Objective:

To describe a rare case of peripheral neuropathy associated with IgG4-RD and emphasize the importance of considering this entity in the differential diagnosis of progressive, treatment-resistant neuropathies.

Background:

IgG4-Related Disease (IgG4-RD) is a systemic fibroinflammatory disorder characterized by IgG4-positive plasma cell infiltration and tissue fibrosis. It commonly affects the pancreas, salivary glands, and kidneys, but neurological involvement is rare. Central nervous system manifestations such as hypertrophic pachymeningitis and hypophysitis are recognized, whereas peripheral neuropathy remains exceptionally uncommon and underreported.

Design/Methods:

A 64-year-old man presented with two months of progressive distal paresthesias in all limbs, evolving to weakness despite Vitamin B12 supplementation for presumed pernicious anemia. Neurological examination revealed distal sensory loss and areflexia. Nerve conduction studies showed a demyelinating polyneuropathy. Extensive workup, including autoimmune, infectious, and paraneoplastic panels, was negative. PET imaging revealed mild FDG uptake in omentum and mesentery. Omental biopsy demonstrated lymphoplasmacytic infiltrates with fibrosis, and serum IgG4 levels were elevated (338 mg/dL).

Results:

A diagnosis of IgG4-related disease with peripheral neuropathy was established based on clinical, serological, and histopathological findings. The patient received intravenous methylprednisolone (1 g/day for 5 days) followed by oral prednisolone taper. Over six months, he demonstrated marked improvement in motor and sensory symptoms, with serum IgG4 levels normalizing (58 mg/dL)

Conclusions:

This case highlights a rare but treatable cause of peripheral neuropathy secondary to IgG4-RD. Peripheral nerve involvement should be suspected in atypical or refractory neuropathies, especially when multisystem features are present. Early recognition and immunosuppressive therapy can prevent irreversible nerve damage and improve outcomes.