阿达木单抗治疗Blau综合征1家系3例

Adalimumab for the treatment of three cases of Blau syndrome in a pedigree

先证者男,1岁9个月,周身丘疹1年半,面部、躯干及四肢密集分布米粒大小红色扁平光滑丘疹。无发热或关节肿痛。先证者姐姐,7岁,2岁时出现双手指关节肿痛,间断发热时周身出现丘疹,热退后丘疹可逐步消退。先证者母亲,27岁,幼时出现双手指关节肿痛,逐渐出现双手指关节畸形,12岁后间断出现膝关节肿痛,周身未出现明显皮疹。3例患者眼科及系统查体无异常。全外显子基因检测显示,先证者、其姐姐与母亲在NOD2基因第4号外显子存在一杂合错义变异c.1001G>A(p.R334Q)。诊断:Blau综合征。治疗:先证者全身外用润肤乳,随访52周,未出现关节肿痛及眼部症状,面部、躯干及四肢可见红斑及凹陷性瘢痕。先证者姐姐及母亲分别给予阿达木单抗40 mg、80 mg皮下注射,1周后分别注射20 mg、40 mg,之后每2周分别注射20 mg、40 mg。治疗12周随访,先证者姐姐及母亲关节肿痛较前明显减轻,先证者姐姐皮疹基本消退。随访至52周,先证者姐姐无关节肿痛及皮疹,先证者母亲膝关节无肿痛,双手指关节畸形无改变。先证者姐姐及母亲在治疗中未出现眼部症状且未见不良反应发生。

A 1-year and 9-month-old male proband presented with clustered rice-grain-sized flat smooth red papules distributed on the face,trunk and limbs for 1.5 years,without fever,joint swelling,or pain.The proband′s sister aged 7 years ever experienced swelling and pain in the finger joints of both hands at the age of 2 years,and had intermittent fever and papules all over the body at the same time,and the papules gradually regressed with the subsidence of fever.The proband′s mother aged 27 years suffered from swelling and pain in the finger joints of both hands when she was young,gradually leading to finger deformities,and developed intermittent knee swelling and pain at the age of 12 years without obvious skin lesions all over the body.No abnormality was found in ophthalmological and systemic physical examinations of the 3 patients.Whole-exome sequencing showed the proband,his sister and mother all had a heterozygous missense mutation c.1001G>A(p.R334Q)in exon 4 of the NOD2 gene.A diagnosis of Blau syndrome was made.The proband was treated with topical moisturizing cream all over the body;during the 52-week follow-up,no joint swelling and pain or eye symptoms were found in the proband,while erythema and depressed scars were observed on the face,trunk and limbs.The proband′s sister and mother were treated with subcutaneous injections of adalimumab at initial doses of 40 mg and 80 mg respectively,followed 1 week later by injections at 20 mg and 40 mg respectively,and then treated with injections at 20 mg and 40 mg respectively every 2 weeks;after 12-week treatment,the joint swelling and pain were markedly relieved in the proband′s sister and mother,and most skin lesions subsided in the proband′s sister;at week 52 during the follow-up,no joint swelling and pain or skin lesions were observed in the proband′s sister,and there was no swelling or pain in the knee joints of the proband′s mother,while no improvement was observed in her finger deformities.During the treatment,no eye symptoms or adverse reactions were observed neither in the proband′s sister nor in his mother.