Rituximab治療風濕免疫疾病罹患肺囊蟲肺炎的風險

Characteristics of Pneumocystis jirovecii pneumonia in patients with autoimmune diseases undergoing rituximab therapy

目的：過去發現接受細胞毒性藥物和免疫抑製劑治療的患者有較高肺囊蟲肺炎感染的風險。本研究目的在於研究接受Rituximab（RTX）治療的風濕免疫疾病患者罹患肺囊蟲肺炎的特色和危險因子。方法：此回溯性研究納入一家醫學中心於2000年1月至2021年1月間接受RTX治療的風濕免疫疾病患者，分析肺囊蟲肺炎感染的相關危險因子。並且搜索了PubMed資料庫中關於接受RTX治療的風濕免疫疾病患者罹患肺囊蟲肺炎的文獻研究。結果：在91名患者中，3名在RTX治療期間感染肺囊蟲肺炎（發生率：3%）。男性和罹病時間短（4 ± 2.65年）為肺囊蟲肺炎感染的風險因子。所有罹患肺囊蟲肺炎患者均同時接受高劑量皮質類固醇治療。患者多在RTX治療的第一個週期後即感染肺囊蟲肺炎，從最後一次給藥到感染平均時間為6.1 ± 4.26週（範圍：1-13週）。自身免疫性疾病或RTX累積劑量在是否感染肺囊蟲肺炎沒有統計學上的顯著差異。結論：肺囊蟲肺炎可能發生在接受RTX治療的風濕免疫疾病患者中，尤其是在第一個RTX週期結束後6.1 ± 4.26週。男性和罹病時間短是危險因素。臨床醫師應在高危險風濕免疫患者族群中留意肺囊蟲肺炎感染。

Objectives: Pneumocystis jiroveci pneumonia (PJP) has been reported in patients treated with cytotoxic and immunosuppressive agents. This study identified the risk factors for PJP following rituximab (RTX) therapy in patients with autoimmune diseases. Methods: In this retrospective cohort study, we reviewed the medical records of patients with autoimmune diseases who received RTX from January 2000 through January 2021. Firth logistic regression with selective stepwise elimination procedure was performed to identify the most important factors of the PJP infection. We also searched the PubMed database for studies on PJP in patients with autoimmune disease undergoing RTX therapy. Results: Of the 91 patients reviewed, three developed PJP during RTX therapy (incidence rate: 3%). Male sex and short disease duration (4 ± 2.65 years) were associated with a higher risk of PJP in our cohort. All patients with PJP received high-dose corticosteroid concomitantly. Most of them developed PJP just after the first cycle of RTX therapy, approximately 6.1 ± 4.26 weeks (range: 1-13 weeks) after the last dose. No significant differences were noted in underlying autoimmune diseases or cumulative dose of RTX infusion between patients with and without PJP. Conclusion: PJP may occur in patients with autoimmune diseases undergoing RTX therapy at 6.1 ± 4.26 weeks after the end of the first cycle of RTX. Male sex and short disease duration were the risk factors. Clinicians should be mindful of this possibility in this patient population.