Invasive pulmonary aspergillosis in children: clinical analysis of nine patients

doi:10.3877/cma.j.issn.1673-5250.2017.01.016

Objective

To investigate the diagnosis and treatment of invasive pulmonary aspergillosis (IPA) in children.

Methods

From January 2004 to July 2016, nine children with proven IPA or possible IPA in West China Second University Hospital, Sichuan University were included into this study. The risk factors, clinical manifestations, chest radiographic findings, microbiological and pathological evidence, treatment and prognosis were retrospectively reviewed in nine patients.

Results

Among nine patients (four boys, five girls), four cases were proven IPA, and five cases were possible IPA.The risk factors were found in seven cases. Pulmonary tuberculosis coexisted in three cases. Cough, fever, moist rales were the most common manifestations, and only two cases had hemoptysis. The most common chest imaging was nodules and patchy shadow. Halo sign was found in three cases, and air crescent sign was not found. Blood culture was negative in all nine patients. The positive children of sputum and bronchoalveolar lavage fluid (BALF) culture were two cases and four cases, respectively. Lung biopsy was conducted in three cases. Eight cases were treated with anti-fungal therapy (voriconazole, itraconazole, micafungin used alone), and only one case was treated with combination therapy (voriconazole and liposomal amphotericin B). Seven cases recovered, and two cases are still receiving treatment.

Conclusions

The clinical manifestations and chest imaging of IPA are nonspecific. Repeated sputum and BALF culture are essential to clinical diagnosis of IPA. The patients in whom the antifungal therapy are initiated early have a good outcome.

Key words: Invasive pulmonary aspergillosis, Diagnosis, Treatment, Child

表1 9例IPA患儿主要临床特征

患儿编号	年龄	宿主高危因素	发热情况	有无气促	肺部有无湿啰音	是否合并肺结核	影像学表现	G实验	GM实验	痰涂片结果	痰培养结果	BALF涂片结果	BALF培养结果	病理检查结果
1	12岁	AML(M_2a型) 、中性粒细胞减少症	高热	有	无	是	结节影、斑片影、空洞、团块影	－	/	＋	－	－	－	咯出物可见曲霉
2	6个月	面部血管瘤、支气管肺炎、中性粒细胞减少症	高热	有	有	无	斑片影、磨玻璃影、条索影、胸膜增厚	－	/	－	＋	－	－	/
3	5个月	先天性食道闭锁合并食管-气管瘘	低热	有	有	无	斑片影、空洞、网格影、条索影、胸膜增厚	＋	/	－	－	－	＋	/
4	11个月	无	高热	有	有	无	实变影、斑片影、磨玻璃影、条索影胸膜增厚、胸腔积液	－	＋	－	－	－	＋	/
5	1岁	重症支气管肺炎及中毒性脑病接受甲基泼尼松龙治疗	高热	无	有	无	结节影、实变影、斑片影、纵隔气肿	＋	/	－	＋	－	－	/
6	9岁	粟粒性肺结核	低热	无	有	是	结节影、空洞、粟粒影、肺门淋巴结大、胸膜增厚	－	－	－	－	＋	＋	经纤维支气管镜下活组织检查(＋)
7	3岁	无	高热	无	有	无	结节影、晕轮征、磨玻璃影、斑片影、胸膜增厚	－	/	－	－	－	－	经纤维支气管镜下活组织检查(＋)
8	8岁	左腹股沟淋巴管瘤、接受西罗莫司治疗	低热	无	有	是	结节影、团块影、厚壁脓肿、晕轮征、实变影、胸膜增厚	＋	/	－	－	－	－	开胸肺活组织检查(＋)
9	12岁	X-连锁无丙种球蛋白血症	高热	无	有	无	结节影、斑片影、小树芽征、条索影、支气管扩张、网格影、马赛克征、实变影、晕轮征、胸膜增厚、胸腔积液	－	/	－	－	－	＋	/

表1 9例IPA患儿主要临床特征

患儿编号	年龄	宿主高危因素	发热情况	有无气促	肺部有无湿啰音	是否合并肺结核	影像学表现	G实验	GM实验	痰涂片结果	痰培养结果	BALF涂片结果	BALF培养结果	病理检查结果
1	12岁	AML(M_2a型) 、中性粒细胞减少症	高热	有	无	是	结节影、斑片影、空洞、团块影	－	/	＋	－	－	－	咯出物可见曲霉
2	6个月	面部血管瘤、支气管肺炎、中性粒细胞减少症	高热	有	有	无	斑片影、磨玻璃影、条索影、胸膜增厚	－	/	－	＋	－	－	/
3	5个月	先天性食道闭锁合并食管-气管瘘	低热	有	有	无	斑片影、空洞、网格影、条索影、胸膜增厚	＋	/	－	－	－	＋	/
4	11个月	无	高热	有	有	无	实变影、斑片影、磨玻璃影、条索影胸膜增厚、胸腔积液	－	＋	－	－	－	＋	/
5	1岁	重症支气管肺炎及中毒性脑病接受甲基泼尼松龙治疗	高热	无	有	无	结节影、实变影、斑片影、纵隔气肿	＋	/	－	＋	－	－	/
6	9岁	粟粒性肺结核	低热	无	有	是	结节影、空洞、粟粒影、肺门淋巴结大、胸膜增厚	－	－	－	－	＋	＋	经纤维支气管镜下活组织检查(＋)
7	3岁	无	高热	无	有	无	结节影、晕轮征、磨玻璃影、斑片影、胸膜增厚	－	/	－	－	－	－	经纤维支气管镜下活组织检查(＋)
8	8岁	左腹股沟淋巴管瘤、接受西罗莫司治疗	低热	无	有	是	结节影、团块影、厚壁脓肿、晕轮征、实变影、胸膜增厚	＋	/	－	－	－	－	开胸肺活组织检查(＋)
9	12岁	X-连锁无丙种球蛋白血症	高热	无	有	无	结节影、斑片影、小树芽征、条索影、支气管扩张、网格影、马赛克征、实变影、晕轮征、胸膜增厚、胸腔积液	－	/	－	－	－	＋	/

[1]	Meersseman W, Vandecasteele SJ, Wilmer A, et al. Invasive aspergillosis in critically ill patients without malignancy[J]. Am J Respir Crit Care Med, 2004, 170(6): 621-625.
[2]	Koehler P, Cornely OA. Contemporary strategies in the prevention and management of fungal infections[J]. Infect Dis Clin North Am, 2016, 30(1): 265-275.
[3]	中华医学会儿科学分会呼吸学组，《中华儿科杂志》编辑委员会. 儿童侵袭性肺部真菌感染诊治指南(2009版)[J]. 中华儿科杂志,2009, 47(2): 96-98.
[4]	Trof RJ, Beishuizen A, Debets-Ossenkopp YJ, et al. Management of invasive pulmonary aspergillosis in non-neutropenic critically ill patients[J]. Intensive Care Med, 2007, 33(10): 1694-1703.
[5]	Kosmidis C, Denning DW. The clinical spectrum of pulmonary aspergillosis[J]. Thorax, 2015, 70(3): 270-277.
[6]	Horger M, Hebart H, Einsele H, et al. Initial CT manifestations of invasive pulmonary aspergillosis in 45 non-HIV immunocompromised patients: association with patient outcome[J]. Eur J Radiol, 2005, 55(3): 437-444.
[7]	Kim MJ, Lee KS, Kim J, et al. Crescent sign in invasive pulmonary aspergillosis: frequency and related CT and clinical factors[J]. J Comput Assist Tomogr, 2001, 25(2): 305-310.
[8]	中华医学会呼吸病学分会感染学组，中华结核和呼吸杂志编辑委员会. 肺真菌病诊断和治疗专家共识[J]. 中华结核和呼吸杂志，2007，30(11): 821-834.
[9]	Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America[J]. Clin Infect Dis, 2008, 46(3): 327-360.
[10]	Ruhnke M, Böhme A, Buchheidt D, et al. Diagnosis of invasive fungal infections in hematology and oncology: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)[J]. Ann Hematol, 2003, 82(Suppl 2): S141-S148.
[11]	Cadena J, Thompson GR, Patterson TF. Invasive aspergillosis: current strategies for diagnosis and management[J]. Infect Dis Clin North Am, 2016, 30(1): 125-142.
[12]	Limper AH, Knox KS, Sarosi GA, et al. An official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients[J]. Am J Respir Crit Care Med, 2011, 183(1): 96-128.
[13]	Liss B, Vehreschild JJ, Bangard C, et al. Our 2015 approach to invasive pulmonary aspergillosis[J]. Mycoses, 2015, 58(6): 375-382.
[14]	Steinbach WJ. Invasive aspergillosis in pediatric patients[J]. Curr Med Res Opin，2010, 26(7)：1779-1787.

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