From inflammatory initiation to fibrotic remodeling: mechanisms and precision therapeutic strategies in otorhinolaryngologic involvement of IgG4-related disease

IgG4-related disease is a systemic fibroinflammatory disorder characterized by complex immune-mediated mechanisms that remains substantially underdiagnosed in clinical practice. The head and neck region is one of the most commonly involved anatomical domains, including major salivary glands, lacrimal glands, nasal cavity, paranasal sinuses, larynx, thyroid gland, middle ear, and cervical lymph nodes. The core immune pathogenesis involves clonally expanded CD4+ cytotoxic T lymphocytes and activated follicular helper T cells that, within a Th2-skewed cytokine environment, promote IgG4 class-switch recombination and plasmablast expansion. 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, showed significant benefit in a phase III randomized controlled trial. Dupilumab, which targets IL-4/IL-13 signaling, has shown potential in case reports but requires further prospective validation.