多部位黏膜类天疱疮的部位特异性治疗与缓解模式

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中文摘要

重要性： 黏膜类天疱疮（MMP）是一种慢性自身免疫性大疱性疾病，与进行性黏膜瘢痕形成和显著发病率相关。既往研究常在合并局限性和多部位疾病的队列中报告缓解率，关于多部位疾病患者所有受累部位同时缓解的数据有限。
目的： 评估多部位MMP患者的多部位完全缓解（mCR）及部位特异性治疗反应模式。
设计、设置和参与者： 这项回顾性队列研究于2013年1月1日至2025年1月1日在德克萨斯大学西南医学中心的一个三级皮肤科和眼科转诊中心进行。纳入经免疫病理学确诊的MMP、疾病累及2个或以上解剖部位、且治疗后随访12个月的患者。
主要结局和测量指标： 主要结局为mCR，定义为无论采用何种治疗，所有受累部位同时达到完全缓解。次要结局包括部位特异性缓解和复发模式、缓解时间以及治疗相关不良事件。
结果： 在77例患者中（55例[71%]为女性；诊断时中位[IQR]年龄为66[59-72]岁），68例（88%）患有累及眼部、喉部、食管或肛门生殖器部位的高危疾病。口腔疾病最常见，见于73例患者（95%），其次为眼部疾病51例（66%）和鼻部疾病38例（49%）。35例患者（45%）在中位（IQR）32.0（20.7-55.3）个月内达到mCR。尽管所有患者均显示改善，且64例（83%）在1个或以上部位达到CR，但持续存在的口腔和眼部疾病常妨碍mCR。64例患者中有28例（44%）在部位水平CR后出现复发，最常见于口腔黏膜（28例中18例[64%]）和眼部黏膜（28例中14例[50%]）；部分患者出现多个部位复发。以利妥昔单抗为基础的方案和Janus激酶抑制剂治疗与高改善率相关。严重不良事件最常发生于环磷酰胺单药治疗和Janus激酶抑制剂治疗。
结论和意义： 在这项队列研究中，尽管部位水平反应率较高，但不到一半的多部位MMP患者达到同时多部位缓解。持续存在的口腔和眼部疾病不成比例地限制了整体疾病控制，支持疾病行为的部位特异性模型，并强调未来研究需要标准化的多部位缓解结局。

英文摘要

IMPORTANCE: Mucous membrane pemphigoid (MMP) is a chronic autoimmune blistering disease associated with progressive mucosal scarring and substantial morbidity. Prior studies have often reported remission rates in cohorts combining localized and multisite disease, with limited data on simultaneous remission across all involved sites in patients with multisite disease.
OBJECTIVE: To evaluate multisite complete remission (mCR) and site-specific treatment response patterns in patients with multisite MMP.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study took place at a single tertiary dermatology and ophthalmology referral center at the University of Texas Southwestern Medical Center between January 1, 2013, and January 1, 2025. Patients with MMP confirmed by immunopathology, disease involving 2 or more anatomic sites, and 12 months posttreatment follow-up were included.
MAIN OUTCOMES AND MEASURES: The primary outcome was mCR, defined as concurrent complete remission across all involved sites regardless of therapy. Secondary outcomes included site-specific remission and relapse patterns, time to remission, and treatment-associated adverse events.
RESULTS: Among 77 patients (55 [71%] female; median [IQR] age at diagnosis, 66 [59-72] years), 68 (88%) had high-risk disease involving ocular, laryngeal, esophageal, or anogenital sites. Oral disease was most common, present in 73 patients (95%), followed by ocular disease in 51 (66%) and nasal disease in 38 (49%). Thirty-five patients (45%) achieved mCR in a median (IQR) of 32.0 (20.7-55.3) months. Although all patients demonstrated improvement and 64 (83%) achieved CR at 1 or more sites, persistent oral and ocular diseases frequently prevented mCR. Relapses following site-level CR occurred in 28 of the 64 patients (44%), most frequently at the oral (18 of 28 patients [64%]) and ocular mucosa (14 of 28 patients [50%]); some patients experienced relapse at multiple sites. Rituximab-based regimens and Janus kinase inhibitor therapy were associated with high rates of improvement. Serious adverse events occurred most frequently with cyclophosphamide monotherapy and Janus kinase inhibitor therapy.
CONCLUSIONS AND RELEVANCE: In this cohort study, fewer than half of patients with multisite MMP achieved simultaneous multisite remission despite high rates of site-level response. Persistent oral and ocular diseases disproportionately limited global disease control, supporting a site-specific model of disease behavior and highlighting the need for standardized multisite remission outcomes in future studies.