Crayne Courtney B, Eloseily Esraa, Mannion Melissa L, Azerf Saji P, Weiser Peter, Beukelman Timothy, Stoll Matthew L, Feig Daniel I, Prescott Atkinson T, Cron Randy Quentin
Department of Pediatrics, Division of Rheumatology, University of Alabama at Birmingham, 1600 7th Ave S, CPPN G10, Birmingham, AL, 35233, USA.
School of Medicine, University of Alabama at Birmingham, 510 20th St S, #12, Birmingham, AL, 35233, USA.
Pediatr Rheumatol Online J. 2018 Nov 14;16(1):71. doi: 10.1186/s12969-018-0285-2.
Henoch-Schonlein purpura (HSP) is a small vessel vasculitis that is characterized by non-thrombocytopenic purpura, abdominal pain, arthritis, and glomerulonephritis. Typically, HSP is self-limited requiring only supportive care, but more severe cases may require corticosteroid (CS) treatment. Rarely, a subset of these patients has persistent rash, arthritis, abdominal involvement, or renal disease despite treatment with CS, or has disease recurrence on CS tapering. Refractory HSP has been effectively treated with a variety of CS sparing therapies. For life-threatening refractory HSP, the B cell depleting agent, rituximab (RTX), has been reported as beneficial for children with substantial renal or central nervous system involvement. However, RTX use for children with less severe HSP, but chronic CS dependent disease refractory to CS sparing immunomodulatory agents, has been less well explored. Herein, we describe 8 children treated with RTX for chronic refractory HSP and report a reduction in recurrent hospitalizations and eventual CS discontinuation.
This is a retrospective analysis of eight children who were treated with RTX for chronic CS dependent HSP during the years 2006-2014 at a single institution. A chart review of the electronic medical record was performed to determine the presenting symptoms, the type and duration of treatment received, and the number of hospitalizations prior to and after RTX. The number of hospitalizations and oral corticosteroid burden were analyzed using the Wilcoxon signed rank test.
Prior to receiving RTX, seven patients had at least one hospitalization for HSP (median 1.5, range 0-3). Following RTX, only two patients were hospitalized, each a single time for recurrent abdominal pain. The median oral CS burden was 0.345 mg/kg/day before RTX and 0 mg/kg/day at 6 months (p = 0.078), 1 year (p = 0.0625), and 2 years (p = 0.03) following RTX infusion. Seven out of eight children met remission criteria, defined as no active rash, arthritis, nephritis (hematuria and proteinuria), or gastrointestinal distress following RTX. No serious adverse events were noted.
Overall, RTX effectively reduced the number of hospital admissions and oral CS burden. RTX also helped most all children achieve clinical remission. RTX appears to be an effective and safe alternative for chronic CS dependent and immunomodulatory refractory childhood HSP.
过敏性紫癜（HSP）是一种小血管炎，其特征为非血小板减少性紫癜、腹痛、关节炎和肾小球肾炎。通常，HSP为自限性疾病，仅需支持治疗，但更严重的病例可能需要使用糖皮质激素（CS）治疗。极少数情况下，尽管接受了CS治疗，这些患者中的一部分仍有持续性皮疹、关节炎、腹部受累或肾脏疾病，或者在CS减量时疾病复发。难治性HSP已通过多种糖皮质激素节省疗法得到有效治疗。对于危及生命的难治性HSP，据报道，B细胞耗竭剂利妥昔单抗（RTX）对有严重肾脏或中枢神经系统受累的儿童有益。然而，对于病情较轻但对糖皮质激素节省免疫调节剂难治的慢性CS依赖型HSP患儿，RTX的应用研究较少。在此，我们描述了8例接受RTX治疗慢性难治性HSP的儿童，并报告了住院次数的减少以及最终停用CS的情况。
这是一项对2006年至2014年在单一机构接受RTX治疗慢性CS依赖型HSP的8例儿童的回顾性分析。对电子病历进行图表审查，以确定出现的症状、接受治疗的类型和持续时间以及RTX治疗前后的住院次数。使用Wilcoxon符号秩和检验分析住院次数和口服糖皮质激素负担。
在接受RTX之前，7例患者因HSP至少住院1次（中位数1.5次，范围0 - 3次）。接受RTX治疗后，只有2例患者住院，均因复发性腹痛各住院1次。RTX治疗前口服CS的中位数负担为0.345mg/kg/天，在RTX输注后6个月（p = 0.078）、1年（p = 0.0625）和2年（p = 0.03）时为0mg/kg/天。8例儿童中有7例符合缓解标准，定义为接受RTX治疗后无活动性皮疹、关节炎、肾炎（血尿和蛋白尿）或胃肠道不适。未观察到严重不良事件。
总体而言，RTX有效减少了住院次数和口服CS负担。RTX还帮助大多数儿童实现了临床缓解。RTX似乎是慢性CS依赖型和免疫调节难治性儿童HSP的一种有效且安全的替代治疗方法。
