AQP4-IgG Seropositive NMOSD and Systemic Lupus Erythematosus Shown to Overlap


A recent systematic review showed that AQP4+NMOSD in patients with systemic lupus erythematosus can mimic neuropsychiatric manifestations, frequently occur after the onset of lupus or may predate, and necessitate indefinite treatment.

Chirag Rajkumar Kopp, MD, MBBS, DM, associate consultant at Apollomedics Super Specialty Hospital in Lucknow, India

Chirag Rajkumar Kopp, MD, MBBS, DM

Findings from a recently published systematic review in the journal of Lupus showed that antiaquaporin (AQP4) antibody-positiveneuromyelitis optica spectrum disorder (NMOSD) and systemic lupus erythematosus (SLE) tend to have a relapsing disease course, with lupus onset usually predating NMOSD. These results may help providers become more sensitized about the mosaic presentation of overlap syndrome and management with appropriate immunosuppressive therapy.1

In the overlap between SLE and AQP4+NMOSD (n = 46), 91.3% (n = 42) were women and nearly half of the NMOSD cases (47.8%) had onset after lupus, with a median diagnosis of 5 years between the 2 conditions. More than half patients with SLE experienced hematological (63%), mucocutaneous (54.3%), and musculoskeletal (52.2%) manifestations. The most common hematological manifestation being lymphopenia (n = 9), followed by thrombocytopenia (n = 8) and leukopenia (n = 7). Notably, transverse myelitis (TM)(89.1%) was the most common core manifestation of NMOSD followed by optic neuritis (48.8%) and others.

Lead author Chirag Rajkumar Kopp, MD, MBBS, DM, associate consultant at Apollomedics Super Specialty Hospital in Lucknow, India, and colleagues, aimed to describe and outline the clinical course and outcomes of AQP4+ NMOSD-SLE overlap cases. Kopp and colleagues conducted a systematic review of individual patient data from case reports and case series reported in major databases. The research extracted clinic-demographic features, imaging and laboratory profiles, treatment approaches, and outcomes of these patients. Patients were required to have positivity for AQP4 or NMO in the blood and/or cerebrospinal fluid and exhibit at least 1 manifestation of both NMOSD and SLE.

Myelitis was detected in 43 cases among all the patients that undergone spinal MRI. Of the cases, 87% (n = 40) of cases were of longitudinally extensive TM and 13% (n = 6) were cases of short TM. The most commonly affected site of spinal cord involvement was the cervicodorsal area, which was detected in 15 (48.4%) scans, followed by thoracic in 7 (22.6%), cervical in 6 (19.4%), and whole spine in 3 (3.7%) imaging scans. Among the brain MRI scans (n = 35), 27 (58.7%) had abnormal findings, 6 (22.2%) had optic nerve involvement, 6 (22.2%) had dorsal medulla/area postrema involvement, 8 (29.6%) had brainstem involvement, 5 (18.5%) had diencephalon involvement, and 5 (18.5%) had cerebral involvement.

READ MORE: Antinuclear Antibodies Associated With Higher Disability and Disease Severity in NMOSD

For the treatment of NMOSD in patients with SLE, intravenous methylprednisolone was administered to 40 (87%) patients, 21 (45.7%) of which received plasma exchange, and 11 (23.9%) received intravenous immunoglobulin during acute neurological attacks. There were high doses of oral prednisone were used in 33 (71.7%) patients, followed by tapering, to induce remission. In addition, patients received 1 or more steroid-sparing immunosuppressants for induction and/or maintenance therapy, including cyclophosphamide in 30 (65.2%), rituximab in 18 (39.1%), azathioprine in 21 (45.7%), and mycophenolate mofetil in 11 (23.9%) patients.

All told, the median total follow-up duration was 2 years for the patients with NMOSD and SLE. The disease course was monophasic in 1 patient (2.1%) and relapsing in 30 (65.2%), with a median relapse rate of 3. In the last follow-up visit, 38 (82.6%) patients demonstrated improvement, 5 (10.9%) showed stabilization, 3 (6.5%) showed worsening of their NMOSD manifestations, and 1 patent died because of respiratory failure.

One of the main limitations of this review was the inclusion of case reports and 2 case series, which were heterogenous in terms of the duration of follow-up and reporting of outcome measures. Thus, authors extracted individual patient data to maintain the homogeneity of observations. Despite this effort, the overall quality of evidence remained low, and authors recommended that additional data from a more extensive range of studies is needed to conduct a more detailed analysis. Researchers studied the AQP4+ subset of NMOSD only and did not include AQP4-negative NMOSD, and thus there may be cases of these subsets with SLE overlap. In addition, the analysis of neurological outcomes according to immunosuppression was unfeasible because of inconsistent regimens and durations of treatment, as well as a lack of standardized follow-up schedules.

1. Kopp CR, Prasad CB, Naidu S, et al. Overlap syndrome of anti-aquaporin-4 positive neuromyelitis optica spectrum disorder and systemic lupus erythematosus: A systematic review of individual patient data. Lupus. 2023;9612033231191180. doi:10.1177/09612033231191180
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