A case of biopsy proven IGG4 related recalcitrant nodular scleritis

Background: IgG4-related disease (IgG4-RD) is a chronic, immune-mediated fibroinflammatory condition recognized as a multisystem disorder, often presenting with organomegaly, fibrosis, and organ dysfunction (1,2,10). Histopathologically, it is characterized by dense lymphoplasmacytic infiltrates enriched in IgG4-positive plasma cells, frequently accompanied by elevated serum IgG4 concentrations (2,3). IgG4-RD can affect multiple organs, including the pancreas, salivary glands, kidneys, lungs, retroperitoneum, and lymph nodes (1–3,10). In the orbit, IgG4-related ophthalmic disease (IgG4-ROD) most commonly manifests as lacrimal gland enlargement but may also involve extraocular muscles, orbital soft tissue, infraorbital nerve, and, less commonly, the sclera (4–6,10,11). IGG4 related nodular scleritis remains rare and poorly understood, with only 3 cases reported in the literature from our estimates. (7–9).

Case Presentation: A 68-year-old woman with gastro-oesophageal reflux disease, hypertension, and a transient ischaemic attack presented with a two-week history of left ocular pain and redness. Best- corrected visual acuity was 6/6 bilaterally, with intraocular pressures of 22 and 19 mmHg. Examination revealed inferotemporal scleral injection with mild tenderness; the anterior chamber was quiet, and posterior segment imaging including OCT was unremarkable. B-scan ultrasonography was negative for posterior scleritis (T-sign), and phenylephrine testing confirmed non-blanching deep episcleral vessels. She was diagnosed with non-necrotising anterior scleritis and commenced on topical prednisolone and oral NSAIDs. One week later, vision remained 6/6, but scleral injection worsened with new chemosis. Topical dexamethasone and oral naproxen were initiated. Subsequently, a new inferotemporal scleral nodule (5.5 × 5.5 mm) was noted without thinning or necrosis; B-scan remained negative. High-dose oral prednisolone initially improved symptoms; however, she relapsed within one month with recurrent nodular scleritis and steroid-induced ocular hypertension (39 mmHg). Prednisolone was tapered, and topical fluorometholone substituted for stronger steroids. Given the relapsing course, she was referred to immunology and started on methotrexate. Symptoms persisted, prompting initiation of rituximab. Repeat bloodwork showed persistently elevated serum IgG (3.7 g/L). Scleral biopsy revealed a dense lymphohistiocytic and plasmacytic infiltrate without germinal centre formation. Immunohistochemistry demonstrated approximately 225 IgG+ and 130 IgG4+ plasma cells per high-power field, confirming IgG4-ROD, subsequently verified by expert review. Systemic evaluation, including whole-body FDG-PET/CT and MRI of the brain and orbits, excluded systemic involvement or malignancy. At follow-up, visual acuity remained 6/6 bilaterally, with marked improvement in scleral injection and tenderness, though mild intermittent discomfort persisted.

Discussion: This case illustrates the diagnostic and therapeutic challenges of IgG4-related nodular scleritis (IgG4-RNS), a rare manifestation of IgG4-RD. While IgG4-ROD is increasingly recognized, nodular scleritis is uncommon, with few biopsy-confirmed reports (7–9). Resistance to corticosteroids and methotrexate highlights the role of biologic therapy, such as rituximab, in refractory cases. Histopathology and systemic imaging were essential for diagnosis and exclusion of alternative aetiologies, with persistently elevated serum IgG4 providing supportive evidence.

Conclusion: IgG4-RNS should be considered in relapsing or treatment-resistant scleritis. Early recognition, histopathologic confirmation, and a multidisciplinary approach are critical. Biologic therapy with rituximab may be required in refractory disease, emphasizing the need for individualized, stepwise management and long-term surveillance for systemic involvement.