"Lupus Myelitis" Revisited: A Retrospective Single-Center Study of Myelitis Associated With Rheumatologic Disease.

Background and objectives: Previous reports of patients with myelitis associated with rheumatologic disease may have had unrecognized aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease (MOGAD). We clinicoradiologically and serologically characterized patients with myelitis associated with rheumatologic disease evaluated in the era of availability of MOG-IgG and more sensitive AQP4-IgG cell-based assays.

Methods: A retrospective cohort (2018-2023) at Johns Hopkins Medicine with diagnoses of myelopathy and rheumatologic comorbidity was identified by electronic medical record (EMR) query. All patients with myelitis unrelated to typical multiple sclerosis (MS) were included and analyzed by chart review.

Results: Of 238 patients identified by EMR query, 197 were excluded (148 not meeting prespecified inclusion criteria, 49 had typical MS), resulting in 41 patients for review. The mean age at myelitis onset was 44 ± 15 years; 39 (95%) were female. Rheumatologic diagnoses included 17 (41.5%) with systemic lupus erythematosus (SLE), 10 (24.3%) Sjögren syndrome (SS), 6 (15%) undifferentiated connective tissue disease (UCTD), 5 (12%) combinations of SLE/SS/UCTD with antiphospholipid antibody syndrome, 1 (2.4%) rheumatoid arthritis, 1 (2.4%) psoriatic arthritis, and 1 (2.4%) Behçet disease. 20 patients (49%) were diagnosed with AQP4-IgG seropositive NMOSD, 3 (7%) with MOGAD, and 18 (44%) had "double-seronegative" myelitis. Of these 18, 3 were diagnosed with AQP4-IgG seronegative NMOSD, 1 neuro-Behçet disease, and 14 other (unclassifiable) myelitis. Excluding 1 patient with neuro-Behçet disease, 18 (90%) of 20 AQP4-IgG seropositive patients had longitudinally extensive cord lesions compared with 5 (29%; p < 0.001) of 17 "double-seronegative" patients and 2 (67%) of 3 with MOGAD. "Double-seronegative" patients more commonly had CSF-restricted oligoclonal bands. Functional outcomes did not differ by diagnosis, and most patients received acute immunotherapy at the time of initial myelitis diagnosis with at least partial recovery over a median follow-up of 38 (interquartile range: 9-74) months.

Discussion: Approximately half of our rheumatologic disease cohort with myelitis unrelated to MS had AQP4-IgG seropositive NMOSD while MOGAD accounted for a small but clinically relevant proportion of patients. Further research is needed to characterize myelitis etiology in patients who are seronegative for both AQP4-IgG and MOG-IgG.