A 38-year-old Asian man with a history of sinusitis status presented at the Ophthalmology outpatient department following a surgical intervention at another hospital 3 months previously, with complaints of gradual painless blurred vision and proptosis for 6 months. There was no periocular sensory change or recent trauma. His family history was unremarkable.\nOn ophthalmic examination, best-corrected visual acuity (BCVA) was 20/30 on the right eye (OD) and 20/40 on the left eye (OS). Slit-lamp and funduscopic examination results were normal. The pupil reacted sluggishly without a relative afferent pupillary defect. Color vision was normal. Ocular motility was intact without diplopia, but exophthalmometry measurements were 21.5 mm with base 112 mm using one accurately calibrated Inami exophthalmometer (Hertel K-0161; Inami & Co., Ltd., Bunkyo-ku, Tokyo, Japan) on both eyes (OU). There was neither periocular sensory change nor palpated mass in the lower eyelid.\nThyroid function tests revealed normal free thyroxine and thyroid-stimulating hormone levels, but serological studies showed extremely high serum concentrations of IgG4 (2650 mg/dL; normal range < 135 mg/dL); elevated serum concentrations of IgG (2630 md/dL; normal range 751.0–1560.0 mg/dL); abnormal erythrocyte sedimentation rate (31 mm/h; normal range < 15 mm/1 h); and high levels of total IgE (1903.00 IU/dL; normal range < 87.00 IU/mL). The calculated serum IgG4/IgG ratio was 100% (normal range < 6%). No eosinophilia was found in the blood.\nPostcontrast T1-weighted fat-saturated magnetic resonance imaging (MRI) images showed a “doughnut” sign encircling the right optic nerve, and inferior sheath enhancement surrounding the left optic nerve was visible on the coronal MRI images (Fig. a). Bilateral “tram-track” signs were evident on the axial images (Fig. b). Bilateral enhancing lesions at the pterygoid plate, pterygomaxillary fissure, and sella region, with involvement of both maxillary nerves, were visualized using gadolinium-enhanced T1-weighted MRI (Fig. c, d). Bilateral infraorbital nerve involvement was also evident on the MR images (Fig. d, e). Enlargement of extraocular muscles, especially severe at the bilateral inferior rectus, right medial rectus, bilateral superior rectus, and bilateral lateral rectus muscles, was noted on coronal MRI images (Fig. e). Mucosal thickening in the ethmoid, maxillary, sphenoid, and frontal sinuses was also visible.\nWe referred this patient to the Department of Otolaryngology in our hospital for surgical biopsy. Biopsy with functional endoscopic sinus surgery was performed, and a tissue specimen measuring 0.5 × 0.3 × 0.2 cm was sent to the Department of Pathology for further testing. The result revealed chronic sinusitis with dense infiltrate of lymphocytes and plasma cells. Chronic inflamed granulation tissue, aggregates of foamy histiocytes, and fibrosis of sinonasal tissue were also noted (Fig. a–c). Organisms were not identified in the Periodic Acid-Schiff stain and the Acid-fact stain tests. Immunhistochemistry revealed CD138 accentuated plasma cells (Fig. d) and highlighted numerous IgG4-positive plasma cells (> 50 IgG4-positive plasma cells per high-power field), of which over 40% were IgG-positive plasma cells (Fig. e, f).\nThe patient underwent a treatment regimen comprising oral systemic corticosteroids (prednisolone 1 mg per kg body weight daily) for 2 weeks followed by slow tapering. Visual acuity improved to 20/25 (OU) 1 month after initiating treatment. Four months after the initial treatment, the vision got worse again, with the BCVA dropping to 20/30 (OD) and 20/50 (OS), respectively. Visual field test showed parafoveal scotoma (OD) and an enlarged blind spot (OS). Visual evoked potentials indicated bilateral delayed P100 latency (Fig. f). No active lesions were found after systemic screening. Based on the combined clinical, radiographic, and histopathologic findings, the final diagnosis was IgG4-RD with bilateral optic perineuritis, branches of trigeminal nerves involvement, and pansinusitis.\nThe patient underwent another course of oral prednisolone daily for 2 weeks with gradually tapering of dosage. This was followed by treatment with the immunosuppressive agent azathioprine (50 mg, twice daily). The final BCVA was 20/20 (OD) and 20/25 (OS) during the follow-up period of 2 years.
A 54-year-old man with a 4-month history of recurrent sinusitis, 100-lb unintentional weight loss, gait instability, and generalized weakness presented with headache and painless, bilateral visual loss. Bilateral temporal artery biopsies were performed and showed no arteritis. Magnetic resonance imaging (MRI) of the brain revealed mild meningeal enhancement and a chronic subdural hematoma causing mild midline shift. Following surgical drainage, visual acuity remained unchanged, and his headaches worsened. Pertinent clinical findings were no light perception in both eyes, amaurotic pupils, and bilateral mild, temporal optic disc pallor. Ocular coherence tomography (OCT) of both optic nerves demonstrated normal nerve fiber layer thickness. Laboratory tests failed to suggest an etiology of his vision loss. Lumbar puncture showed lymphocytic pleocytosis but cytology and flow cytometry were negative for lymphoma. Repeat brain MRI was performed and demonstrated diffuse pachymeningeal enhancement (Fig. a) with possible involvement of the optic nerve sheath (Fig. b); a dural biopsy was performed.\nHistopathology demonstrated a dense infiltrate of lymphocytes and plasma cells, with no definite vasculitis or granulomatous inflammation (Fig. c, d). The possibility of marginal zone lymphoma was considered but was ruled out by immunohistochemistry, with T cells (CD3-positive) outnumbering B cells (CD20-positive), and with in situ hybridization revealing a kappa:lambda ratio of <4:1 among the plasma cells (not shown). In situ hybridization for Epstein-Barr virus was negative (not shown). Additionally, molecular genetic studies did not show any evidence of a clonal IgH gene rearrangement by polymerase chain reaction (PCR). However, IgG4 immunostain was markedly positive, with 40 IgG4-positive cells per high-power field (HPF), comprising over 40 % of the total plasma cell population (Fig. e, f). (The total plasma cell population was assessed with CD138 immunostain, and IgG immunostain was also obtained, showing that all IgG-positive cells were also IgG4-positive, i.e., IgG4:IgG ratio of 1, not shown). Subsequent bone marrow biopsy also showed no evidence of lymphoma (small CD19-positive B-cell population with normal kappa:lambda light chain ratio), and fine-needle aspiration biopsy of a left supraclavicular lymph node showed similar findings negative for lymphoma.\nOn his systemic work-up, p-ANCA was borderline positive, and serum IgG showed elevated IgG4 subclasses (148.0; normal range 2.4–121.0). Accordingly, the diagnosis of IgG4-related meningeal disease was made. The patient was started on aggressive immunosuppression with high-dose corticosteroids to be followed by either cyclophosphamide or rituximab. However, due to insurance issues, he was able to receive only methotrexate. There was near-total resolution of meningeal enhancement on repeat MRI, but his visual acuity improved to only bare light perception in both eyes. He remains stable on methotrexate almost 1 year from his diagnosis.