厄洛替尼致重度皮疹和致死性间质性肺病一例临床分析

Clinical Analysis of Erlotinib-induced Severe Rash and Fatal Interstitial Lung Disease:A Case Report and Literature Review

目的提高对厄洛替尼引起重度皮疹和致死性间质性肺病(ILD)的认识。方法分析解放军第八一医院收治的1例晚期非小细胞肺癌(NSCLC)患者使用厄洛替尼引起重度皮疹和致死性ILD的临床表现和影像学特点,并复习相关文献报道。结果患者为78岁不吸烟男性,确诊右下肺鳞癌Ⅳ期,表皮生长因子受体(EGFR)基因第21外显子突变。有慢性阻塞性肺疾病伴轻度肺纤维化病史。吉西他滨、顺铂化疗1周期。接受厄洛替尼治疗150 mg/d,第40 d肺癌病灶明显减小,伴重度皮疹。间断靶向治疗100 mg/d 4次及50 mg/d 2次后,出现重度皮疹和致死性ILD。立即停药,并经验性糖皮质激素冲击和序贯治疗,皮疹及ILD基本消退,但肿块较前显著增大。结论警惕发生厄洛替尼相关性重度皮疹和致死性ILD。若NSCLC患者手术切除标本病理示寻常型间质性肺炎证据或临床诊断肺纤维化,不宜接受厄洛替尼靶向治疗,否则易于发生严重的肺毒性。

Objective To improve the knowledge of erlotinib-induced severe rash and fatalinterstitial lung disease （ ILD） .Methods The clinical feature and radiology of erlotinib-associated severerash and fatal ILD were analyzed in one patient with advanced non-small cell lung cancer （ NSCLC） in the81st Hospital of Chinese PLA, and the related literatures were reviewed.Results The patient was a 78-yearoldmale non-smoker with stage Ⅳ right lower lobe squamous cell carcinoma, and his epidermal growth factorreceptor gene showed mutation at exon 21. He had a history of chronic obstructive pulmonary disease andmild pulmonary fibrosis. Following one cycle of chemotherapy with gemcitabine plus cisplatin, he receivederlotinib 150 mg daily. After 40 days of targeting therapy, the size of the lung cancer was decreasedsignificantly concomitant with severe rash. Again, severe rash and fatal ILD appeared after using erlotinib100 mg daily for 4 days and 50 mg daily for 2 days, respectively. The tumor progressed markedly althoughboth rash and ILD were almost abolished following withdrawal of erlotinib as well as empirical impact ofglucocorticoid and sequential therapy.Conclusions Physicians should be alerted to the possibility oferlotinib-induced severe rash and fatal ILD. Those with pathologic findings of usual interstitial pneumonia onresected lung specimens or known pulmonary fibrosis may be at particular risk for erlotinib-related pulmonarytoxicity.