Neurological Manifestations of IgG4-Related Disease

Abstract

Opinion statementIgG4-related disease (IgG4-RD) is a multisystem inflammatory disorder. Early recognition of IgG4-RD is important to avoid permanent organ dysfunction and disability. Neurological involvement by IgG4-RD is relatively uncommon, but well recognised—hypertrophic pachymeningitis and hypophysitis are the most frequent manifestations. Although the nervous system may be involved in isolation, this more frequently occurs in conjunction with involvement of other systems. Elevated circulating levels of IgG4 are suggestive of the condition, but these are not pathognomonic and exclusion of other inflammatory disorders including vasculitis is required. Wherever possible, a tissue diagnosis should be established. The characteristic histopathological changes include a lymphoplasmacytoid infiltrate, storiform fibrosis and obliterative phlebitis. IgG4-RD typically responds well to treatment with glucocorticoids, although relapse is relatively common and treatment with a steroid-sparing agent or rituximab may be required. Improved understanding of the pathogenesis of IgG4-RD is likely to lead to the development of more specific disease treatments in the future.

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“…7 The presence of anti-CCP antibodies may precede clinical features onset of RA by many years. 2,21 To close the loop, RA pathology may present with abundant IgG4 plasma cells, fulfilling histological diagnostic criteria for IgG4-related disease. 1 Significant IgG4þ plasma cell infiltrates might be observed in rheumatoid arthritis, granulomatosis with polyangiitis, and lymphoma.…”

A case report of IgG4-related disease: an insidious path to the diagnosis through kidney, heart and brain

“…Moreover, IgG4-RD peripheral nerve disease has been also described, with symptoms caused both by the mass effect and by the contribution of the epineurium. Ohyama et al reported the first case of IgG4-related neuropathy where the patient exhibited sensory and motor disturbances in the extremities; the authors showed the histopathological findings of a sural nerve biopsy, characterized by a clear thickening with abundant collagen fibers and infiltration of IgG4-positive plasma cells in the epineurium [12].…”

Clinical Reasoning: Accumulating endocrinopathies in a car salesman

“…Neurologic manifestations are uncommon in IgG4-RD and include pachymeningitis sometimes leading to parenchymal involvement, intraparenchymal, meningeal, orbital, or sinus inflammatory masses (pseudotumors), possibly (multifocal) neuropathy, and hypophysitis. 4 IgG4-related hypophysitis is a recently described manifestation that is probably rare, although the incidence has not been systemically evaluated. 5 In a retrospective study, approximately 40% of cases previously diagnosed as primary lymphocytic hypophysitis were shown to be manifestations of IgG4-RD after reassessment of biopsies, indicating the growing awareness of this diagnosis.…”