BACKGROUND Sarcoidosis and granuloma annulare (GA) are cutaneous granulomatous disorders that can be difficult to treat. There is evidence of underlying Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway activation in sarcoidosis, suggesting that JAK inhibition might be effective. OBJECTIVE To evaluate treatment with tofacitinib, a JAK inhibitor, in patients with recalcitrant sarcoidosis and GA. METHODS A prospective evaluation of tofacitinib in 4 consecutive patients with recalcitrant cutaneous sarcoidosis (n = 3) and generalized GA (n = 1) was conducted. Immunohistochemical analysis of skin biopsy specimens from other patients with sarcoidosis (n = 21) and GA (n = 17) was performed to characterize patterns of JAK-STAT pathway activation. RESULTS Tofacitinib resulted in a mean improvement in the baseline Cutaneous Sarcoidosis Activity and Morphology Instrument and Granuloma Annulare Scoring Index scores of 96% (standard deviation, 2%). Histologic resolution of disease was documented in all patients (3 out of 3) who had skin biopsies while receiving therapy. Constitutive STAT1 and STAT3 activation was observed in both sarcoidosis and GA, albeit in different patterns. Signal regulatory protein α may explain the differences in JAK-STAT signaling between sarcoidosis and GA. LIMITATIONS The study is limited by the small number of participants. CONCLUSIONS Tofacitinib resulted in dramatic improvement in 4 patients with cutaneous sarcoidosis and GA. Larger studies are underway to better understand this effect.

中文翻译：

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Janus 激酶抑制诱导皮肤结节病和环状肉芽肿的疾病缓解。

背景结节病和环状肉芽肿（GA）是难以治疗的皮肤肉芽肿性疾病。有证据表明在结节病中潜在的 Janus 激酶 (JAK) 信号转导和转录激活剂 (STAT) 通路激活，表明 JAK 抑制可能是有效的。目的 评估托法替尼（一种 JAK 抑制剂）对顽固性结节病和 GA 患者的治疗。方法 在连续 4 名患有顽固性皮肤结节病 (n = 3) 和全身性 GA (n = 1) 的患者中对托法替尼进行了前瞻性评估。对来自其他结节病 (n = 21) 和 GA (n = 17) 患者的皮肤活检标本进行免疫组织化学分析，以表征 JAK-STAT 通路激活的模式。结果 Tofacitinib 导致基线皮肤结节病活动和形态学仪器和肉芽肿评分指数评分平均改善 96%（标准偏差，2%）。在接受治疗时进行皮肤活检的所有患者（3 名中的 3 名）都记录了疾病的组织学消退。在结节病和 GA 中均观察到组成性 STAT1 和 STAT3 激活，尽管模式不同。信号调节蛋白 α 可以解释结节病和 GA 之间 JAK-STAT 信号传导的差异。局限性 该研究受参与者人数少的限制。结论 托法替尼使 4 名皮肤结节病和 GA 患者显着改善。正在进行更大规模的研究以更好地了解这种影响。