氨苯砜成功治疗2例妊娠合并线状IgA大疱性皮病并文献复习

Dapsone Successfully Treated Two Cases of Pregnancy-Associated Linear IgA Bullous Dermatosis and Literature Review

摘要: 线状IgA大疱性皮病(LABD)作为罕见自身免疫性皮肤病，其与妊娠相关的病例在近20年全世界仅报道3例。本研究组在临床工作中首次发现2例成年后发病的妊娠合并LABD病例，其中1例发生于孕9周(目前文献记载中唯一早期妊娠病例)，另1例发生于妊娠中晚期。通过皮肤病理活检、直接/间接免疫荧光检测及典型皮损特征，两例均获得明确诊断，填补了该领域妊娠相关LABD病例的临床证据空白。本研究重点揭示了妊娠相关LABD的治疗挑战：两例患者对常规糖皮质激素治疗(0.5 mg/kg/d)均呈现疗效不佳，调整激素方案(包括剂量强化及种类变更)后仍未获显著改善。在排除葡萄糖-6-磷酸脱氢酶缺乏(G6PD活性阴性)及HLA-B*13:01基因风险后，创新性应用小剂量氨苯砜(50 mg/d)联合治疗，取得突破性疗效——治疗1周内皮损即获显著控制，且未观察到药物相关严重并发症。值得注意的是，其中孕早期病例成功应用氨苯砜治疗属全球首报，证实该药在不同妊娠阶段的潜在应用价值。出院后随访5个月，长期随访显示，尽管患者因对氨苯砜远期风险的顾虑(1例孕早期患者终止妊娠后改用度普利尤单抗，另1例产后改用托法替布)，但氨苯砜在急性期治疗中展现的快速应答优势具有重要临床意义。本系列病例首次系统论证了氨苯砜在妊娠相关LABD中的关键治疗地位，同时验证了生物制剂及JAK抑制剂作为后续维持治疗的可行性。研究结果为临床医师在母胎安全平衡这一医学伦理困境中提供了创新性解决方案，尤其氨苯砜的早期应用经验，为同类罕见病例的规范化诊疗建立了重要参考范式。

Abstract: Linear IgA bullous dermatosis (LABD) is a rare autoimmune skin disease, and only three cases associated with pregnancy have been reported worldwide in the past two decades. Our team identified two cases of pregnancy-associated LABD with disease onset in adulthood, one occurring at 9 weeks of gestation (the only first-trimester case documented to date) and the other in the second/third trimester. Both cases were definitively diagnosed through skin biopsy, direct/indirect immunofluorescence, and characteristic skin lesions, filling a gap in clinical evidence for pregnancy-associated LABD in this field. This study highlights the therapeutic challenges of pregnancy-associated LABD: Both patients responded poorly to conventional glucocorticoid therapy (0.5 mg/kg/d), and no significant improvement was achieved after adjusting the corticosteroid regimen (including dose escalation and switching to different glucocorticoids). After excluding glucose-6-phosphate dehydrogenase deficiency (negative G6PD activity) and HLA-B*13:01 genetic risk, low-dose dapsone (50 mg/d) was innovatively added as combination therapy, achieving a breakthrough efficacy—skin lesions were significantly controlled within one week of treatment, with no observed severe drug-related complications. Notably, the successful use of dapsone in the first-trimester case represents the first such report globally, confirming the potential value of this drug across different stages of pregnancy. During follow-up for 5 months after discharge, long-term observation showed that although patients switched to other treatments due to concerns about the long-term risks of dapsone (one first-trimester patient discontinued pregnancy and later switched to dupilumab, and the other switched to tofacitinib postpartum), the rapid response advantage of dapsone in acute-phase management holds important clinical significance. This case series systematically demonstrates, for the first time, the key therapeutic role of dapsone in pregnancy-associated LABD, while also validating the feasibility of biologics and JAK inhibitors as subsequent maintenance therapies. Our findings provide clinicians with innovative solutions to the ethical dilemma of balancing maternal and fetal safety, and the experience with early application of dapsone in particular establishes an important reference paradigm for the standardized management of such rare cases.