Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a rare, immune-mediated fibroinflammatory condition that can affect multiple organs. It is characterized by elevated serum IgG4 levels, lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis. Diagnosis can be challenging due to limited awareness amongst clinicians and its wide range of clinical manifestations. We present a case of an elderly woman with bilateral orbital IgG4-RD and perineural spread, a rare manifestation of the disease. Serological testing showed markedly elevated IgG4 levels, and imaging revealed bilateral extraocular muscle enlargement and inflammatory involvement of the lacrimal glands, orbital fat, and trigeminal nerves. The patient initially responded to oral prednisone but discontinued therapy due to side effects. Rituximab, a second-line treatment, caused anaphylaxis, prompting a switch to azathioprine, which led to normalization of IgG4 levels and resolution of symptoms. This patient's positive response to azathioprine highlights the importance of individualized therapeutic strategies in managing this complex condition. This case also underscores the importance of recognizing IgG4-RD as a potential cause of orbital and neurological symptoms. Increased awareness of its diverse clinical and imaging features can facilitate early diagnosis and treatment. To date, this is one of the few documented cases of orbital IgG4-RD with perineural spread, emphasizing the need for further research and reporting to enhance understanding of this rare manifestation.