This patient’s severe visual loss and degree of intraconal fat stranding was atypical for demyelinating ON or multiple sclerosis. She did not have any atherosclerotic risk factors or elevated levels of erythrocyte sedimentation rate to suggest non-arteritic and arteritic ischemic optic neuropathy respectively. The severe asymmetric bilateral optic neuropathy prompted a search for NMO and associated systemic autoimmune diseases such as SS.
CNS involvement in patients with Sjögren’s syndrome is much less common than peripheral nervous system involvement and ranges from 2% to 25% among patients
[4, 5]. Delalande et al. reviewed the neurologic manifestations in 82 patients with Sjögren’s syndrome and found that 13 out of 82 (16%) of patients had visual loss secondary to ON
. In another study by Gono et al., three of 17 (18%) primary Sjögren’s syndrome patients had ON
NMO is characterized by significant morbidity in more than 90% of cases and more than half of the affected patients will be unable to ambulate without assistance and/or be functionally blind by five years
An association between NMO, NMOSD and systemic autoimmune disease has been reported in the literature. To date, 26 cases of overlap SS and NMO have been identified
. Present studies indicate that ON in patients with SS who are seropositive for NMO-IgG signifies the coexistence of two autoimmune diseases rather than a secondary vasculitic complication of the systemic disease. Pittock et al. studied NMO or NMOSD patients who may or may not have overlap SS or systemic lupus erythematosus (SLE) disease and compared them with a control group of SS and/or SLE patients
. NMO-IgG was detected only in patients with NMO or NMOSD with or without SS or SLE and was consistently negative in the controls. Jarius et al. also studied serum samples from 109 patients with established or possible systemic autoimmune disease, and vasculitis for the presence of NMO-IgG
. They found that NMO-IgG was present only in patients with neurological manifestations consistent with NMO, NMOSD, recurrent ON or LETM. Patients with other neurological manifestations were seronegative. Furthermore, NMO-IgG serum titres in patients with NMOSD and systemic autoimmune disease did not differ significantly from those in a group of unselected control patients with NMOSD but no systemic autoimmune disease. The above studies support the concept of NMO-IgG being involved in the pathogenesis of these neurological diseases and argue against it being part of the polyclonal B cell activation found in systemic autoimmune disease.
There is no current published literature regarding screening for SS in patients with NMO. However, Sánchez-Guerrero et al. assessed the validity of several screening tests (European questionnaire for sicca symptoms
, Schirmer’s test, and wafer test
) in a group of 336 ambulatory patients with chronic diseases. They found that the combined use of a model consisting of the European questionnaire with at least one affirmative answer, a positive result for Schirmer’s test of less than five mm in five minutes, and positive wafer test results had the best performance in terms of prediction for SS with a likelihood ratio of 9:4. Given the suitability, ease of administration, low cost and minimal discomfort of the tests, they recommended their use in parallel to identify SS in ambulatory patients with chronic diseases. The availability and use of these tests may vary among different institutional practices; however, it is useful to keep in mind these tests when faced with NMO patients with possible SS.
There are therapeutic implications of the diagnosis of NMO and the interrelationships between NMO and/or NMOSD and systemic autoimmune disease. Recognition of the distinct entity of NMO and/or NMOSD from multiple sclerosis (MS) is important because treatment recommended for MS-like ON is not applicable. Patients with NMO-IgG seropositivity have been known to have a high risk of relapse at 50% or greater, and may need maintenance therapy with azathioprine for a minimum of five years
. Our patient was advised on long-term immunosuppression with azathioprine; however, she declined treatment due to financial issues. She has remained relapse-free for the past 22 months. It is possible that control of autoimmune disease may be beneficial for the treatment of NMOSD. Although treatment strategies for NMO and/or NMOSD and systemic autoimmune disease are similar and may overlap, care must be taken when treatment involves use of biologic agents targeting tumor necrosis factor and its receptors because there have been reports of associated CNS demyelinating events. Their specific effects on NMO and/or NMOSD are still unknown.