Pneumocystis jirovecii pneumonia in systemic rheumatic diseases: risk assessment and prophylaxis with emphasis on reduced-dose sulfamethoxazole/trimethoprim

Abstract

Pneumocystis jirovecii pneumonia (PCP) is a serious opportunistic infection in patients with systemic rheumatic disease (SRD). Although less common than in HIV infection, PCP in patients with SRD worsens rapidly and is associated with high mortality, highlighting the importance of early recognition and prevention. However, risk stratification, indications for PCP prophylaxis, and optimal dosing regimens remain uncertain in patients with SRD. This review summarizes current evidence on the risk factors for PCP in patients with SRD, particularly clinically relevant determinants such as disease-specific risk profiles, glucocorticoid exposure, concomitant immunosuppressive therapies, biologics, and targeted agents. Based on these risk determinants, the current status of prophylactic strategies is discussed. In addition, current evidence on PCP prophylaxis is summarized, with particular attention to the effectiveness and safety of sulfamethoxazole/trimethoprim (SMX/TMP) and the use of reduced-dose regimens to improve tolerability. Overall, this narrative review highlights key challenges of reduced-dose SMX/TMP for PCP prophylaxis in patients with SRD, particularly in balancing efficacy and long-term tolerability.