Lenalidomide therapy in treatment-refractory cutaneous lupus erythematosus: Histologic and circulating leukocyte profile and potential risk of a systemic lupus flare
Lenalidomide therapy in treatment-refractory cutaneous lupus erythematosus: Histologic and circulating leukocyte profile and potential risk of a systemic lupus flare
复制标题
DOI：
10.1016/j.jaad.2011.01.015
复制
发表时间：
2012-04-01
影响因子：
13.8
通讯作者：
Werth, Victoria P.
中科院分区：
文献类型：
--
作者：
Braunstein, Inbal;Goodman, Noah G.;Werth, Victoria P.
背景：来那度胺是一种沙利度胺类似物，可作为难治性皮肤红斑狼疮（CLE）的辅助治疗。目的：我们评估来那度胺在CLE中的应用，并描述治疗难治性患者治疗前后的皮肤和循环白细胞谱。方法：在一项非盲法开放标签研究中，5名受试者接受来那度胺治疗。治疗前后对皮肤进行免疫组化，检测t细胞标志物、糖胺聚糖和干扰素诱导的趋化因子CXCL10。治疗前后对外周血单个核细胞进行免疫分型和干扰素诱导基因测定。结果：四名受试者表现出皮肤的临床改善，然而其中一名应答者随后出现了系统性红斑狼疮症状。治疗过程中观察到罕见的循环白细胞亚群、浆细胞样树突状细胞和调节性T细胞的微小变化，这可能与临床反应有关。无论临床反应如何，治疗与循环HLA-DR表达增加和干扰素介导途径标记物减少相关。局限性：我们的结果受到样本量小和稀有循环细胞亚群测量的限制。结论：来那度胺可用于治疗严重难治性CLE。然而，我们的初步数据表明，来那度胺可能会激活T细胞，并在一些CLE患者中引发全身性疾病。在无反应的受试者中，我们也看到了不同的组织学和循环白细胞表型。进一步表征难治性患者的皮肤和循环白细胞谱将提高我们对CLE的理解。[J] .中华皮肤科杂志，2012;66:571-82。
Background: Lenalidomide is a thalidomide analogue that may serve as an adjunctive therapy for treatment-refractory cutaneous lupus erythematosus (CLE).Objectives: We evaluate the use of lenalidomide in CLE and describe the skin and circulating leukocyte profile of treatment-refractory patients before and after treatment.Methods: Five subjects were treated with lenalidomide in an unblinded open-label study. Immunohistochemistry of skin was performed for T-cell markers, glycosaminoglycans, and CXCL10, an interferon-inducible chemokine, before and after treatment. Immunophenotyping and measurement of interferon-inducible genes from peripheral blood mononuclear cells was also performed before and after treatment.Results: Four subjects demonstrated clinical improvement of their skin, however one of these responders subsequently developed symptoms of systemic lupus erythematosus. Small changes in rare circulating leukocyte subsets, plasmacytoid dendritic cells, and regulatory T cells were observed with treatment and may correlate with clinical response. Treatment was associated with increased circulating HLA-DR expression and decreased markers of interferon-mediated pathways, regardless of clinical response.Limitations: Our results are limited by small sample size and the measurement of rare populations of circulating cell subsets.Conclusions: Lenalidomide may have usefulness as therapy for severe, treatment-refractory CLE. However, our preliminary data suggest that lenalidomide may activate T cells and trigger systemic disease in some patients with CLE. We also saw a different histologic and circulating leukocyte phenotype in the nonresponding subject. Further characterization of the skin and circulating leukocyte profile of treatment-refractory patients will improve our understanding of CLE. (J Am Acad Dermatol 2012;66:571-82.)