Case Report: IgG4-related disease presenting with prominent oculomotor nerve palsy

Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder that uncommonly involves cranial nerves. Oculomotor nerve palsy as the predominant manifestation of IgG4-RD is exceptionally rare and may elude timely diagnosis due to nonspecific symptoms.

A 76-year-old man presented with a two-month history of bilateral plantar numbness and pain, followed by nausea, vomiting, and headache. The patient was hospitalized twice: first in August 2025 in the Department of Hematology, and subsequently in October 2025 in the Department of Rheumatology and Immunology. Laboratory evaluation revealed markedly elevated immunoglobulins, prompting a comprehensive workup including bone marrow aspiration, positron emission tomography-computed tomography (PET-CT), and lymph node biopsy. Histopathology demonstrated reactive lymphoid hyperplasia with abundant IgG4 + plasma cell infiltration (IgG4+ > 100 cells/HPF; IgG4/IgG ratio >40%), which established the diagnosis of IgG4-RD according to the 2019 ACR/EULAR classification criteria. During the second hospitalization, the patient developed right ptosis and diplopia, and neurological examination confirmed isolated right oculomotor nerve palsy. Contrast-enhanced brain MRI showed no structural abnormalities, and CTA, along with CSF analysis, excluded alternative etiologies such as aneurysm, neoplasm, or infection. Treatment with intravenous methylprednisolone (40 mg daily) followed by oral mycophenolate mofetil (500 mg twice daily) led to significant clinical improvement of oculomotor palsy within 4 months, with normalization of serum IgG4 levels (from a peak of 74.3 g/L to 8.94 g/L at follow-up) and reduction of inflammatory markers.

IgG4-RD should be considered in the differential diagnosis of unexplained cranial neuropathies, even in the absence of radiographic abnormalities. This case highlights that neurological recovery may be gradual and require sustained immunosuppression, and underscores the importance of multidisciplinary collaboration in managing atypical manifestations of IgG4-RD.