polymerase chain reaction on specimens from induced sputum or bronchoalveolar lavage fluids from 55 patients with RA. At that point in time, they showed no evidence of PCP development. We found six patients (10.9%) having asymptomatic carriage of P. jiroveci. The mean age of the P. jiroveci-positive patients was 74.7 years, which was significantly older than the P. jiroveci-negative patients (mean age 63.6 years). Of the RA patients over the age of 65, 18.8% (6 cases out of 32) were carriers of P. jiroveci. There were no significant differences in RA duration or counts of white blood cells or lymphocytes between the positive and negative groups. Notably, we encountered a case of PCP occurring in an asymptomatic carrier of P. jiroveci during low-dose MTX therapy for RA. This case appeared to be a reactivation of latent infection. By careful follow-up on the carriers of P. jiroveci, we succeeded in promptly diagnosing PCP, and we employed the appropriate therapeutic strategies for this possibly life-threatening complication.