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[21例非血液系统疾病儿童侵袭性肺曲霉病的诊断与治疗]

[Diagnosis and treatment of invasive pulmonary aspergillosis in 21 children with non-hematologic diseases].

作者信息

Zhang Xiao-yan, Zhao Shun-ying, Qian Su-yun, Hu Ying-hui, Zeng Jin-jin, Jiang Zai-fang

机构信息

Department of Pediatric Internal Medicine, Beijing Children's Hospital Affiliated to the Capital Medical University, Beijing 100045, China.

出版信息

Zhonghua Er Ke Za Zhi. 2009 Oct;47(10):730-4.

PMID:20021805
Abstract

OBJECTIVE

To explore diagnosis and treatments of invasive pulmonary aspergillosis (IPA) in children with non-hematologic diseases.

METHOD

Twenty one patients without hematological malignancy were diagnosed with proven or possible IPA from July 2002 to June 2008. The risk factors, clinical manifestations, chest radiographic findings, microbiological and histopathological evidence, diagnostic procedures, treatment and prognosis were retrospectively reviewed.

RESULT

Five children had proven IPA, and 16 patients had possible IPA. Thirteen children were classified as having acute invasive pulmonary aspergillosis (AIPA), eight children as having chronic necrotizing pulmonary aspergillosis (CNPA). Definitive diagnosis of primary immunodeficiency (PID) was made in 6 children (4 with chronic granulomatous disease, 2 with cellular immunodeficiency); three children were suspected of having PID. Corticosteroids and multiple broad-spectrum antibiotics had been administered in 5 patients (3 of these 5 patients also had invasive mechanical ventilation). Two children had underlying pulmonary disease. Three patients had unknown risk factors. Among these three patients, two had history of environmental exposure. Fever and cough were present in all the children. Fine rales were found in nineteen children. Six children had hepatosplenomegaly. The common roentgenographic feature of AIPA in 13 patients was nodular or mass-like consolidation with multiple cavity. "air-crescent" was seen in 10 of patients with AIPA. Lobar consolidation with cavity and adjacent pleural thickening was found in all children with CNPA. The positive rate of sputum and/or BALF culture in AIPA and CNPA were 72.1% and 22.4%, respectively. A large number of septate hyphae on wet smear were found in all of the children whose sputum and/or BALF culture were positive. Lung biopsy was performed in 3 children with CNPA, and necrosis, granulomatous inflammation, as well as septate, branching hyphae were observed on histopathologic examination. Fifteen children were treated with anti-fungal therapy (amphotericin B, voriconazole, itraconazole and caspofungin used alone or in combination), symptoms and lung lesions resolved in 12 children. Three children died. Six children did not receive anti-fungal therapy and died. The side effects of amphotericin B include chill, fever, hypokalemia and transient increase in BUN, none of which needed discontinuation of the antifungal therapy. Children had a good tolerance to fluconazole and caspofungin, there were no apparent side effects.

CONCLUSION

Most of the children without hematologic diseases who suffered from invasive pulmonary aspergillosis had risk factors or exposure history. Roentgenographic findings were relatively characteristic for invasive pulmonary aspergillosis. Risk factors and roentgenographic findings were clues to consider clinically invasive pulmonary aspergillosis. Sputum culture was the key point to clinical diagnosis. The patients in whom the antifungal therapy was initiated early had a good outcome.

摘要

目的

探讨非血液系统疾病患儿侵袭性肺曲霉病(IPA)的诊断与治疗。

方法

回顾性分析2002年7月至2008年6月期间21例非血液系统恶性肿瘤患儿确诊或疑似为IPA的病例。对其危险因素、临床表现、胸部X线表现、微生物学和组织病理学证据、诊断方法、治疗及预后进行回顾性分析。

结果

5例患儿确诊为IPA,16例为疑似IPA。13例患儿被归类为急性侵袭性肺曲霉病(AIPA),8例为慢性坏死性肺曲霉病(CNPA)。6例患儿确诊为原发性免疫缺陷病(PID)(4例为慢性肉芽肿病,2例为细胞免疫缺陷);3例患儿疑似患有PID。5例患儿曾使用糖皮质激素和多种广谱抗生素(其中3例同时接受有创机械通气)。2例患儿有基础肺部疾病。3例患儿危险因素不明,其中2例有环境暴露史。所有患儿均有发热和咳嗽症状。19例患儿可闻及细湿啰音。6例患儿有肝脾肿大。13例AIPA患儿胸部X线常见表现为结节状或肿块样实变伴多发空洞,10例AIPA患儿可见“空气新月征”。所有CNPA患儿均有肺叶实变伴空洞及邻近胸膜增厚。AIPA和CNPA患儿痰和/或支气管肺泡灌洗(BALF)培养阳性率分别为72.1%和22.4%。痰和/或BALF培养阳性的患儿湿片镜检均可见大量分隔菌丝。3例CNPA患儿接受了肺活检,组织病理学检查可见坏死、肉芽肿性炎症以及分隔、分支的菌丝。15例患儿接受了抗真菌治疗(单独或联合使用两性霉素B、伏立康唑、伊曲康唑和卡泊芬净),12例患儿症状及肺部病变缓解。3例患儿死亡。6例未接受抗真菌治疗的患儿死亡。两性霉素B的副作用包括寒战、发热、低钾血症及血尿素氮短暂升高,但均无需停用抗真菌治疗。患儿对氟康唑和卡泊芬净耐受性良好,无明显副作用。

结论

大多数非血液系统疾病患儿发生侵袭性肺曲霉病有危险因素或暴露史。胸部X线表现对侵袭性肺曲霉病具有相对特征性。危险因素及胸部X线表现是临床考虑侵袭性肺曲霉病的线索。痰培养是临床诊断的关键。早期开始抗真菌治疗的患儿预后良好。

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