Head and neck manifestations of IgG4-related disease: current understanding.

IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition characterized by elevated serum IgG4 levels and dense infiltration of IgG4-positive plasma cells with fibrosis in affected organs. Since its initial recognition, clinical awareness of IgG4-RD has expanded, and head and neck involvement has become increasingly well described. Among these, IgG4-related dacryoadenitis and sialadenitis (IgG4-DS), historically referred to as Mikulicz’s disease, represents the most common manifestation. Patients typically present with persistent, painless swelling of the major salivary and lacrimal glands, often accompanied by xerostomia, mild taste disturbance, or sinonasal involvement such as chronic rhinosinusitis and olfactory dysfunction. Unlike autoimmune pancreatitis, IgG4-DS affects men and women in nearly equal proportions and predominantly occurs in older individuals. Laboratory findings usually include elevated serum IgG4, hypergammaglobulinemia, eosinophilia, and high IgE levels, though none are entirely disease-specific. Diagnosis of IgG4-RD in the head and neck region requires integration of clinical, radiological, serological, and histopathological findings. Recent Japanese criteria incorporate both comprehensive and organ-specific diagnostic frameworks, while international classification criteria developed by ACR/EULAR aim to standardize patient cohorts for research. Imaging plays an important role: ultrasonography often reveals diffuse or nodular hypoechoic lesions in the salivary glands, whereas CT and MRI can delineate glandular swelling, sinonasal opacification, or pachymeningeal thickening. PET/CT may further identify multiorgan involvement, including emerging sites such as the tubarial glands. Differential diagnosis is crucial, as Sjögren’s disease, multicentric Castleman’s disease, sarcoidosis, ANCA-associated vasculitis, and malignant lymphoma can present with overlapping features, and increased IgG4-positive cells are occasionally observed in non-IgG4-related disorders. Despite uncertainties regarding its etiology, substantial progress has been made in understanding IgG4-DS, and awareness among head and neck specialists is essential to ensure accurate diagnosis and appropriate management.