Qin Qianfeng, Cao Cunwei, Liang Jiarong, Li Bingkun, Su Jiaguang
Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Fangchenggang Wanqing Institute of Mycosis Prevention and Control, Fangchenggang, Guangxi, China.
Front Med (Lausanne). 2025 Aug 8;12:1557540. doi: 10.3389/fmed.2025.1557540. eCollection 2025.
PASH syndrome is a rare autoinflammatory disorder characterized primarily by pyoderma gangrenosum, acne, and suppurative hidradenitis. It is frequently misdiagnosed or underdiagnosed due to its diverse clinical manifestations. PASH syndrome is considered a polygenic autoinflammatory disease associated with multiple gene variants, among which variants may play a significant role. This case report describes a PASH syndrome patient with the variant (NM_000243.3.442G > C; p.Glu148Gln). The E148Q variant appears with high frequency as a homozygote in the gnomAD database, and its pathogenicity remains controversial.
This case report describes a Chinese male patient with PASH syndrome who initially presented with severe acne and suppurative hidradenitis that were unresponsive to conventional therapy, subsequently developing pyoderma gangrenosum, leading to the diagnosis of PASH syndrome. Whole-exome sequencing performed during the diagnostic workup revealed the gene variant (p.E148Q). Treatment with adalimumab ultimately achieved favorable therapeutic outcomes.
This case report represents the first documentation of a PASH syndrome patient carrying the homozygous E148Q variant. Adalimumab demonstrated good therapeutic efficacy; however, disease recurrence occurred due to poor medication adherence, highlighting the importance of long-term management. The pathogenicity of E148Q alone is relatively weak and likely depends on polygenic accumulation or epigenetic dysregulation. It may contribute to disease pathogenesis through a "variant load" mechanism in conjunction with ethnic differences and other genetic or environmental factors.
PASH综合征是一种罕见的自身炎症性疾病，主要特征为坏疽性脓皮病、痤疮和化脓性汗腺炎。由于其临床表现多样，该病常被误诊或漏诊。PASH综合征被认为是一种与多种基因变异相关的多基因自身炎症性疾病，其中某些变异可能起重要作用。本病例报告描述了一名携带该变异（NM_000243.3.442G > C；p.Glu148Gln）的PASH综合征患者。E148Q变异在gnomAD数据库中以纯合子形式高频出现，其致病性仍存在争议。
本病例报告描述了一名患有PASH综合征的中国男性患者，最初表现为严重痤疮和化脓性汗腺炎，对传统治疗无反应，随后发展为坏疽性脓皮病，从而诊断为PASH综合征。诊断检查期间进行的全外显子测序揭示了该基因变异（p.E148Q）。使用阿达木单抗治疗最终取得了良好的治疗效果。
本病例报告是首例记录携带纯合E148Q变异的PASH综合征患者。阿达木单抗显示出良好的治疗效果；然而，由于药物依从性差导致疾病复发，凸显了长期管理的重要性。单独的E148Q致病性相对较弱，可能依赖于多基因积累或表观遗传失调。它可能通过“变异负荷”机制，结合种族差异和其他遗传或环境因素，对疾病发病机制产生影响。
