Misra Srimanta Chandra, Gabriel Laurence, Nacoulma Eric, Dine Gérard, Guarino Valentina
Department of Hematology Biology Clinic, Hôpital des Hauts Clos, 101 Avenue Anatole France, 10000, Troyes, France.
Central Pharmacy, Hôpital des Hauts Clos, 101 Avenue Anatole France, 10000, Troyes, France.
Drug Saf Case Rep. 2017 Dec;4(1):4. doi: 10.1007/s40800-017-0047-y.
Interstitial pneumonitis is a classical complication of many drugs. Pulmonary toxicity due to 5-azacytidine, a deoxyribonucleic acid methyltransferase inhibitor and cytotoxic drug, has rarely been reported. We report a 67-year-old female myelodysplastic syndrome patient treated with 5-azacytidine at the conventional dosage of 75 mg/m for 7 days. One week after starting she developed moderate fever along with dry cough and subsequently her temperature rose to 39.5 °C. She was placed under broad-spectrum antibiotics based on the protocol for febrile neutropenia, including ciprofloxacin 750 mg twice daily, ceftazidime 1 g three times daily (tid), and sulfamethoxazole/trimethoprim 400 mg/80 mg tid. High-resolution computed tomography of the chest disclosed diffuse bilateral opacities with ground-glass shadowing and pleural effusion bilaterally. Mediastinal and hilar lymph nodes were moderately enlarged. polymerase chain reaction for Mycobacterium tuberculosis, Pneumocystis jiroveci, and cytomegalovirus were negative. Cultures including viral and fungal were all negative. A diagnosis of drug-induced pneumonitis was considered and, given the negative bronchoalveolar lavage in terms of an infection, corticosteroid therapy was given at a dose of 1 mg/kg body weight. Within 4 weeks, the patient became afebrile and was discharged from hospital. Development of symptoms with respect to drug administration, unexplained fever, negative workup for an infection, and marked response to corticosteroid therapy were found in our case. An explanation could be a delayed type of hypersensitivity (type IV) with activation of CD8 T cell which could possibly explain most of the symptoms. We have developed a decision algorithm in order to anticipate timely diagnosis of 5-azacitidine-induced pneumonitis, and with the aim to limit antibiotics abuse and to set up emergency treatment.
间质性肺炎是许多药物的典型并发症。5-氮杂胞苷是一种脱氧核糖核酸甲基转移酶抑制剂和细胞毒性药物，其引起的肺毒性鲜有报道。我们报告一例67岁女性骨髓增生异常综合征患者，接受常规剂量75mg/m²的5-氮杂胞苷治疗7天。开始治疗一周后，她出现中度发热伴干咳，随后体温升至39.5°C。根据发热性中性粒细胞减少的治疗方案，给予她广谱抗生素治疗，包括每日两次750mg环丙沙星、每日三次1g头孢他啶以及每日三次400mg/80mg磺胺甲恶唑/甲氧苄啶。胸部高分辨率计算机断层扫描显示双侧弥漫性混浊，伴有磨玻璃影和双侧胸腔积液。纵隔和肺门淋巴结中度肿大。结核分枝杆菌、耶氏肺孢子菌和巨细胞病毒的聚合酶链反应均为阴性。包括病毒和真菌培养在内的所有培养结果均为阴性。考虑诊断为药物性肺炎，鉴于支气管肺泡灌洗未发现感染，给予1mg/kg体重的皮质类固醇治疗。4周内，患者退热并出院。在我们的病例中发现了与药物给药相关的症状、不明原因发热、感染检查结果阴性以及对皮质类固醇治疗的显著反应。一种解释可能是CD8 T细胞激活导致的迟发型超敏反应（IV型），这可能解释了大部分症状。我们制定了一种决策算法，以便及时诊断5-氮杂胞苷引起的肺炎，旨在限制抗生素滥用并建立紧急治疗方案。
