Biological use influences the impact of inflammation on risk of major adverse cardiovascular events in rheumatoid arthritis.

OBJECTIVES: Chronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA. METHODS: We studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease. RESULTS: Over 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk. CONCLUSIONS: RA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation.

Prevalence and target attainment of traditional cardiovascular risk factors in patients with systemic lupus erythematosus: a cross-sectional study including 3401 individuals from 24 countries.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterised by increased cardiovascular morbidity and mortality risk. We aimed to examine the prevalence of traditional cardiovascular risk factors and their control in an international survey of patients with systemic lupus erythematosus. METHODS: In this multicentre, cross-sectional study, cardiovascular risk factor data from medical files of adult patients (aged ≥18) with SLE followed between Jan 1, 2015, and Jan 1, 2020, were collected from 24 countries, across five continents. We assessed the prevalence and target attainment of cardiovascular risk factors and examined potential differences by country income level and antiphospholipid syndrome coexistence. We used the Systemic Coronary Risk Evaluation algorithm for cardiovascular risk estimation, and the European Society of Cardiology guidelines for assessing cardiovascular risk factor target attainment. People with lived experience were not involved in the research or writing process. FINDINGS: 3401 patients with SLE were included in the study. The median age was 43·0 years (IQR 33-54), 3047 (89·7%) of 3396 patients were women, 349 (10.3%) were men, and 1629 (48·1%) of 3390 were White. 556 (20·7%) of 2681 patients had concomitant antiphospholipid syndrome. We found a high cardiovascular risk factor prevalence (hypertension 1210 [35·6%] of 3398 patients, obesity 751 [23·7%] of 3169 patients, and hyperlipidaemia 650 [19·8%] of 3279 patients), and suboptimal control of modifiable cardiovascular risk factors (blood pressure [target of <130/80 mm Hg], BMI, and lipids) in the entire SLE group. Higher prevalence of cardiovascular risk factors but a better blood pressure (target of <130/80 mm Hg; 54·9% [1170 of 2132 patients] vs 46·8% [519 of 1109 patients]; p<0·0001), and lipid control (75·0% [895 of 1194 patients] vs 51·4% [386 of 751 patients], p<0·0001 for high-density lipoprotein [HDL]; 66·4% [769 of 1158 patients] vs 60·8% [453 of 745 patients], p=0·013 for non-HDL; 80·9% [1017 of 1257 patients] vs 61·4% [486 of 792 patients], p<0·0001 for triglycerides]) was observed in patients from high-income versus those from middle-income countries. Patients with SLE with antiphospholipid syndrome had a higher prevalence of modifiable cardiovascular risk factors, and significantly lower attainment of BMI and lipid targets (for low-density lipoprotein and non-HDL) than patients with SLE without antiphospholipid syndrome. INTERPRETATION: High prevalence and inadequate cardiovascular risk factor control were observed in a large multicentre and multiethnic SLE cohort, especially among patients from middle-income compared with high-income countries and among those with coexistent antiphospholipid syndrome. Increased awareness of cardiovascular disease risk in SLE, especially in the above subgroups, is urgently warranted. FUNDING: None.

What does artificial intelligence mean in rheumatology?

Intelligence is the ability of humans to learn from experiences to ascribe conscious weights and unconscious biases to modulate their outputs from given inputs. Transferring this ability to computers is artificial intelligence (AI). The ability of computers to understand data in an intelligent manner is machine learning. When such learning is with images and videos, which involves deeper layers of artificial neural networks, it is described as deep learning. Large language models are the latest development in AI which incorporate self-learning into deep learning through transformers. AI in Rheumatology has immense potential to revolutionize healthcare and research. Machine learning could aid clinical diagnosis and decision-making, and deep learning could extend this to analyze images of radiology or positron emission tomography scans or histopathology images to aid a clinician's diagnosis. Analysis of routinely obtained patient data or continuously collected information from wearables could predict disease flares. Analysis of high-volume genomics, transcriptomics, proteomics, or metabolomics data from patients could help identify novel markers of disease prognosis. AI might identify newer therapeutic targets based on in-silico modelling of omics data. AI could help automate medical administrative work such as inputting information into electronic health records or transcribing clinic notes. AI could help automate patient education and counselling. Beyond the clinic, AI has the potential to aid medical education. The ever-expanding capabilities of AI models bring along with them considerable ethical challenges, particularly related to risks of misuse. Nevertheless, the widespread use of AI in Rheumatology is inevitable and a progress with great potential.

Prevalence, Predictors, and Prognosis of Serious Infections in Takayasu Arteritis: A Cohort Study.

OBJECTIVE: To describe the incidence, risk factors, and outcomes associated with serious infections in patients with Takayasu arteritis (TA). METHODS: Serious infections, defined as infections resulting in hospitalization or death or unusual infections like tuberculosis, were identified from a cohort of patients with TA. Corticosteroid and disease-modifying antirheumatic drug (DMARD) use at the time of serious infection was noted. Demographic characteristics, clinical presentation, angiography, and disease activity at presentation, and the use of DMARDs during follow-up were compared between patients with TA with or without serious infections. Mortality in patients with TA who developed serious infections was compared to those who did not using hazard ratios (HR; with 95% CI). RESULTS: Of 238 patients with TA, 38 (16%) had developed serious infections (50 episodes, multiple episodes in 8; 3 episodes resulted in death). Among the 38 initial episodes, 11/38 occurred in those not on corticosteroids and 14/38 in those not on DMARDs. Pneumonia (n = 19) was the most common infection, followed by tuberculosis (n = 12). Patients with TA who developed serious infections vs those who did not had higher disease activity at presentation (active disease 97.4% vs 69.5%, mean Indian Takayasu Arteritis Activity Score 2010 12.7 (SD 7.3) vs 10.2 (SD 7.0), mean Disease Extent Index in Takayasu Arteritis 11.2 (SD 6.1) vs 8.8 (SD 6.1) and were more frequently initiated on corticosteroids or DMARDs. HRs calculated using exponential parametric regression survival-time model revealed increased mortality rate in patients with TA who developed serious infections (HR 5.52, 95% CI 1.75-17.39). CONCLUSION: Serious infections, which occurred in the absence of immunosuppressive treatment in approximately one-fifth of patients with TA, were associated with increased mortality in patients with TA.

Pediatric-onset Takayasu arteritis is associated with greater risk of mortality than adult-onset Takayasu arteritis-A systematic review with meta-analysis of observational cohort studies.

A subset of Takayasu arteritis (TAK) has onset in the pediatric age group (≤18 years). The differences in mortality between pediatric-onset and adult-onset TAK are unclear. Therefore, we undertook a systematic review with meta-analysis to compare mortality risk in pediatric-onset with adult-onset TAK. Scopus, Pubmed (MEDLINE and Pubmed Central), recent conference abstracts, clinicaltrials.gov, and the Cochrane database were searched up to August 2023 for relevant studies. Five studies (all of moderate or high quality on the Newcastle Ottawa scale) were identified which had compared mortality between 151 pediatric-onset and 499 adult-onset TAK. Pediatric-onset TAK was associated with a significantly higher risk of death than adult-onset TAK (pooled risk ratio 2.27, 95% confidence interval 1.05 - 4.85, I2=0%). Cardiovascular disease and infections were the major causes of death in both pediatric-onset and adult-onset TAK. Sub-group analyses identified a greater mortality risk with pediatric-onset TAK in retrospective (but not prospective) studies and in studies of high quality (but not in those of moderate quality). Meta-regression did not reveal a significant influence of differences in sex distribution or age or the proportions of patients with pediatric-onset or adult-onset TAK on the pooled mortality risk. An increased mortality risk with pediatric-onset TAK on meta-analysis is consistent with more frequent severe organ manifestations of pediatric-onset TAK (heart failure, renal failure) when compared with adult-onset TAK. Future studies should systematically evaluate differences in the pathogenesis between pediatric-onset and adult-onset to understand the reasons for such observed differences in the mortality risk.

Renal artery involvement is associated with increased morbidity but not mortality in Takayasu arteritis: a matched cohort study of 215 patients.

BACKGROUND: We analyzed differences in presentation and survival of Takayasu arteritis (TAK) with or without renal artery involvement (RAI) from a large monocentric cohort of patients with TAK. METHODS: Clinical and angiographic features were compared between TAK with versus without RAI, with bilateral versus unilateral RAI, and with bilateral RAI versus without RAI using multivariable-adjusted logistic regression. Inter-group differences in survival were analyzed [hazard ratios (HR) with 95% confidence intervals (95%CI)] adjusted for gender, age at disease onset, diagnostic delay, baseline disease activity, and significant clinical/angiographic inter-group differences after multivariable-adjustment/propensity score matching (PSM). RESULTS: Of 215 TAK, 117(54.42%) had RAI [66(56.41%) bilateral]. TAK with RAI or with bilateral RAI had earlier disease onset than without RAI (p < 0.001). Chronic renal failure (CRF) was exclusively seen in TAK with RAI. TAK with RAI (vs without RAI) had more frequent hypertension (p = 0.001), heart failure (p = 0.047), abdominal aorta (p = 0.001) or superior mesenteric artery involvement (p = 0.018). TAK with bilateral RAI (vs unilateral RAI) more often had hypertension (p = 0.011) and blurring of vision (p = 0.049). TAK with bilateral RAI (vs without RAI) more frequently had hypertension (p = 0.002), heart failure (p = 0.036), abdominal aorta (p < 0.001), superior mesenteric artery (p = 0.002), or left subclavian artery involvement (p = 0.041). Despite higher morbidity (hypertension, CRF), mortality risk was not increased with RAI vs without RAI (HR 2.32, 95%CI 0.61-8.78), with bilateral RAI vs unilateral RAI (HR 2.65, 95%CI 0.52-13.42) or without RAI (HR 3.16, 95%CI 0.79-12.70) even after multivariable adjustment or PSM. CONCLUSION: RAI is associated with increased morbidity (CRF, hypertension, heart failure) but does not adversely affect survival in TAK. Key Points •Renal artery involvement in TAK is associated with chronic renal failure. •TAK with renal artery involvement more often have heart failure and hypertension. •Bilateral renal artery involvement (compared with unilateral) is more often associated with hypertension and visual symptoms. •Renal artery involvement is not associated with an increased risk of mortality in TAK.

Increased mortality rate in Takayasu arteritis is largely driven by cardiovascular disease-a cohort study.

OBJECTIVES: To analyze the risk, causes, and predictors of mortality in Takayasu arteritis (TAK). METHODS: Survival was assessed in a cohort of patients with TAK using Kaplan-Meier curves. Age- and sex-standardized mortality ratio (SMR = observed: expected deaths) for TAK were calculated by applying age- and sex-specific mortality rates for the local population to calculate expected deaths. Hazard ratios (HR with 95%CI) for predictors of mortality based on demographic characteristics, presenting features, baseline angiographic involvement, disease activity, number of immunosuppressive medications used, procedures related to TAK, and any serious infection were calculated using Cox regression or exponential parametric regression models. RESULTS: Among 224 patients with TAK (159 females, mean follow-up duration 44.36 months), survival at 1, 2, 5, and 10 years was 97.34%, 96.05%, 93.93%, and 89.23%, respectively. Twelve deaths were observed, most of which were due to cardiovascular disease (heart failure, myocardial infarction, stroke). Mortality risk was significantly higher with TAK (SMR 17.29, 95%CI 8.95-30.11) than the general population. Earlier age at disease onset (HR 0.90, 95%CI 0.83-0.98; or pediatric-onset vs adult-onset disease, HR 5.51, 95%CI 1.57-19.32), higher disease activity scores (ITAS2010: HR 1.15, 95%CI 1.05-1.25, DEI.TAK: HR 1.18, 95%CI 1.08-1.29), any serious infections (HR 5.43, 95%CI 1.72-17.12), heart failure (HR 7.83, 95%CI 2.17-28.16), or coeliac trunk involvement at baseline (HR 4.01, 95%CI 1.26-12.75) were associated with elevated mortality risk. CONCLUSION: Patients with TAK had an elevated risk of mortality as compared with the general population. Cardiovascular disease was the leading cause of death in TAK.

Clinical metabolomics by NMR revealed serum metabolic signatures for differentiating sarcoidosis from tuberculosis.

BACKGROUND: Pulmonary sarcoidosis (SAR) and tuberculosis (TB) are two granulomatous lung-diseases and often pose a diagnostic challenge to a treating physicians. OBJECTIVE: The present study aims to explore the diagnostic potential of NMR based serum metabolomics approach to differentiate SAR from TB. MATERIALS AND METHOD: The blood samples were obtained from three study groups: SAR (N = 35), TB (N = 28) and healthy normal subjects (NC, N = 56) and their serum metabolic profiles were measured using 1D 1H CPMG (Carr-Purcell-Meiboom-Gill) NMR spectra recorded at 800 MHz NMR spectrometer. The quantitative metabolic profiles were compared employing a combination of univariate and multivariate statistical analysis methods and evaluated for their diagnostic potential using receiver operating characteristic (ROC) curve analysis. RESULTS: Compared to SAR, the sera of TB patients were characterized by (a) elevated levels of lactate, acetate, 3-hydroxybutyrate (3HB), glutamate and succinate (b) decreased levels of glucose, citrate, pyruvate, glutamine, and several lipid and membrane metabolites (such as very-low/low density lipoproteins (VLDL/LDL), polyunsaturated fatty acids, etc.). CONCLUSION: The metabolic disturbances not only found to be well in concordance with various previous reports, these further demonstrated very high sensitivity and specificity to distinguish SAR from TB patients suggesting serum metabolomics analysis can serve as surrogate method in the diagnosis and clinical management of SAR.

It's Not All About the Journal Impact Factor.

We read with great interest the recent Panorama article that discussed the rise in the Journal Impact Factor (JIF) of rheumatology journals and the potential effect of the coronavirus disease 19 (COVID-19) pandemic in this rise.1 Although there has definitely been a rise in the JIF of journals following the COVID-19 pandemic, there are concerns about some aspects of the paper that we wish to discuss in this letter.2.

Artificial intelligence-based preventive, personalized and precision medicine for cardiovascular disease/stroke risk assessment in rheumatoid arthritis patients: a narrative review.

The challenges associated with diagnosing and treating cardiovascular disease (CVD)/Stroke in Rheumatoid arthritis (RA) arise from the delayed onset of symptoms. Existing clinical risk scores are inadequate in predicting cardiac events, and conventional risk factors alone do not accurately classify many individuals at risk. Several CVD biomarkers consider the multiple pathways involved in the development of atherosclerosis, which is the primary cause of CVD/Stroke in RA. To enhance the accuracy of CVD/Stroke risk assessment in the RA framework, a proposed approach involves combining genomic-based biomarkers (GBBM) derived from plasma and/or serum samples with innovative non-invasive radiomic-based biomarkers (RBBM), such as measurements of synovial fluid, plaque area, and plaque burden. This review presents two hypotheses: (i) RBBM and GBBM biomarkers exhibit a significant correlation and can precisely detect the severity of CVD/Stroke in RA patients. (ii) Artificial Intelligence (AI)-based preventive, precision, and personalized (aiP3) CVD/Stroke risk AtheroEdge™ model (AtheroPoint™, CA, USA) that utilizes deep learning (DL) to accurately classify the risk of CVD/stroke in RA framework. The authors conducted a comprehensive search using the PRISMA technique, identifying 153 studies that assessed the features/biomarkers of RBBM and GBBM for CVD/Stroke. The study demonstrates how DL models can be integrated into the AtheroEdge™-aiP3 framework to determine the risk of CVD/Stroke in RA patients. The findings of this review suggest that the combination of RBBM with GBBM introduces a new dimension to the assessment of CVD/Stroke risk in the RA framework. Synovial fluid levels that are higher than normal lead to an increase in the plaque burden. Additionally, the review provides recommendations for novel, unbiased, and pruned DL algorithms that can predict CVD/Stroke risk within a RA framework that is preventive, precise, and personalized.

Paediatric-onset Takayasu's arteritis associates with worse survival than adult-onset Takayasu's arteritis. A matched retrospective cohort study.

OBJECTIVES: A subset of Takayasu's arteritis (TAK) begins in the paediatric age group (≤18 years). Differences in prognosis between paediatric-onset and adult-onset TAK are unclear. We compared the differences in the presentation and survival between paediatric-onset and adult-onset TAK in our cohort of TAK. METHODS: From a retrospective cohort of TAK, clinical presentation, angiographic features, treatments received, disease activity, and survival were compared between paediatric-onset and adult-onset TAK. Multivariable-adjusted logistic regression models were used to compute adjusted odds ratio (aOR) with 95% confidence intervals (95%CI) for paediatric-onset vs. adult-onset TAK. Hazard ratios (HR, with 95%CI) for mortality with paediatric-onset vs adult-onset TAK (crude, adjusted for prognostic covariates or differences in presentation) and propensity score-matched survival analyses were estimated. RESULTS: Among 56 paediatric-onset and 135 adult-onset TAK, chest pain (aOR 3.21, 95%CI 1.06-9.74), heart failure (aOR 3.16, 95%CI 1.05-9.53), headache (aOR 2.60, 95%CI 1.01-6.74), ascending aorta (aOR 3.02, 95%CI 1.04-8.80) and left renal artery involvement (aOR 2.45, 95%CI 1.04-5.80) were more frequent in paediatric-onset TAK. Despite similar longitudinal patterns of disease activity and glucocorticoid or disease-modifying antirheumatic drug (DMARD) use, mortality was higher for paediatric-onset TAK (HR, unadjusted 6.13, 95%CI 1.51-24.91; adjusted for prognostic covariates gender, diagnostic delay, baseline disease activity, number of conventional and biologic/targeted synthetic DMARDs used, 4.97, 95%CI 1.20-20.58; adjusted for differences between groups 5.54, 95%CI 1.22-25.09; after propensity-score matching for prognostic covariates, 54 pairs, log-rank p-value 0.026). CONCLUSIONS: Considering the greater mortality risk, greater vigilance is required while managing paediatric-onset TAK.

Overlap syndrome of anti-aquaporin-4 positive neuromyelitis optica spectrum disorder and systemic lupus erythematosus: A systematic review of individual patient data.

BACKGROUND: Neurological involvement can occur in systemic lupus erythematosus (SLE) due to co-existing neuromyelitis optica spectrum disorder (NMOSD). The symptoms can mimic those of neuropsychiatric manifestations of SLE. Pathogenic anti-aquaporin-4 (AQP4) antibodies, commonly found in NMOSD, are responsible for the neuroinflammatory response and secondary demyelinating lesions. These anti-AQP4 antibodies can be the drivers of neuroinflammatory process in SLE patients, which is distinct from the immunopathogenesis seen in traditional neuropsychiatric SLE. The clinical course is often a relapsing one and is managed differently. In this review, we describe and outline the clinical course and outcomes of AQP4+ NMOSD/SLE overlap cases. METHODS: To investigate the co-existence of SLE with AQP4+NMOSD, we conducted a systematic review of individual patient data from case reports and case series reported in major databases. The study extracted clinic-demographic features, imaging and laboratory profiles, treatment approaches, and outcomes of these patients. Inclusion criteria for the review required patients to have positivity for AQP4 or NMO in the blood and/or cerebrospinal fluid (CSF) and exhibit at least one manifestation of both NMOSD and SLE. RESULTS: In this overlap between SLE and AQP4+NMOSD, a high female preponderance was observed, with 42 out of 46 patients (91.3%) being female. Nearly half of the NMOSD cases (47.8%) had onset after lupus, with a median of 5 years between the two diagnoses. Hematological manifestations were seen in the majority of patients (63%), as well as longitudinally extensive transverse myelitis (87%), and brainstem involvement on imaging (29.6%). Cerebrospinal fluid analysis showed a dominantly lymphocytic pleocytosis, with oligoclonal bands being reported scarcely. Although cyclophosphamide was the most common steroid sparing agent used for maintenance, robust evidence for both efficacy and safety in AQP4+NMOSD is available for mycophenolate mofetil, azathioprine, and rituximab. The majority of reported cases showed a relapsing course, while one patient had a monophasic course. CONCLUSION: AQP4+NMOSD in SLE patients is a relapsing and neurologically disabling disorder that can mimic neuropsychiatric manifestations, frequently occurs after the onset of lupus or may predate, responds to immunosuppressants, and necessitates indefinite treatment.

Long-standing and poorly controlled disease in juvenile dermatomyositis is associated with calcinosis: a real-world experience from a low-middle income country.

To study the prevalence and predictors of calcinosis in Juvenile Dermatomyositis (JDM). Medical records over 20 years at a tertiary care rheumatology center in Northern India were reviewed to identify patients with JDM and clinical details were recorded. The frequency of calcinosis, predictors, specific treatment, and its outcomes were studied. Data are expressed as median and interquartile range. In eighty-six patients (median age 10) of JDM, the frequency of calcinosis was 18.2% (8.5% at presentation). Younger age at presentation, longer follow-up, heliotrope rash [Odds Ratio (95% confidence interval), 11.4 (1.4-92.12)], chronic or polycyclic course [4.4 (1.2-15.5)] and cyclophosphamide use [8.2 (1.6-41.9)] were associated with calcinosis. Dysphagia [0.14 (0.02-1.2)] and elevated muscle enzymes [0.14 (0.04-0.5)] were negatively associated with calcinosis. Treatment with pamidronate had a good to moderate response to calcinosis in five of seven children. Calcinosis in JDM is associated with long-standing, poorly controlled disease, and the use of bisphosphonates like pamidronate offer promise in the future for its treatment.

Overlap syndrome of anti-aquaporin 4 positive neuromyelitis optica spectrum disorder and primary Sjögren's syndrome: a systematic review of individual patient data.

Central nervous system (CNS) involvement can occur in primary Sjögren's syndrome (pSS) due to co-existing neuromyelitis optica spectrum disorder (NMOSD) which has a highly relapsing course requiring indefinite immunosuppression, and if not diagnosed early, damage accrual occurs over time leading to permanent disability and morbidity. In this review, we describe and outline the clinical course and outcomes of anti-aquaporin 4 (AQP4) antibody seropositive NMOSD with pSS overlap cases. To investigate the co-existence of AQP4 + NMOSD with pSS, we conducted a review of individual patient data from case reports and case series found in major databases. The study extracted clinico-demographic features, imaging and laboratory profiles, treatment approaches, and outcomes of these patients. Inclusion criteria for the review required patients to have positivity for anti-AQP4 or NMO-IgG autoantibodies in the blood and/or cerebrospinal fluid (CSF) and exhibit at least one manifestation of both pSS and NMOSD. In this overlap between AQP4 + NMOSD and pSS, 44 patients were included of whom 41 (93.2%) were females. The mean age of pSS onset was 44.8 ± 18.4 years and NMOSD onset was 43.2 ± 19.8 years. In 20 (45.5%) patients, NMOSD preceded pSS onset, 13 (29.5%) NMOSD occurred after pSS onset, and 11 (25%) patients had a simultaneous presentation. 31 (70.5%) patients experienced acute transverse myelitis, 21 (47.7%) optic neuritis, 14 (31.8%) cerebral syndrome, 10 (22.7%) acute brainstem syndrome, 5 (11.4%) area postrema syndrome, and 2 (4.5%) diencephalic clinical syndromes. For the treatment of acute phase, 40 (90.9%) patients received intravenous methylprednisolone, 15 (34.1%) received plasma exchange, and 10 (22.7%) received intravenous immunoglobulin; and for the induction/maintenance therapy, 16 (36.4%) patients received cyclophosphamide, 6 (13.6%) received rituximab, 16 (36.4%) received azathioprine, and 10 (22.7%) received mycophenolate mofetil. Disease course was monophasic in 2 (4.5%) and relapsing in 27 (61.4%) patients. At median (IQR) follow-up duration of 2.4 (6) years, 39 (88.6%) patients showed improvement, 3 (6.8%) showed stabilization and 2 (4.5%) showed worsening of their NMOSD manifestations. In this overlap syndrome of AQP4 + NMOSD and pSS, patients have a neurologically disabling disorder that can mimic neurological manifestations of pSS, frequently occurs prior to the onset of pSS, has a relapsing course, responds well to immunosuppressants, and necessitates indefinite treatment. Collaborative multicentre studies are needed to clarify the natural history and outcomes of this rare overlap syndrome.