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The epidemiology of Sjögren syndrome (SS) has been extensively studied in America, Europe, and Asia.To summarize available data on the epidemiology of SS in Africa.MEDLINE, EMBASE, and African Journals Online were searched from inception up to May 17, 2020, to identify relevant articles. Data gleaned from these reports have been summarized narratively in this review.Twenty-one hospital-based studies were included. These studies reported 744 cases of SS. The mean age at diagnosis varied between 28 and 73.6 years, and the female proportion ranged from 83.3% to 100%. There was no population-based incidence or prevalence. Among people with autoimmune and other rheumatic conditions, the frequency of primary SS was in the range 1.9% to 47.6%, whereas that of rheumatoid arthritis-associated secondary SS was in the range 4.3% to 100%. Sicca symptoms were the commonest features, with most frequently involved organs being joints, lungs, and neurological structures. Main autoantibodies were anti-Ro/SS antigen A, anti-La/SS antigen B, and antinuclear antibodies.The epidemiology of SS is poorly characterized in Africa. Available data are broadly consistent with those from other populations. Extensive and high-quality research is urgently needed.

The aims of this pilot investigation were to calculate the levels of sensitivity and specificity of salivary glands ultrasonography (SGUS) in diagnosing Sjögren syndrome (SS) and to assess the ultrasonographic findings of parotid and submandibular glands.Patients diagnosed with SS or dry mouth and healthy controls were enrolled. Bilateral parotid and submandibular glands were assessed for (1) parenchymal inhomogeneity (PIH), (2) median size of the glands, (3) visibility of glandular posterior borders, and (4) size of sialolith, if present.This study included 34 female patients, of whom 12 had SS (35.3%), 12 had dry mouth (35.3%), and 10 were healthy controls (29.4%). Patients with SS showed higher PIH scores in all glands with the median differences being statistically higher in the right and left parotids and left submandibular glands (P.001, P = .012, and P.001, respectively). SGUS, with a PIH cutoff ≥2, showed a sensitivity of 100% and a specificity of 81.6% for detecting SS. The majority of SS had invisible glandular posterior borders (P.001). Median size of the glands and size of the sialolith did not show any statistically significant differences between groups.SGUS is a noninvasive imaging modality with good sensitivity and specificity that might be valuable as a diagnostic aid for SS.

Purpose To compare the burden related to dry eye with systemic symptoms of Sjogren syndrome; to estimate the burden related to ocular treatments; and to compare the impact of dry eye and extraocular manifestations of Sjogren 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 Sjogren 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 Sjogren 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 Sjogren-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.

Purpose of review This article discusses peripheral neuropathies associated with vasculitis (isolated or in the setting of systemic vasculitis) and autoimmune connective tissue disease and provides a brief overview of their diagnostic evaluation and management. Recent findings The classification of systemic vasculitic neuropathy and nonsystemic vasculitic neuropathy continues to evolve. Classification according to the presence of antineutrophil cytoplasmic antibodies and their subtypes facilitates prognostication and management. Recent research on antineutrophil cytoplasmic antibody-associated vasculitis has added to our understanding of its neurologic complications. The treatment of vasculitis is also evolving, and new nonsystemic vasculitic neuropathy classification has impacted the treatment and management of this disorder. New classification criteria for Sjogren syndrome (which commonly causes neurologic complications) facilitate accurate and timely diagnosis. Summary Vasculitis and autoimmune connective tissue disease are underrecognized and treatable causes of peripheral neuropathy. Furthermore, peripheral neuropathy may reveal an underlying rheumatologic or vasculitic disorder. Rapid recognition and treatment are essential. Familiarity with the diagnosis and treatment of neuropathies in the setting of connective tissue disease and vasculitis reduces morbidity and, in some cases, mortality.

Objective Menopausal women appear to report a higher risk of Sjogren syndrome (SS). Although Chinese herbal medicines (CHMs) are proven to lower SS risk, the scientific evidence of whether it can lessen the occurrence of SS among menopausal women is limited. This longitudinal cohort study aimed to clarify the relationship between CHMs use and SS risk in menopausal women. Methods Using a nationwide claims data, we enrolled 31,917 women with first-time diagnosed menopause who simultaneously were free of SS between 2000 and 2007. Among them, we randomly selected 12,757 CHMs users and 12,757 non-CHMs users using propensity scores matching. All participants were followed until the end of 2012 to record SS incidence. The hazard ratio of SS with regard to CHMs use was estimated using the Cox proportional hazards regression model. Results In the follow-up period, 589 CHMs users and 644 non-CHMs users developed SS, representing incidence rates of 5.12 and 6.40, respectively, per 1,000 person-years. CHMs use was associated with a 21% lower subsequent risk of SS (adjusted hazard ratio, 0.79; 95% CI, 0.71-0.89). Six commonly prescribed CHMs were discovered to be associated with lower SS risk: Ge-Gen-Tang, Zhi-Gan-Cao-Tag, Da-Huang, Ye-Jiao-Teng, Tian-Hua-Fen, and Bo-Zi-Ren. Conclusions A statistically significant association was found between CHMs use and lower risk of SS onset in menopausal women, suggesting that CHMs could be considered to integrate it into conventional therapy to reduce subsequent SS risk for menopausal women.

Objective Sjogren syndrome is a systemic inflammatory disease causing gland dysfunction. Few (and contradictory) reports on the mucosal effects of Sjogren syndrome have appeared. Here, we objectively demonstrate nasal dryness in Sjogren syndrome patients and explore the effect of such dryness on olfaction. Methods Thirty-four consecutive patients with primary Sjogren syndrome were enrolled in this cross-sectional study. The control group consisted of 21 age- and sex-matched volunteers. Medical histories and nasal findings were recorded. The Connecticut Chemosensory Clinical Research Center test was used to evaluate olfactory function. All subjects underwent mucucociliary clearance analysis (the saccharin test and peak nasal inspiratory flowmetry). The intranasal Schirmer test was used to evaluate the nasal cavity. Results The nasal Schirmer test scores were 8.4 mm (right) and 8 mm (left) (P = .041, P = .016, respectively, compared to controls). The Chi-squared test revealed significant differences (compared to controls) in nasal dryness (P = .001), postnasal drip (P = .04), and smell (a decrease) (P = .005). Neither olfactory function nor mucociliary clearance differed between the groups. We noted a trend toward a positive correlation between olfactory function and the nasal Schirmer score but statistical significance was not attained. Conclusion The intranasal Schirmer test objectively showed that Sjogren syndrome patients exhibited nasal cavity dryness; this is useful in terms of follow-up. This did not affect olfactory function. Level of evidence 4 Laryngoscope, 131:370-373, 2021.

A 52-year-old woman was diagnosed as having anti-centromere antibody (ACA)-positive primary Sjögren syndrome (pSS). Eight years later, she visited our hospital because she had developed dyspnoea. She was diagnosed as having pulmonary arterial hypertension (PAH) with pulmonary veno-occlusive disease on the basis of the results of right heart catheterisation, a severe decrease in diffusing capacity of the lung for carbon monoxide (D

Background Cerebellar degeneration is a rare and severe presentation of primary Sjögren syndrome. There are few case reports of cerebellar degeneration associated with different autoimmune diseases, especially with systemic lupus erythematosus and neuro-Behcet’s disease. There are only six patients reported worldwide to be affected by cerebellar atrophy associated with primary Sjögren syndrome. In this report, we describe a patient with primary Sjögren syndrome who presented with ataxia due to cerebellar degeneration. Case presentation We report the case of a 37-year-old Chinese woman with primary Sjögren syndrome who presented with ataxia over 3 months associated with tremor of the limbs. Magnetic resonance imaging of the brain revealed bilateral cerebellar atrophy. Based on the presence of cerebellar signs with magnetic resonance imaging brain findings, she was diagnosed as cerebellar degeneration secondary to primary Sjögren syndrome. She was treated with methylprednisolone, hydroxychloroquine, and two cycles of monthly intravenous cyclophosphamide. Subsequently, she refused further treatment, and her neurological symptoms remained the same upon the last clinic review. Primary cerebellar degeneration is rarely associated with primary Sjögren syndrome. The pathogenesis of the neurological manifestations in primary Sjögren syndrome is unclear. Treatment involves corticosteroids and immunosuppressive agents with no consensus of a specific therapy for the management of primary Sjögren syndrome with central nervous system involvement. Conclusions Cerebellar degeneration is a rare presentation of primary Sjögren syndrome. Early diagnosis and treatment of this condition is needed to ensure a good outcome.

An association of polymorphic marker rs2228262 in the THBS1 gene with the risk of developing dry eye in Sjögren syndrome was revealed. Confocal microscopy data suggest that this polymorphic marker is responsible for the high probability of corneal nerve fiber lesion in Sjögren syndrome even in the absence of clinical and functional signs of dry eye syndrome. A significant correlation was established between polymorphic markers rs1478604, rs2228262 in THBS1 gene and the coefficients of anisotropy and orientation symmetry of corneal nerve fibers. These results allow considering these polymorphic markers as a genetic factor of predisposition to dry eye syndrome in patients with Sjögren syndrome.

This study aims to investigate ultrasound (US) findings on salivary glands (SG) in patients with Sjögren syndrome (SS) vs. other connective tissue diseases (CTDs) and to assess the relationship of SGUS abnormalities with autoantibody profile in both groups. We enrolled 81 patients, 45 diagnosed with SS (39 with primary SS, 6 with secondary SS) and 36 diagnosed with other CTDs. All patients underwent a prospective evaluation of sicca symptoms, a Schirmer's test, and a B-mode US assessment of the parotid and submandibular glands, all blinded to the diagnosis. Each SG was semi-quantitatively scored 0-3; a grade ≥ 2 was considered pathological. SGUS involvement was classified as normal or pathological at the patient level and for each pair at the gland level. In addition, a total SGUS score of 0-12 and a parotid/submandibular score of 0-6 were calculated for each patient. Autoimmunity laboratory data were also obtained. All SGUS scores were higher in SS patients than in those with CTD (p 0.001) and significantly more SS patients showed a pathological global (p 0.001), parotid (p 0.001), or submandibular (p = 0.001) US score compared with CTD patients. In SS patients, the presence of autoantibodies was significantly associated with pathological SGUS and higher scores, particularly at the parotid level, while in CTD patients, xerostomia and a pathological Schirmer's test were associated with pathological US and higher scores at the submandibular level (p 0.05). SGUS showed a different grade of abnormality, site involvement, and associated autoantibody profile in SS patients as compared with other CTD. KEY POINTS: • Patients with SS and other CTDs showed different grades of SGUS abnormality. • Patients with SS and other CTDs showed different gland involvement and associated autoantibody profiles. • Anti-Ro60 and anti-Ro52 Ro60 positivity were associated with the severity of parotid involvement in SS patients.

Background Human α-fucosidase (EC 3.2.1.51) is a hydrolase the importance of which has been increasing in the latest years. However, data about its plasma level in children with autoimmune disorders, particularly Sjogren's syndrome (SS), are lacking. In this study, the plasma activity of L-α-fucosidase-1 (α-L-FUCA-1) was assayed in hospitalized children and adults and its association with SS and other rheumatic disorders further evaluated. Methods In total 73 Hungarian hospitalized patients, 32 children (2.5-10 years) and 41 adults (32-68 years), were enrolled in the study and underwent plasma assay of α-L-FUCA1 activity. Linear regression, Durbin-Watson (DW), and Pearson tests were evaluated to investigate the relationship between α-L-FUCA-1 plasma levels and autoimmune manifestations. Results α-L-FUCA-1 correlated with SS both in children (2-sided t test, P = 0.0023) and in adults (2-sided t test, P = 0.00035). Linear regressions showed that in other rheumatic disorders, α-L-FUCA1 did not show any differential distribution related to the particular pathology (r = 0.2042, P = 0.1531, DW test = 2.2139 positive), while this trend was radically opposite for patients with SS (r = 0.1462, P = 0.0032, DW test = 1.3664, negative). Conclusions Alterations in plasma level of α-L-FUCA-1 were significantly associated with SS. This preliminary result should encourage further research on α-L-FUCA-1 as a possible differential serological marker of SS.

Purpose: To compare meibomian gland (MG) imaging findings and lipid layer thickness (LLT) between patients with primary Sjogren syndrome (SS) dry eyes (DE) and non-SS DE.Methods: A total of 60 patients-30 with SS DE and 30 with non-SS DE were evaluated. Infrared image findings of MGs and LLT were assessed using the LipiView II interferometer.Results: The maximum LLT was significantly lower in the SS DE group. SS DE exhibited significantly higher MG dropout compared to the non-SS DE. Average and maximal LLT showed significant negative correlations with MG dropout in both groups (p

Connective tissue disorders are now understood to include autoimmune and genetic diseases affecting organs, blood vessels, and surrounding fascia. Many of these diseases predominantly affect women in childbearing years and are associated with neurologic complications. Pregnancy can affect disease activity (such as flares of systemic lupus erythematosus), and the diseases can affect pregnancy outcome (such as increased risk of preterm labor). We review the neurologic complications and changes with pregnancy for systemic lupus erythematosus, Sjögren syndrome, idiopathic inflammatory myopathy, and Marfan syndrome.

Sjögren syndrome (SS) is an autoimmune condition that targets the salivary and lacrimal glands, with cardinal clinical signs of dry eye (keratoconjunctivitis sicca, KCS) and dry mouth. The conjunctiva of SS patients is often infiltrated by immune cells that participate in the induction and maintenance of local inflammation. The purpose of this study was to investigate immune-related molecular pathways activated in the conjunctiva of SS patients. Female SS patients (n=7) and controls (n=19) completed a series of oral, ocular surface exams. Symptom severity scores were evaluated using validated questionnaires (OSDI and SANDE). All patients fulfilled the ACR/EULAR criteria for SS and the criteria for KCS. Fluorescein and lissamine green dye staining evaluated tear-break-up time (TBUT), corneal and conjunctival disease, respectively. Impression cytology of the temporal bulbar conjunctiva was performed to collect cells lysed and subjected to gene expression analysis using the NanoString Immunology Panel. 53/594 differentially expressed genes (DEGs) were observed between SS and healthy controls; 49 DEGs were upregulated, and 4 were downregulated (TRAF5, TGFBI, KLRAP1, and CMKLRI). The top 10 DEGs in descending order were BST2, IFITM1, LAMP3, CXCL1, IL19, CFB, LY96, MX1, IL4R, CDKN1A. Twenty pathways had a global significance score greater or equal to 2. Spearman correlations showed that 29/49 upregulated DEGs correlated with either TBUT (inverse) or OSDI or conjunctival staining score (positive correlations). Venn diagrams identified that 26/29 DEGs correlated with TBUT, 5/26 DEGs correlated with OSDI, and 16/26 correlated with conjunctival staining scores. Five upregulated DEGs (CFB, CFI, IL1R1, IL2RG, IL4R) were uniquely negatively correlated with TBUT. These data indicate that the conjunctiva of SS patients exhibits a phenotype of immune activation, although some genes could be inhibitory. Some of the DEGs and pathways overlap with previous DEGs in salivary gland biopsies, but new DEGs were identified, and some of these correlated with symptoms and signs of dry eye. Our results indicate that gene analysis of conjunctiva imprints is a powerful tool to understand the pathogenesis of SS and develop new therapeutic targets.

Made available in DSpace on 2022-04-29T08:30:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-07-01 Objective: Sjögren syndrome in children is a poorly understood autoimmune disease. We aimed to describe the clinical and diagnostic features of children diagnosed with Sjögren syndrome and explore how the 2016 ACR/EULAR classification criteria apply to this population. Methods: An international workgroup retrospectively collected cases of Sjögren syndrome diagnosed under 18 years of age from 23 centres across eight nations. We analysed patterns of symptoms, diagnostic workup, and applied the 2016 ACR/EULAR classification criteria. Results: We identified 300 children with Sjögren syndrome. The majority of patients n = 232 (77%) did not meet 2016 ACR/EULAR classification criteria, but n = 110 (37%) did not have sufficient testing done to even possibly achieve the score necessary to meet criteria. Even among those children with all criteria items tested, only 36% met criteria. The most common non-sicca symptoms were arthralgia [n = 161 (54%)] and parotitis [n = 140 (47%)] with parotitis inversely correlating with age. Conclusion: Sjögren syndrome in children can present at any age. Recurrent or persistent parotitis and arthralgias are common symptoms that should prompt clinicians to consider the possibility of Sjögren syndrome. The majority of children diagnosed with Sjögren syndromes did not meet 2016 ACR/EULAR classification criteria. Comprehensive diagnostic testing from the 2016 ACR/EULAR criteria are not universally performed. This may lead to under-recognition and emphasizes a need for further research including creation of paediatric-specific classification criteria. Division of Pediatric Rheumatology Department of Pediatric and Adolescent Medicine Mayo Clinic Division of Rheumatology Department of Pediatrics University of Utah School of Medicine Division of Rheumatology The Children's Hospital of Philadelphia Department of Internal Medicine and Pediatrics The University of Chicago Medical Center Department of Pediatrics Duke University School of Medicine Department of Pediatrics Hematology and Oncology Medical University of Gdansk Children's Mercy Hospital University of Missouri-Kansas City Division of Rheumatology Irccs Ospedale Pediatrico Bambino Gesù Department of Pediatric Rheumatology Institute of Rheumatology Department of Pediatrics Columbia University Medical Center Division of Rheumatology Children's National Hospital George Washington University School of Medicine and Health Sciences National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases Department of Pediatrics University of Texas McGovern Medical School at Houston Division of Pediatric Rheumatology Children's Healthcare of Atlanta Emory University School of Medicine Instituto de Puericultura e Pediatria Martagão Gesteira Universidade Federal Do Rio de Janeiro Pediatric Rheumatology Hospital Sant Joan de Déu Universitat de Barcelona Barcelona Rheumatology Unit Department of Medicine School of Medical Science University of Campinas Division of Rheumatology Department of Pediatrics University of Indiana School of Medicine Riley Hospital for Children at Indiana University Health Pediatric Rheumatology Unit São Paulo State University (UNESP), Botucatu Rheumatology Service Royal Children's Hospital Melbourne and Murdoch Children's Research Institute Division of Pediatric Allergy Immunology and Rheumatology Department of Pediatrics College of Medicine University of Florida Division of Oral Medicine Department of Oral and Maxillofacial Diagnostic Sciences College of Dentistry University of Florida Rheumatology Department Hospital General Universitario Gregorio Marañón Division of Immunology Boston Children's Hospital Department of Pediatrics Harvard Medical School Department of Rheumatic Diseases Tokyo Metropolitan Tama Medical Center Division of Rheumatology Allergy and Immunology Stead Family Department of Pediatrics Carver College of Medicine University of Iowa Pediatric Rheumatology Unit São Paulo State University (UNESP), Botucatu

BackgroundLacrimal gland secretory dysfunction in Sjögren syndrome (SS) causes ocular surface desiccation that is associated with increased cytokine expression and number of antigen-presenting cells (APCs) in the conjunctiva. This study evaluated the hypothesis that desiccating stress (DS) alters the percentage and gene expression of myeloid cell populations in the conjunctiva.MethodsDS was induced by pharmacologic suppression of tear secretion and exposure to drafty low humidity environment. Bone marrow chimeras and adoptive transfer of CD45.1+ bone marrow cells to CD45.2+ C-C chemokine receptor 2 knockout (CCR2-/-) mice were used to track DS-induced myeloid cell recruitment to the conjunctiva. Flow cytometry evaluated myeloid cell populations in conjunctivae obtained from non-stressed eyes and those exposed to DS for 5 days. CD11b+ myeloid lineage cells were gated on monocyte (Ly6C), macrophage (CD64, MHCII) and DC (CD11c, MHCII) lineage markers. NanoString immune arrays were performed on sorted MHCII+ and MHCII- monocyte/macrophage cell populations.ResultsDS significantly increased the recruitment of adoptively transferred MHCII positive and negative myeloid cells to the conjunctiva in a CCR2 dependent fashion. The percentage of resident conjunctival monocytes (Ly6C+CD64-) significantly decreased while CD64+MHCII+ macrophages increased over 5 days of DS (P- monocyte and MHCII+ populations in non-stressed conjunctiva revealed a ≥ 2 log2 fold increase in 95 genes and decrease in 46 genes. Upregulated genes are associated with antigen presentation, cytokine/chemokine, M1 macrophage and NLRP3 inflammasome pathways. DS increased innate inflammatory genes in monocytes and MHCII+ cells and increased M1 macrophage (Trem1, Ido1, Il12b, Stat5b) and decreased homeostasis (Mertk) and M2 macrophage (Arg1) genes in MHCII+ cells.ConclusionsThere are myeloid cell populations in the conjunctiva with distinct phenotype and gene expression patterns. DS recruits myeloid cells from the blood and significantly changes their phenotype in the conjunctiva. DS also alters expression of an array of innate inflammatory genes. Immature monocytes in the unstressed conjunctiva appear to cascade to MHCII+ macrophages during DS, suggesting that DS promotes maturation of monocytes to antigen presenting cells with increased expression of inflammatory genes that may contribute to the pathogenesis of SS keratoconjunctivitis sicca.

Sj&ouml, gren syndrome (SS) is an immunologically complex, chronic autoimmune disease targeting lacrimal and salivary glands. Nonobese diabetic (NOD) mice spontaneously develop inflammation of lacrimal and salivary glands with histopathological features similar to SS in humans including focal lymphocytic infiltrates in the affected glands. The innate immune signals driving lymphocytic infiltration of these glands are not well-defined. Here we evaluate the role of Toll-like receptor (TLR) 7 in the development of SS-like manifestations in NOD mice. We created a Tlr7 knockout NOD mouse strain and performed histological and gene expression studies to characterize the effects of TLR7 on autoimmunity development. TLR7 was required for male-specific lacrimal gland inflammation but not for female-specific salivary gland inflammation. Moreover, TLR7 was required for type 1 diabetes development in male but not female NOD mice. RNA sequencing demonstrated that TLR7 was associated with a type I interferon (IFN) response and a type I IFN-independent B cell response in the lacrimal glands. Together these studies identify a previously unappreciated pathogenic role for TLR7 in lacrimal gland autoimmunity and T1D development in male NOD mice adding to the growing body of evidence supporting sex differences in mechanisms of autoimmune disease in NOD mice.

Rationale: Neuromyelitis optica spectrum disorder (NMOSD) patients, especially those with anti-aquaporin-4 antibody positivity, a water channel expressed on astrocytes, is often accompanied by autoimmune diseases (ADs) including Sjogren syndrome (SS). Here, we report a case of a young Chinese woman with recurrent optic neuritis who was diagnosed with asymptomatic SS and NMOSD. Patient concerns: A 22-year-old Chinese woman suffered from optic neuritis for 3 years. The main manifestation was recurrent loss of vision. The anti-aquaporin-4 antibody was positive in the cerebrospinal fluid, and she was diagnosed with NMOSD. Other laboratory tests revealed positive anti-SSA and anti-SSB antibodies, and labial gland biopsy showed lymphocytic infiltration. She also fulfilled the international criteria for SS. Diagnosis: On the basis of recurrent vision loss and laboratory examination, we defined the patient with SS accompanied by NMOSD. Interventions: When the patient first experienced vision loss, the corticosteroid treatment in the external hospital was effective, and her visual acuity improved significantly. However, in several later attacks, such treatment was no longer obviously effective. Considering the patient's condition, she was treated with corticosteroids, cyclophosphamide, and immunoglobulin therapy on admission. Outcomes: The patient's visual acuity was increased to the right eye 20/800 and left eye finger counting when she was discharged from the hospital. Lessons: SS accompanied with NMOSD is common in clinical practice, and always with the positive Anti-AQP4 antibody as a potential biomarker. Patients with SS and NMOSD showed significant neurological symptoms and had a worse prognosis than SS patients with negative anti-AQP4 antibody because of cross-immunity between anti-SSA antibody and anti-AQP4 antibody. Rheumatologists and ophthalmologists should pay attention to this and perform appropriate tests.

Rationale: Tracheobronchial amyloidosis (TBA) associated with Sjögren syndrome is very rare. Here, we describe a case with this phenomenon, in order to better understand the condition. Patient concerns: A 52-year-old woman presented after 6 months of coughing, sputum, and dyspnea. Chest computed tomography revealed thickened bronchial walls, which were irregular on the left side the trachea. She had a history of dry eye and dry mouth of at least 3 years’ duration. Diagnoses: Sjögren syndrome was diagnosed based on her symptoms, ophthalmological and parotid examination, and immunological and autoantibody tests. The diagnosis of TBA was confirmed by Congo red staining of a tracheal biopsy. Interventions: The patient was given glucocorticoids without any other immunosuppressants. Outcomes: The symptoms improved after 6 months. Lessons: TBA associated with Sjögren syndrome is a rare condition. TBA is characterized by amyloid deposition to the trachea in the absence of systemic amyloidosis. Diagnosis requires tissue biopsy with demonstration of amyloid deposition.

Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune neurological diseases of the central nervous system, which are characterized by the presence of serum anti-aquaporin-4 autoantibodies (AQP4-IgG). An association between Sjogren syndrome (SjS) and AQP4-IgG-positive NMOSD has been proposed, but the rate of coexistence has not been determined. In this study, 4,447 patients suspected of having NMOSD with acute neurological episodes were evaluated for the positivity of serum AQP4-IgG, serum SS-A/Ro antibody, and the presence of SjS-related symptoms (dry eye, dry mouth). Of the 4,447 patients, 1,651 were positive for serum AQP4-IgG, and the remaining 2,796 were negative. A significantly higher proportion of AQP4-IgG-positive patients were positive for serum anti-SSA/Ro antibody (26.3 vs. 4.5%; p

Introduction: To report the first case of severe corneal complications in a patient with Sjögren syndrome after receiving erlotinib treatment. Case description: A 51-year-old woman with Sjögren syndrome presented with persistent corneal epithelial defects, which did not respond to conservative therapies. She had been diagnosed with lung cancer and was being treated with erlotinib, a kind of epidermal growth factor receptor (EGFR) inhibitor, for over 2 years. Cornea stromal melting and perforation were not avoided and a total of four penetrating keratoplasties were performed. Stable corneal surface was achieved after the erlotinib treatment was paused. Conclusion: This report, to the best of our knowledge, is the first description of severe ocular complications present in a patient with Sjögren syndrome after receiving the EGFR inhibitor. The underlying ocular or system diseases that were thought to be irrelevant upon receiving the EGFR inhibitors might negatively influence the tumor patients planning to take these kinds of targeted medication. Therefore, it is important to have eye examinations before and during the EGFR inhibitors treatment and supplement the relative contraindications (such as Sjögren syndrome) to EGFR inhibitor treatments as necessary.

Background The European League Against Rheumatism (EULAR) Sjögren Syndrome Disease Activity Index (ESSDAI) has been utilized to assess Sjögren syndrome-related systemic involvement in adult patients. To date, however, the ESSDAI has not been validated in children with primary Sjögren’s syndrome. This study evaluated the applicability of the ESSDAI to Japanese children with primary Sjögren’s syndrome. Methods The medical records of children who had been diagnosed with Sjogren syndrome at age ≤ 16 years between June 2011 and October 2016 were collected, and their ESSDAIs at initial presentation were calculated. Clinical symptoms and treatment regimens were surveyed by questionnaire, and patients were divided into groups based on ESSDAI and glucocorticoid dosages. The associations of ESSDAI scores with treatment regimens were analyzed statistically. Results The study subjects included 31 children (3 boys, 28 girls) with primary Sjögren’s syndrome. Their median age at disease onset was 10 years (interquartile range [IQR], 8–13 years), and their median initial ESSDAI was 7.0 (IQR; 5.0–15.0). ESSDAI-determined disease activity was high in nine patients (29.0%), moderate in 15 (48.4%), and low in seven (22.6%). During the first year after their initial visit, 14 patients (45.2%) were treated with prednisolone (PSL) and six (19.4%) with immunosuppressants. Dose of PSL was significantly associated with ESSDAI score. Median ESSDAI score was significantly higher in patients treated with high/medium- than with no/low-dose PSL (16.5 [IQR 10.5–18.0] vs 5.0 [IQR 3.0–8.5]). Eight (66.7%) of 12 patients administered medium/high-dose PSL and one (5.3%) of 19 administered no/low-dose PSL had high disease activity on ESSDAI. Conclusion Disease activity assessed by ESSDAI tended to be consistent with disease activity assessed by pediatric rheumatologists in determining treatment regimens. ESSDAI is useful for assessing disease activity in Japanese children with primary Sjögren’s syndrome.

Interleukin 27 (IL-27) plays diverse immune regulatory roles in autoimmune disorders and promotes the generation of IL-10 producing CD4+ T cells characterized by producing the immunosuppressive cytokine IL-10. However, whether IL-27 participates in pathological progress of Sjogren’s syndrome (SS) through regulating CD4+IL-10+ T cells remains unknown. Here we aimed to explore the potential role of IL-27 and CD4+IL-10+ T cells in the pathogenesis of SS. The IL-27 gene knockout non-obese diabetic (Il-27-/-NOD) mice were generated and injected with exogenous IL-27. Exogenous injection of IL-27 and neutralization of IL-27 with anti-IL27 antibody in NOD mice were performed. The histopathological changes in submandibular glands, lacrimal glands and lung, salivary flow rate and percentages of CD4+IL-10+ T cells were determined. And, ovalbumin (OVA) immunized C57L/B6 mice were injected with IL-27 to detect the percentage of CD4+IL-10+ T cells. In vitro, splenic naive T cells from C57L/B6 mice were cultured with IL-27 for 4 days to induce the differentiation of CD4+IL-10+ T cells. In addition, IL-27, IL-10 and CD4+IL-10+ T cells were determined in health control (HC) and SS patients. The results showed that Il-27-/-NOD mice had more severe disease and lower level of CD4+IL-10+ T cells than control mice. And IL-27 promoted the generation and differentiation of CD4+IL-10+ T cells in vivo and in vitro significantly. In agree with the findings in the SS-like mice, patients with SS showed lower levels of IL-27, IL-10 and CD4+IL-10+ T cells. Our findings indicated that IL-27 deficiency aggravated SS by regulating CD4+IL-10+ T cells. Targeting IL-27 and CD4+IL-10+ T cells may be a novel therapy for patients with SS.

Author(s): Gonzales, John A; Shiboski, Stephen C; Bunya, Vatinee Y; Akpek, Esen K; Rose-Nussbaumer, Jennifer; Seitzman, Gerami D; Criswell, Lindsey A; Shiboski, Caroline H; Lietman, Thomas M | Abstract: PurposeTo evaluate the ocular signs and tests for keratoconjunctivitis sicca (KCS) in the absence of a gold standard.MethodsCross-sectional study of participants from the Sjogren's International Collaborative Clinical Alliance (SICCA) registry. Participants had oral/ocular/rheumatologic examinations, blood/saliva samples collected, and salivary gland biopsy. Latent class analysis (LCA) identified clusters of patients based on 3 to 4 predictor variables relating to signs or tests of KCS. The resulting model-based "gold standard" classification formed the basis for estimated sensitivity and specificity associated with these predictors.ResultsA total of 3514 participants were enrolled into SICCA, with 52.9% classified as SS. LCA revealed a best-fit model with 2 groups. For the gold standard-positive group, an abnormal tear breakup time, ocular staining score (OSS), and Schirmer I had a sensitivity of 99.5%, 91.0%, and 47.4%, respectively. For the gold standard-negative group, an abnormal tear breakup time, OSS, and Schirmer I had a specificity of 32.0%, 84.0%, and 88.5%, respectively. OSS components (fluorescein and lissamine staining), exhibited a sensitivity of 82.6% and 90.5%, respectively, in the gold standard-positive group, whereas these signs in the gold standard-negative group had a specificity of 88.8% and 73.0%, respectively.ConclusionsOSS and its components (fluorescein and lissamine staining) differentiated 2 groups from each other better than other KCS parameters and had relatively high sensitivity and specificity.

Introduction: Patients with systemic autoimmune rheumatic diseases (SARDs) such as rheumatoid arthritis, systemic lupus erythematosus (SLE), Sjögren syndrome, and systemic sclerosis, which are chronic inflammatory diseases, are prone to develop renal dysfunction, which is related to vascular endothelial cell damage. Material and Methods: We evaluated plasma levels of von Willebrand factor (VWF), VWF propeptide (VWF-pp), disintegrin-like and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), and VWF multimer pattern in patients with SARDs at diagnosis and investigated whether they may serve as markers to identify patients destined to develop renal dysfunction within 1 year. Renal dysfunction was defined as subsequent reduced estimated glomerular filtration rate (eGFR) by >25% or the new appearance of abnormal urine findings such as proteinuria (protein > 30 mg/dL) or hematuria (red blood cells >20/HPF in urine sediments). Overall, 63 patients with SARDs were studied. Results and Conclusions: We observed a significant increase of VWF-pp and a significant decrease of ADAMTS13 in patients with SARDs compared with normal healthy controls. The highest level of VWF-pp was observed in patients with SLE among the groups. The levels of VWF and multimer pattern of VWF were not different compared with normal healthy controls. Von Willebrand factor propeptide predicted a subsequent decrease in eGFR at a cutoff point of 210% (sensitivity, 78.6%; specificity, 73.5%) and new urinary abnormal findings at a cutoff point of 232% (sensitivity, 77.8%; specificity, 77.8%) Using these cutoff points, multivariable analysis revealed that VWF-pp was a significant risk factor for renal dysfunction at an odds ratio of 8.78 and 22.8, respectively, and may lead to a new therapeutic approach to prevent vasculitis and renal dysfunction.

Ultrasound-guided core biopsy is a minimally invasive technique able to identify lymphoma accompanying Sjögren syndrome, neoplasms or infiltrative diseases, with less complications compared to open biopsy. With these images, we aim to describe the ultrasound-guided core biopsy procedure, in a female patient with rheumatoid arthritis who presented evident inhomogeneity of the parotid gland. The procedure was performed by rheumatologists, trained in ultrasonography of the salivary glands, demonstrating that ultrasound-guided core biopsy is an easy and safe method to obtain salivary gland tissue.

Purpose Demodex mites infestation, typically asymptomatic, is a problem for patients with weakened immune systems because it often takes the form of symptomatic, massive infection. The Demodex mites play an important role in the occurrence of a range of eye surface diseases such as Demodex blepharitis, Meibomian gland dysfunctions, conjunctivitis and corneal changes. The ocular infection is closely related to the systemic invasion. Our goal was to minimize infestation and alleviate the symptoms of massive demodicosis so as to prevent further damage to the cornea. Methods Our research note involves a 61-year old woman diagnosed with secondary Sjögren syndrome due to rheumatoid arthritis. On the background of the autoimmune disease, corneal perforation of the left eye occurred that was cured by surgery. Then during the follow-up visit the patient was found (microscopically) massively infected with Demodex mites and the developed symptoms were particularly severe. Results Adequate dry eye syndrome and massive demodicosis therapy significantly reduced the number of Demodex mites and improved the patient’s condition. Conclusion We would like to draw the attention of the physicians of different specialties that special care should be taken with respect to the therapy of dry eye syndrome and ocular demodicosis in patients with immunological disorders to achieve therapeutic success and avoid particularly dangerous consequences of these diseases.

Sjögren’s syndrome (SS) is a chronic autoimmune inflammatory disease that affects primarily older women and is characterized by irreversible damage of the exocrine glands, including tear (xerophthalmia) and salivary glands (xerostomia). Secretory glands lose their functionality due to the infiltration of immune cells, which produce cytokines and cause inflammation. Primary SS is characterized by dry syndrome with or without systemic commitment in the absence of other pathologies. Secondary SS is accompanied by other autoimmune diseases with high activation of B lymphocytes and the production of autoantibodies, including the rheumatoid factor. Other cells, such as CD4+ T cells and mast cells (MCs), participate in SS inflammation. MCs are ubiquitous, but are primarily located close to blood vessels and nerves and can be activated early in autoimmune diseases to express a wide variety of cytokines and chemokines. In the SS acute phase, MCs react by generating chemical mediators of inflammation, tumor necrosis factor (TNF), and other pro-inflammatory cytokines such as interleukin (IL)-1 and IL-33. IL-33 is the specific ligand for ST2 capable of inducing some adaptive immunity TH2 cytokines but also has pro-inflammatory properties. IL-33 causes impressive pathological changes and inflammatory cell infiltration. IL-1 family members can have paracrine and autocrine effects by exacerbating autoimmune inflammation. IL-37 is an IL-1 family cytokine that binds IL-18Rα receptor and/or Toll-like Receptor (TLR)4, exerting an anti-inflammatory action. IL-37 is a natural inhibitor of innate and acquired immunity, and the level is abnormal in patients with autoimmune disorders. After TLR ligand activation, IL-37 mRNA is generated in the cytoplasm, with the production of pro-IL-37 and later mature IL-37 caspase-1 mediated; both precursor and mature IL-37 are biologically active. Here, we discuss, for the first time, the current knowledge of IL-37 in autoimmune disease SS and propose a new therapeutic role.

Background Sjogren syndrome (SS) is one of the most common autoimmune disorders that classically affects exocrine glands, resulting in keratoconjunctivitis sicca and xerostomia, and frequently is associated with other systemic symptoms. SS appears to have a particular predilection for involving the autonomic nervous system. Study question Does immunotherapy improve signs and symptoms of autonomic nervous system impairment in SS? Study design This is a retrospective review of patients seen in the autonomic clinic at our institution who underwent an evaluation for a suspected autonomic disorder that ultimately was attributed to SS. SS patients who were treated with immunotherapy and completed autonomic testing before and after treatment were included in this review. Results A total of 4 patients were identified who were treated for SS-related autonomic dysfunction with immunotherapy and underwent repeat autonomic testing after treatment. Marked clinical and functional improvement was seen after treatment with intravenous immunoglobulin in all patients and adjunctive rituximab therapy in 1 patient. The clinical improvement with immunotherapy in these patients correlated with markedly improved findings on autonomic testing in all. Measures and outcomes Clinical symptoms and results of autonomic testing prior to and following immunotherapy were assessed. Conclusions Autonomic signs and symptoms in SS are potentially immunoresponsive, but immunotherapy in these patients may require repeated, ongoing, or adjunctive therapy for optimal and sustained improvement.

PURPOSE: To describe associations between symptoms and signs of dry eye disease (DED) and meibomian gland (MG) morphology. METHODS: Cross-sectional study utilizing data from the Dry Eye Assessment and Management (DREAM) Study. Readers graded MG features in the middle third of upper and lower lids on infrared meibography images. Associations with signs and symptoms of DED were evaluated with adjustment for age and sex. RESULTS: Among 268 patients, no MG features were associated with symptom scores (p>0.08). Among 394 upper eyelids, better tear break-up times (2- 5 −10, and >10 mm) were associated with increasing composite scores (22.02 (9.29), 23.80 (10.34), 24.96 (9.96), p=0.03). Patients with Sjogren syndrome compared to other patients had fewer distorted MGs (mean 3.4(2.3) vs 4.3(2.3), p=0.03) and fewer ghost glands (mean 0.33(0.88) vs 0.89 (1.8), p=0.006) in the upper lid. CONCLUSION: In the DREAM study, most MG morphologic features were not associated with the severity of DED symptoms or signs. Tortuous glands and a higher composite score for MG features were associated with longer tear break-up times and longer Schirmer test length in the upper eyelid only. Patients with Sjogren syndrome had fewer distorted and ghost glands.

To compare goblet cell (GC) number and area in the covered superior (SB) versus exposed temporal (TB) bulbar conjunctiva in control versus aqueous tear deficient eyes (ATD) and evaluate correlation with tear MUC5AC protein. SB and TB impression cytology performed on control eyes, Sjögren syndrome (SS) ATD, and non-SS ATD was stained with period acid Schiff. GC number and area were measured with image analysis software. Protein-normalized MUC5AC level was measured in Schirmer strip-collected tears. Compared to control conjunctiva, GC number and area were significantly lower in SS, non-SS, and combined ATD groups in exposed TB, and were also significantly lower in SS and combined ATD groups in covered SB. In all ATD, GC number and area were significantly correlated, but differences between SB and TB were non-significant. Normalized tear MUC5AC protein was lower in all ATD groups versus control eyes, and correlated only with GC area. GCs are significantly decreased in the covered and exposed conjunctiva in SS. GC area may be a better disease measure than number for ATD. Correlation between tear MUC5AC concentration and GC area suggests tear MUC5AC mucin can be used as a disease-relevant biomarker for conjunctiva GC health.

Rationale: Primary biliary cholangitis (PBC) is a rare autoimmune cholestatic liver disease. It is often associated with extrahepatic autoimmune disorders. However, the concurrence of PBC and Sjögren syndrome (SS) with the subsequent onset of autoimmune hemolytic anemia (AIHA) is extremely rare. Patient concerns: This study investigated a 60-year-old woman admitted to our hospital with complaints of xerostomia for 5 years, pruritus for 3 years, and abnormal liver function for 3 months. Diagnoses: The patient was suffering from typical clinical PBC and SS, and developed decompensated liver cirrhosis after 32 months of ursodeoxycholic acid (UDCA) therapy. In May 2018, she was readmitted to the hospital with a high fever of 39 °C, coughing, and sever fatigue without remission after 3 days of cephalosporin antibiotic therapy. During the clinical course of PBC, her antimitochondrial antibodies (AMA) titers fluctuated from 1:1000 to negative and then to weakly positive, determined by indirect immunofluorescence (IIF), immunoblotting, and enzyme-linked immunosorbent assay (ELISA) based on recombinant mitochondrial antigens; furthermore, her titers of anti-gp210, an antinuclear antibody (ANA), increased sharply. Laboratory tests and imaging were performed to diagnose PBC and SS in September 2015. However, she was subsequently diagnosed with AIHA after 32 months of UDCA therapy based on the identification of pancytopenia, increased reticulocyte (RET) count, and a positive result from the direct Coombs test. Interventions: UDCA, hepatic protectant, albumin infusion, chest drainage, rational antibiotic use, diuretics, and methylprednisolone were used to treat the patient. Outcomes: Liver cirrhosis was complicated by the development of AIHA, which became severe at 42 months of follow-up. Lessons: This is the first case report showing a patient with comorbid PBC and SS, as well as the sequential development of AIHA with decreased AMA and increased anti-gp210 titers; this may have been due to immunodeficiency. These findings stress the importance of the serological screening of ANA profile, as well as repeated measurement of ANA and AMA to track PBC progression and prognosis.

Objective The objective of this paper is to assess overactive bladder (OAB) symptom bother (SB) and health-related quality of life (HRQL) among patients with systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS). Methods We recruited adult SLE and pSS patients and two groups of age- and sex-matched controls. We applied the OAB questionnaire-short form (OABq-SF) to all participants to assess SB and HRQL and collected clinical information relevant for OAB. We compared the OABq-SF scores for SB and HRQL between patients and controls using univariate and multivariate linear regression analysis. Results We recruited 95 rheumatic patients (68 SLE, 27 pSS) and 231 controls. Compared to controls SLE patients showed higher OABq-SF SB scores (22.6 ± 20.4 vs 14.7 ± 17.0, p = 0.004) and lower HRQL scores (89.8 ± 15.8 vs 93.8 ± 11.4, p = 0.044). On multivariate analysis SLE was significantly associated with a higher SB score (ß-coefficient 7.13, p = 0.008) and tended to be associated with worse HRQL values (ß-coefficient –3.53, p = 0.055). Patients with pSS had numerically higher mean SB scores (22.8 ± 22.5 vs 16.2 ± 18.0, respectively, p = 0.107) and lower HRQL scores (91.0 ± 10.7 vs 93.2 ± 11.6, respectively, p = 0.369), although these differences were not statistically significant. Diagnosis of pSS was not significantly associated with SB or HRQL scores on univariate or multivariate analysis. Conclusions Patients with SLE have significantly worse OAB-SB and poorer HRQL compared to controls. A similar trend was seen for pSS patients, especially for SB. These findings suggest that clinically subtle OAB symptoms may be present in rheumatic patients for whom, later on, bladder pain syndrome may occur.

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 prepare a drug delivery system of rapamycin poly-3-hydroxybutyrate-co-3-hydroxyvalerate microspheres (RPM) and analyze its effect on the eyes of a Sjogren’s syndrome mouse model.Methods...

Sjögren syndrome (SS) is an autoimmune connective tissue disorder (CTD) that principally affects the lacrimal and salivary glands. Although SS is 1 of the 3 most common autoimmune CTDs alongside systemic lupus erythematosus and progressive systemic sclerosis, it is the least researched CTD overall. SS poses a particular diagnostic challenge because it shares multiple clinical and immunologic features with other CTDs. However, there are some characteristic cutaneous clinical features that can precede the well-known sicca symptoms by years. By familiarizing themselves with these clinical features and having a high suspicion for SS, dermatologists can play an important role in the early diagnosis and treatment of this disease.

Background Cutaneous lupus erythematosus (CLE) includes a broad range of dermatologic manifestations. Periorbital involvement, however, is a relatively rare clinical presentation of CLE. Objectives This clinical study aimed to investigate the characteristics of this unique presentation of CLE in tertiary medical centers. Methods We enrolled patients with periorbital erythema and swelling as the presenting sign of lupus erythematosus, from January 2003 to November 2017, using the data of 553 pathologically proven CLE cases from the registration database of the Chang Gung Memorial Hospitals in Taiwan. Results We enrolled a total of 25 patients. The mean age was 46.7 years and 68% of the patients were female. Most of the patients (84.0%) presented with unilateral involvement, with the left orbit involved in 15 patients (60%); the upper eyelid was the most frequently involved (72%). Mean duration between the onset of clinical manifestations and the diagnosis of CLE was approximately 59 weeks. Nineteen patients had been previously misdiagnosed. All patients had features compatible with CLE on histopathological examination. In contrast, laboratory analysis of the autoimmune profile often revealed negative results, including those for antinuclear antibodies (25%). Notably, anti-SSA/SSB (45.5%) showed the highest positive rate. During follow-up, six patients developed systemic lupus erythematosus (SLE) and two patients developed Sjögren syndrome. Conclusions The diagnosis of CLE presenting as periorbital erythema and swelling is often delayed because of clinical mimicry and the high proportion of negative results on autoantibody tests. Increased clinical suspicion and prompt histopathological examination are crucial for early diagnosis. Moreover, one-fourth of the patients ultimately developed SLE, which highlights the importance of clinical awareness.

Purpose Sjogren syndrome is an autoimmune disease that occurs primarily in women, and is associated with lacrimal gland inflammation and aqueous-deficient dry eye. We hypothesize that sex-associated differences in lacrimal gland gene expression are very important in promoting lymphocyte accumulation in this tissue and contribute to the onset, progression, and/or severity of the inflammatory disease process. To test our hypothesis, we explored the nature and extent of sex-related differences in gene expression in autoimmune lacrimal glands. Methods Lacrimal glands were collected from age-matched, adult, male and female MRL/MpJ-Tnfrsf6lpr (MRL/lpr) and nonobese diabetic/LtJ (NOD) mice. Glands were processed for the analysis of differentially expressed mRNAs by using CodeLink Bioarrays and Affymetrix GeneChips. Data were evaluated with bioinformatics and statistical software. Results Our results show that sex significantly influences the expression of thousands of genes in lacrimal glands of MRL/lpr and NOD mice. The immune nature of this glandular response is very dependent on the Sjogren syndrome model. Lacrimal glands of female, as compared with male, MRL/lpr mice contain a significant increase in the expression of genes related to inflammatory responses, antigen processing, and chemokine pathways. In contrast, it is the lacrimal tissue of NOD males, and not females, that presents with a significantly greater expression of immune-related genes. Conclusions These data support our hypothesis that sex-related differences in gene expression contribute to lacrimal gland disease in Sjogren syndrome. Our findings also suggest that factors in the lacrimal gland microenvironment are critically important in mediating these sex-associated immune effects.

Chimerism is a phenomenon in which an individual has cells with different genetic content from different zygotes. In dizygotic twins (DTs), chimerism is believed to occur through placental anastomoses that enable the bidirectional exchange of hematopoietic stem cells. Little is still known about chimerism frequency in twins, but several studies have shown a relation between chimerism and some conditions such as autism, Alzheimer’s disease, and a group of autoimmune diseases such as Sjögren syndrome, systemic lupus erythematosus, and systemic sclerosis. In addition to chimerism of ABO blood groups being possibly mistaken for ABO subgroups, these autoimmune diseases may affect other serologic immunohematologic tests. This study aimed to determine the frequency of chimerism in DTs through ABO and D testing using the tube method, column agglutination, and short tandem repeat (STR) assays. Among the 103 subjects assessed for this study, 24 subjects (12 pairs) were excluded because STR assays showed they were monozygotic; of the remaining, 70 subjects (35 pairs) were DTs and 9 subjects came from gestations of trizygotic triplets. No ABO or D chimerism was detected in any subject through serologic assays, and STR assays did not detect any blood chimerism. Although there was no evidence of chimerism found in this study, we emphasize the importance of observing the family background of individuals with suspected ABO subgroup in complex immunohematologic studies because ABO antigen–antibody reactions are similar in both circumstances, and chimerism can be overlooked. Moreover, the use of the STR analysis method in chimerism studies can be important to help differentiate chimerism and ABO subgroups. Immunohematology 2018;34:151–157.

Background: Retinal involvement in systemic lupus erythematosus (SLE) and Sjögren syndrome (SS) may be subclinical and thus underdiagnosed. Objectives: We aimed at evaluating morphological and functional visual abnormalities in a cohort of SLE and SS patients in the absence of an overt clinical visual impairment. We also investigated potential associations between retinal disorders and disease activity, organ involvement, and treatment with steroid and/or hydroxychloroquine. Methods: The study comprised 42 SLE and 36 primary SS patients and 76 healthy controls (HC). Ophthalmological examination, standard automated perimetry, spectral-domain optical coherence tomography, and fundus perimetry were performed. Results: Retinal thickness of the posterior pole was not different between SLE and HC groups, but it was reduced in the SS group compared with both the HC and the SLE group. In SLE and SS patients, mean defect and pattern standard deviation by standard automated perimetry were higher than in HC. Visual field index values were lower in both SLE and SS patients than in HC. SLE patients with nephritis displayed increased mean defect and pattern standard deviation and reduced visual field index values compared to patients without nephritis. In SLE and SS patients, fundus perimetry differential sensitivity was reduced, and mean defect values were higher than in HC. Disturbances in fundus perimetry in the SLE group were more prevalent in steroid-naïve patients and in SS patients who received a cumulative hydroxychloroquine dose > 1,000 g. Conclusions: Functional eye impairment was demonstrated in SLE patients, possibly associated with kidney involvement. In SLE, corticosteroids might exert a protective role. Morphological alterations and functional impairment were detected in SS patients, which may be linked to hydroxychloroquine toxicity.

To compare the stability of the tear film after instillation of eye drops containing hyaluronic acid (HA) or crosslinked hyaluronic acid (CLHA)-based in patients with Sjögren syndrome-related dry eye (SSDE).Forty subjects were included in this study and were divided into 2 groups: the first group (control group) consisted of 20 healthy volunteers; the second group (study group) constituted of 20 suffering from SSDE; before and 5, 30, and 60 min after instillation of eye drops the surface regularity index (SRI) and surface asymmetry index (SAI) were registered.Comparing HA and CLHA, in the control group, SAI show statistically significant difference in the time 0 and in time 5, whereas there is no a statistically significant difference after 30 and 60 min from instillation. For SRI there is no statistically significant difference at any time. In SSDE group there is no statistically significant difference in the time 0 and 5, whereas there is a statistically significant difference after 60 min for SAI, and after 30 and 60 min for SRI from instillation. Both SRI and SAI in dry eyes were significantly greater than in control eyes (P 0.05).Our study showed a better efficacy of CLHA compared with HA in maintaining the stability of the tear film in a patient suffering from SSDE.

Acquired Gitelman's syndrome (GS) associated with Sjögren syndrome (SS) is rare. A 50‐year‐old woman was admitted to our department because of nausea, acratia and sicca complex. Laboratory tests after admission showed renal failure, hypokalaemia, metabolic alkalosis, hypomagnesaemia and hypocalciuria, all of which met the diagnostic criteria for GS. Diagnostic evaluation identified primary SS as the cause of the acquired GS. Light microscopy of the renal tissue from the patient showed severe membranoproliferative glomerunephritis and tubulointerstitial nephritis. Immunohistochemical staining of the renal tissue showed the absence of sodium‐chloride co‐transporter (NCCT) in distal convoluted tubules. Genetic analysis of chromosomal DNA extracted from the patient's peripheral blood showed SLC12A3 gene heterozygous mutation. The reported case was comprehensively analyzed on the basis of the clinical features, and laboratory, pathological and genetic test findings. The patient has achieved a complete remission after meticulous care and appropriate treatment.

Purpose: Recent literature suggests that sialendoscopy of the major salivary glands could alleviate symptoms of Sjögren syndrome (SS) and restore salivary function. The aim of this study was to evaluate the authors’ experience of sialendoscopy of the salivary glands in patients with SS. Materials and Methods: In this retrospective case series study, the surgical data of patients with SS who had undergone sialendoscopy at the VU University Medical Center (Amsterdam, The Netherlands) from November 2014 through April 2015 were used. Outcome measurements were successful entry to the salivary gland and completion of sialendoscopy as planned. Furthermore, pre- and postoperative complications were scored. Descriptive analysis of the data was performed. Results: Surgical data of sialoendoscopic procedures in 26 patients with SS (24 women and 2 men; mean age, 57 yr; range, 27 to 72 yr) were analyzed. Sialendoscopy was successfully performed in 78 of 104 salivary glands (75%; 50 parotid and 28 submandibular glands) in the 26 patients. Sialendoscopy failed in 26 of the 104 sialoendoscopic procedures (25%; 2 parotid and 24 submandibular glands). In 16 salivary glands, the ductal orifice could not be identified. In 7 salivary glands, sialendoscopy could not be performed because of partial or complete stenosis of the salivary duct. In 3 salivary glands, sialendoscopy was not performed because of a ductal perforation. Three patients developed a postoperative infection. Conclusion: The overall rate of complications was limited and the sialoendoscopic complications in patients with SS could be regarded as minor. Most complications were seen for sialendoscopy of the submandibular glands in this specific patient category. Careful preoperative selection of patients and salivary glands could contribute to a lower rate of complications and more predictable results.

In vivo corneal confocal microscopy allows the examination of each layer of the cornea in detail and the identification of pathological changes at the cellular level. The purpose of this study was to identify the possible effects of a three-month treatment with autologous serum eye-drops in different corneal layers of patients with severe dry eye disease using corneal confocal microscopy.Twenty-six patients with dry eye disease were included in the study. Corneal fluorescein staining was performed. The corneas of the right eyes were examined using in vivo corneal confocal microscopy before and after a three-month treatment with autologous serum drops. The densities of superficial and basal epithelial cells, Langerhans cells, the keratocytes and activated keratocytes, the density of endothelial cells and the status of the sub-basal nerve plexus fibres were evaluated.A significant decrease in corneal fluorescein staining was found after the three-month autologous serum treatment (p = 0.0006). The basal epithelial cell density decreased significantly (p = 0.001), while the density of superficial epithelial cells did not change significantly (p = 0.473) nor did the number of Langerhans cells or activated keratocytes (p = 0.223; p = 0.307, respectively). There were no differences in the other corneal cell layers or in the status of the nerve fibres.The results demonstrate the ability of corneal confocal microscopy to evaluate an improvement in the basal epithelial cell layer of the cornea after autologous serum treatment in patients with dry eye disease. More studies with longer follow-up periods are needed to elucidate the suitability of corneal confocal microscopy to follow the effect of autologous serum treatment on nerve fibres or other corneal layers in dry eye disease patients.

// Yu-Hsiang Chiu 1 , Chi-Hsiang Chung 2 , Kuen-Tze Lin 3 , Chin-Sheng Lin 4 , Jia-Hong Chen 5 , Hsiang-Cheng Chen 1 , Ren-Yeong Huang 6 , Chi-Tsung Wu 7 , Feng-Cheng Liu 1 and Wu-Chien Chien 2,8 1 Department of Internal Medicine, Division of Rheumatology/Immunology/Allergies, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 2 School of Public Health, National Defense Medical Center, Taipei, Taiwan 3 Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 4 Department of Internal Medicine, Division of Cardiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 5 Department of Internal Medicine, Division of Hematology/Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 6 Department of Periodontology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 7 Department of Oral and Maxillofacial Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 8 Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Correspondence to: Wu-Chien Chien, email: // Feng-Cheng Liu, email: // Keywords : Sjogren syndrome, non-Hodgkin’s lymphoma, diffuse large B-cell lymphoma, immunosuppressive agents, lip biopsy Received : August 04, 2016 Accepted : January 23, 2017 Published : February 04, 2017 Abstract Sjogren syndrome (SS) is commonly known to be correlated with lymphoma. This study included 16,396 individuals in the SS cohort and 65,584 individuals in the non-SS cohort, all of whom were enrolled in the Taiwan National Health Insurance database between 2000 and 2010. We evaluated the risk factors of non-Hodgkin’s lymphoma (NHL) in the primary SS cohort by applying a Cox multivariable proportional-hazards model. We increased the correlation of patients with SS and NHL, with an adjusted HR of 4.314 (95% CI 2.784 – 6.685). Of the 16,396 SS patients, 66 individuals had salivary gland slices without NHL development, while the other 16,330 individuals that did not have salivary gland slices revealed 30 individuals that developed NHL. Of the 16,396 SS patients, 128 individuals underwent immunomodulator agent therapy (including hydroxychloroquine, azathioprine, cyclosporine, methotrexate, and rituximab) without NHL development. None of the 30 individuals that developed NHL from SS received immunomodulator agents. We found that patients with SS were at an increased risk of developing NHL, with the most common NHL subgroup being diffused large B-cell lymphoma. SS patients who were candidates for salivary gland slices or immunomodulator agents were associated with a lower risk of developing lymphoma over time. We recommend that patients at a higher risk upon diagnosis of SS receive close follow-up and aggressive treatment.