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Purpose: To examine the ocular signs and symptoms in participants of the Sjögren's International Collaborative Clinical Alliance cohort, and to compare them across Sjögren's disease (SjD) status., Methods: Our study population comprised 3380 Sjögren's International Collaborative Clinical Alliance participants who had no missing data relevant to this study. Participants' SjD status was assessed using the updated 2016 American College of Rheumatism/European League Against Rheumatism SjD classification criteria. Participants completed baseline questionnaires of ocular symptoms and underwent ocular examinations. Differences in the ocular signs and symptoms between SjD and non-SjD groups were assessed. We used multivariable linear and linear mixed-effects models to investigate the impact of SjD on Ocular Surface Disease Index-6 and OSS., Results: Among 1532 participants classified as SjD, their Ocular Surface Disease Index-6 did not clinically differ from those classified as non-SjD (adjusted difference, -0.97; 95% confidence interval, -1.52 to -0.41). However, SjD participants exhibited an elevated ocular staining score (adjusted difference, 3.47; 95% confidence interval, 3.36-3.57; P < 0.001) compared with non-SjD participants. In addition, SjD was associated with increased odds of ocular signs, such as reduced tear break-up time, abnormal Schirmer I test, and corneal abnormalities, and was strongly related to more intense corneal and conjunctival staining, as well as additional corneal staining points., Conclusions: SjD is associated with a higher risk of ocular signs and pathology compared with non-SjD, whereas ocular symptoms remain similar. In addition, corneal abnormalities and corneal staining patterns could serve as a potential biomarker in identifying SjD-related dry eye.

Background: The Primary Sjögren's Syndrome Quality of Life questionnaire (PSS-QoL) is the first specific instrument to assess health-related quality of life (HRQoL) in Sjögren's disease (SjD). The aim is to translate and cross-culturally adapt the PSS-QoL into Brazilian Portuguese and to evaluate its psychometric properties., Methods: The original English version was translated into Brazilian Portuguese by two native Brazilians who were proficient in the English language. The retranslation was conducted by two native Americans proficient in Brazilian Portuguese. A committee undertook an analysis of the translated and retranslated versions, resulting in the generation of the first Brazilian version, which was submitted to the cross-cultural adaptation phase. In this phase, 50 participants with SjD responded to the instrument in Stages I and II, resulting in the generation of the second and final Brazilian version. To assess the psychometric properties, demographic and clinical data were collected from 75 patients. The HRQoL questionnaires (final Brazilian version of the PSS-QoL, Short Form-36 Health Survey (SF-36) and EuroQoL-5 dimension (EQ-5D)) were completed. Construct validity was analyzed using the Pearson or Spearman correlation coefficient. Reliability was analyzed using Cronbach's alpha and the intraclass correlation coefficient (ICC)., Results: Eight questions and one response item were revised due to an incomprehension rate of greater than 15% among the participants in the cross-cultural adaptation phase. The final Brazilian version of the PSS-QoL was validated, revealing a high correlation between the total score and functional capacity (r= -0.713, p < 0.001), and vitality (r= -0.770, p < 0. 001) and mental health (r= -0.742, p < 0.001) domains of the SF-36 and a moderate correlation with the other domains of the SF-36 and a moderate correlation with the EQ-5D-tto (r= -0.573, p < 0.001), and EQ-5D-VAS (r= -0.559, p < 0.001). The intraobserver (ICC = 0.939; Cronbach's alpha = 0.964) and interobserver (ICC = 0.965; Cronbach's alpha = 0.964) reliability of the total score showed very high consistency., Conclusion: The Brazilian version of the PSS-QoL has been demonstrated to be a valid and reproducible instrument for the assessment of HRQoL in patients with SjD., (© 2024. The Author(s).)

Purpose: Sjögren disease (SjD) cohorts represent rich resources to study associations between dry eye/mouth (sicca) signs/symptoms and depression. Because SjD affects mainly women, little is known about men with sicca signs/symptoms and associations with depression. The Sjögren's International Collaborative Clinical Alliance contained many men allowing for studying associations between sicca signs/symptoms and depression. We hypothesized that sicca symptoms would be positively associated with depression in males., Design: Cross-sectional study., Methods: At baseline, participants completed questionnaires and underwent ocular and oral examinations. Depression was assessed using the Patient Health Questionnaire-9. Logistic regression models were used to identify associations between depression and SjD diagnostic criteria and sicca symptoms., Results: Of 309 males, 98 were classified as SjD, whereas 198 were classified as non-SjD. We found that having a labial salivary gland biopsy with focus score ≥1 foci/mm 2 was associated with a lower odds of being classified as depressed (odds ratio [OR]: 0.36, 95% CI: 0.18-0.73, P = .01). Having positive anti-Sjögren syndrome antigen A antibody was associated with lower odds of being classified as depressed (OR: 0.44, 95% CI: 0.23-0.88, P = .02). Higher odds of depression were found with ocular burning (OR: 3.16, 95% CI: 1.74-5.73, P < .001), light sensitivity (OR: 2.59, 95% CI: 1.48-4.55, P = .001), and complaints of dry mouth (OR: 4.58, 95% CI: 1.54-13.63, P = .006)., Conclusion: Ophthalmologists should be specific when inquiring about ocular discomfort (focusing on burning and light sensitivity) and consider querying about depression and/or providing mental health resources to those who endorse such qualities., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Although symptom relief is a critical aspect for successful drug development in Sjögren's disease, patient experiences with Sjögren's-related symptoms are understudied. Our objective was to determine how pain, dryness, and fatigue, the cardinal symptoms of Sjögren's disease, drive cluster phenotypes., Methods: We used data from the Sjögren's International Collaborative Clinical Alliance (SICCA) Registry and a Sjögren's Foundation survey. We performed hierarchical clustering of symptoms by levels of dryness, fatigue, and pain. Using international and US cohorts, we performed multiple logistic regression analysis to compare the clusters, which included comparisons of differences in symptoms, quality of life (QoL), medication use, and systemic manifestations., Results: Four similar clusters were identified among 1,454 SICCA registrants and 2,920 Sjögren's Foundation survey participants: 1) low symptom burden in all categories (LSB); 2) dry with low pain and low fatigue (DLP); 3) dry with high pain and low to moderate fatigue (DHP); and 4) high symptom burden in all categories (HSB). Distribution of SICCA registrants matching the symptom profile for each cluster was 10% in the LSB cluster, 30% in the DLP cluster, 23% in the DHP cluster, and 37% in the HSB cluster. Distribution of survey participants matching the symptom profile for each cluster was 23% in the LSB cluster, 14% in the DLP cluster, 21% in the DHP cluster, and 42% in the HSB cluster. Individuals in the HSB cluster had more total symptoms and lower QoL but lower disease severity than those in the other clusters. Despite having milder disease as measured by laboratory tests and organ involvement, individuals in the HSB cluster received immunomodulatory treatment most often., Conclusion: We identified 4 symptom-based Sjögren's clusters and showed that symptom burden and immunomodulatory medication use do not correlate with Sjögren's end-organ or laboratory abnormalities. Findings highlight a discordance between objective measures and treatments and offer updates to proposed symptom-based clustering approaches., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Purpose: To develop a screening questionnaire to identify patients with dry eye with a high likelihood of having underlying Sjögren syndrome (SS)., Methods: This was a cross-sectional study of participants with dry eye complaints who were self-referred or referred by an ophthalmologist to the Sjögren's International Collaborative Clinical Alliance study. Symptoms and ocular surface examination findings were candidate predictors. Univariable and multivariable logistic regression analyses were performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for the association of a symptom and/or ocular sign with SS. Area under the receiver operating characteristic curve (AUC) was used to summarize the predictive ability of different regression models and the derived likelihood score., Results: Four questions were statistically significant in the final multivariable model: 1) Is your mouth dry when eating a meal? [Yes = OR 1.63 (1.18-2.26)]; 2) Can you eat a cracker without drinking a fluid or liquid? [No = OR 1.46 (1.06-2.01)]; 3) How often do you have excessive tearing? [None of the time = OR 4.06 (1.81-9.10)]; and 4) Are you able to produce tears? [No = OR 2.24 (1.62-3.09)]. The SS likelihood score had an AUC of 0.70 (95% CI, 0.66-0.73), and when including tear break-up time and conjunctival staining, it yielded an AUC of 0.79 (95% CI, 0.77-0.82)., Conclusions: This questionnaire can be used to identify patients with dry eye with a high likelihood of having SS. With future refinement and validation, this screening tool could be used alone or in combination with examination findings to identify patients with SS earlier, thereby facilitating better clinical outcomes., Competing Interests: V. Y. Bunya: Bausch & Lomb (funding for research study); Celularity (consultant); Verily (consultant). E. K. Akpek: Allergan Inc. (institutional support), Novalique Gmb. (consultant), Regeneron (consultant), Sjogren's Syndrome Foundation (unpaid board member). M. Massaro-Giordano: Celularity (consultant); PRN (personal financial interest); Verily (consultant). F. B. Vivino: Novartis (consultant), Biogen-Idec (consultant), Celularity (consultant), Boston Pharmaceuticals (consultant) Bristol-Myers Squibb (consultant), Immco Diagnostics (consultant). A. N. Baer: Bristol-Myers Squibb (consultant), Abbvie (consultant), Sanofi (consultant). The remaining authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

To gain insight into the Sjögren's disease (SjD) patient experience using a survey generated by patients and providers. We evaluated the results of the 2016 Sjögren's Foundation survey, with 25 questions designed in a collaborative effort between the Foundation, patients with SjD, SjD provider experts, and a marketing research company. We used descriptive statistics to provide a thorough understanding of SjD demographics, symptoms, quality of life (QoL), cost, and treatments. Analyses revealed high symptoms, QoL, and financial burdens in SjD. Dry mouth and eye were the most commonly reported symptoms (94 and 93%, respectively). The most frequent extra-glandular symptoms included fatigue, dry or itchy skin, and morning stiffness. The top three aspects of QoL most impaired included (i) sex life (53%), (ii) participating in hobbies/social activities/extracurricular activities (52%), and (iii) job/career or ability to work (49%). SjD respondents commonly reported taking health food supplements/remedies, vitamin D, and exercising, in addition to taking treatments for symptomatic dryness. SjD costs were high, including a total yearly cost, on average, of $2026 for dental care. SjD respondents reported that dryness and risk factors for lymphoma and fatigue are essential to address with new therapies. In this comprehensive overview of the SjD experience, we demonstrated a high burden of disease to SjD respondents, including symptoms, QoL, and financial burden. We also identify the top goals of therapy for new systemic SjD therapies. Key Points • The top three symptoms or signs that patients with Sjögren's hope new treatments will address are dryness, fatigue, and reduction in lymphoma or blood cancer risk • The top aspects of quality of life reported to be impaired by Sjögren's are sex life, hobbies, social activities and extracurricular activities, job/career or ability to work, and finding the correct word during conversations • Patients with Sjögren's have a yearly mean dental cost of $2026 but also have high costs associated with prescription medications, healthcare appointments, over-the-counter medications, alternative therapies, and medical equipment., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: Sjögren's syndrome (SS) is frequently undetected or misdiagnosed as other rheumatologic diseases. We aimed to develop an SS screening questionnaire for the rheumatology practice., Methods: We developed the Sjögren's Syndrome Screening Questionnaire (SSSQ) via secondary analysis of data from 974 participants referred by rheumatologists to the Sjögren's International Collaborative Clinical Alliance (SICCA) study. Participants answered 88 questions regarding symptoms, medical history, and demographics. They underwent ocular, dental, and serologic tests and were classified as SS or non-SS using the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria. We conducted univariate and multivariate logistic regression to identify questions most discriminative of SS, from which we derived an individual's likelihood of SS ("SSSQ score")., Results: Five questions were significantly discriminative of SS in the multivariate analysis (p < 0.05): (1) Can you eat a cracker without drinking a fluid/liquid? (no: odds ratio [OR], 1.39; 95% confidence interval [CI], 1.06-1.82]); (2) How would you describe your dental and oral health in general? (fair/poor: OR, 1.68; 95% CI, 1.04-2.75); (3) During the last week, have you experienced tearing? (none of the time: OR, 2.26; 95% CI, 1.23-4.34); (4) Are you able to produce tears? (no: OR, 1.62; 95% CI, 1.12-2.37); and (5) Do you currently smoke cigarettes? (no: OR, 2.83; 95% CI, 1.69-4.91). SSSQ score ≥7 (possible range, 0-11) distinguishes SS from non-SS patients with 64% sensitivity and 58% specificity (area under receiver operating characteristic curve, 0.65)., Conclusions: The SSSQ is a simple 5-item questionnaire designed to screen for SS in clinical practice, with a potential impact to reduce delays in diagnosis., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: This review aims to enhance understanding of juvenile Sjögren's disease (jSjD) by exploring diagnostic criteria, ocular clinical features, ancillary ophthalmic testing, and management strategies specific to this rare pediatric condition., Recent Findings: Unlike adults, children with jSjD often present with recurrent parotitis and extra-glandular symptoms before developing sicca symptoms. Adult SjD classification criteria do not consider pediatric-specific symptoms and physiological differences. Underutilization of diagnostic tests such as the ocular staining score (OSS) and Schirmer I may result in an incomplete understanding of the prevalence of keratoconjunctivitis sicca in jSjD., Summary: Timely referral to an ophthalmologist can address perceived feasibility issues with respect to ocular features in jSjD. Management of keratoconjunctivitis sicca in jSjD includes improving ocular surface lubrication and decreasing inflammation. Recognition of pediatric-specific clinical features and development of universally accepted jSjD classification criteria will allow for better identification of potential participants for future jSjD studies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To define the association between oral and systemic manifestations of Sjögren syndrome (SS) and quality of life (QOL)., Methods: We analyzed a cross-sectional survey conducted by the Sjögren's Foundation in 2016, with 2961 eligible responses. We defined oral symptom and sign exposures as parotid gland swelling, dry mouth, mouth ulcers/sores, oral candidiasis, trouble speaking, choking or dysphagia, sialolithiasis or gland infection, and dental caries. Systemic exposures included interstitial lung disease, purpura/petechiae/cryoglobulinemia, vasculitis, neuropathy, leukopenia, interstitial nephritis, renal tubular acidosis, autoimmune hepatitis, primary biliary cholangitis, or lymphoma. Outcomes included SS-specific QOL questions generated by SS experts and patients., Results: Using multivariable regression models adjusted for age, sex, race, and employment, we observed that mouth ulcers or sores, trouble speaking, and dysphagia were associated with poor quality of life. The following oral aspects had the greatest effect on the following QOL areas: (1) mouth ulcers/sores on the challenge and burden of living with SS (OR 4.26, 95% CI 2.89-6.28); (2) trouble speaking on memory and concentration (OR 4.24, 95% CI 3.28-5.48); and (3) dysphagia on functional interference (OR 4.25, 95% CI 3.13-5.79). In contrast, systemic manifestations were associated with QOL to a lesser extent or not at all., Conclusion: Oral manifestations of SS, particularly mouth ulcers or sores, trouble speaking, and dysphagia, were strongly associated with worse QOL. Further study and targeted treatment of these oral manifestations provides the opportunity to improve quality of life in patients with SS., (Copyright © 2021 by the Journal of Rheumatology.)

Objective: To evaluate how ocular, oral, and bodily neuropathic pain symptoms, which characterize small fiber neuropathies, are associated with Sjögren's syndrome (SS) classification based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria., Methods: Participants enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) registry had ocular, rheumatologic, oral, and labial salivary gland (LSG) biopsy examinations, blood and saliva samples collected, and completed questionnaires at baseline. We used mixed effects modeling with age, country, gender, and depression being fixed effects and study site, a random effect, to determine if neuropathic pain indicators (assessed via questionnaires) were associated with being classified as SS., Results: A total of 3,514 participants were enrolled into SICCA, with 1,541 (52.9%) meeting the 2016 ACR/EULAR classification criteria for SS. There was a negative association between being classified as SS and experiencing bodily neuropathic pain features of needle-like pain, prickling/tingling sensation, ocular neuropathic pain of constant burning, and constant light sensitivity, and having a presumptive diagnosis of neuropathic oral pain., Conclusions: We found that those classified as SS had lower scores/reports of painful neuropathies compared with those classified as non-SS. Non-SS patients with dry eye disease or symptoms could benefit from pain assessment as they may experience painful small-fiber neuropathies (SFNs). Pain questionnaires may help identify pain associated with SFNs in patients with SS and non-SS dry eye. Future studies would be helpful to correlate self-reports of pain to objective measures of SFNs in those with SS, non-SS dry eye, and healthy controls., (© 2021 World Institute of Pain.)

The purpose of this review is to delve into the clinical and research understanding of the pathophysiology and presentation of Sjögren's-related keratoconjunctivitis sicca in order address the diagnostic and management challenge that it represents, as well as to provide a basis for appreciating the pharmacotherapies designed to treat the ophthalmic symptoms of Sjögren's disease.

Purpose: This study analyzed the association between anti-Ro/SSA and anti-La/SSB antibody levels with quantitative and visual sialoscintigraphy patterns in patients suspected of having Sjögren or sicca syndrome., Patients and Methods: Medical records of patients who underwent sialoscintigraphy between April 2020 and May 2022 were reviewed. Associations between antibody levels and sialoscintigraphy parameters were evaluated using linear regression. Receiver operating characteristic curve analysis was used to identify antibody cutoff values for predicting flat-type patterns and the risk of Sjögren or sicca syndrome., Results: Of the 170 patients (mean age, 56.6 years; 78.8% female), 95.3% had dry mouth and eyes, 30% experienced polyarthralgia, and 66.5% were prescribed hydroxychloroquine. The most common sialoscintigraphy finding was the median-type time-activity curve (TAC) pattern. Anti-Ro/SSA and anti-La/SSB levels were significantly correlated with maximum accumulation or maximum secretion in the salivary glands. Receiver operating characteristic analysis for anti-Ro/SSA predicting a flat-type TAC pattern showed an area under the curve (AUC) of 0.659 to 0.780, with specificity between 82.1% and 86.3% for antibody levels greater than 85.2 units. Anti-Ro/SSA levels greater than 49.75 units predicted a higher risk of Sjögren or sicca syndrome, with an AUC of 0.622 and 83.9% specificity. Anti-La/SSB levels had no significant predictive value, with an AUC of 0.554., Conclusions: Anti-Ro/SSA levels greater than 85.2 units were strong predictors of flat-type TAC patterns, indicating near-total salivary gland dysfunction and supporting their diagnostic utility in Sjögren or sicca syndrome., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To compare the burden related to dry eye with systemic symptoms of Sjögren syndrome; to estimate the burden related to ocular treatments; and to compare the impact of dry eye and extraocular manifestations of Sjögren syndrome on various aspects of patient life., Design: Cross-sectional study., Methods: We conducted a postal survey of adult patients with a history of physician-diagnosed Sjögren syndrome., Results: The survey was completed by 2,961 patients (mean age 65.1 years, standard deviation 11.7 years), most of whom were women (96%) and white (94%). Forty-one patients younger than 18 years of age were excluded. More than half (53%) experienced severe dry eye (ie, dry eye daily/almost daily with major impact on their life). Corresponding proportions for dry mouth and fatigue were 48% and 45%, respectively. Almost all patients (97%) had used nonprescription eye drops/artificial tears/ointments. Compared with patients who did not experience dry eye, those who experienced significant dry eye (ie, daily/almost daily dry eye) more often agreed that living with Sjögren syndrome made every day a challenge (adjusted odds ratio [OR] 3.81, 95% confidence interval [CI] 2.49 to 5.86) and added a significant emotional burden (adjusted OR 2.22, 95% CI 1.49 to 3.31). Adjusted ORs for the impact of dry eye were generally lower than those for fatigue, but were similar to dry mouth and considerably higher than use of systemic treatments for serious manifestations of the disease and diagnosis of lymphoma., Conclusions: Sjögren-related dry eye is more burdensome than systemic manifestations of the disease. While fatigue has the greatest impact on patient life, the impact of dry eye is comparable to that of other systemic manifestations., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Our study aimed to make a bibliometric analysis on Sjögren's syndrome-related dry eye disease (SS-DED), explore its potential research hotspots, and provide critical information for future research interest and undeveloped topics in this field, which can benefit clinicians and researchers., Methods: We extracted all publications relating to SS-DED from 2003 to 2022 from the Web of Science Core Collection database. Original articles and reviews in English were included. The contributions of different countries, institutions, journals, and authors were compared, and the research hotspots were visualized for network analysis through GraphPad Prism, CiteSpace, and VOSviewer., Results: We enrolled a total of 987 publications. The United States contributed the most publications (281, 28.5%), followed by China (157, 15.9%) and Japan (80, 8.11%). Publications from the United States were cited more frequently (13,060 citations), with the highest H-index of 57. China ranked second in the total number of publications, the papers were not cited frequently (3790 citations), and the H-index ranked second (H-index = 31). PLoS One (32, 3.24%) published the most papers, and the University of California system had the highest number of publications (45, 4.56%). Bootsma H from the Netherlands published the most papers. The trend of research hotspots evolved mainly from the basic manifestation to pathogenesis and treatment of SS-DED and paid more attention to distinguishing SS-DED from that dry eye disease without SS., Conclusions: Based on the bibliometric, co-citation, and network analyses in this study, we obtained the annual publications and citations, the growth trends of publications, the productivity of countries, organizations, journals, and authors, high-quality publications, and the emerging hotspots of SS-DED, which may open new doors for promising research directions., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To evaluate the prevalence of novel candidate autoantibodies associated with Sjögren syndrome (SS) and their ability to identify those with SS among participants with dry eye enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) study at the University of Pennsylvania (Penn)., Methods: All participants previously underwent a full ocular and systemic evaluation for possible SS as part of the SICCA study. An enzyme-linked immunosorbent assay was used to detect IgG, IgA, and IgM autoantibodies to salivary protein 1 (SP-1), parotid secretory protein (PSP), and carbonic anhydrase 6 from previously banked baseline serum samples from SICCA study participants enrolled at Penn. The prevalence rate of each autoantibody, calculated by considering the presence of any isotype as antibody positive, was compared between participants with dry eye with SS (n = 81) or without SS (n = 129) using the Fisher exact test., Results: The prevalence of SP-1 IgM autoantibodies was higher in those with SS compared with those without SS (14% vs. 5%; P = 0.03). Similarly, the prevalence of PSP IgA autoantibodies was higher in those with SS compared with non-SS dry eye participants (21% vs. 11%; P = 0.048). There was no statistically significant difference in the prevalence of carbonic anhydrase 6 autoantibodies between those with or without SS (15% vs. 20%; P = 0.36)., Conclusions: In the Penn SICCA cohort, SP-1 IgM and PSP IgA autoantibodies were more prevalent in the serum of SS-related dry eye participants compared with those without SS. Further longitudinal studies are needed to determine the clinical significance of these findings.

Purpose: To determine whether signs and symptoms of ocular surface disease improve after placement of a self-retained, cryopreserved amniotic membrane (CAM) in patients with Sjögren syndrome (SS)., Methods: The medical records of SS patients who received a self-retained CAM implant (Prokera or Prokera Slim; TissueTech Inc, Doral, FL) for the treatment of ocular surface disease between August 2012 and August 2016 at a single, large academic institution were reviewed retrospectively. Visual acuity, results of slit-lamp examination of the cornea and conjunctiva, and dry eye symptoms, were evaluated before and after CAM insertion., Results: A total of 6 eyes of 6 patients (all female; mean age, 62.5 ± 13.0 years [range, 49-86 years]) were included. All patients were on topical medications at the time of the study and had signs of ocular surface dryness. There were reductions in corneal and/or conjunctival staining in 5 eyes (83%) after the CAM dissolved. All patients who completed therapy (5/5) experienced a relapse in their signs and symptoms within 1 month of removal of the CAM, with an average time to relapse of 24.6 days. Mean follow-up time was 54.5 days. Foreign body sensation and blurred vision were the most common complaints associated with the CAM implant., Conclusions: In this small case series, self-retained CAM implantation was found to be beneficial in SS patients with ocular surface disease that is refractory to standard therapies; however, we found that the effects were temporary. Future larger studies are needed to confirm these benefits.

Purpose: Sjögren's syndrome (SS) is a common autoimmune disease affecting about four million Americans. Although approximately 1 in 10 patients with clinically-significant aqueous deficient dry eye has underlying SS, widespread underappreciation of SS leads to significant underdiagnosis, delays in diagnosis, and consequent morbidity and mortality. The purpose of this article is to illustrate that in addition to dry eye, SS can cause serious, vision-threatening extraglandular ocular manifestations., Methods: We conducted a narrative review of studies that have examined the dry eye and extraglandular ocular complications of SS., Results: SS-related dry eye is a progressive condition with major negative impact on the quality-of-life of afflicted patients, not only due to symptoms of ocular discomfort but also visual dysfunction. In addition, SS can lead to corneal melt/perforation, uveitis, scleritis, retinal vasculitis, and optic neuritis. A major problem with currently-available SS disease activity measurement instruments is the lack of domains evaluating dry eye-related visual dysfunction. For example, one of the most commonly-used instruments for assessing patient symptoms in SS (the EULAR Sjögren's Syndrome Patient Reported Index [ESSPRI]) only includes one item (out of three) that addresses the severity of overall dryness, without mention of dry eye symptoms or vision-related quality-of-life. Similarly, no extraglandular ocular complications are included in currently-available SS disease activity instruments (e.g., the EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI])., Conclusions: There needs to be a paradigm shift in which eye care providers and rheumatologists become more familiar with various SS-related extraglandular ocular manifestations. Existing disease activity measurement instruments must incorporate dry eye symptoms, particularly those related to visual dysfunction. An evidence-based screening algorithm for determining which patients with dry eye should be tested for underlying SS may be particularly helpful in preventing delays in diagnosis.

Background: While retinal vessel changes are evident in the eyes of patients with relapsing-remitting multiple sclerosis (RRMS), changes in the vasculature of possible MS mimics such as primary Sjögren's syndrome (pSS) remain to be determined. We investigated the potential of retinal optical coherence tomography (OCT) angiography (OCTA) as diagnostic tool to differentiate between patients with RRMS and pSS., Methods: This cross-sectional study included patients with RRMS (n = 36), pSS (n = 36) and healthy controls (n = 30). Participants underwent clinical examination, assessment of visual acuity, retinal OCT, OCTA, and serum markers of glial and neuronal damage. We investigated the associations between OCTA parameters, visual functions, and serum markers. Eyes with a history of optic neuritis (ON) were excluded from analysis., Results: We observed a significant thinning of the combined ganglion cell and inner plexiform layer in the eyes of patients with RRMS but not with pSS, when compared to healthy controls. Retinal vessel densities of the superficial vascular complex (SVC) were reduced in both patients with RRMS and pSS. However, retinal vessel rarefication of the deep vascular complex (DVC) was only evident in patients with pSS but not RRMS. Using multivariate regression analysis, we found that DVC vessel loss in pSS patients was associated with worse visual acuity., Conclusions: Compared to patients with RRMS, rarefication of deep retinal vessels is a unique characteristic of pSS and associated with worse visual function. Assuming a disease-specific retinal vessel pathology, these data are indicative of a differential affliction of the gliovascular complex in the retina of RRMS and pSS patients., (© 2024. The Author(s).)

Background: Interstitial lung disease (ILD) is a common pulmonary manifestation of Sjögren's syndrome (SjS) and associated with an increased risk of death. Early detection and treatment of ILDs and knowing the risk factors are very important for prognosis in rheumatic diseases., Aims: This study was performed to determine ILD and associated factors in patients with SjS., Methods: Four hundred three SjS patients were evaluated in this cross-sectional cohort study. Clinical, laboratory, serological, and imaging features were compared of patients with and without pulmonary involvement. Logistic regression analyses were used to identify risk factors for lung involvement and to identify independent risk factors., Results: Thirty-five (8.7%) of SjS patients had ILD and 368 (91.3%) had no ILD. The presence of Raynaud's phenomenon was significantly more common in ILD. The geriatric age group over the age of 65 years (OR 8198; 95% CI 3788-17,742; p < 0.001), Raynaud's phenomenon (OR 17,852; 95% CI 6155-51,779; p < 0.001), and smoking (OR 3598; 95% CI 1495-8657; p = 0.003) were risk factors to be associated for ILD in the multivariable analysis. The most common abnormality was non-specific interstitial pneumonia in 20 patients (57.1%) and usual interstitial pneumonia in 15 (42.9%) patients., Conclusions: The distribution of male patients compared to female patients was higher in patients with lung involvement than in patients without lung involvement. This may be related to older age, higher smoking rate, and longer nicotine consumption in men. Age, smoking, and severity of lung involvement are more important than inflammation status and autoantibodies for prognosis., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

To identify the value of salivary gland ultrasound (SGUS) combined with magnetic resonance imaging (MRI) and magnetic resonance sialography (MRS) in predicting the results of labial salivary gland biopsy (LSGB) in patients with suspected primary Sjögren syndrome (pSS), and construct a nomogram model to predict LSGB results. A total of 181 patients who were admitted with suspected pSS from December 2018 to April 2023 were examined and divided into a training set (n = 120) and a validation set (n = 61). Baseline data of the two groups were examined, and the value of SGUS, MRI, and MRS in predicting LSGB was analyzed. Multivariate logistic analysis was used to screen for risk factors, and nomogram prediction models were constructed using these results. In the training set, the SGUS, MRI, and MRS scores of patients in the LSGB + group were higher than those in the LSGB - group (all P < 0.001). The positive prediction value (PPV) was 91% for an SGUS score of 3, and 82% for MRI and MRS scores of 2 or more. We developed a nomogram prediction model based on SGUS, MRI, and MRS data, and it had a concordance index (C-index) of 0.94. The Hosmer-Lemeshow test (χ 2  = 3.17, P = 0.92) also indicated the nomogram prediction model had good accuracy and calibration for prediction of LSGB results. A nomogram model based on SGUS, MRI, and MRS results can help rheumatologists decide whether LSGB should be performed in patients with suspected pSS., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: To survey ophthalmologists about current practice patterns regarding the evaluation of dry eye patients and referrals for a Sjogren syndrome (SS) workup., Methods: An online survey was sent to ophthalmologists affiliated with the Scheie Eye Institute or Wills Eye Hospital using REDCap in August 2015. Descriptive statistics were used to summarize the data., Results: Four hundred seventy-four survey invitations were sent out and 101 (21%) ophthalmologists completed the survey. The common traditional dry eye test performed was corneal fluorescein staining (62%) and the most common newer dry eye test performed was tear osmolarity (18%). Half of respondents (51%) refer fewer than 5% of their dry eye patients for SS workups, with 18% reporting that they never refer any patients. The most common reasons for referrals included positive review of systems (60%), severe dry eye symptoms (51%) or ocular signs (47%), or dry eye that is refractory to treatment (42%). The majority (83%) felt that there is a need for an evidence-based standardized screening tool for dry eye patients to decide who should be referred for evaluation for SS., Conclusions: Ophthalmologists continue to prefer the use of traditional dry eye tests in practice, with the most common test being corneal fluorescein staining. There is an underreferral of dry eye patients for SS workups, which is contributing to the continued underdiagnosis of the disease. Most respondents felt that there was a need for an evidence-based standardized screening tool to decide which dry eye patients should be referred for SS evaluations.

Purpose: To evaluate the prevalence of novel candidate Sjogren syndrome (SS) autoantibodies [salivary protein-1 (SP-1), parotid secretory protein, carbonic anhydrase 6] in the DRy Eye Assessment and Management (DREAM) cohort, a study evaluating the effectiveness of omega-3 fatty acid supplements for the treatment of dry eye., Methods: Participants underwent ocular surface examinations and serological testing for traditional and novel SS autoantibodies. Dry eye assessment and management participants were categorized into the following 3 groups: 1) no history of SS or other autoimmune diseases and negative traditional SS autoantibodies (n = 352); 2) no history of SS but a history of other autoimmune diseases (n = 66); and 3) those who met the 2012 American College of Rheumatology SS classification criteria (n = 52)., Results: Eleven percent had a history of SS, and 6% of those without a history of SS most likely had undiagnosed SS. The SS group had a higher prevalence of SP-1 autoantibodies than the group without SS or other autoimmune diseases (33% vs. 19%; P = 0.02) but had no difference in carbonic anhydrase 6 (P = 0.31) or parotid secretory protein autoantibodies (P = 0.33). Participants who were positive for the traditional autoantibodies alone or positive for both traditional and novel autoantibodies had the highest scores for corneal (P = 0.002) and conjunctival staining (P < 0.001)., Conclusions: Data from this multicenter, prospective study demonstrated that one of the novel candidate autoantibodies, SP-1, is associated with underlying SS and that novel autoantibodies may be associated with worse ocular surface disease. Future longitudinal studies are needed to evaluate their utility in screening patients with dry eye for SS.

Purpose: To determine whether ocular phenotypic features of keratoconjunctivitis sicca (KCS) and/or participant-reported symptoms of dry eye disease are associated with depression in women participants enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA)., Design: Cross-sectional study., Methods: Women enrolled in the SICCA registry from 9 international research sites. Participants met at least 1 of 5 inclusion criteria for registry enrollment (including complaints of dry eyes or dry mouth, a previous diagnosis of Sjögren syndrome (SS), abnormal serology (positive anti-Sjögren syndrome antigen A and/or B [anti-SSA and/or anti-SSB]), or elevated antinuclear antibody and rheumatoid factor), bilateral parotid gland enlargement, or multiple dental caries). At baseline, participants had oral, ocular, and rheumatologic examination; blood and saliva collection; and a labial salivary gland biopsy (LSGB). They also completed an interview and questionnaires including assessment of depression with the Patient Health Questionnaire 9 (PHQ-9). Univariate logistic regression was used to assess the association between depression and demographic characteristics, participant-reported health, phenotypic features of Sjögren syndrome, and participant-reported symptoms. Mixed-effects modeling was performed to determine if phenotypic features of KCS and/or participant-reported symptoms of dry eye disease were associated with depression, controlling for health, age, country or residence, and sex and allowing for nonindependence within geographic site., Results: Dry eye complaints produced a 1.82-fold (95% confidence interval [CI] 1.38-2.40) higher odds of having depression compared to being symptom-free (P < .001). Additionally, complaints of specific ocular sensations were associated with a higher odds of depression including burning sensation (odds ratio 2.25, 95% CI 1.87-2.72, P < .001) compared to those without complaints. In both women with and without SS, the presence of symptoms of dry eyes and/or dry mouth rather than SS itself resulted in higher odds of depression. One particular ocular phenotypic feature of SS, a positive ocular staining score, was inversely correlated with depression., Conclusions: Participant-reported eye symptoms, particularly specific ocular sensations such as burning, were found to be positively associated with individual American College of Rheumatology/EUropean League Against Rheumatism (ACR/EULAR) SS criteria items., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Sjogren's syndrome (SS) is an autoimmune disease. Its mechanism and treatment methods are unclear. The purpose of this study was to investigate the effects of rutin (Ru) on SS. Proteomics was used to detect differential proteins in the submandibular glands of normal mice and SS mice. Salivary secretion (SAS) and salivary gland index (SGI) were detected. Oxidative stress and inflammatory cytokine in submandibular glands were detected. The levels of NLRP3, ASC, Caspase-1, IL-1β, and p-NF-κBp65 in submandibular gland tissues and submandibular gland cells of overexpressed calcium-sensing receptor (over-CaR) mice and overexpressed CaR primary submandibular gland cells (over-CaR-PSGs) were detected. In total, 327 differential proteins were identified in the submandibular gland tissues of SS mice compared to control mice. CaR was one of the most differential proteins and significantly increased compared to control mice. Ru could significantly increase SGI and SGI, and inhibit oxidative stress and inflammatory cytokine in submandibular glands. In addition, Ru was shown to further improve SS via regulation of the CaR/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/nuclear factor kappa-B (NF-κB) signal pathway. Overexpression of CaR counteracted partial activity of Ru. CaR may be an important target for the treatment of SS. In addition, Ru improved the SS via the CaR/NLRP3/NF-κB signal pathway. This study provides a basis for the treatments for SS., (© 2024. The Society for In Vitro Biology.)

Approximately 1% of all patients with Sjögren's syndrome (SS) are children. Unlike the adult form, in which sicca syndrome is the main presentation, in children, the most common clinical finding is recurrent enlargement of the salivary glands. In pediatric SS, extraglandular manifestations represent a significant feature and, among these, kidney manifestations are relevant. Kidney involvement is observed in 5-20.5% of children with SS, most frequently tubulointerstitial nephritis. This injury can lead to serious phenotypes, including distal kidney tubular acidosis with the development of severe hypokalemia, which can lead to ECG abnormalities, weakness, and hypokalemic periodic paralysis. Kidney implications in pediatric SS also include nephrolithiasis, nephrocalcinosis, and various types of glomerular damage, which often require immunosuppressive therapies. Laboratory findings are usually comparable to adults, including hyperglobulinemia and high rates of antinuclear antibodies (ANA, 63.6-96.2%), and anti-Ro/SSA (36.4-84.6%). The current classification criteria for SS are inaccurate for the pediatric population, and more specific criteria are needed to improve the diagnostic rate. Due to the rarity of the disease, strong recommendations for treatment are lacking, and several therapeutic strategies have been reported, mostly based on glucocorticoids and disease-modifying antirheumatic drugs, with different outcomes. The aim of this paper is to provide an overview of the kidney implications of pediatric SS based on the latest evidence of the medical literature., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Purpose: The present study aims to evaluate the optic nerve, macula, and choroidal changes in both rheumatoid arthritis (RA) and primary Sjögren's syndrome (SjS) patients, and to compare these findings with age-matched healthy volunteers., Methods: This study included 46 RA patients, 33 primary SjS patients, and 37 age-matched healthy volunteers. All of the patients underwent a thorough ophthalmological examination, during which measurements of the retinal nerve fiber layer (RNFL), ganglion cell layer(GCL), and subfoveal choroidal thickness (CT) were taken using OCT (optical coherence tomography). The measurements taken from the right eye of each patient were used to compare among the groups., Results: RNFL thickness in superior quadrant was found to be statistically significantly thinner in the eyes with RA when compared to the control group (p = 0.022). In the nasal quadrant, the RNFL thickness was significantly thinner in patients with primary SjS compared to healthy individuals (p = 0.036). Also, the temporal quadrant RNFL was significantly thinner in RA patients than in the primary SjS patients (p = 0.033). GCL thickness was observed to be thinner in all quadrants of both RA and primary SjS groups compared to the control group. However, the difference was not found to be statistically significant. Subfoveal CT was observed to be thicker in RA and SjS groups compared to the control group, but this difference was also not statistically significant., Conclusion: Systemic autoimmune diseases like RA and primary SjS can lead to a decrease in RNLF and GCL thickness, which can impair visual acuity even in the absence of ocular symptoms. Therefore, monitoring changes in the optic nerve, retina, and choroid layer are crucial in these patients., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Juvenile Sjögren's disease (jSjD) is a rare autoimmune disease characterized by exocrine gland involvement and systemic manifestations, including small vessel vasculitis and Raynaud's phenomenon (RP). We aimed to investigate the microvascular status in jSjD patients by nailfold videocapillaroscopy (NVC) and the potential correlations with clinical and serological features., Methods: Clinical data from thirteen consecutive jSjD patients (11 females and 2 males), with a mean age of 16 ± 4 years, diagnosed before 16 years of age (mean age at diagnosis 12 ± 3) according to the 2016 American College of Rheumatology/EULAR criteria for adult SjD, were collected including age- and sex-matched healthy controls (HCs). Clinical, laboratory, and instrumental data were collected, together with NVC examination. Non-specific and specific NVC parameters were investigated, such as capillary density, capillary dilations, giant capillaries, microhaemorrhages and abnormal shapes. Associations between NVC findings and clinical/serological features were explored and analysed using parametrical and non-parametrical tests., Results: Capillary density reduction correlated significantly with articular involvement (arthralgias) (p = 0.024). Microhaemorrhages correlated with lower C3 levels (p = 0.034). No specific NVC pattern for jSjD was identified, whereas abnormal capillary shapes were significantly higher in jSjD patients than HCs (p = 0.005). NVC abnormalities were not associated with SjD-specific instrumental tests (biopsy, imaging, Schirmer's test). RP was present in 8% of jSjD patients., Conclusions: The reduction of capillary density, as well as microhaemorrhages at NVC analysis, are significantly associated with some clinical aspects like articular involvement and serum biomarkers (C3 reduction). The NVC is suggested as safe and further analysis in jSjD patients., (© 2024. The Author(s).)

The management of Sjögren's disease is challenging because of several factors. Indeed, the clinical presentations are heterogeneous, and one must be able to identify prognostic markers to adapt the follow-up. In addition, there is no validated treatment. Nevertheless, international experts have been working for several years to establish recommendations to guide management. Since research in this field is extremely active, we anticipate the development of effective treatments for our patients in the near future., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

This study aimed to explore the mode of action of Yiqiyangyinquyu prescription (YP) against Sjögren's syndrome (SS) by combining network pharmacology with molecular docking techniques. YP's active components and target proteins were identified using the BATMAN-traditional Chinese medicine database. Concurrently, targets associated with SS were extracted from databases, including Genecards, Online Mendelian Inheritance in Man, and Therapeutic Target Database. The standard targets were then imported into the STRING database to construct a protein-protein interaction network. We then conducted gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses, which were succeeded by molecular docking studies to validate core active components and key targets. Finally, in vitro experiments and molecular dynamics simulation were conducted to substantiate the therapeutic efficacy of YP in treating SS. A total of 206 intersection targets and 46 active compounds were identified. Gene ontology analysis unveiled that YP targets were primarily enriched in cellular responses to chemical stress, inflammation, and cell proliferation. Key enriched signaling pathways encompassed the interleukin 17, hypoxia-inducible factor-1, tumor necrosis factor (TNF-α), and advanced glycation end products-receptor for AGEs (AGE-RAGE) signaling pathways. Molecular docking results demonstrated high-affinity between neotanshinone C, tanshiquinone B, miltionone I, TNF-α, interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). Noteworthy, TNF-α, considered the most important gene in YP against SS, binds to YP most stably, which was further validated by molecular dynamics simulation. In vitro experiments confirmed YP's capacity to reduce TNF-α, IL-1β, and IL-6 expression, effectively alleviating SS-related inflammation. YP demonstrated a significant anti-inflammatory effect by suppressing inflammatory cytokines (TNF-α, IL-6, and IL-1β), providing experimental evidence for its clinical application in treating SS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To identify a screening strategy for dry eye patients with a high likelihood of having Sjogren syndrome (SS) through the evaluation of the association of ocular surface tests with the extraocular signs used for the diagnosis of SS., Design: Multicenter cross-sectional study., Methods: The Sjogren's International Clinical Collaborative Alliance (SICCA) registry enrolled 3514 participants with SS or possible SS from 9 international academic sites. Ocular surface evaluation included Schirmer I testing, tear breakup time (TBUT), and staining of the cornea (0-6 points) and conjunctiva (0-6 points). Multivariate logistic regression analysis was performed to identify predictive factors for (1) histopathologic changes on labial salivary gland (LSG) biopsies (positive = focus score of ≥1 focus/4 mm 2 ) and (2) positive anti-SSA/B serology., Results: The adjusted odds of having a positive LSG biopsy were significantly higher among those with an abnormal Schirmer I test (adjusted OR = 1.26, 95% CI 1.05-1.51, P = .014) and positive conjunctival staining (for each additional unit of staining 1.46; 95% CI 1.39-1.53, P < .001) or corneal staining (for each additional unit of staining 1.14; 95% CI 1.08-1.21, P < .001). The odds of having a positive serology were significantly higher among those with an abnormal Schirmer I test (adjusted OR = 1.3; 95% CI 1.09-1.54, P = .004) and conjunctival staining (adjusted OR = 1.51; 95% CI 1.43-1.58, P < .001)., Conclusions: In addition to corneal staining, which was associated with a higher likelihood of having a positive LSG biopsy, conjunctival staining and abnormal Schirmer I testing are of critical importance to include when screening dry eye patients for possible SS, as they were associated with a higher likelihood of having a positive LSG biopsy and serology., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To determine the intra-observer and inter-observer reliability of a novel ocular staining score among trained ophthalmologists., Design: Reliability analysis within a prospective, observational, multicenter cohort study., Methods: Those enrolled in the National Institutes of Health-funded Sjögren's International Collaborative Clinical Alliance (SICCA) who presented for follow-up at the University of California San Francisco, Aravind Eye Hospital, Johns Hopkins University, and the University of Pennsylvania were included. Study participants were graded using the ocular staining score by at least 2 masked SICCA-trained ophthalmologists. The primary outcome for this study was the intraclass correlation coefficient (ICC) for the total ocular staining score. ICCs were also calculated for tear break-up time (TBUT) and conjunctival and corneal staining., Results: Total ocular staining score had an ICC of 0.91 for the right eye (95% confidence interval [CI] 0.85-0.96) and 0.90 for the left eye (95% CI 0.83-0.97). Corneal staining (right eye 0.86, 95% CI 0.76-0.93, left eye 0.90, 95% CI 0.81-0.95) and conjunctival staining (right eye 0.87, 95% CI 0.80-0.93, left eye 0.85, 95% CI 0.75-0.93) demonstrated excellent agreement. The ICC for TBUT was slightly lower (right eye 0.77, 95% CI 0.64-0.89; left eye 0.81, 95% CI 0.68-0.90)., Conclusions: Previous studies have shown that the ocular staining score is correlated with other diagnostic components of Sjögren syndrome. In this study, we demonstrate high reliability in grading among trained ophthalmologists, completing the validation of this test., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Importance: Knowledge about the variability of measurements using the TearLab Osmolarity System is necessary when evaluating the clinical utility of readings., Objective: To examine the variability of tear osmolarity measured by the TearLab Osmolarity System in patients with Sjögren syndrome (SS), patients with blepharitis, and control participants., Design, Setting, and Participants: Cross-sectional study at a tertiary care academic center from June 13, 2012, to March 21, 2013. Participants included 74 eyes of 37 patients from a volunteer sample (18 patients with SS, 11 patients with blepharitis, and 8 control participants) who were evaluated using the TearLab Osmolarity System, with 3 consecutive osmolarity measurements taken at 1-minute intervals in a session; 15 of these patients had the same measurements taken by the same examiner in 2 additional sessions on the same day (9 AM-10 AM, 12 PM-1 PM, or 3 PM-4 PM). Most patients with SS and patients with blepharitis were taking systemic or topical dry eye medications at the time of enrollment., Main Outcomes and Measures: Mean osmolarity and its variability calculated from a linear mixed model for each disease group that accounts for the variations attributable to different patients, eyes, and sessions and measurement error specific to each disease group., Results: Mean tear osmolarity was 307 mOsm/L, 304 mOsm/L, and 301 mOsm/L in the SS, blepharitis, and control groups, respectively (P = .46). The error associated with repeated measurements within a session in the patients without dry eye (10.5 mOsm/L [95% CI, 9.0-12.4]) was significantly lower than in the patients with blepharitis (14.6 mOsm/L [95% CI, 12.5-17.5]; P = .006) and patients with SS (15.8 mOsm/L [95% CI, 14.2-17.8]; P < .001) but a difference in the error of repeated measurements between patients with blepharitis and patients with SS was not identified (P = .46)., Conclusions and Relevance: There was increased variability attributable to error in repeated measurements in patients with SS and patients with blepharitis compared with control participants. The high variability of TearLab osmolarity readings in all groups makes the clinical interpretation of measurements unclear.

Objectives: To quantify the impact of dry eye disease (DED) on health and vision related quality of life (HR-QOL, VR-QOL) in patients with Primary Sjögren's Syndrome (pSS)., Methods: Thirty-four participants with a confirmed diagnosis of pSS as per the 2016 ACR EULAR criteria participated. Main outcome measures included ocular surface parameters and HR-QOL and VR-QOL questionnaires. Clinical examination included visual acuity, Schirmer I testing, ocular surface staining (OSS) and measurement of tear film breakup time. The questionnaires included Ocular Surface Disease Index, National Eye Institute Visual Function Questionnaire-25, Short Form-36 (SF-36) and EULAR Sjogren's Syndrome Patient Reported Index., Results: Despite the majority of participants (28 female, 6 male, mean age 61.3 years) having attained LogMAR 0.3 or better visual acuity, participants scored low on VR-QOL measures, representing DED related fluctuation in functional vision. All participants suffered from moderate to severe DED. OSS did not correlate with DED symptoms or QOL parameters. Lubricant usage and symptom severity had a statistically moderate to strong negative correlation with VR-QOL and HR-QOL. This was most evident in relation to physical and physiological wellbeing. Compared with normative data, participants had a lower HR-QOL in all scales of the SF-36 ((MD = 9.91 ± 5.16); t(7) = 5.43, p = 0.001)., Conclusions: Participants with pSS have a lower perceived QOL especially in relation to physical and mental wellbeing, correlating to severity of DED symptoms and treatment burden. Clinical signs do not align with symptoms. Therefore, clinicians should remain cognisant, adjusting treatment in accordance with patient reported perceptions., (© 2023. The Author(s).)

Purpose: The purpose of this study was to assess the safety, tolerability, dosing, and efficacy of the active 19 amino acid fragment of lacritin (Lacripep), a broad regulator of ocular surface homeostasis, in the treatment of ocular surface disease associated with primary Sjögren syndrome., Methods: Two hundred four subjects were randomized to receive vehicle, 22 μM Lacripep, or 44 μM Lacripep 3 times daily for 28 days, preceded by a 14-day run-in and followed by 14-day washout. Outcome measures were corneal fluorescein staining (CFS), lissamine conjunctival staining, Schirmer with anesthesia, tear break-up time, SANDE scoring, and visual analog scale assessment of symptoms., Results: This study established the safety and tolerability of topical treatment with Lacripep in patients with primary Sjögren syndrome. There were few adverse events: Only mild irritation was found in less than 3 percent of patients dosed with Lacripep. Total CFS and Eye Dryness Score were not significantly changed at day 28. Post hoc analysis of patients with Eye Dryness Severity scores of 60 or greater at baseline revealed significant improvements in inferior CFS at 14 and 28 days and complaints of burning and stinging at 14 days. Significant improvement in regional lissamine conjunctival staining was seen at 14 and 28 days., Conclusions: This first-in-human study of Lacripep in patients with primary Sjögren syndrome demonstrated clinically significant improvements in specific signs and symptoms on which to base future studies. This study established safety and tolerability and potential metrics of efficacy in patients with moderate to severe disease. Further work on appropriate dosing and concentration is ongoing., Competing Interests: G. W. Laurie: Cofounder and CSO of TearSolutions, Inc; Financial interest in TearSolutions, Inc. E. C. Parsons: Consultant to TearSolutions, Inc. MGO: CMO of Tear Solutions, Inc; Financial interest in TearSolutions, Inc. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The Schirmer test is one of the 2 ocular surface tests included in the current classification criteria for Sjögren syndrome (SS). Tear osmolarity may also be a useful test for the diagnosis of dry eye disease. The purpose of this study was to examine the relationship between tear osmolarity, the Schirmer test I, and dry eye symptoms in SS., Methods: Patients with a diagnosis of SS were assessed for tear osmolarity with the TearLab Osmolarity System, tear production with Schirmer testing, symptoms with the Ocular Surface Disease Index (OSDI), and discomfort associated with each test., Results: Forty-nine patients with a mean age of 53.7 years and a female (92%) predominance were enrolled. The majority of patients (86%) were receiving systemic therapy for severe SS. Higher tear osmolarity was moderately associated with lower scores on the Schirmer test I (ρ = -0.39, P < 0.01) and OSDI (ρ = -0.45, P < 0.01). Schirmer test I results and lower OSDI scores were not correlated significantly (ρ = 0.20, P = 0.17). Tear osmolarity testing was significantly less painful than Schirmer testing (P < 0.01)., Conclusions: Signs and symptoms of dry eye in SS patients were not strongly correlated. An unexpected finding was that higher tear osmolarity was associated with lower symptom severity. Tear osmolarity testing in the clinical setting was feasible and was associated with significantly less discomfort than Schirmer testing in patients with severe SS.

Background: We investigated the safety and efficacy of short-term treatment with topical low-dose hydrocortisone sodium phosphate 0.335% (PFH) in patients with moderate to severe primary Sjögren syndrome (SS)-related dry eye disease (DED)., Methods: A retrospective single-centre interventional study. All patients received PFH for 6 days with a pulsed posology: three times daily for 2 days, twice daily for 2 days, and once daily for 2 days. This scheme was repeated for 3 consecutive months and then alternated for 3 months. Data were collected at baseline, 3 months, and 6 months of follow-up., Results: A total of 40 SS patients were enrolled. Conjunctival hyperaemia and corneal-conjunctival stain significantly improved (p < 0.001). Ocular Surface Disease Index score reduced significantly between baseline and 3 months and between baseline and 6 months (p < 0.001). The tear film osmolarity lowered significantly in each eye from baseline to 3 months and from baseline to 6 months (p = 0.002 and p = 0.037, respectively). Comparing results at 3 and 6 months, the Ocular Surface Disease Index score (p = 1.000), the frequency of lacrimal substitutes installation (p = 0.632), and tear film osmolarity (right eye p = 0.518, left eye p = 1.000) did not change significantly. Intraocular pressure did not change during the study period., Conclusion: PFH eye drops with a pulsed posology improve signs and symptoms, not affecting the intraocular pressure in SS-related DED. Therefore, this pulsed treatment is safe and efficacious., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The aim of this study was to analyze the risk factors for primary Sjögren's Syndrome (pSS) by conducting a meta-analysis of observational studies., Methods: Four electronic databases were searched from inception to August 2022. The search strategy included medical subject headings (MeSH) and text words. Outcomes were calculated and reported as the odds ratio (OR) and 95% confidence interval (CI)., Results: Twelve studies consisting of nine case-control and three cohort studies were analyzed. Significant positive relationships between infection, a family history of autoimmune disease in first-degree relatives, negative stressful life events, CGGGG insertion/deletion polymorphisms in the IRF5 gene and the onset of pSS were found, with pooled ORs and 95% CIs of 2.73 (1.93, 3.86), 5.93 (3.34, 10.52), 1.69 (1.27, 2.24) and 2.69 (1.97, 3.66), respectively. In contrast, the results showed that a history of smoking was not associated with the onset of pSS, with a pooled OR and 95% CI of 1.39 (0.76, 2.53). However, a statistically significant negative association between current smoking and pSS was detected, with a pooled OR and 95% CI of 0.4 (0.29, 0.83)., Conclusions: Our research indicated that infection, a family history of autoimmune disease in first-degree relatives, negative stressful life events and CGGGG insertion/deletion polymorphisms in the IRF5 gene might be risk factors for pSS. In contrast, our study demonstrated that a history of smoking was not associated with the onset of pSS, whereas current smoking was negatively associated with pSS onset., Systematic Review Registration: We registered this review on INPLASY ( https://inplasy.com/ ) under registration number INPLASY202230005., (© 2022. The Author(s).)

Background: Sjögren Syndrome (SS) is a systemic autoimmune disease with a wide spectrum of manifestations that can lead to misdiagnosis. This study describes and compares demographic, clinical, serological, and histopathological data from subjects with SS and non-Sjögren Syndrome (NSS). It also details specific features within the primary SS (pSS) and secondary SS (sSS) groups identifying sub-groups., Methods: The sample included individuals referred to an academic medical center in Brazil for investigation of SS from 2012 to 2020. Patients were retrospectively classified as primary SS (pSS), secondary SS (sSS), or NSS, based on the American-European Consensus Group criteria (AECG-2002), after multi-professional clinical and laboratory evaluation., Results: A total of 676 individuals were screened and 510 (75.4%) completed the assessments; 198 patients were classified as pSS, 149 as sSS, and 163 as NSS. Symptoms and glandular dysfunction tests were similar in the groups. Concerning pSS, extraglandular manifestations were present in 59% of patients; the elderly had more dry symptoms and peripheral neurological disorders; and 2.5% developed non-Hodgkin lymphoma. In sSS, each overlap promoted distinct clinical and laboratory variants. Several alternative diagnoses were identified as a cause of sicca complex in NSS group., Conclusions: The diagnosis of SS remains a challenge behind dryness. Up to 31% of the suspected cases had other conditions associated to the symptoms. Histopathological analysis of LSG and SSa determined the diagnostic. Aging in pSS and overlap disease in sSS were responsible for distinct phenotypes and characteristic sub-groups in SS., (© 2022. The Author(s).)

Sjogren's Syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, these systemic manifestations are not routinely evaluated and there is no homogenous approach to their diagnosis or evaluation. To close this gap, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of epidemiologic and clinical features of these manifestations and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. The first part of this guideline summarizes the most important topics, and 11 recommendations are provided for the articular, pulmonary, and renal care of SS patients., (© 2022. The Author(s).)

The objective of this review was to assess and evaluate whether the published diagnostic accuracy studies provide evidence to sustain the current diagnostic guidelines put forth by ACR/EULAR used for patients with suspected Sjögren's syndrome (SS). Literature databases, including Medline, Embase, and EBM Reviews, were searched for relevant studies on the correlation between ACR/EULAR criteria, particularly those with a direct comparison between their accuracy in diagnosing Sjögren's syndrome. We followed Cochrane, QUADAS-2, and STARD guidelines and the four-phase flow diagram by the PRISMA Statement. Reports in several languages, but only human studies were considered. Three studies assessed the accuracy of the current diagnostic tests, and these did not present adequate designs that would allow a well-supported conclusion with a high level of certainty. Due to significant clinical and methodological heterogeneity, a meta-analysis was not performed. A qualitative review of the papers was undertaken. Neither the comparative nor the non-comparative study designs permit conclusive recommendations regarding an alternative diagnostic pathway for SS. Well-designed studies of the diagnostic accuracy of SS tests are needed to validate current guidelines or to suggest changes to the current guidelines., (© 2021. International League of Associations for Rheumatology (ILAR).)

Purpose: Systemic implications necessitate the identification of dry eye patients with Sjögren syndrome (SS). This study aims to explore the utility of tear MUC5AC and inflammatory cytokine levels in the differential diagnosis of SS-related dry eye., Methods: A prospective, observational, case-control study was conducted on 62 patients (those with a definitive diagnosis of SS dry eye, non-SS dry eye, and age-matched healthy controls with no dry eye). Clinical evaluations included the following tests in the order listed here: noninvasive tear break-up time, osmolarity, tear sampling, Schirmer test without anesthesia, and ocular surface staining (lissamine green for conjunctiva and fluorescein for cornea). Tear MUC5AC levels were assessed with enzyme-linked immunosorbent assay, and cytokines [interferon-gamma, tumor necrosis factor alpha, interleukin (IL)-6, IL-17a, IL-1β, IL-8, IL-10, and IL-12p70] were measured using a Luminex assay in a masked fashion., Results: The Bulbar conjunctival lissamine green staining score was significantly greater in patients or controls with SS versus non-SS dry eye. This greater conjunctival staining was associated with a reduction in tear MUC5AC (B = -17.8 ng/mL, 95% confidence interval = -31.8 to -3.9, P = 0.01). Among the tear cytokines, a significant association was found between IL-8 levels (hazard ratio [HR] = 1.002, 95% confidence interval = 1.000-1.003, P = 0.03) and SS diagnosis. When patients were stratified based on tear MUC5AC levels, significantly increased tear IL-8 levels were detected in patients with SS dry eye but not with non-SS dry eye, in comparison with healthy controls., Conclusions: Tear levels of goblet cell-specific MUC5AC combined with IL-8 can potentially serve as a useful biomarker for differential diagnosis of SS dry eye from non-SS dry eye.

Background: Sjögren's syndrome is an autoimmune disease characterized by sicca symptoms and various extraglandular manifestations including vasculitis. Neurological involvement occurs frequently (Neuro-Sjögren) and often mimics immune neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP). Objectives: We aim to assess relevant differences in vessel density (VD) in Optical Coherence Tomography Angiography (OCTA) in those diseases to use it as an easily available diagnostic tool. Design: Prospective, monocentric pilot-study. Methods: OCTA (Heidelberg Engineering OCT SPECTRALIS) of the superficial vascular plexus, intermediate capillary plexus (ICP) and deep capillary plexus (DCP) of the retina was prospectively performed in Neuro-Sjögren, age-matched CIDP patients (n = 31, each), and healthy controls (n = 30). Vessel density (VD) and foveal avascular zone (FAZ) was measured with Erlangen Angio Tool. Results: Significantly lower VD were found for the DCP and ICP in Neuro-Sjögren and CIDP patients compared to healthy controls (p = 0.0002 and <0.0001). When group comparison was age-adjusted, these differences were not found anymore. Different frequencies of "low" retinal blood flow in each layer comparing Neuro-Sjögren and CIDP patients were not found. FAZ revealed no significant differences between patients with Neuro-Sjögren, CIDP and healthy controls. Conclusion: This study found no significant differences in VD or the foveal avascular zone between Neuro-Sjögren and CIDP patients using OCTA, suggesting that inflammatory vascular changes in the retina are uncommon in Neuro-Sjögren patients. [ABSTRACT FROM AUTHOR]