Neuromyelitis optica spectrum disorder (NMOSD) encompasses autoimmune neurological diseases that result in central nervous system (CNS) lesions, such as optic neuritis, acute myelitis, and area postrema syndrome. They are also characterized by the presence of serum anti-aquaporin-4 autoantibodies (AQP4-IgG).
Currently, the main treatment strategy against NMOSD is the long-term administration of immunosuppressants to prevent relapses from occurring. This is highly important, given that the progression of neurological disturbances almost always occurs during attack episodes.
Although we can be sure that AQP4-IgG plays a fundamental role in driving disease pathology in NMOSD, the exact principles and mechanisms underpinning its role in the pathophysiology of the disease are still not fully understood. However, scientists have observed that patients who have comorbidities such as Sjögren syndrome (SjS) have a more severe presentation of the disease.
SjS is an autoimmune disorder that affects mostly females (more than 90%) and is characterized by the presence of serum anti-SSA/Ro antibodies. SjS alone affects nearly 1% of the general population.
Read more about NMOSD etiology
“Patients with SjS often have coexisting autoimmune diseases (eg, rheumatoid arthritis, systemic lupus erythematosus, Hashimoto thyroiditis, scleroderma) or hematologic diseases (eg, malignant lymphoma),” Akaishi and colleagues wrote in the Journal of Neurology. “Traditionally, the disease has been considered to be characterized by exocrine dysfunction based on glandular damage with lymphatic infiltration.”
A Combined Effect
To understand the simultaneous occurrence of the diseases, Akaishi and colleagues conducted a study recruiting 4447 patients who had neurological symptoms consistent with multiple sclerosis or a demyelinating disease. They were evaluated for positivity of serum AQP4-IgG, as well as serum anti-SSA/Ro and anti-SSB/La antibodies. They were also assessed for symptoms of SjS, such as dry eyes or dry mouth.
The results demonstrated that roughly 37.1% of participants (1651 out of 4447) were positive for serum AQP4-IgG. Patients in the AQP4-IgG category had a significantly higher probability of having comorbid SjS.
And what of their combined effects? The researchers found that the attack frequency increased among patients with AQP4-IgG-positive NMOSD with comorbid SjS.
“These suggest that the two diseases have common underlying mechanisms or susceptibility factors,” Akaishi and colleagues wrote.
An Illustrative Case Study
To better visualize how both diseases interact and progress in a single patient, we refer to a case study presented by Komai and colleagues in Modern Rheumatology.
The case details a 38-year-old female who presented with worsening muscle weakness/paresthesia, nausea, and abdominal pain. Her muscle weakness and paresthesia were more pronounced in her left lower extremity.
She had a 10-year history of longitudinally extensive transverse myelitis (LETM) based on spinal MRI and cerebrospinal fluid studies. This was diagnosed upon the presentation of lower extremity muscle weakness, nausea, and urinary incontinence, all of which were relieved upon the initiation of methylprednisolone pulse therapy.
“The patient was diagnosed with [SjS] due to xerostomia, keratoconjunctivitis, serum anti SS-A and SS-B antibodies, and massive lymphocyte infiltration in a lip biopsy specimen 9 years before her admission,” the authors of the study wrote.
Upon admission, her physicians took note of lower extremity muscle weakness, lower limb hyperreflexia, hypesthesia beneath Th5, and rectal and bladder irregularities. No ocular abnormalities were present. Her physicians estimated her Expanded Disability Status Scale to be 8.5.
Laboratory findings revealed that her C-reactive protein, interleukin-6, anti-SSA antibody, and anti-SSB antibody levels were elevated. Considering she met all the criteria of LETM, and her serum anti-AQP4 antibody was highly suggestive of the classification, she was newly diagnosed as having NMOSD with SjS.
High-dose steroid therapy was initiated, to no avail. She was then given tocilizumab, which gradually improved her symptoms. She continues to receive 8 mg/kg of tocilizumab once per month.
Following the Clues
In the case study described, the patient demonstrated pathognomonic symptoms, confirmed with laboratory findings, that would point a physician clearly in the direction of a diagnosis of NMOSD with SjS. Most of the time, a thorough physical examination combined with an exhaustive laboratory investigation is enough to reveal the underlying condition without much room for doubt.
Read more about NMOSD prognosis
The important thing to note is that both diseases can be treated simultaneously with some form of immunosuppressive therapy. In the case of this patient, while high-dose steroid therapy failed, tocilizumab worked excellently, reducing her symptoms to a controllable level. Although tocilizumab has long been touted as a therapeutic option in patients with NMOSD and SjS, this was the first case study in which its effectiveness in this combination of autoimmune diseases was described.
“High-dose intravenous steroids, including steroid pulse therapy, and immunosuppressive agents, such as azathioprine, are typically used as an initial therapy for LETM or NMO,” Komai and colleagues wrote. “Plasma exchange therapy is sometimes effective in patients, even those with steroid-resistant inflammatory demyelinating disease.”
Akaishi T, Takahashi T, Fujihara K, et al. Impact of comorbid Sjögren syndrome in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders. J Neurol. 2021;268(5):1938-1944. doi:10.1007/s00415-020-10377-6
Komai T, Shoda H, Yamaguchi K, et al. Neuromyelitis optica spectrum disorder complicated with Sjogren syndrome successfully treated with tocilizumab: a case report. Mod Rheumatol. 2016;26(2):294-296. doi:10.3109/14397595.2013.861333