慢性肉芽肿病48例临床分析

Clinical features of chronic granulomatous disease

目的探讨48例慢性肉芽肿病（CGD）临床特点。方法对于2004年1月至2011年6月在复旦大学附属儿科医院诊断的48例CGD患儿临床表现、实验室检查、治疗及预后进行总结分析。结果通过二氢若丹明分析以明确诊断。48例CGD，男43例，女5例。皆在出生后6个月以内起病；平均诊断年龄2．42岁（1个月-10岁），其中0-6个月12例，-12个月10例，-2岁9例，-3岁5例，-5岁4例，-10岁8例；CGD临床主要累及呼吸系统及消化系统，表现为反复呼吸道感染91．67％（44／48）及反复慢性腹泻64．58％（31／48）；其他伴有皮肤损害表现者45．83％（22／48）；尿路感染6．25％（3／48）。另有64．58％（31／48）患儿病程中出现淋巴结肿大，其中19例考虑与卡介苗接种相关。感染病原方面主要包括分枝杆菌感染52．08％（25／48），真菌感染43．75％（21／48）。明确基因诊断者37例（其中CYBB31例、CYBA1例、NCF12例、NCF23例）。预防和治疗主要采用人重组γ-干扰素联合磺胺甲基异嗯唑以及针对性抗感染治疗，细菌和真菌感染频率及严重程度有所减轻。结论本组患儿发病年龄及诊断较早，临床表现为反复分枝杆菌、真菌及化脓菌感染，主要累及呼吸道、消化道、皮肤及淋巴结。人重组γ-干扰素治疗和预防可部分改善预后。

Objective Chronic granulomatous disease （CGD） is a rare primary immunodeficiency of phagocytic oxidative bursts leading to recurrent severe bacterial and fungal infections as well as granuloma formation. There were few reports on the clinical characteristics of this disease in China. The purpose of this study was to evaluate the clinical features of 48 Chinese cases with CGD which were confirmed by clinical features, dihydrorhodamine （DHR） assay and gene mutation analysis. Method The study cohort was the population of CGD patients diagnosed in Children＇s Hospital of Fudan University from January, 2004, to June, 2011. Cases included in our analysis were restricted to those who had complete data of the clinical symptoms and laboratory tests. The patients were followed up by outpatient visiting and telephone call regularly for O. 5 to 6 years. The history and data of physical examination and treatment of 48 cases were collected and reviewed. Result All the patients were diagnosed by DHR analysis. The age of onset of all the 48 patients were less than 6 months, including 43 male and 5 female. The mean age at diagnosis was 2.42 years; 12 patients were infants under six months, 10 were between 6 and 12 months, 9 were between 1 and 2 years, 5 patients were between 2 and 3 years, 4 were between 4 and 5 years, and 8 were between 6 and 10 years. Recurrent respiratory infection （44/48） and chronic diarrhea （31/48） were the common symptoms in all the patients, and then skin lesion （22/48）, including marked reaction at BCG infected site, pustular eruption and infected skin ulcer and urinary tract infection（3/48）were also general symptoms in our study. In addition, lymphadenectasis occurred in 31 cases and 23 of them were considered to be associated with BCG vaccination. The pathogens caused the infection were mycobacteria （52. 08% ）, fungi （43.75%） and pyogenic bacteria. Thirty-seven patients had mutations in CYBB/CYBA/NCF1/NCF2 genes. Recombinant human interferon-gamma （rhIFN-γ） plus sulfamethoxazole were used for the prevention and treatment of infection, the frequency and severity of the disease could be reduced. Conclusion The age at onset and diagnosis of the present group of CGD was younger. Clinical symptoms were associated with recurrent mycobacterial, fungal and pyogenic bacterial infection, which involved respiratory tract, alimentarytract, skin and lymph node. rhIFN-~ partially improved the prognosis of CGD.