Association of Neuromyelitis Optica Spectrum Disease and Sjogren Syndrome in a Tunisian Patient
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.325317
Source of Support: None, Conflict of Interest: None
Neuromyelitis optica spectrum disorders (NMOSD) represent a severe inflammatory disease of the central nervous system (CNS) that predominantly affects the optic nerves and spinal cord. Antibodies (Ab) against aquaporin-4 (AQP4) are present in 60–80% of NMOSD patients. NMOSD is strongly associated with other systemic autoimmune diseases such as Sjögren's syndrome (SS) and systemic lupus erythematosus, and with the presence of non-organ-specific autoantibodies (NOSAs)., Herein, we report a case of NMOSD associated with SS. Further, we discuss the underlying mechanisms and therapeutic options.
A 75-year-old woman was referred to our department in August 2017 for numbness, progressive weakness of the lower limbs associated with urinary incontinence evolving since June 2017. Her family history was unremarkable. She has a history of arterial hypertension, complete arrhythmia with atrial fibrillation, and breast cancer operated and then treated with chemo and radiotherapy in 2015. The examination showed flaccid paraplegia. Spinal magnetic resonance imaging (MRI), made at the beginning of symptoms, showed anterior and intramedullary T2 hypersignal extending from D2 to D9 [Figure 1]. Brain MRI was normal. There were no abnormalities of the optic nerves. Routine biological tests were normal apart from regenerative normochromic anemia. Infectious serology (HSV, CMV, EBV, HIV, VZV, HVC, HVB, syphilis, and Lyme) was negative. Cerebrospinal fluid (CSF) analysis showed normal cell count and protein level. Onconeuronal and tumor markers were negative. The immunological assessment showed positivity of antinuclear antibody at 1/400 and anti-SSA-Ab. anti-SSB, ANCA, and antiphospholipid antibodies were absent. The vitamin B12 level was normal. An ophthalmological examination showed a positive Schirmer's test. Visual acuity was normal. Evoked visual potentials were normal. Given the extensive myelitis, NMOSD was suspected. Aquaporin-4 antibodies were positive. The diagnosis of NMOSD associated with SS was retained. Our patient was treated with corticosteroids (intravenous methylprednisolone at the dose of 1 mg/kg/day for five days then oral prednisone) and immunosuppressant drug (azathioprine). The evolution was marked by a discreet improvement in the motor skills of lower limbs. A control of spinal MRI 2 months after onset showed persistence of the medullar hypersignal with spinal cord atrophy.
Our case illustrates the association between NMOSD and SS.
NMOSD is a group of rare autoimmune diseases. They represent an idiopathic inflammatory demyelinating disease of the central nervous system that mainly affects the optic nerves and spinal cord. NMOSD is often associated with systemic autoimmune diseases or serological markers of NOSAs and has been most frequently associated with SS and anti-Ro/SSA antibody (SSA-Ab) positivity.,
The co-occurrence of NMOSD and SS has been suggested by Asian population studies. In those studies, many patients had initial neurological manifestations before the development of other features of systemic SS, such as our patient, which may result in an underestimation of NMOSD associated with SS at the time of initial neurological presentation., Around 10.5% of 153 American NMOSD patients and 44.4% of 18 French patients were SSA-Ab positives.
SSA-Ab, found in our patient, is more frequently detected than anti-La/SSB antibody (SSB-Ab) in patients with NMOSD and is associated with recurrent transverse myelitis and/or bilateral or recurrent optic neuritis.
The mechanisms underlying the co-association of SS and aquaporin-4 antibodies (AQP4-Ab) in patients with NMOSD presenting with myelitis and optic neuritis remain to be elucidated. An intrinsic link between SS and NMOSD has been suggested. Autoimmunity in the salivary gland, in the context of SS, may result in an immune response against AQP4.
According to some authors, this co-association could be due to common genetic and/or environmental factors that predispose to autoimmunity. Others suggested that SSA-Ab may contribute to the disruption of the blood-brain barrier. SSA-antigen is present in endothelial cells and SSA-Ab is thought to cause endothelial damage allowing AQP4-Ab to gain access to AQP4 in the CNS, the target antigen of AQP4-Ab, after disruption of the blood-brain barrier. Finally, others argue that the formation of AQP4-Ab is an epiphenomenon, possibly without direct pathogenic significance, that occurs as a result of secondary autoimmune sensitization to autoantigens.
There are diagnostic and therapeutic implications of interrelationships between NMOSD and SS. In fact, some studies have suggested that patients with SS with neurologic deficits, especially optic neuritis and/or longitudinally extensive transverse myelitis, should have an examination for AQP4-Ab which is an important data for prognosis and treatment. Our patient had positive anti-SSA and AQP4-Ab.
From the therapeutic standpoint, patients with NMOSD are typically treated with immunosuppressive therapies that suppress B cells or antibody production, most commonly azathioprine, rituximab, or mycophenolate. Recommended therapies for NMOSD and SS are often similar. Our patient was treated by corticosteroid and immunosuppressor drugs. The monoclonal antibody or fusion protein therapies that interfere with tumor necrosis factor-alpha function such as infliximab, adalimumab, or etanercept should be avoided because they have been associated with CNS demyelinating events and we do not know their effects on NMOSD. Komai et al. show that tocilizumab could be effective in patients with NMOSD with SS who were an unresponsive case to other immunosuppressive therapies.
Our patient illustrates a rare case of association SS and NMOSD which has not been reported in the African population before.
In conclusion, current evidence supports the hypothesis that SS and NMOSD can coexist in patients with a susceptibility to autoimmunity. We should recognize this association to ensure complete clinical and serological evaluations of these patients. Systematic prospective studies of patients with the association of NMOSD and SS may better define this relationship.
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