Characterization of the neuromuscular manifestations in patients with IgG4-related disease: a systematic review

Immunoglobulin G4-related disease (IgG4-RD) neurological involvement typically presents as pachymeningitis. However, there have been reports of neuromuscular manifestations. To review the involvement of the peripheral nerves, neuromuscular junction, and muscles in IgG4-RD, we conducted a systematic review of case reports and case series of patients with IgG4-related disease (IgG4-RD) presenting with neuromuscular manifestations, using the PubMed/MEDLINE, Embase, and Scopus databases. Articles were analyzed for demographic characteristics, neurological presentations, systemic involvement, and investigative findings (laboratory, electrophysiological, and pathological). A total of 38 articles, encompassing 42 cases of neuromuscular manifestations in patients with IgG4-RD, were included. Peripheral nerve involvement was frequently reported (25/42, 60%). The most common clinical presentations were mononeuritis multiplex (48%) and polyneuropathy (20%). Electrodiagnostic studies revealed an axonal pattern in 88% of cases, while nerve biopsies were compatible with vessel and nerve infiltration by IgG4-positive cells in 46% (6/13) of cases. Involvement of the neuromuscular junction was infrequently reported (n = 4), presenting as Lambert-Eaton syndrome (25%) or myasthenia gravis (75%), with all cases being negative for anti-acetylcholine receptor antibodies. Muscle involvement (n = 13) manifested as focal myositis in 53% and a limb-girdle muscle weakness pattern in 47%. Creatine kinase levels were elevated in 53%, and muscle biopsy demonstrated IgG4-positive cell infiltration in all focal myositis cases. Our review suggests that typical neuromuscular manifestations in patients with IgG4-RD include mononeuritis multiplex, polyneuropathy, and focal myopathy. However, comorbid conditions should also be considered as potential contributors to neuromuscular manifestations.