Periocular nasociliary lesion with elevated serum IgG4 levels: A case report on the risks of overdiagnosis in IgG4-related disease

Introduction: IgG4-related disease is a systemic fibroinflammatory condition characterized by tumefactive lesions, a lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and, in a variable proportion of patients, elevated serum IgG4 levels (1–3). Its clinical spectrum is broad and may involve virtually any organ, including salivary glands, lacrimal glands, orbital tissues, pancreas, biliary tract, kidneys, lungs, lymph nodes, retroperitoneum, skin, and the gastrointestinal tract (1,4). IgG4-related ophthalmic disease represents a particular diagnostic challenge due to its clinical and histopathological overlap with inflammatory, infectious, granulomatous, and even lymphoproliferative conditions (5,6).
Case presentation: We report the case of an 80-year-old male patient with a history of narrow-angle glaucoma and blindness, evaluated for an indurated lesion in the left nasociliary region. Laboratory studies demonstrated a markedly elevated serum IgG4 level of 1,605 (upper reference limit: 0.864), along with significantly increased total IgE. Available autoimmune workup, including ANA, anti-dsDNA, anti-Ro, rheumatoid factor, and VDRL, was negative, and no clinical features suggestive of systemic connective tissue disease were identified on targeted history-taking. The patient had previously received methotrexate, which was discontinued due to intolerance reported as alopecia. Treatment with low-dose prednisolone with a gradual taper and azathioprine as a steroid-sparing immunomodulatory agent was initiated.
Discussion: The case is consistent with a clinical-serological phenotype suggestive of probable IgG4-related ophthalmic disease; however, the absence of orbital imaging, tissue biopsy, quantification of IgG4-positive plasma cells per high-power field, IgG4/IgG ratio, storiform fibrosis, and obliterative phlebitis precludes a definitive diagnosis. Current literature emphasizes that serum IgG4 elevation is non-specific and that IgG4-related ophthalmic disease requires rigorous exclusion of mimickers, including MALT lymphoma, orbital pseudotumor, sarcoidosis, granulomatosis with polyangiitis, mycobacterial or fungal infections, and histiocytic disorders (1,5,6).
Conclusion: This case highlights the importance of a systematic, critical, and multidisciplinary diagnostic approach to periocular lesions associated with elevated serum IgG4. Although serology may raise suspicion for IgG4-related disease, it is insufficient for a definitive diagnosis. Careful exclusion of inflammatory, infectious, and lymphoproliferative mimickers is essential prior to initiating long-term immunosuppressive therapy.