目的

探究药物超敏反应综合征(drug-induced hypersensitivity syndrome, DIHS)继发肺孢子菌肺炎(pneumocystis pneumonia, PCP)患者的临床特征和危险因素。

方法

通过医院病历系统进行检索，回顾性分析北京协和医院从2019年1月至2025年4月期间诊治的10例DIHS继发PCP患者的临床表现、实验室检查、治疗情况及疗效。按1∶2配对设计方法，以性别相同、年龄±3岁、病情严重程度相同进行成组匹配，选取同期到北京协和医院诊治的未继发PCP的DIHS患者20例作为对照组，应用单因素分析比较两组患者在糖皮质激素（以下简称激素）减量至泼尼松当量20毫克/天（mg/d）所需时间、巨细胞病毒(cytomegalovirus, CMV)再激活、DIHS复发、白蛋白水平、外周淋巴细胞计数、CD4+T淋巴细胞计数等方面是否存在差异。

结果

1. 共纳入10例DIHS继发PCP患者，男性7例，女性3例，平均年龄(60.1±22.0)岁，最常见的基础合并症为高尿酸血症（7例）。

2. 10例患者均为确诊的DIHS，病情严重程度均为重度，最常见的致敏药物为别嘌醇（6例），最常见的临床皮疹为红皮病样（7例），最常见受累器官是肝脏(7例），治疗DIHS均应用了大剂量激素，9例联合了静脉注射用人免疫球蛋白（intravenous immunoglobulin, IVIG）、免疫抑制剂、生物制剂或Janus激酶(Janus kinase, JAK)抑制剂。后续激素减量过程中10例患者均存在DIHS复发，8例患者出现了病毒的再激活，最常见病毒再激活类型为CMV。

3. 10例患者发生PCP时均出现咳嗽、呼吸困难，5例患者出现发热。诊断PCP时治疗药疹的激素剂量均≥泼尼松当量15mg/d。确诊PCP依靠诱导痰或支气管肺泡灌洗液（bronchoalveolar lavage fluid, BALF）中肺孢子菌DNA阳性。10例患者中9例抗PCP治疗后好转，1例病情恶化后死亡。

4. 单因素分析显示，相较于无继发PCP的DIHS患者，DIHS继发PCP患者泼尼松当量＞20mg/d应用时间更长，外周淋巴细胞计数、CD4+T淋巴细胞计数、白蛋白水平更低，病程中易出现DIHS复发、CMV再激活 (P＜0.05)。

结论

1. DIHS患者继发PCP的诊断应结合临床表现、病原学及影像学改变来综合考虑，早期诊断尤为重要。

2. 泼尼松当量超过20mg/d应用时间长、DIHS复发、CMV再激活、外周淋巴细胞减少、CD4+T淋巴细胞减少、白蛋白减低是DIHS继发PCP的可能危险因素。

3. 对于存在≥3个发生PCP可能危险因素的DIHS患者，预防的获益可能超过DIHS复发加重的风险。

Objective To investigate the clinical characteristics and risk factors of patients with drug-induced hypersensitivity syndrome (DIHS) who subsequently developed pneumocystis pneumonia (PCP). Methods A retrospective analysis was conducted on 10 patients with DIHS developing PCP diagnosed and treated at Peking Union Medical College Hospital from January 2019 to April 2025. Clinical presentations, laboratory findings, treatment regimens, and outcomes were reviewed. A 1:2 matched design was employed, matching patients by gender, age (±3 years), and severity of illness. Twenty control patients with DIHS who did not develop PCP during the same period were selected for comparison. Univariate analysis was used to assess differences between the two groups regarding time to tapering corticosteroids to a prednisone equivalent of 20 milligrams per day (mg/d), cytomegalovirus (CMV) reactivation, DIHS recurrence, serum albumin levels, peripheral lymphocyte counts, and CD4+ T lymphocyte counts. Results 1. A total of 10 patients with DIHS developing PCP were included, comprising 7 males and 3 females, with a mean age of 60.1 ± 22.0 years. Hyperuricemia was the most common comorbidity (7 cases). 2. All 10 patients were diagnosed with DIHS of severe severity, most commonly triggered by allopurinol (6 cases). Erythroderma-like rash was the most frequent cutaneous manifestation (7 cases), and liver involvement was the most common organ manifestation (7 cases). All patients received high-dose glucocorticoids for DIHS, and 9 patients also received intravenous immunoglobulin (IVIG), immunosuppressants, biologics, or Janus kinase (JAK) inhibitors. All 10 patients experienced DIHS relapse during glucocorticoid tapering, and 8 patients developed viral reactivation, most commonly CMV. 3. All 10 patients with PCP presented with cough and dyspnea, and 5 patients had fever. At the time of PCP diagnosis, all patients were taking glucocorticoids at doses ≥ the equivalent of 15 mg of prednisone per day. PCP diagnosis was confirmed by detection of Pneumocystis jirovecii DNA in induced sputum or bronchoalveolar lavage fluid (BALF). Nine patients improved after anti-PCP treatment, while one patient deteriorated and died. 4. Univariate analysis revealed that, compared to DIHS patients without PCP, DIHS patients with PCP received a longer duration of prednisone equivalent > 20mg/d, lower peripheral lymphocyte counts, CD4+ T lymphocyte counts, and albumin levels. Additionally, there was a higher frequency of DIHS recurrence and CMV reactivation during illness (P < 0.05). Conclusions 1. The diagnosis of PCP secondary to DIHS should be comprehensively considered in conjunction with clinical manifestations, pathogen, and imaging findings, with early diagnosis being particularly crucial. 2. The duration of prednisone equivalent exceeding 20mg/d for a long time, decreased peripheral lymphocytes, decreased CD4+ T lymphocytes, DIHS recurrence, CMV reactivation, and reduced albumin levels are possible risk factors for concurrent PCP in DIHS patients. 3. For DIHS patients with ≥3 possible risk factors for PCP occurrence, the benefit of prevention may outweigh the risk of exacerbating DIHS.