{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T02:29:41Z","timestamp":1771036181660,"version":"3.50.1"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2504800"],"award-info":[{"award-number":["2022YFC2504800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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 <jats:italic>MEFV<\/jats:italic> variants may play a significant role. This case report describes a PASH syndrome patient with the <jats:italic>MEFV<\/jats:italic> variant (NM_000243.3.442G\u202f&amp;gt;\u202fC; p.Glu148Gln). The E148Q variant appears with high frequency as a homozygote in the gnomAD database, and its pathogenicity remains controversial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>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 <jats:italic>MEFV<\/jats:italic> gene variant (p.E148Q). Treatment with adalimumab ultimately achieved favorable therapeutic outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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 \u201cvariant load\u201d mechanism in conjunction with ethnic differences and other genetic or environmental factors.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1557540","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T04:10:46Z","timestamp":1754626246000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Diagnostic difficulties, treatment, and association of the MEFV E148Q variant in a patient with PASH syndrome"],"prefix":"10.3389","volume":"12","author":[{"given":"Qianfeng","family":"Qin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cunwei","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiarong","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingkun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaguang","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.jaad.2010.12.025","article-title":"Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)--a new autoinflammatory syndrome distinct from PAPA 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