长疗程利妥昔单抗治疗难治性幼年型特发性炎症性肌病3例

特发性炎症性肌病是一组具有临床表现异质性的自身免疫性疾病,以骨骼肌无力和肌肉炎症病变为特征.临床分型包括皮肌炎、多发性肌炎、散发的包涵体肌炎、免疫介导的坏死性肌病和抗合成酶抗体综合征等1-3].在儿童期,皮肌炎为最常见的临床类型,约占80％4].特发性炎症性肌病为临床罕见病,年发病率约为每年每百万人1 ～ 19例5].美国儿童皮肌炎的发病率约为每年每百万人2.5～4.1例6],国内尚未见流行病学资料.特发性炎症性肌病的治疗一直非常具有临床挑战性,尤其是一线治疗药物失败的病例7].近年来,对难治性病例的精准治疗成为特发性炎症性肌病领域的研究重点8].自20世纪初期开始,利妥昔单抗在国外就被尝试用于难治性特发性炎症性肌病的治疗,但关于利妥昔单抗的应用剂量和疗程,目前尚无统一认识9],国内也尚未见相关临床研究报道.本文分享了3例传统药物治疗反应欠佳、经长疗程(2年7个月至3年2个月)利妥昔单抗联合治疗后获得临床缓解的特发性炎症性肌病患者的治疗过程,以期为该疾病的治疗提供参考.本观察研究开始前获北京大学第一医院生物医学研究伦理委员会审查批准(批准号:2021科研263).

Long-term rituximab treatment of refractory idiopathic inflammatory myopathy:A report of 3 cases

Idiopathic inflammatory myopathies are a group of rare but serious diseases. The treatment of refractory idiopathic inflammatory myopathy is always challenging, especially in children. Three cases of refractory idiopathic inflammatory myopathy treated by rituximab were reported and discussed with the review of relevant literature. All were female with on-set age of 8 years and 6 months, 11 years and 7 months, 4 years and 2 months old, respectively. All had acute onset, presenting with progressive and severe muscle weakness. All lost ambulation within 1 or 2 months, with difficult swallowing and low voice. Respiratory distress occurred in case 2 after an attack of asphyxia due to an aspiration of sputum, and ventilator support was required for 1 month. Rashes were detected at the initial stage of the disease in cases 2 and 3. Patient 2 showed facial erythematous papules, spreading to her neck and hands. Patient 3 showed purplish eyelids with peri-orbital swelling, generalized edema involving all her limbs. Creatine kinase (CK) levels were markedly elevated in all the patients, ranging from 6 000 IU/L to 28 819 IU/L. Anti-SRP antibody was identified in cases 1, and anti-NXP2 antibodies were confirmed in cases 2 and 3. MRI of both thighs in all the patients showed profound muscle and fascial edema. Muscle pathology of patient 1 showed prominent fiber variation and endomysial fibrosis, with overexpression of MHC-Ⅰ. While muscle pathology in patients 2 and 3 showed scattered fiber necrosis, regeneration, endomysial edema without inflammatory cell infiltration. All the patients were diagnosed with idiopathic inflammatory myopathy and failed to the initial treatment including adequate glucocorticoids and high-dose immunoglobulin therapy. Other immunosuppressants (methotrexate, cyclophosphamide) were also tried in cases 2 and 3 with poor response. Then all the patients were treated with rituximab combined with glucocorticoids. Patient 1 regained normal strength and discontinued rituximab at the end of her last follow-up (2 years and 7 mouths). Though calcinosis developed during the follow-up period, significant improvement was noticed in cases 2 and 3 (both regained the ability to walk independently) at the end of their last follow-up after 2 years and 8 months, 3 years and 2 months respectively. Long-term rituximab therapy may improve the prognosis of refractory idiopathic inflammatory myopathy, especially with positive anti-SRP and anti-NXP2 antibodies.