病理确诊药物诱导的肺嗜酸细胞增多症1例并文献复习
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摘要
目的探讨药物诱导的肺嗜酸细胞增多症的临床特点、免疫机制、常见诱导药物等,以提高临床对药物诱导的肺嗜酸细胞增多症的认识。方法对北京医院2018年7月收治的1例由重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白诱导的肺嗜酸细胞增多症患者的临床表现、实验室检查、影像学特征及治疗方案等临床资料进行分析,同时复习药物诱导的肺嗜酸细胞增多症的相关文献。结果患者男,19岁,患强直性脊柱炎,经重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白等药物治疗后出现发热、咳嗽、外周血嗜酸细胞升高、双肺胸膜下多发斑片影,抗感染治疗无效,肺组织活检提示嗜酸细胞性肺炎,停用可疑药物,未予特殊治疗,上述临床表现逐渐好转,最终诊断为药物诱导的肺嗜酸细胞增多症。药物诱导的肺嗜酸细胞增多症需基于明确用药史,排除感染、放射性肺炎等疾病,符合嗜酸细胞性肺炎诊断条件方可诊断。嗜酸细胞参与的免疫反应可能存在Ⅰ型速发型变态反应和Ⅳb型迟发型变态反应的叠加效应,使发病迅速而病程延迟,不同于特发性急性嗜酸细胞性肺炎和慢性嗜酸细胞性肺炎。肿瘤坏死因子拮抗剂可引起药物诱导的肺嗜酸细胞增多症。结论药物诱导的肺嗜酸细胞增多症既属于肺嗜酸细胞增多症的特殊类型,又属于药物诱导肺疾病的范畴,诊断与鉴别诊断需详细、全面,药物诱导肺疾病值得临床进一步关注及探讨。
Objective To explore the clinical characteristics, immunologic mechanism and common culprit medications of drug-induced pulmonary eosinophilia. To improve the clinical understanding of drug-induced pulmonary eosinophilia. Method The clinical manifestations, laboratory examination, imaging features, treatment and pharmacogenomics of a patient with drug-induced pulmonary eosinophilia by etanercept was analyzed and the literatures were reviewed.Result A young male patient with new onset ankylosing spondylitis, was prescibed with recombinant human tumor necrosis factor receptor-antibody fusion protein and some other drugs, gradually developing fever, cough, elevated peripheral blood eosinophils, multiple subpleural opacities in bilateral lungs and no response to antimicrobial therapy. Eosinophilic pneumonia was characterized pathologically through lung biopsy. His clinical manifestations gradually improved by drug withdrawal and without any other therapy. Drug-induced pulmonary eosinophilia was finally diagnosed. Drug-induced pulmonary eosinophilia can only be diagnosed by identifying the medical history, excluding infectious pneumonia, radiation pneumonitis and other diseases, and meeting the diagnostic criteria of pulmonary eosinophilia.Immune responses involved in pulmonary eosinophilia,type I rapid allergy and type Ⅳb delayed allergy, might overlap and lead to a rapid onset of pulmonary eosinophilia and a prolonged course of disease, different from either idiopathic acute eosinophilic pneumonia or chronic eosinophilic pneumonia.Drug-induced pulmonary eosinophilia can be caused by TNF antagonists such as etanercept. Conclusion Drug-induced pulmonary eosinophilia, a subtype of pulmonary eosinophilia, also could be considered a special form of drug-induced lung disease. The diagnosis and differential diagnosis of drug-induced lung disease are worthy to be taken more concerns in the future.
Objective To explore the clinical characteristics, immunologic mechanism and common culprit medications of drug-induced pulmonary eosinophilia. To improve the clinical understanding of drug-induced pulmonary eosinophilia. Method The clinical manifestations, laboratory examination, imaging features, treatment and pharmacogenomics of a patient with drug-induced pulmonary eosinophilia by etanercept was analyzed and the literatures were reviewed.Result A young male patient with new onset ankylosing spondylitis, was prescibed with recombinant human tumor necrosis factor receptor-antibody fusion protein and some other drugs, gradually developing fever, cough, elevated peripheral blood eosinophils, multiple subpleural opacities in bilateral lungs and no response to antimicrobial therapy. Eosinophilic pneumonia was characterized pathologically through lung biopsy. His clinical manifestations gradually improved by drug withdrawal and without any other therapy. Drug-induced pulmonary eosinophilia was finally diagnosed. Drug-induced pulmonary eosinophilia can only be diagnosed by identifying the medical history, excluding infectious pneumonia, radiation pneumonitis and other diseases, and meeting the diagnostic criteria of pulmonary eosinophilia.Immune responses involved in pulmonary eosinophilia,type I rapid allergy and type Ⅳb delayed allergy, might overlap and lead to a rapid onset of pulmonary eosinophilia and a prolonged course of disease, different from either idiopathic acute eosinophilic pneumonia or chronic eosinophilic pneumonia.Drug-induced pulmonary eosinophilia can be caused by TNF antagonists such as etanercept. Conclusion Drug-induced pulmonary eosinophilia, a subtype of pulmonary eosinophilia, also could be considered a special form of drug-induced lung disease. The diagnosis and differential diagnosis of drug-induced lung disease are worthy to be taken more concerns in the future.
引文
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[8]Posadas SJ,Pichler WJ.Delayed drug hypersensitivity reactionsnew concepts[J].Clin Exp Allergy,2007,37(7):989-999.
[9]Yun J,Cai F,Lee FJ,et al.T-cell-mediated drug hypersensitivity:immune mechanisms and their clinical relevance[J].Asia Pac Allergy,2016,6(2):77-89.
[10]Cacoub P,Musette P,Descamps V,et al.The DRESS syndrome:a literature review[J].Am J Med,2011,124(7):588-597.
[11]Kim PW,Sorbello AF,Wassel RT,et al.Eosinophilic pneumonia in patients treated with daptomycin:review of the literature and USFDA adverse event reporting system reports[J].Drug Saf,2012,35(6):447-457.
[12]Haroon M,Daly M,Harney S.Re-challenge with Etanercept in patients with Etanercept-induced Neutropenia[J].Clin Rheumatol,2012,31(1):151-155.
[13]Miyagi R,Ideguchi H,Soga T,et al.Development of pulmonary and cardiac sarcoidosis during etanercept therapy[J].Int J Rheum Dis,2014,17(7):810-812.
[14]Tallon K,Cockcroft D.Adalimumab drug induced pulmonary infiltrates and eosinophilia[J].Can J Respir Crit Care Sleep Med,2018:1-4.
[2]Bernheim A,McLoud T.A review of clinical and imaging findings in eosinophilic lung diseases[J].AJR Am J Roentgenol,2017,208(5):1002-1010.
[3]Akuthota P,Weller PF.Tosinophilic pneumonias[J].Clin Microbiol Rev,2012,25(4):649-660.
[4]Johkoh T,Müller NL,Akira M,et al.Eosinophilic lung diseases:diagnostic accuracy of thin-section CT in 111 patients[J].Radiology,2000,216(3):773-780.
[5]Jederlinic PJ,Sicilian L,Gaensler EA.Chronic eosinophilic pneumonia.A report of 19 cases and a review of the literature[J].Medicine,1988,67(3):154-162.
[6]Rhee CK,Min KH,Yim NY,et al.Clinical characteristics and corticosteroid treatment of acute eosinophilic pneumonia[J].Eur Respir J,2013,41(2):402-409.
[7]Philit F,Etienne-Mastro?anni B,Parrot A,et al.Idiopathic acute eosinophilic pneumonia:a study of 22 patients[J].Am J Respir Crit Care Med,2002,166(9):1235-1239.
[8]Posadas SJ,Pichler WJ.Delayed drug hypersensitivity reactionsnew concepts[J].Clin Exp Allergy,2007,37(7):989-999.
[9]Yun J,Cai F,Lee FJ,et al.T-cell-mediated drug hypersensitivity:immune mechanisms and their clinical relevance[J].Asia Pac Allergy,2016,6(2):77-89.
[10]Cacoub P,Musette P,Descamps V,et al.The DRESS syndrome:a literature review[J].Am J Med,2011,124(7):588-597.
[11]Kim PW,Sorbello AF,Wassel RT,et al.Eosinophilic pneumonia in patients treated with daptomycin:review of the literature and USFDA adverse event reporting system reports[J].Drug Saf,2012,35(6):447-457.
[12]Haroon M,Daly M,Harney S.Re-challenge with Etanercept in patients with Etanercept-induced Neutropenia[J].Clin Rheumatol,2012,31(1):151-155.
[13]Miyagi R,Ideguchi H,Soga T,et al.Development of pulmonary and cardiac sarcoidosis during etanercept therapy[J].Int J Rheum Dis,2014,17(7):810-812.
[14]Tallon K,Cockcroft D.Adalimumab drug induced pulmonary infiltrates and eosinophilia[J].Can J Respir Crit Care Sleep Med,2018:1-4.