干扰素-γ受体1缺陷病一例并文献复习

Interferon-gamma receptor 1 deficiency in a 19-month-old child： case report and literature review

目的 总结干扰素-γ受体1（IFN-γR1）缺陷病的临床特点和诊治过程.方法 报道南京医科大学附属南京儿童医院确诊的1例IFN-γR1缺陷病患儿的临床资料并进行文献复习.结果 患儿女,19个月,于生后18个月接种卡介苗,1～2周后全身出现皮疹,近1个月来皮疹退而复现,反复发作.查体可触及右腋下一肿块,大小3 cm×3 cm,突出皮面,质韧,活动度差.胸部B超示右腋下不均质低回声包块;腹部B超示胰头及腹主动脉周围淋巴结轻度肿大;胸X线片示右侧腋下淋巴结肿大,双肺纹理增多.初步诊断为（1）支气管炎;（2）卡介苗接种反应;（3）败血症？.入院后分别给予利福平＋异烟肼抗结核治疗,并先后给予拉氧头孢、阿莫西林克拉维酸钾、美罗培南、夫西地酸、丙种球蛋白和甲泼尼龙等抗感染、抗炎治疗后体温降至正常.出院后继续利福平＋异烟肼抗结核治疗3个月,腋下淋巴结缩小至不可触及,停药后腋下淋巴结反复肿大,卡介苗接种6个月后发生骨结核,髋关节及左膝CT提示：双髋关节积液,左股骨远端及左胫骨近端骨破坏.基因检测发现患儿存在IFN-γR1基因纯合子突变,突变位点为c.114_135del （p.E38fsX54）,其父亲、母亲均为杂合子突变.文献报道的99例IFN-γR1缺陷病,95％的病例均出现播散性结核病,其中卡介苗接种后出现播散性结核病者60例.结论 IFN-γR1缺陷病极其罕见.临床上出现播散性结核感染或局灶性/多灶性骨结核感染,特别是在卡介苗接种后,应考虑IFN-γR1缺陷病可能,并尽早进行基因检测以明确诊断.

Objective To analyze the clinical manifestation of interferon gamma receptor 1 deficiency （IFN-γR1 deficiency） and to improve the recognition of this disease in children,decrease diagnostic errors and missed diagnosis.Method The information of one case with IFN-γR1 deficiency （past history of illness,clinical manifestation,laboratory examination and treatment） were analyzed.Result The patient was a 19-month-old girl with IFN-γR1 deficiency,1-2 weeks after she was vaccinated with BCG at the age of 18 months,she manifested with lymph nodes at the same site as vaccination site,and repeated rash.Examination found a mass in the right armpit,the size was 3 cm × 3 cm,protruded on the skin,tenacious in nature,poorly mobile.B-mode ultrasound showed right armpit chest heterogeneous hypoechoic mass; abdominal B-mode ultrasound showed pancreatic lymph nodes around the abdominal aorta and mild swelling; chest X-ray showed right axillary lymph nodes,increased double markings.Initial diagnosis was （1） bronchitis,（2） BCG vaccination reaction,（3） Sepsis？.After admission,the patient was given rifampicin ＋ isoniazid ＋ latamoxef ＋ amoxicillin and clavulanate potassium,and then changed to meropenem and Fusidic acid,but treatment showed no improvement.After adding the treatment with antiinflammatory treatment,i.e.,gamma globulin and methylprednisolone,the fever subsided.Conventional treatment with rifampicin ＋ isoniazid 3 months after discharge from hospital were effective,and the axillary lymph nodes were not palpable.Six months after BCG vaccination bone tuberculosis occurred.CT of left hip and left knee showed bilateral hip joint effusion,left distal femur and left proximal tibia bone destruction.Gene detection showed the presence of homozygous IFNγ-R1 gene mutation of c.114_135del （p.E38fsX54）.Her parents are consanguinity,both were carriers.In the literature,99 cases with IFN-γR1 deficiency were reported,95％ of the cases had disseminated tuberculosis,and in 60 cases the dissemination occurred after BCG vaccination.Conclusion IFN-γR1 is an extremely rare disease in children.If disseminated tuberculosis infection occured,especially after BCG vaccination,or if there were focal/multifocal bone tuberculosis,immune function with conventional detection is considered normal,then IFN-γR1 deficiency should be considered,and early genetic testing for confirming the diagnosis and selecting the appropriate treatment are needed.