Department of Dermatology and Venereology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
J Dermatol. 2019 Sep;46(9):808-811. doi: 10.1111/1346-8138.14981. Epub 2019 Jul 10.
Disseminated granuloma annulare (GA) is a rare granulomatous dermatitis of unknown etiology. Treatment is often challenging and lack of a uniformly effective treatment, adds to the disease morbidity. Tumor necrosis factor (TNF)-α is an important cytokine in granuloma formation and previous reports have shown improvement of disseminated GA with anti-TNF-α therapy. Nevertheless, the underlying mechanism of actions of TNF-α inhibitors in GA remains unclear. Our aim was to evaluate alterations in the inflammatory infiltrate in a patient who experienced complete clearance of GA after treatment with infliximab. A skin biopsy was obtained before and 24 weeks after treatment with infliximab 5 mg/kg at weeks 0, 2, 6, 14 and 24. Immunohistochemical stains were performed in pre- and post-treatment biopsy specimens using CD1a, CD4, CD8, CD11c, CD32, CD68, CD69, CD163, CD183 and human leukocyte antigen (HLA)-DR to characterize alterations of the infiltrates. Parallel with clinical improvement, we observed a marked decrease in myeloid (CD11c) dendritic cells, different macrophage subsets (CD68, CD32, CD163) and T cells. In addition, a marked reduction of activation markers (HLA-DR, CD69) and CD183 (CXCR3) cells was observed in post-treatment biopsy specimens. In conclusion, the clinical improvement of disseminated GA by infliximab is paralleled by inhibition of activated myeloid dendritic cells, different macrophage subsets and type 1 T cells.
播散性环状肉芽肿（GA）是一种病因不明的罕见肉芽肿性皮肤病。由于缺乏普遍有效的治疗方法，该病的治疗常常具有挑战性，这增加了该病的发病率。肿瘤坏死因子（TNF）-α 是肉芽肿形成的重要细胞因子，先前的报告表明，抗 TNF-α 治疗可改善播散性 GA。然而，TNF-α 抑制剂在 GA 中的作用机制仍不清楚。我们的目的是评估在接受英夫利昔单抗治疗后 GA 完全清除的患者中炎症浸润的变化。在接受英夫利昔单抗 5mg/kg 治疗前（第 0 周）和治疗后 24 周（第 2、6、14 和 24 周）时，采集皮肤活检标本。在治疗前后的活检标本中，使用 CD1a、CD4、CD8、CD11c、CD32、CD68、CD69、CD163、CD183 和人类白细胞抗原（HLA）-DR 进行免疫组织化学染色，以描述浸润物的变化。随着临床改善，我们观察到髓样（CD11c）树突状细胞、不同的巨噬细胞亚群（CD68、CD32、CD163）和 T 细胞明显减少。此外，在治疗后的活检标本中还观察到活化标志物（HLA-DR、CD69）和 CD183（CXCR3）细胞的明显减少。总之，英夫利昔单抗治疗播散性 GA 的临床改善与抑制活化的髓样树突状细胞、不同的巨噬细胞亚群和 1 型 T 细胞有关。
