CNS demyelinating events in primary Sjögren's syndrome: A single-center case series on the clinical phenotype

Abstract

Objective: The study aimed to assess the prevalence, clinical characteristics, and therapeutic outcomes of the central nervous system (CNS) demyelinating disease in a large cohort of primary Sjögren's syndrome (pSS).

Methods: This is an explorative cross-sectional study of patients with pSS seen in the departments of rheumatology, otorhinolaryngology, or neurology of a tertiary university center between January 2015 and September 2021.

Results: In a cohort of 194 pSS patients, 22 patients had a CNS manifestation. In this CNS group, 19 patients had a lesion pattern suggestive of demyelination. While there were no obvious differences in the patients' epidemiological disposition or rate of other extraglandular manifestations, the CNS group differed from the remaining patients with pSS by having less glandular manifestations but a higher seroprevalence for anti-SSA/Ro antibodies. Notably, patients with CNS manifestations were often diagnosed with multiple sclerosis (MS) and treated as such, although age and disease course were atypical of MS. Many first-line MS agents were ineffective in these "MS look-alikes"; however, the disease course was benign with B-cell-depleting agents.

Conclusion: Neurological symptoms of pSS are common and clinically manifest mainly as myelitis or optic neuritis. Notably, in the CNS, the pSS phenotype can overlap with MS. The prevailing disease is crucial since it has a major impact on the long-term clinical outcome and the choice of disease-modifying agents. Although our observations neither confirm pSS as a more appropriate diagnosis nor rule out simple comorbidity, physicians should consider pSS in the extended diagnostic workup of CNS autoimmune diseases.

Keywords: MS; NMOSD; anti-SSA/Ro antibody; anti-SSB/La antibody; primary Sjögren's syndrome; salivary gland biopsy; sicca.

Figure 1

PRISMA flow diagram. PRISMA flow diagram showing the different steps of the systematic review of patients' electronic files. CNS, central nervous system; ESSDAI, EULAR Sjögren's syndrome disease activity index; ICD-10, 10th revision of the International Classification of Disease; pSS, primary Sjögren's syndrome.

Figure 2

Representative clinical case vignette of patient ID-11.

Figure 3

Representative clinical case vignette of patient ID-14.

Figure 4

Individual disease course in the CNS group. The Swimmer plot showing individual disease course and treatment response to immunotherapy since disease onset. The color of any text within bars indicates treatment. The colored lines indicate disease activity. Specific events were inserted into the bars as indicated. In the medical records of two patients, treatment history was summarized as >3 disease-modifying antirheumatic drugs (DMARD) and not further specified. AZA, azathioprine; CNS, central nervous system; CYC, cyclophosphamide; ECU, eculizumab; GA, glatiramer acetate; GSC, glucocorticosteroid; HQL, hydroxychloroquine; IFN-β, interferon β; IVIG, intravenous immunoglobulin; MS, multiple sclerosis; MTX, methotrexate; NMOSD, neuromyelitis optica spectrum disease; RTX, rituximab.

Figure 5

Pattern-based visualization of axial T2 hyperintensities distributed along with the spinal cord in the CNS group. The pattern-based approach of visualizing the distribution of axial T2 hyperintensities analyzed on axial T2-weighted magnetic resonance imaging (MRI) along with the spinal cord. The spinal cord was divided into a cervical and thoracolumbar regions as to neuroanatomical nomenclature. Within a schematic drawing of an axial slice of the spinal cord, three types of lesion patterns are shown: peripheral lesion (orange color), central lesion (red color), and dorsal lesion (green color). Numbers within colored drawings indicate the frequency among all lesions counted.