Beerepoot Shanice, Grinwis Lucas, Vanderver Adeline L, van der Knaap Marjo S, Kuijpers Taco W
Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children'S Hospital, Amsterdam University Medical Centers, VU University, 1081 HV, Amsterdam, The Netherlands.
Amsterdam Neuroscience, Cellular & Molecular Mechanisms, 1081 HV, Amsterdam, The Netherlands.
Orphanet J Rare Dis. 2025 Apr 2;20(1):155. doi: 10.1186/s13023-025-03675-7.
The purpose of this letter to the editor is to illustrate the effect of tofacitinib on psoriatic skin lesions in a patient with Aicardi-Goutières syndrome (AGS) type 7/Singleton-Merten syndrome 1. AGS is characterized by an encephalopathy of variable severity and systemic autoinflammatory manifestations due to continuous type I interferon (IFN) induction. While traditional JAK 1/2 inhibitors like baricitinib and ruxolitinib have proven effectiveness for systemic inflammatory symptoms, they face reimbursement issues in some countries. Tofacitinib, a JAK 1/3 inhibitor, significantly improved psoriatic skin lesions in our patient without the need for additional immunosuppressive therapy. Within one month of starting tofacitinib, psoriatic rashes and ulcerative skin lesions markedly improved, in the absence of a reduction in the IFN-stimulated gene signature or CD169 expression on monocytes. The clinical benefits persisted until the treatment was discontinued, after which symptoms recurred. Resuming tofacitinib treatment again led to improvement. No adverse effects were observed. This case highlights the potential of tofacitinib as a clinically effective treatment for psoriatic skin lesions in AGS and offers a viable alternative for JAK 1/2 inhibitors for this target symptom. Further studies are needed to confirm the long-term safety of JAK 1/3 inhibitors in AGS as well as their possible efficacy and dosing to address other systemic symptoms or neurologic manifestations.
这封致编辑的信旨在阐述托法替布对一名7型艾卡迪-古铁雷斯综合征（AGS）/辛格尔顿-默滕综合征1患者银屑病性皮肤病变的影响。AGS的特征是由于持续性I型干扰素（IFN）诱导导致严重程度不一的脑病和全身性自身炎症表现。虽然像巴瑞替尼和鲁索替尼这样的传统JAK 1/2抑制剂已被证明对全身性炎症症状有效，但它们在一些国家面临报销问题。托法替布是一种JAK 1/3抑制剂，在我们的患者中显著改善了银屑病性皮肤病变，无需额外的免疫抑制治疗。在开始使用托法替布的一个月内，银屑病皮疹和溃疡性皮肤病变明显改善，而单核细胞上的IFN刺激基因特征或CD169表达并未降低。临床益处持续到治疗停止，之后症状复发。再次恢复托法替布治疗导致病情改善。未观察到不良反应。该病例突出了托法替布作为AGS中银屑病性皮肤病变临床有效治疗方法的潜力，并为针对该目标症状的JAK 1/2抑制剂提供了可行的替代方案。需要进一步研究来证实JAK 1/3抑制剂在AGS中的长期安全性以及它们针对其他全身性症状或神经学表现的可能疗效和给药方案。
