{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:48:06Z","timestamp":1782362886112,"version":"3.54.5"},"reference-count":180,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder characterized by complex immune-mediated mechanisms and broad organ involvement that remains substantially underdiagnosed in clinical practice. The head and neck region is one of the most commonly involved anatomical domains, encompassing the major salivary glands, lacrimal glands, nasal cavity and paranasal sinuses, larynx and subglottis, thyroid gland, middle ear, orbit, and cervical lymph nodes. This review integrates current understanding of the immunopathological mechanisms underlying IgG4-RD with organ-specific clinical features and therapeutic considerations across these head and neck subregions. The core immune pathogenesis involves clonally expanded CD4\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic T lymphocytes and activated follicular helper T cells that, within a Th2-skewed cytokine environment, promote IgG4 class-switch recombination and plasmablast expansion, driving the transition from inflammatory infiltration to progressive fibrotic remodeling. Although head and neck subtypes share this common immunopathological framework, they differ considerably in the relative balance between inflammatory and fibrotic features, clinical severity, and organ-specific risk profiles. These differences may reflect local microenvironmental factors, including epithelial characteristics, innate immune responsiveness, and the functional properties of resident stromal fibroblasts, though the precise mechanisms remain to be fully established. Therapeutically, glucocorticoids remain the standard first-line treatment for remission induction but are limited by high relapse rates after withdrawal. Rituximab has demonstrated efficacy in refractory and relapsing disease. Inebilizumab, an anti-CD19 monoclonal antibody, has shown significant benefit in a phase III randomized controlled trial. Dupilumab, which targets the IL-4\/IL-13 signaling axis, has shown potential in case reports and small series, but prospective validation is required before it can be recommended as a standard therapeutic option. By mapping organ-specific immunopathological differences onto differentiated therapeutic approaches, this review aims to support a more individualized, biologically informed framework for managing IgG4-RD in the head and neck.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1859866","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:22:08Z","timestamp":1782361328000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["From inflammatory initiation to fibrotic remodeling: mechanisms and precision therapeutic strategies in otorhinolaryngologic involvement of IgG4-related disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Minfang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Jiaxing Hospital of Traditional Chinese Medicine","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongcai","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Jiaxing Hospital of Traditional Chinese Medicine","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Jiaxing Hospital of Traditional Chinese Medicine","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Jiaxing Hospital of Traditional Chinese Medicine","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"i24","DOI":"10.1093\/rheumatology\/keaf008","article-title":"IgG4-related disease: lessons from the first 20 years","volume":"64","author":"Stone","year":"2025","journal-title":"Rheumatology (Oxford)"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1056\/NEJMra1104650","article-title":"IgG4-related disease","volume":"366","author":"Stone","year":"2012","journal-title":"N Engl J Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1002\/art.41120","article-title":"The 2019 american college of rheumatology\/european league against rheumatism classification criteria for IgG4-related disease","volume":"72","author":"Wallace","year":"2020","journal-title":"Arthritis 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