Background/Purpose:  Pneumocystis jiroveci pneumonia (PJP) is a serious complication during the treatment in patients with variety of rheumatic disease. Postmarketing surveillance of infliximab and etnercept in Japan reported that the incidence of PJP was higher than those in Western countries. Harigai et al. reported that in patients under the treatment with infliximab, there are 3 risk factors, i.e., more than 65 years of age, more than 6 mg/day of prednisolone (PSL), and coexisting pulmonary diseases (Harigai M, N Engl J Med 2007). We again tried to find risk factors of PJP in this study and also possible protective factors.

Methods:

Subjects were 310 patients with RA. Out of 310 patients, PJP developed in 26 patients. Patients who took cotrimoxazole were excluded from the control group even duration of administration was short. Diagnosis of PJP was done according to the report of Harigai et al. Diagnosis of PJP was definitive if P. jiroveci was found on microscopical analysis of respiratory samples from patients with clinical manifestations, hypoxemia, and radiologic findings compatible with PJP. The diagnosis of PJP was presumptive if a patient met all three criteria and had either a positive PCR test for P. jiroveci DNA or an increased serum level of (1→3) β-d-glucan with an appropriate response to the treatments for PJP. We picked up items that may relate to the development of PJP, such as age, gender, stage, class, duration of illness, presence of interstitial lung disease (ILD), and drugs for the treatment of RA including the dose. Univariate and multivariate analysis were done to find out risk and protective factors.

Results: Out of 26 cases of PJP, 4 cases were definitive and 22 cases were presumptive. By univariate analysis, advanced age, advanced stage and class, high daily dose of prednisolone (PSL), and high weekly dose of MTX were significantly related to the development of PJP. Moreover, patients with PJP had significantly higher % of ILD, and higher % use of bDMARDS. However, patients with PJP had significantly lower % use of sulfasalazine (SSZ) (7.7 % vs. 30.0 %). By multivariate analysis, 5 significant positive coefficients for the development of PJP were obtained, i.e. advanced age, advanced class, high daily dose of PSL, high weekly dose of MTX, and use of bDMARDS. Use of SSZ tended to be related to no development of PJP (p < 0.1). SSZ has been shown to be protective for P. jiroveci in vitro (Wang J, PRoS Pathogen 2010).

Conclusion: We obtained factors related to the development of PJP which suggest that RA is highly active and advanced. In contrast, SSZ may act as protective agents, but further study is needed to reach definitive conclusion.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-factors-of-pneumocystis-jiroveci-pneumonia-pjp-in-patients-with-ra-and-sulfasalazine-as-a-possible-protective-agent/