Lazar Jozef, Poonawalla Tasneem, Teng Joyce M C
Department of Dermatology, University of Wisconsin, Madison, Wisconsin 53715, USA.
Pediatr Dermatol. 2011 Mar-Apr;28(2):172-5. doi: 10.1111/j.1525-1470.2010.01301.x. Epub 2011 Mar 15.
Sclerodermatous graft-versus-host disease (sGVHD) is a rare, late complication of hematopoietic cell transplantation. Classified as a variant of chronic graft-versus-host disease, sGVHD is thought to be predominantly an immune-mediated response characterized by aberrant T-cell function and dysregulation of tyrosine kinase cascades. Recently, the profibrotic cytokine transforming growth factor B and stimulatory autoantibodies against the platelet-derived growth factor receptor have been implicated in the pathogenesis of sGVHD. Treatment of sGVHD remains disappointing and largely limited by systemic side effects. Imatinib mesylate is a small molecule tyrosine kinase inhibitor that has been shown to selectively inhibit both the platelet-derived growth factor receptor and transforming growth factor-β signaling pathways. We report a case of sGVHD in a pediatric patient that was resistant to traditional therapy but showed improvement in cutaneous symptoms following daily treatment with 400 mg of imatinib mesylate. Due to its favorable side-effect profile, specificity for molecular pathways deranged in sGVHD and proven efficacy in other sclerodermoid diseases, imatinib mesylate is a promising new tool in the management of this challenging disease.
硬皮病样移植物抗宿主病（sGVHD）是造血细胞移植罕见的晚期并发症。sGVHD被归类为慢性移植物抗宿主病的一种变体，被认为主要是一种免疫介导的反应，其特征为异常的T细胞功能和酪氨酸激酶级联反应失调。最近，促纤维化细胞因子转化生长因子β和针对血小板衍生生长因子受体的刺激性自身抗体被认为与sGVHD的发病机制有关。sGVHD的治疗仍然令人失望，并且在很大程度上受到全身副作用的限制。甲磺酸伊马替尼是一种小分子酪氨酸激酶抑制剂，已被证明可选择性抑制血小板衍生生长因子受体和转化生长因子-β信号通路。我们报告了一例儿科sGVHD患者，该患者对传统治疗耐药，但在每日服用400 mg甲磺酸伊马替尼治疗后皮肤症状有所改善。由于其良好的副作用特征、对sGVHD中紊乱分子途径的特异性以及在其他硬皮病样疾病中的已证实疗效，甲磺酸伊马替尼是治疗这种具有挑战性疾病的一种有前景的新工具。
