Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA.
J Am Acad Dermatol. 2011 Jul;65(1):25-34. doi: 10.1016/j.jaad.2010.09.016. Epub 2011 Apr 29.
Dermatomyositis (DM) is a multisystem autoimmune disease, in which serologic evidence of immune responses to disease-specific antigenic targets is found in approximately 50% to 70% of patients. Recently, melanoma differentiation-associated gene 5 (MDA5) has been identified as a DM-specific autoantigen that appears to be targeted in patients with DM and mild or absent muscle inflammation and with an increased risk of interstitial lung disease.
We wished to understand the role of MDA5 in DM skin inflammation by testing it to determine if a specific cutaneous phenotype is associated with MDA5 reactivity.
We retrospectively screened plasma from 77 patients with DM in the outpatient clinics at the Stanford University Department of Dermatology in California.
We found that 10 (13%) patients had circulating anti-MDA5 antibodies, and had a characteristic cutaneous phenotype consisting of skin ulceration, tender palmar papules, or both. Typical areas of skin ulceration included the lateral nailfolds, Gottron papules, and elbows. Biopsy specimens of the palmar papules showed a vasculopathy characterized by vascular fibrin deposition with variable perivascular inflammation. Patients with anti-MDA5 antibodies also had an increased risk of oral pain and/or ulceration, hand swelling, arthritis/arthralgia, and diffuse hair loss. Consistent with previous reports, these patients had little or no myositis and had increased risk of interstitial lung disease.
This study was conducted at a tertiary referral center. Multiple associations with MDA5 antibodies were tested retrospectively on a relatively small cohort of 10 anti-MDA5-positive patients.
We suggest that MDA5 reactivity in DM characterizes a patient population with severe vasculopathy.
皮肌炎（DM）是一种多系统自身免疫性疾病，约 50%至 70%的患者存在针对疾病特异性抗原的血清免疫反应证据。最近，黑色素瘤分化相关基因 5（MDA5）已被确定为 DM 特异性自身抗原，似乎是 DM 患者、轻度或无肌肉炎症以及间质性肺病风险增加的靶点。
我们希望通过测试 MDA5 来了解其在 DM 皮肤炎症中的作用，以确定是否存在与 MDA5 反应性相关的特定皮肤表型。
我们回顾性筛选了加利福尼亚斯坦福大学皮肤科门诊的 77 例 DM 患者的血浆。
我们发现 10 例（13%）患者存在循环抗 MDA5 抗体，具有特征性的皮肤表型，包括皮肤溃疡、压痛性掌部丘疹或两者兼有。典型的皮肤溃疡部位包括侧甲皱襞、Gottron 丘疹和肘部。掌部丘疹的活检标本显示出一种血管病变，其特征是血管纤维蛋白沉积和不同程度的血管周围炎症。抗 MDA5 抗体的患者也有口腔疼痛和/或溃疡、手肿胀、关节炎/关节痛和弥漫性脱发的风险增加。与之前的报告一致，这些患者几乎没有肌炎，间质性肺病的风险增加。
本研究在三级转诊中心进行。对 10 例抗 MDA5 阳性患者的相对较小队列进行了回顾性测试，与 MDA5 抗体存在多种关联。
我们认为 DM 中的 MDA5 反应性特征是一种严重血管病变的患者人群。
