Researchers from India examined the clinical course and outcomes of anti-aquaporin 4 antibody positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) overlapping with primary Sjögren’s syndrome (pSS). Their systematic review was published in the journal Rheumatology International

In the case of NMOSD and pSS, central nervous system involvement usually has a highly relapsing course, the authors said, and added that if diagnosis is delayed and lifelong immunosuppression is not prescribed, damage accrual can cause permanent disability. It is therefore important to recognize the co-occurrence of the diseases.

In the present study, the team led by Aman Sharma, PhD, from the clinical immunology and rheumatology unit, department of internal medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India, reviewed individual patient data from case reports and case series from major databases.

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The team identified 44 patients with co-occurring pSS and NMOSD. The mean age of onset of pSS was 44.8 years while that of NMOSD was 43.2 years. 

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In about half of the patients (20), NMOSD preceded pSS, while in 13 patients, pSS preceded NMOSD. In 11 patients the diseases presented at the same time. 

The majority of patients (70.5%) had acute transverse myelitis, while a little less than half (47.7%) had optic neuritis. About a third of patients had cerebral syndrome (31.8%) and about a quarter had acute brainstem syndrome (22.7%). Finally, 11.4% of patients had area postrema syndrome and 4.5% had diencephalic clinical syndromes. 

In terms of treatment, almost all patients (90.9%) were treated with intravenous methylprednisolone in the acute phase of the disease while 34.1% were treated with plasma exchange and 22.7% were given intravenous immunoglobulin. 

In the induction/maintenance therapy phase, 36.4% of patients were given cyclophosphamide, 13.6% were treated with rituximab, 36.4% with azathioprine, and 22.7% with mycophenolate mofetil.

Only 2 patients had a monophasic disease course while in 61.4% the disease was relapsing. 

At a median follow-up of 2.4 years, the majority of patients (88.6%) had improvements while a small proportion showed either disease stabilization (6.8% of patients) or NMOSD worsening (4.5% of patients). 

“In this overlap syndrome of AQP4 + NMOSD and pSS, patients have a neurologically disabling disorder that can mimic neurological manifestations of pSS, frequently occurs prior to the onset of pSS, has a relapsing course, responds well to immunosuppressants, and necessitates indefinite treatment,” the authors of the study wrote. “Collaborative multicentre studies are needed to clarify the natural history and outcomes of this rare overlap syndrome.”


Prasad CB, Kopp CR, Naidu G, et al. Overlap syndrome of anti-aquaporin 4 positive neuromyelitis optica spectrum disorder and primary Sjögren’s syndrome: a systematic review of individual patient data. Rheumatol Int. Published online July 27, 2023. doi:10.1007/s00296-023-05397-0