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

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.

Clinical significance of anti-SSA/Ro antibody in Neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system (CNS), also described as CNS autoimmune astrocytopathy, due to the production of pathogenic antibodies against aquaporin-4 (AQP4) expressed on the foot of astrocytes. NMOSD coexists with autoimmune diseases and related autoantibodies [anti-Sjogren's syndrome A (anti-SSA)/Ro antibody, anti-Sjogren's syndrome B (anti-SSB)/La antibody, anti-nuclear (anti-ANA) antibodies, anti-double-stranded DNA (anti-dsDNA) antibody, anti-thyroglobulin antibody, and anti-thyroid peroxidase antibody]. OBJECTIVES: No precise conclusion has been drawn on the role of the anti-SSA/Ro antibody in NMOSD. Therefore, the aim of this work was to evaluate whether the anti-SSA/Ro antibody has an impact on the clinical manifestation or prognosis of NMOSD. METHODS: Data were retrospectively collected from 102 patients with NMOSD diagnosed by experienced neurologists. The study population was divided into two groups based on the serum anti-SSA/Ro antibody status: NMOSD with or without anti-SSA/Ro antibody. The clinical, neuroimaging and laboratory parameters were compared between the two groups, including the neurological symptoms, MRI results, frequency of systemic autoantibodies, Expanded Disability Status Scale (EDSS), and NMOSD relapse rate. The EDSS and relapse were applied as measures of the NMOSD patient prognostic value. Cox regression analysis was used to evaluate the prognostic impact of anti-SSA/Ro antibody on NMOSD. RESULTS: Among the 102 NMOSD patients, striking differences were observed in the positive rate of AQP4-IgG (89.2% vs. 72.3%, p = 0.046) between those patients with and without the anti-SSA/Ro antibody. In addition, NMOSD patients with anti-SSA/Ro antibody showed the presence of more frequent anti-ANA antibodies (p = 0.002), anti-SSB/La antibody (p < 0.001), anti-dsDNA antibody (p < 0.002), Sjogren's syndrome (SS, p < 0.001) and systemic lupus erythematosus (SLE, p = 0.045). Univariate and multivariate Cox regression analysis were performed to confirm that the anti-SSA/Ro antibody affected the EDSS score and the relapse of NMOSD patients. The analysis of the survival curve revealed that the EDSS score in the NMOSD patients positive for the anti-SSA/Ro antibody reached 4.0 (p = 0.035) and relapsed (p = 0.039) earlier than in the negative group. CONCLUSION: The anti-SSA/Ro antibody could be associated with disease activity and severe disability in NMOSD.

Long-term physical and neurodevelopmental outcomes after antenatal betamethasone administration for congenital heart block prevention.

INTRODUCTION: Congenital heart block (CHB) is associated with a mortality rate of 20% and requires a pacemaker in 70% of cases. Steroids can reduce morbidity and prevent the onset of CHB but may have adverse effects on growth and neurodevelopment. This study aimed to clarify the long-term effects of antenatal betamethasone administration on growth and neurodevelopment. METHODS: The subjects were children with a high risk of CHB due to a high level of maternal anti-SSA/Ro antibody or a maternal history of a previous delivery of a offspring with CHB to whom antenatal betamethasone was administered. Data on body weight, height, and blood pressure were collected as physical outcomes. The Wechsler Intelligence Scale for Children (fourth edition) or the Kyoto Scale of Psychological Development and the Pervasive Developmental Disorders Autism Society Japan Rating Scale was administered to assess the neurodevelopmental outcome. RESULTS: Fourteen children were enrolled. The body weight and height were within normal range in all children. All children had normal intelligence, and none had autism. CONCLUSION: Our study suggested that antenatal betamethasone administration has no negative effects on long-term physical and neurodevelopmental outcomes.

Impact of comorbid Sjögren syndrome in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune neurological diseases of the central nervous system, which are characterized by the presence of serum anti-aquaporin-4 autoantibodies (AQP4-IgG). An association between Sjögren syndrome (SjS) and AQP4-IgG-positive NMOSD has been proposed, but the rate of coexistence has not been determined. METHODS: In this study, 4,447 patients suspected of having NMOSD with acute neurological episodes were evaluated for the positivity of serum AQP4-IgG, serum SS-A/Ro antibody, and the presence of SjS-related symptoms (dry eye, dry mouth). RESULTS: Of the 4,447 patients, 1,651 were positive for serum AQP4-IgG, and the remaining 2,796 were negative. A significantly higher proportion of AQP4-IgG-positive patients were positive for serum anti-SSA/Ro antibody (26.3 vs. 4.5%; p < 0.0001) and anti-SSB/La antibody (7.2 vs. 1.2%; p < 0.0001) and had dry eye (9.1 vs .4.9%; p < 0.0001) and dry mouth symptoms (8.9 vs. 3.7%; p < 0.0001). More than 80% of the patients with SjS with acute neurological events such as myelitis or optic neuritis were AQP4-IgG positive. AQ4-IgG-positive patients with comorbid SjS showed a higher female rate (97.1 vs. 89.0%; p = 0.0062), a higher positivity rate for oligoclonal bands (15.4 vs. 7.5%; p = 0.029), and a higher relapse frequency (p = 0.027) than AQP4-IgG-positive patients without comorbid SjS. CONCLUSIONS: The prevalence of SjS is higher among AQP4-IgG-positive than AQP4-IgG-negative patients, with the potential prevalence of 10-20% at the diagnosis of AQP4-IgG-positive NMOSD. Comorbid SjS is more prevalent in females, and it has a higher relapse frequency among AQP4-IgG-positive patients.

Possible role of anti-SSA/Ro antibodies in the pathogenesis of pulmonary hypertension.

INTRODUCTION: There are many different causes of pulmonary hypertension and the pathogenesis of the disease is still being elucidated. Although they are not the most common, autoimmunity and inflammation have been identified as possible causes. No one autoantibody has been identified as the definite cause of pulmonary hypertension. We present a rare association of anti-SSA/Ro antibodies and isolated pulmonary hypertension. CASE PRESENTATION: A 53 year old African American female presented with abdominal pain, nausea, weight loss, dyspnea and fatigue. Upon further exam she was found to have high titers of antinuclear antibodies and anti-SSA/Ro antibodies. This antibody profile would typically be suggestive of Sjögren's Syndrome, which is characterized by dry eyes and poor salivary gland function. However, since this patient did not have any symptoms consistent with the disease a diagnosis of Sjögren's Syndrome could not be made. A combination of laboratory, imaging and diagnostic studies were done that revealed a final diagnosis of pulmonary hypertension. CONCLUSION: It is known that pulmonary hypertension has association with autoimmune diseases, however no clear markers yet exist. Anti-SSA/Ro antibodies have been rarely described in cases of pulmonary disease, and less so in pulmonary hypertension. This case describes a unique association between isolated pulmonary hypertension and anti-SSA/Ro antibody, thereby illustrating the need to investigate this autoantibody and others in the pathogenesis of autoimmune pulmonary hypertension.

Serum antinuclear antibody may be associated with less severe disease activity in neuromyelitis optica.

BACKGROUND AND PURPOSE: Antinuclear antibody-positive multiple sclerosis (MS) patients have shorter disease duration and lower Expanded Disability Status Scale (EDSS) scores. The aim of this study was to compare clinical and laboratory features between MS and neuromyelitis optica (NMO) patients with and without autoantibodies and to investigate the prognosis of NMO in patients with and without autoantibodies. METHODS: The frequencies of antinuclear, anti-Sjögren's syndrome A (SSA)/Ro, anti-Sjögren's syndrome B (SSB)/La and anti-thyroid peroxidase (TPO) antibodies in the sera of 75 NMO patients and 131 MS patients were compared. Clinical and laboratory profiles were also compared between NMO patients with and without autoantibodies, including annual relapse rate and time from onset of NMO to EDSS scores of 4.0 (limited walking but without aid) and 6.0 (walking with unilateral aid). RESULTS: More NMO than MS patients had antinuclear and anti-SSA/Ro antibodies (31% vs. 10%, P < 0.001, and 21% vs. 3%, P < 0.001, respectively). Antinuclear antibody-positive NMO patients had a lower annual relapse rate from disease onset to serum sampling compared with antinuclear antibody-negative NMO patients, independent of treatment regimen. Antinuclear antibody-negative NMO patients reached an EDSS score of 6.0 earlier than antinuclear antibody-positive NMO patients (P = 0.026). Cerebrospinal fluid cell counts were higher in anti-SSA/Ro-positive than in anti-SSA/Ro-negative NMO patients. More anti-TPO antibody-positive than anti-TPO antibody-negative NMO patients had oligoclonal immunoglobulin G bands (60% vs. 11%, P = 0.048). CONCLUSIONS: Autoantibodies possibly modulate the pathophysiology of NMO. Antinuclear antibody may be associated with less severe disease activity or less disability in NMO.

Feto-maternal outcome in pregnancies complicated by isolated fetal congenital complete heart block.

A retrospective analysis of eleven pregnancies complicated by isolated fetal congenital complete heart block (CCHB) in anti-SSA/Ro antibody positive women was carried out at a tertiary hospital in India to study the perinatal outcome. The mean gestational age at the time of detection of fetal CCHB was 24.5 ± 3.1weeks. Six mothers were asymptomatic; two had Sjögren's syndrome and three had systemic lupus erythematosus. Oral dexamethasone was given to all the patients after the diagnosis was made. There was one case of intrauterine death. Seven (63.6%) neonates needed a permanent pacemaker. There was no significant difference in the perinatal outcome in asymptomatic women with fetal CCHB and in women with connective tissue disorder and fetal CCHB. To conclude, fetal CCHB is associated with high morbidity but the presence of underlying connective disorder in the mother does not worsen the prognosis of the affected neonate.

An 11-year and 10-month-old girl with purpura and chest pain.

Mucosa-associated lymphoid tissue lymphoma (MALToma) is a type of B-cell lymphoma. Case reports of childhood thymic MALToma and its association with vasculitis are rarely found in the related literature. Herein, we present a report of an 11-year and 10-month-old girl who was initially diagnosed with cutaneous vasculitis characterized by nonthrombocytopenic palpable purpura, positive antinuclear antibody and anti-SSA (Ro) antibody. Eight months later, a thymic mediastinal mass was found. Surgical excision was performed and results of pathological analysis revealed an extranodal marginal zone CD20(+) B-cell MALToma. Benign response to the chemotherapeutic regimen of Berlin-Frankfurt-Münster group NHL-BFM 90 R2 without relapse was noted in 2 years of follow-up. For the first time, our case demonstrated some clinical evidence of the association between vasculitis and childhood MALToma.

Neonatal Lupus Erythematosus: Showing Target-like Skin Lesions / 대한피부과학회지

Neonatal lupus erythematosus(NLE) is a rare disease characterized by the transplacental passage from the mother to the fetus of autoantibodies, particularly autoantibodies of Ro family. The patient with NLE exhibits one or more of the following findings: congenital heart block, cutaneous lupus lesions, hepatobiliary disease and hematologic disorders(thrombocytopenia, anemia). We report a case of NLE in a 2-week-old male infant, born of a clinically asymptomatic mother, presenting multiple, round, target-like lesions which have not been reported in the English and Korean literature. Both infant and mother were positive for anti-SSA/Ro and anti-SSB/La.

Neonatal Lupus Erythematosus / 대한피부과학회지

Neonatal lupus erythematosus (NLE) is a transplacentally acquired autoimmune disorder, which is characterized by cutaneous lesions and/or congenital heart block and less commonly hepatic and hematologic abnormalities. Affected infants acquire anti-SSA/Ro antibody, anti-SSB/La antibody or less commonly anti-U1RNP antibody transplacentally from maternal circulation and it is generally thought that these antibodies are pathogenic. We report a case of NLE in a 40-day-old neonate who had erythematous annular patches on his face and extremities. Serological studies were reactive for antinuclear antibody of the speckled pattern and positive for anti-SSA/Ro antibodies and anti-SSB/La antibodies in both mother and infant. Addition to these findings, his mother had complained photosensitivity and arthralgia and showed hematological abnormalities including anemia and leukopenia, so we diagnosed his mother as systemic lupus erythematosus.