Pneumocystis Jirovecii Pneumonia in Systemic Lupus Erythematosus: A Nationwide Cohort Study in Taiwan

Abstract

Objective To evaluate Pneumocystis jirovecii pneumonia (PJP) infection risk in patients with systemic lupus erythematosus (SLE) in Taiwan. Methods We identified 24,367 patients with SLE from the National Health Insurance research database between 1997 and 2012 and compared the PJP incidence rates (IRs) with those in 243,670 age‐ and sex‐matched non‐SLE controls. PJP risk in the patients was evaluated using a Cox multivariate proportional hazards model. Results The SLE patients exhibited a significantly higher PJP risk than the controls, with an IR of 2.63 per 10,000 person‐years and IR ratio of 27.65 (95% confidence interval 17.2–45.3; P < 0.001). Male sex (hazard ratio [HR] 2.42, P < 0.01), end‐stage renal disease (ESRD; HR 1.74, P = 0.01), recent use of mycofenolate mofetil (MMF; HR 4.43, P < 0.001), intravenous steroid pulse therapy (HR 108.73, P < 0.001), and average oral dosage of >7.5 mg/day prednisolone or equivalent treatment (HR 4.83, P < 0.001) were associated with PJP in SLE, whereas hydroxychloroquine use reduced its risk (HR 0.51, P = 0.01). Of note, cyclophosphamide was not associated with PJP infection in the multivariate Cox proportional hazard model. Conclusion Patients with SLE have a considerably high PJP risk. Cyclophosphamide does not increase PJP risk. Male sex, ESRD, MMF use, intravenous steroid pulse therapy, and oral prednisolone or equivalent treatment (>7.5 mg/day) are risk factors for PJP, whereas hydroxychloroquine use reduces PJP risk.

Risk Factors for Pneumocystis jirovecii Pneumonia in Children With Systemic Lupus Erythematosus Exposed to Prolonged High-Dose Glucocorticoids

“…Additional risk factors for PJP in adult SLE patients, such as elevated SLEDAI scores and the use of immunosuppressants, were identified in previous studies. 9,10,17,18 However, our investigation did not validate these risk factors. Further investigation is needed to explore the potential relationship between SLEDAI, the use of immunosuppressants, and the risk of PJP in children with SLE.…”

“…Previous research has indicated that individuals with SLE who experience renal involvement are more susceptible to developing PJP. 9,10,18 This association may be attributed to the fact that SLE patients with renal involvement tend to receive more aggressive immunosuppressive treatment compared with those without renal issues. Furthermore, it should be noted that these individuals exhibit a diminished capacity to eliminate immunosuppressive medications by renal excretion.…”

“…and the administration of immunosuppressants such as cyclophosphamide (CYC), 10,17 mycophenolate mofetil, 18 and rituximab. 19,20 Nevertheless, there is a lack of comprehensive characterization of the potential risk factors associated with PJP in children with SLE.…”

Major infections in newly diagnosed systemic lupus erythematosus: an inception cohort study

“… 22 23 Therefore, prompt recognition of infection and empirical antimicrobial treatment might be a logical strategy for high-risk patients. Appropriate vaccination (such as recombinant zoster vaccine for herpes zoster infection 24 ) and antimicrobial prophylaxis (such as trimethoprim-sulfamethoxazole for P. jirovecii infection 25 ) should be considered as important parts of the strategy to minimise the risk of major infections.…”

“…1 Indeed, short disease duration (<1 year) has been shown to be an independent risk factor associated with infections in different SLE cohorts. [2][3][4] In patients with SLE, infections are largely considered a complication of immunosuppressive therapy; however, as high as 25.9% of severe infections are reported at the time of SLE diagnosis in the absence of immunosuppressive therapy. 5 The high prevalence of severe infection in newly diagnosed SLE implies that infections are attributable to glucocorticoid and immunosuppressive therapy, and may be related to the underlying immune disturbance of SLE itself.…”