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The aim of this study was to investigate the perspective of Romanian patients with Sjögren syndrome (SS) on various aspects of the disease during the SARS-CoV-2 outbreak, including both the impact of COVID-19 on the disease itself as well as the effects of vaccination against SARS-CoV-2 in this group of patients. The study is an online questionnaire-based survey. We received responses from 137 SS patients. Regarding the general emotional status, 33 patients (24.0%) and 47 patients (34.3%) declared to have been sadder/depressive and more agitated/anxious during the SARS-CoV2 outbreak, respectively. During the lockdown, 49 (33.7%) patients strictly and 77 patients (56.2%) did their best to respect the home isolation measures. The income was unchanged for most of the patients (94 patients, 68.6%). Regarding access to healthcare providers, 27 patients (18.7%) postponed the consultation for fear of getting SARS-CoV2. In our study group, 31 patients (22.6%) responded that they have had COVID-19. Only one patient was completely asymptomatic, while the most frequently declared symptom was weakness (84.0%). In 17 patients among the respondents (68%) the symptoms lasted for at least 2 weeks; the most frequent long-lasting symptoms were fatigue (40.0%) and weakness (36.0%). Out of all the respondents, 53 patients (41.4%) were vaccinated against SARS-CoV2 with at least one dose. After the first dose, the most prevalent side effect was pain at the site of injection (89.2%), followed by weakness (25.0%) and myalgias (21.4%). This information will be useful for developing special programs dedicated to SARS-CoV2 infection and vaccination in patients with SS and other autoimmune diseases. [ABSTRACT FROM AUTHOR]

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Background: Sicca syndrome represents a heterogeneous group of conditions, such as Sjögren syndrome, causing xerophthalmiaand xerostomia. This study characterizes in depth patients with Sicca syndrome and evaluates salivary gland ultrasound (SGUS).Methods: Principal component analysis and hierarchical clustering of clinical parameters, such as ESSPRI, ESSDAI and laboratory data, were performed on all referrals for assessment of Sicca symptoms between October 2018 and March 2021. SGUS and labial gland biopsies were compared across groups.Results: A total of 583 patients were assessed. Objective dryness was confirmed in 73% of the patients. Cluster analysis identified 3 groups with post-hoc analysis confirming distinct phenotypes: Somatic Group (283/583; 49%) with more frequent symptoms but limited objective dryness; Dry Without Autoimmune Features (DAFneg, 206/584; 35%), and Dry With Autoimmune Features (DAFpos, 94/584;16%). DAFpos patients had highest autoantibody titers (anti-SSA(Ro) 240 vs. 3.6 vs. 3.8; p < 0.001), most extra-glandular manifestations (p < 0.001), and highest median SGUS Score (DAFpos: 8 [IQR 4–10] vs. SG: 2 [1–4] vs. DAFneg 4 [2–5]; p < 0.001). No tangible correlation with primary Sjögren syndrome criteria was observed.Discussion: SGUS score correlated with a subset of patients with Sjögren syndrome, identified in the DAFpos cluster. This study highlights heterogeneity within sicca and, indeed, Sjögren syndrome, highlighting the need for further studies.

Sjogren's syndrome (SjS) is a chronic, slow-progressing, autoimmune and lymphoproliferative disease. The main symptoms of the syndrome are xerostomia and keratoconjuctivitis sicca as a result of chronic inflammatory infiltration of the salivary and lacrimal glands. Focal Segmental Glomerulosclerosis complicating primary Sjögren's syndrome is extremely rare. We report on a 39-year-old woman with 5 years history of sjogren syndrome who was found to have nephrotic syndrome. Histopathological findings in kidney biopsy compatible with focal segmental glomerulosclerosis. Steroid therapy was initiated (oral prednisolone at a dose of 15 mg/day) and Cyclosporine 2 * 100mg/d. FSGS, which is associated with sjögren's syndrome, was considered suitable for the presentation because of its rare occurrence

The association between estrogen receptor (ER) positive breast cancer (BC) and autoimmune disorders has been recently recognized. In particular exposure to aromatase inhibitors is associated with a significant increased risk of rheumatological autoimmune disorders. The purpose of this study was to investigate Sjogren syndrome (SjS) occurrence in patients with ER-positive BC. This is a prospective study analyzing 110 consecutive patients with ER-positive BC treated with anti-hormonal therapy. New 2016 American College of Rheumatology/European League against Rheumatism (ACR-EULAR) classification criteria were used to identify patients with SjS. Ultrasonography of salivary glands (SG) was used to screen patients with negative disease biomarkers, to candidate them to SGs biopsy. Sicca syndrome was detected in 51 patients (46%), whereas a true primary SjS was diagnosed in 11 patients (10%). Even if the evaluation of incidence and prevalence of primary SjS vary widely, to the best of our knowledge, the data from the present study emphasize a previously unsuspected high prevalence of defined pSjS that causes BC sicca symptoms complaints. Hypothesis, explanation of this link and even possible biases are discussed.

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. [ABSTRACT FROM AUTHOR]

Although the physiological control of salivary secretion has been well studied, the impact of disease on salivary gland function and how this changes the composition and function of saliva is less well understood and is considered in this review. Secretion of saliva is dependent upon nerve-mediated stimuli, which activate glandular fluid and protein secretory mechanisms. The volume of saliva secreted by salivary glands depends upon the frequency and intensity of nerve-mediated stimuli, which increase dramatically with food intake and are subject to facilitatory or inhibitory influences within the central nervous system. Longer-term changes in saliva secretion have been found to occur in response to dietary change and aging, and these physiological influences can alter the composition and function of saliva in the mouth. Salivary gland dysfunction is associated with different diseases, including Sjögren syndrome, sialadenitis, and iatrogenic disease, due to radiotherapy and medications and is usually reported as a loss of secretory volume, which can range in severity. Defining salivary gland dysfunction by measuring salivary flow rates can be difficult since these vary widely in the healthy population. However, saliva can be sampled noninvasively and repeatedly, which facilitates longitudinal studies of subjects, providing a clearer picture of altered function. The application of omics technologies has revealed changes in saliva composition in many systemic diseases, offering disease biomarkers, but these compositional changes may not be related to salivary gland dysfunction. In Sjögren syndrome, there appears to be a change in the rheology of saliva due to altered mucin glycosylation. Analysis of glandular saliva in diseases or therapeutic interventions causing salivary gland inflammation frequently shows increased electrolyte concentrations and increased presence of innate immune proteins, most notably lactoferrin. Altering nerve-mediated signaling of salivary gland secretion contributes to medication-induced dysfunction and may also contribute to altered saliva composition in neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Forkhead box O1 (FoxO1) is a multifunctional initiator, mediator, and repressor of autoimmune diseases in an organ- or disease-specific manner. However, the role of FoxO1 in the salivary gland has not yet been elucidated. In this study, we discovered that FoxO1 and aquaporin 5 (AQP5) are both significantly downregulated in the patients with primary Sjögren syndrome, an autoimmune disease accompanying salivary gland dysfunction. Pharmacologic or genetic perturbation of FoxO1 in the rat salivary gland acinar cell line, SMG-C6, induced a significant downregulation of AQP5 expression, as observed in clinical specimens. There was a strong correlation between FoxO1 and AQP5 expression because FoxO1 is a direct regulator of AQP5 expression in salivary gland acinar cells through its interaction with the promoter region of AQP5. Serial injection of a FoxO1 inhibitor into mice induced a reduction of AQP5 expression in submandibular glands and, consequently, hyposalivation, which is one of the major clinical symptoms of primary Sjögren syndrome. However, there was no sign of inflammation or cell damage in the submandibular glands harvested from mice treated with the FoxO1 inhibitor. In conclusion, our findings indicate that FoxO1 in salivary gland tissue acts as a direct regulator of AQP5 expression. Thus, downregulation of FoxO1 observed in primary Sjögren syndrome is a putative mechanism for hyposalivation without the involvement of previously reported soluble factors in primary Sjögren syndrome patient sera. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to assess the reliability and validity of the Turkish version of the European League Against Rheumatism (EULAR) Sjögren Syndrome Patient Reported Index (ESSPRI) (TR) in patients with primary Sjögren syndrome (pSS). Materials and methods: A cross-sectional survey study design and analysis were used to assess the reliability and validity of the ESSPRI (TR) between March 2019 and July 2019. A total of 30 patients (5 males, 25 females; mean age 54.1±10.5 years; range, 18 to 75 years) diagnosed as pSS according to revised American College of Rheumatology (ACR)/EULAR classification criteria were included. ESSPRI (TR) was applied to the patients with face-to-face interviews twice: on their first visit and after an interval of 15 days. The test-retest reliability was assessed with the intraclass correlation coefficient (ICC), and the internal consistency of the multi-item subscales by calculating Cronbach alpha values. The correlations between basal and stimulated salivary flow (BSF and SSF), Oral Health Impact Profile-14 (OHIP-14) and Oral Health-Related Quality of Life-UK (OHRQOL-UK) questionnaires were evaluated to determine the construct validity. Results: The ICC value for the test/retest reliability of ESSPRI (TR) was 0.925. The internal consistency was 0.682. There were low to moderate correlations between the ESSPRI (TR) total score and BSF (-0.39), SSF (-0.50), OHIP-14 total (0.57) and OHRQOL-UK total (-0.67). Conclusion: The Turkish version of the ESSPRI was found to be clinically valid and reliable to be used in clinical evaluations and rehabilitation interventions in patients with pSS. [ABSTRACT FROM AUTHOR]

Les pathologies parotidiennes peuvent être d'origine inflammatoire (sialite), métabolique ou tumorale. De nombreuses maladies systémiques au premier rang desquelles le syndrome de Sjögren et la sarcoïdose peuvent engendrer une hypertrophie parotidienne. Le diagnostic différentiel, parfois difficile, malgré les examens complémentaires les plus poussés (échographie, IRM, ponction cytologique à l'aiguille fine) sera infectieux, lithiasique ou tumoral. Parotid enlargement can be of inflammatory (sialitis), metabolic or tumoral. Many systemic diseases, mainly Sjögren's syndrome and sarcoidosis, can lead to parotid hypertrophy. The differential diagnosis, which is sometimes difficult, despite radiological investigations) (ultrasound, MRI, cytological fine needle puncture) will be infectious, lithiasis or tumor. [ABSTRACT FROM AUTHOR]

Background/aim: Sjögren’s syndrome (SS) is an autoimmune disease and its pathogenesis is still not completely clear. The wingless (Wnt)/β-catenin pathway has recently been shown to play an important role in inflammation. This study aims to determine the serum and saliva levels of Dickkopf (DKK)1 and sclerostin and to evaluate Wnt-1 and Wnt-3a expression in the salivary gland in patients with primary SS. Materials and methods: This study included 30 patients diagnosed with SS, 30 patients diagnosed with systemic lupus erythematosus (SLE), and 29 healthy controls. Serum and saliva levels of DKK1 and sclerostin were measured and the expressions of Wnt1 and Wnt3a in the salivary gland were measured immunohistochemically. Results: Serum DKK1 and sclerostin levels were lower in the SS and SLE groups compared to the control group (both p < 0.001). Saliva DKK1 levels were higher in the SS group compared to the control and SLE groups (p = 0.004 and p = 0.009, respectively). Wnt1 and Wnt3a expression were found in salivary gland tissue samples in 71.4% of primary SS patients and relatively frequent than control group. Conclusions: Serum DKK1 and sclerostin levels in primary SS and SLE were decreased. Moreover, levels of Wnt1 and Wnt3a expression in the salivary gland were also elevated in primary SS. Therefore, it can be concluded that the Wnt/β-catenin pathway activities may be altered in case of glandular inflammation. [ABSTRACT FROM AUTHOR]

Objective: Sjögren syndrome (SS) is a common autoimmune disease primarily affecting the eyes and mouth. With no single gold standard test for its diagnosis, accurate identification of patients with SS continues to be challenging. We aimed to assess the correlation of ocular and oral symptoms of dryness with objective measures in order to evaluate reliability in the screening of primary SS (pSS) in clinical practice.Methods: We conducted a cross-sectional analysis of pre-screened pSS and sicca control patients assessed in the Multidisciplinary Sjögren's Clinic at the University Health Network in Toronto. The signs, symptoms, and objective measure of oral and ocular dryness and damage of each patient were prospectively recorded using a standardized protocol.Results: Subjective measures of severity for xerophthalmia and xerostomia correlated in general with objective severity. Oral symptoms tend to have a stronger correlation with objective findings than ocular symptoms. Many patients with few or insignificant eye symptoms had profound ocular dryness and damage. Similarly, some patients with few or no symptoms of oral dryness had profound objective salivary hypofunction. The absence of symptoms does not rule out profound eye and mouth dryness or damage.Conclusion: Although objective measures of xerostomia may not be practical for general population screening, it is crucial that practicing specialists perform objective testing of all patients suspected of pSS, instead of relying on symptoms. Without objective testing, the physician cannot ensure the diagnosis of pSS and that the existence of significant damage is not overlooked and left untreated. [ABSTRACT FROM AUTHOR]

The coexistence of Guillain-Barré syndrome (GBS) with autoimmune rheumatic diseases is extremely rare. In addition to flu, infection, trauma, vaccination, blood transfusion, chemotherapy and surgical intervention, rheumatic diseases may be the underlying etiological cause of resistant and prolonged GBS cases. Therefore, appropriate treatments specific to rheumatic diseases may accelerate the healing process, reduce the possibility of neurological sequelae and greatly contribute to the rehabilitation process.

Background: Sjögren's syndrome (SS) is a chronic autoimmune disease with lymphocytic exocrine gland infiltration causing dry mouth and eyes. The disease can develop alone (primary SS, PSS) or with other autoimmune diseases (secondary SS, SSS). PSS has been suggested to increase the acute pancreatitis risk. However, whether all patients with SS share this higher risk remains uncertain. This nationwide population-based cohort study aimed to detect associations between SS and acute pancreatitis. Methods: We identified 11,922 individuals with SS cohort and 47,688 individuals without SS (non-SS cohort) between 2000 and 2010 from the Taiwan National Health Insurance database. We matched the individuals between the SS and non-SS cohorts according to age, gender, and index year at a 1:4 ratio. We used a Cox multivariable proportional-hazards model to determine the effects of SS on the acute pancreatitis risk. Results: The SS cohort had a higher acute pancreatitis risk than the non-SS cohort after covariate adjustments (adjusted hazard ratio [HR], 3.374; 95% confidence interval [CI], 2.869–3.969). Patients with PSS exhibited a 2.872-fold risk (95% CI, 2.611–3.901) and patients with SSS a 4.121-fold risk (95% CI, 3.752–5.124) for acute pancreatitis. Our subgroup analyses revealed that patients with SS and systemic lupus erythematosus (adjusted HR, 3.85; 95% CI, 3.259–4.999), rheumatoid arthritis (adjusted HR, 4.298; 95% CI, 3.862–5.286), systemic sclerosis (adjusted HR, 2.765; 95% CI, 2.26–3.68), or polymyositis (adjusted HR, 2.641; 95% CI,1.847–3.101) and dermatomyositis (adjusted HR, 3.77; 95% CI, 2.894–4.502) had higher acute pancreatitis risk. Conclusions: Patients with SS presented increased acute pancreatitis risks than patients without SS, and patients with SSS had higher acute pancreatitis risks than patients with PSS. Physicians should be aware of this increased risk in patients with SS.

Objective: Breast Cancer (BC) is the most frequently diagnosed malignancy worldwide. Not only may BC be associated with rheumatic symptoms and diseases, but also the drugs used in the treatment of this disease, including aromatase inhibitors (AIs), may lead to musculoskeletal system symptoms. In this study, we aimed to investigate the spectrum of rheumatic symptoms and diseases developing in patients with BC having no previous diagnosis of any inflammatory rheumatic disease.Materials and Methods: Patients with a history of BC referring to Rheumatology Outpatient Clinics with complaints of musculoskeletal system symptoms at two centers between 2008 and 2018 were screened retrospectively. Patients with a previous diagnosis of any inflammatory rheumatic diseases before the occurrence of BC were excluded. Demographic data, onset and duration of BC, as well as onset and duration of rheumatic symptoms/diseases were recorded. Relevant laboratory tests, including autoantibodies, available imaging findings and the treatments received were also registered.Results: Mean age of 128 BC patients at the time of admission was found to be 54.76±8.21 years. Mean durations of disease for BC and rheumatic disorders were 85.705±15.507 and 60.84±19.20 months, respectively. Out of 128 BC patients, nearly one third (n: 41; 32.03%), developed an inflammatory rheumatic disease, and rheumatoid arthritis was the most frequent pathology. Nonspecific arthralgia and myalgia were more frequent in patients receiving AIs than those receiving tamoxifen, despite lack of significant difference (p=0.421, p=0.411).Conclusion: Given that nearly one third of the patients developed an inflammatory rheumatic disease, it should be remembered that locomotor symptoms in patients with BC may be caused not only by bone metastasis or paraneoplastic effects, but they may also suggest the presence of associated rheumatic diseases.

Introduction: Combined central and peripheral demyelination (CCPD) is a rare entity in which central and peripheral nervous system demyelination coexist. Herein, we present a patient with coexistence of Sjögren syndrome (SS) and CCPD. Case Report: A 58-year-old female patient was admitted to our neurology clinic with paraparesis, difficulty walking, imbalance, and paresthesia. Neurological examination showed paraparesis, absence of lower extremity deep tendon reflex, sensory deficit at the T8 level, loss of deep sensory position, and vibration. Spinal magnetic resonance imaging revealed multiple focal T2-hyperintense and contrast-enhancing cord lesions. Fat-suppressed imaging disclosed T2 hyperintensity in lumbar nerve roots, diffuse linear enhancement of the cauda equina, and diffuse increased enhancement in lumbar nerve roots. Electrodiagnostic findings fulfilled the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy. Extensive laboratory workup excluded all possible pathologies. The Schirmer test detected positive in both eyes and minor salivary gland biopsy resulted in grade 3. These results were consistent with SS. The patient received intravenous methylprednisolone, azathioprine hydroxychloroquine. Approximately 2 years later, her complaints had completely disappeared, except for mild sensory complaints. Conclusion: It is unclear whether the association of central nervous system and peripheral nervous system demyelination and SS is a coincidence or a consequence. Our patient shows that patients with SS can have CCPD, and a significant clinical response can be obtained with early treatment. We hope that this unique case sheds light on the pathophysiology of CCPD. [ABSTRACT FROM AUTHOR]

Sjögren Sendromu SjS öncelikle gözyaşı ve tükrük bezleri olmak üzere tüm ekzokrin bezlerin lenfositit infiltrasyonu ile karakterize kronik, sistemik ve otoimmün bir hastalıktır. Kserostomi ve kseroftalmi tablosu hastalığın ana belirtisi olmakla ile birlikte kas iskelet, pulmoner, gastrointestinal, hematolojik, dermatolojik, böbrek ve sinir sistemine uzanan geniş bir yelpazede bozukluğa neden olur. Lökositoklastik vaskülit SjS de sık görülen kutanöz vaskülit tipidir.Granülamatöz polianjitis GPA nedeni belli olmayan, genellikle küçük veya orta boy damarları tuttuğu gibi sistemik tutulum da yapabilen, nekrotizan granülomatöz tipte bir vaskülittir. GPA, alt-üst solunum yolları, böbrek ve diğer organları tutabilmektedir. Özellikle deri lezyonları önemli bir tutulum şeklidir. Hastalık seyrinde optik sinir iskemisine bağlı retroorbital psödotümör gelişebilmektedir. Burada SjS tanısı ile takip edilirken lökositoklastik vaskülit gelişen beyin görüntülemesinde psödotümör orbita saptanmışolan 48 yaşında bir kadın hasta tartışılmıştır. SjS ve GPA birlikteliğine çok sık rastlanılmamaktadır. Bu olgu, bu nadir birlikteliğe değinilmek için sunulmuştur. Psödotümör orbita ile prezente olan hastalarda GPA‘nın ayırıcı tanıda akılda tutulması, erken teşhis, tedavi ve komplikasyonların önlenmesi açısından önemlidir

Introduction: Oral rehabilitation is based on establishing a correct diagnosis and designing a plan to give appropriate treatment to each clinical case. Patients’ aesthetic requirements show an increasing trend in current practice. Sjögren’s syndrome and obesity can have a negative impact on a person’s quality of life, and it is therefore imperative to identify and reduce these significant barriers to paving the way for better oral health and the overall well-being of the individual. Hypertension NYHA II type patients may present oral manifestations like ageusia, burning sensation, xerostomia, lichenoid reactions or gingival hyperplasia. Case presentation: This time, at our clinic, a 71-year-old man requested a complex oral rehabilitation. He presented partial edentulism at both arches. We are talking about a non-smoking patient, with chronical medication treatment for the mentioned pathology. Conclusions: A well-controlled hypertensive patient is not a risk in clinical practice. When choosing an implant based therapy, the old age of the patient can be considered a negative factor for successful results, but it is not a strict contraindication. This case report shows the most suitable treatment solution, regarding all the advantages and disadvantages of other treatment options, represented by implant supported fixed prosthetic restaurations.

Introduction: Autologous serum eye drops (ASED) are used in the treatment of most severe stages of dry eye. Once introduced, it is currently considered impossible to return to other lubricating eye drops or other commercially available therapeutic regimen. Materials and Methods: In a randomized study, non-preserved high-molecular-weight hyaluronic acid eye drops were offered as an alternative to 11 patients using autologous serum treatment for at least 3 months. The control group (n = 5) continued their treatment with ASED. The verum group (n = 6) used very-high-molecular-weight hyaluronic eye drops (Comfort Shield®) instead of the ASED. Results: From four of initially six patients in the verum group that finished the study, 2 (50%) preferred to stay with the very-high-molecular-weight hyaluronic acid eye drops beyond the trial period, the other two returned to the earlier therapy with ASED. The control group continued their treatment as before and finished the study after 8 weeks. Conclusion: For the first time, artificial eye drops, i.e., high-molecular-weight hyaluronic acid eye drops, offered an acceptable alternative to ASED. Some patients perceived these drops as even better than the patient’s own serum. This is the first evidence that optimization of the molecular structure of hyaluronic acid can be used to create eye drops that are perceived to be better than other tested tear substitutes and even patients’ own serum. This offers a new treatment perspective for patients with very severe dry eye disease.

Key Clinical Message Frey's syndrome is the most common adverse event after parotidectomy, and usually, it appears after 6 months. In our case, symptoms appear 20 years from surgery, an uncommon condition. Intralesional botulinum toxin gives excellent results in therapy, regardless of the time elapsed between surgery and the first treatment.

Abstract Background Amyloid tumor of the breast is a rare disease, which was first reported in 1973. To date, only six cases have been reported in Japan. Case presentation A 45-year-old woman who had a medical history of Sjogren’s syndrome presented with a lump of 3 cm in diameter on the outer side of the right breast. Mammography showed no abnormality. Ultrasonography showed a well-defined and rough hypoechoic mass of 32 mm in diameter at the site of the lump. With suspicion of breast cancer, an ultrasound-guided vacuum-assisted breast biopsy was performed. For pathological diagnosis, hematoxylin and eosin staining showed deposits of nonstructural substances in the interstitium. The specimen stained red with Congo red staining and showed green birefringence under a polarizing microscope. Thus, the mass was diagnosed as an amyloid tumor. Since the patient had Sjogren’s syndrome, it was considered a breast finding of autoimmune disease. We considered further therapy to be unnecessary, and annual follow-up was recommended. Conclusions We diagnosed the mass as an amyloid tumor by an ultrasound-guided vacuum-assisted breast biopsy without resection. The patient had no systemic symptoms suspected systemic amyloidosis, and we diagnosed localized amyloidosis. An amyloid tumor of the breast may show findings suggestive of breast cancer. Pathological diagnosis before surgery is important to avoid excessive invasion. If deposits of nonstructural substances are observed by hematoxylin and eosin staining, Congo red staining should be added.

Distal renal tubular acidosis (DRTA) has been reported in association with autoimmune diseases, such as Sjögren’s syndrome, systemic lupus erythematosus (SLE), autoimmune hepatitis, primary biliary cirrhosis, rheumatoid arthritis and autoimmune thyroiditis. Whether we talk about the complete or incomplete form of DRTA associated with autoimmune diseases, the real incidence is unknown because asymptomatic patients usually are not identified, and most of the reported cases are diagnosed due to severe symptoms secondary to hypokalemia, a frequent finding in these cases. The mechanisms involved in DRTA in patients with autoimmune diseases are far from being fully elucidated and most of the data has come from patients with Sjögren’s syndrome. This review will present different hypotheses raised to explain this association. Also, aiming for a better understanding of the association between autoimmune diseases and DRTA, our review summarizes data from 37 case reports published in the last five years. We will emphasize data regarding clinical presentation, biological alterations, treatment and outcome. A very important question is whether immunosuppressive therapy is helpful in DRTA associated with autoimmune diseases. Because the pathology is rather rare, treatment is not standardized, and reported results are often contradictory. Corticosteroids are frequently used, but multiple other immunosuppressive drugs have been proposed and will be approached in this review.

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

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.

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. [ABSTRACT FROM AUTHOR]

Background: Lacrimal 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. Methods: DS 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. Results: DS 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<0.05 for both). Comparison of gene expression between the MHCII- 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. Conclusions: There 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. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The aim of this study was to find out the correlation and evaluate the accuracy of labial minor salivary gland biopsy as a diagnostic tool in the multidisciplinary management of patients with Sjögren syndrome. MATERIALS AND METHODS: Patients, referred to our outpatient office between January 2014 and December 2018 from a rheumatologist for biopsy examination, as part of the complex diagnostic plan for suspected Sjögren syndrome, were included in the current study. Each specimen was examined histomorphometrically by the pathologist to calculate the focus score describing the degree of salivary gland inflammatory infiltration. RESULTS: Fifty patients met the inclusion criteria. From the total number of patients, 39 presented with an established Sjögren syndrome by fulfilling the revised American-European criteria. From those, 27 had a positive lip biopsy. The remaining 12 patients from the total group, who were diagnosed with Sjögren syndrome based on the same criteria, had a negative lip biopsy. CONCLUSION: The labial minor salivary gland biopsy is a valuable diagnostic tool to establish the diagnosis of Sjögren syndrome. However, a positive biopsy result must always be correlated with all the other diagnostic criteria to prove the exact diagnosis (Tab. 1, Fig. 4, Ref. 49). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To analyze the clinical and sociodemographic manifestations in patients with Sjøgren syndrome who were treated at the University Hospital of Santander. MATERIALS AND METHODS: A retrospective cross-sectional descriptive study. The study population was integrated by patients older than 13 years who entered to University Hospital of Santander in Colombia from 2012 to 2016. Patients who did not have a complete and detailed medical history were excluded. RESULTS: Were analyzed 45 patients with Sjøgren syndrome, we got a prevalence of 12/100,000 patients; 41 were women. The average age in the cases was 55.4 years. The median of evolution time of the symptoms was of 48 months. All the patients were caught in the outpatient consultant. Xerostomia was the clinical manifestation most frequently found, followed by the absence of saliva lake; in lesser frequency the ophthalmic disease, while only 6 cases presented Raynaud's phenomenon; 40 out of 45 patients had another systemic disease, 19 of them had rheumatoid arthritis. CONCLUSIONS: The prevalence of Sjøgren syndrome in our study was lesser than the current literature; the gender ratio remained similar to other studies. [ABSTRACT FROM AUTHOR]

Sjogren's syndrome (SS) is an autoimmune disease that is classified as a rheumatic disease and causes inflammation of the exocrine glands, mainly affecting the salivary and lacrimal glands, leading to significant loss of function. It is the second most common systemic autoimmune disease after rheumatoid arthritis and is mainly characterized by a triad of clinical features, namely dry keratoconjunctivitis, dry mouth, and a connective tissue disease (usually Rheumatoid Arthritis). It can also affect many other tissues and organs, especially the glandular tissues and the musculoskeletal system. The cause of SS is multifactorial. The etiology is considered to be related to a combination of genetic, environmental, viral infections and modifications of the immune system. The disease destroys through the immune system the glandular epithelium of the exocrine glands, especially the salivary and lacrimal glands. The clinical picture includes intraoral manifestations (dry mouth, angular cheilitis, secondary infections, significantly increased rate of caries and erosive lesions on the teeth, etc.), ocular manifestations (dry eye, burning sensation in the eyes, etc.). manifestations from the musculoskeletal, gastrointestinal, nervous system etc. Dry skin and rash may also coexist. Treatment of the disease is symptomatic. Patients should take various general measures, such as very meticulous oral hygiene, frequent use of artificial tears and saliva substitutes, lip lubricants, etc. Systemic manifestations and pain (eg arthralgias) are treated with drugs used to treat other autoimmune diseases, such as NSAIDs, corticosteroids, immunosuppressants, etc. The difficulty of diagnosis, the unknown etiology, the complexity of the manifestations of the syndrome, the need for early treatment indicate the need for cooperation of many specialties for both diagnosis and treatment of the syndrome. The dentist, as well as the physician, the otolaryngologist or the ophthalmologist will probably be the first doctors who will be called to diagnose the syndrome, to note the symptoms and to refer patients to more competent doctors or to the appropriate examinations. This requires a good knowledge of the pathophysiology of the syndrome, the methods of diagnosis and the therapeutic approaches, and the present review aims to contribute to this need. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Sjögren syndrome is a chronic autoimmune inflammatory disease characterized by lymphocytic infiltration of exocrine glands, predominantly the parotid and lacrimal glands, thereby resulting in oral and ocular dryness. It has been reported to occur most frequently in women between 40 and 50 years of age. Sjögren syndrome has an insidious onset, is slowly progressive, and presents a wide range of clinical manifestations, leading to delays or challenges in the diagnosis. Early diagnosis of this condition is essential to prevent the associated complications that affect patients' quality of life. This report presents 3 cases of Sjögren syndrome in female patients aged between 40 and 75 years who presented with complaints of persistent dry mouth and burning sensation. The cases highlight the diagnostic value of 3-dimensional cone-beam computed tomographic sialography in the detection of salivary gland pathologies at an early stage. [ABSTRACT FROM AUTHOR]

Background: Acquired Gitelman syndrome is a very rare disorder reported in association with autoimmune disorders, mostly Sjögren syndrome. It is characterized by the presence of hypokalaemic metabolic alkalosis, hypocalciuria, hypomagnesaemia and hyper-reninaemia, in the absence of typical genetic mutations associated with inherited Gitelman syndrome.Case Presentation: A 20 year old woman who was previously diagnosed with primary Sjögren syndrome and autoimmune thyroiditis presented with two week history of lower limb weakness and salt craving. Examination revealed upper limb and lower limb muscle weakness with muscle power of 3/5 on MRC scale and diminished deep tendon reflexes. On evaluation, she had hypokalaemia with high trans-tubular potassium gradient, metabolic alkalosis and hypocalciuria, features suggestive of Gitelman syndrome. New onset hypokalaemic alkalosis in a previously normokalaemic patient with Sjögren syndrome strongly favored a diagnosis of acquired Gitelman syndrome. Daily potassium supplementation and spironolactone resulted in complete clinical recovery.Conclusions: Acquired Gitelman syndrome associated with Sjögren syndrome is rare. It should be considered as a differential diagnosis during evaluation of acute paralysis and hypokalaemic metabolic alkalosis in patients with autoimmune disorders, especially Sjögren syndrome. [ABSTRACT FROM AUTHOR]

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

La diversité et la complexité des toxicités immunes des inhibiteurs de checkpoint immunologique imposent une approche multidisciplinaire pour leur prise en charge. Nous rapportons l'expérience de la réunion de concertation pluridisciplinaire « toxicités et immuno-oncologie » (« ToxImmun ») récemment mise en place en Occitanie-Est, et décrivons 114 dossiers présentés entre le 17 décembre 2018 et le 20 janvier 2020, concernant une majorité de cancers pulmonaires. Le principal motif de recours était la confirmation et la prise en charge d'un effet indésirable immuno-induit suivi de la discussion d'une réintroduction (re-challenge) et enfin de celle de l'introduction de l'immunothérapie en cas d'antécédent de pathologie dysimmune. Les colites, les hépatites et les myocardites étaient les effets indésirables immuno-induits tout grade et de grade ≥ 3 les plus fréquents. Le syndrome sec, avec ou sans critères pour un syndrome de Gougerot–Sjögren, était fréquent (26 % des cas) et semblait associé à la survenue d'une toxicité sévère et d'une multi-toxicité. Le délai moyen de survenue était de 3,8 mois. Ce délai était plus court en cas de combinaison d'immunothérapie et en cas de traitement par un anti-PDL-1. Une majorité des situations examinée provenait d'une prise en charge initiale par un interniste, confirmant le rôle précoce et central de cette spécialité dans la gestion de l'immunotoxicité. La généralisation des RCP régionales, coordonnées par internistes et oncologues médicaux, pourrait permettre d'optimiser cette prise en charge aux bénéfices des patients. Immune checkpoint inhibitors (ICIs) can cause numerous and complex immune-related adverse events whose management need a multidisciplinary approach. Herein, we investigated 114 requests, mostly concerning patients suffering from lung cancer, that were submitted to the « ToxImmun » multidisciplinary meeting in Eastern Occitania between December the 17th 2018 and January the 20th 2020. The leading reasons for the request concerned the putative causal link between immunotherapy and immune-toxicity and its management, followed by possible retreatment after temporary withdrawn because of adverse event, and finally the possibility to initiate ICIs in patients with pre-existing autoimmunity. Colitis, hepatitis and myocarditis were the most frequent immune-related adverse events (IRAEs), both all grade and grade 3–4. Sicca syndrome (with or without Sjogren criteria) was also frequent (26% of cases) and seems to be associated with severe toxicity and multi-toxicity. The mean time to first IRAE was 3.8 months, a time shortened with the use of anti-PD-L1 agents or ICI combination. A majority of requests came from initial evaluation by the internist confirming the early and main role of this specialty in the management of immunotoxicity. Expansion of this regional multidisciplinary meeting, coordinated by internists and medical oncologists, could improve management of immune-related adverse events for the patients' benefits. [ABSTRACT FROM AUTHOR]

In this review, the author shows that simultaneous multiple disorders caused by reactivation of Epstein–Barr virus can lead to salivary gland disorders as part of Sjogren's syndrome (SS). Therefore, clinicians must differentiate SS from other diseases when diagnosing and treating salivary gland disorders. In particular, the author explains how microbial infection in SS overcomes immunological tolerance, leading to pathological changes, and how cytokine overexpression and endocrine disrupters contribute to glandular tissue injury. Also, the author suggests that involvement of reactive oxygen species is a common pathogenesis of salivary gland disorders and SS, so regulation of oxidative stress is an effective treatment for both. The results of clinical studies on restoring salivary gland function and regenerating salivary glands with tissue stem cells may provide clues on elucidating the cause of SS. [ABSTRACT FROM AUTHOR]

Objective: To investigate salivary gland ultrasound (SGUS) abnormalities in relation to clinical phenotype and patient characteristics, disease activity, and disease damage in patients with primary Sjögren syndrome (pSS).Methods: Consecutive outpatients included in our REgistry of Sjögren Syndrome LongiTudinal (RESULT) cohort were selected. Patients with pSS who were included were classified according to the American College of Rheumatology/European League Against Rheumatism (EULAR) criteria and underwent full ultrasonographic examination (Hocevar score 0-48) at baseline. Total SGUS scores of ≥ 15 were considered positive. Patient characteristics, disease activity, and disease damage were compared between the different SGUS groups.Results: In total, 172 of 186 patients with pSS were eligible, of whom 136 (79%) were SGUS positive. Compared with patients who were SGUS negative, SGUS-positive patients had significantly longer disease duration, higher EULAR Sjögren Syndrome Disease Activity Index, higher Sjögren Syndrome Disease Damage Index, and were more likely to have a positive parotid gland biopsy, anti-SSA/SSB antibodies, and abnormal unstimulated whole saliva (UWS) and ocular staining score (OSS), and higher levels of IgG and rheumatoid factor. Regarding patient-reported outcome measurements (PROM), patients who were SGUS positive scored significantly lower on the EULAR Sjögren Syndrome Patient-Reported Index for fatigue and pain, and more often found their disease state acceptable compared with patients who were SGUS negative. SGUS total score showed significant associations with various clinical and serological variables, and with PROM. Highest associations were found for UWS (ρ = -0.551) and OSS (ρ = 0.532).Conclusion: Patients who were SGUS positive show a distinct clinical phenotype in all aspects of the disease compared with patients who were SGUS negative: clinical, functional, serological, and PROM. SGUS could be a helpful tool in selecting patients for clinical trials and estimating treatment need. [ABSTRACT FROM AUTHOR]

Introduction/Objectives: The patient perspective is an essential outcome parameter in the quest for effective therapy in primary Sjögren's Syndrome (PSS). The EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is recommended by EULAR to quantify patient's symptom burden and has been used in several clinical trials. Surprisingly, the patient's perception of dryness quantified with ESSPRI does not correlate with objective measures of salivary or lacrimal flow. Thus, we evaluated a newly developed assessment tool-the Primary Sjögren's Syndrome Quality of Life Questionnaire (PSS-QoL)—for quantifying symptoms of dryness in comparison with the ESSPRI and objective measurements of salivary and lacrimal flow.Methods: Data of patients from the PSS registry of the Medical University of Graz fulfilling the 2016 ACR/EULAR classification criteria for PSS were analyzed. The patient perspective was analyzed by PSS-QoL, ESSPRI, Xerostomia Inventory (XI) and Ocular Surface Disease Index (OSDI). Sicca signs were measured with Schirmer's test, unstimulated salivary flow test (USF) and stimulated salivary flow test (SSF). ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index) and EGA (Evaluator Global Assessment, numeric rating scale from 0 to 10) were obtained. In addition, free light chains (FLC) κ and λ, rheumatoid factor (RF) IgM and IgA were determined.Results: Data from 123 PSS patients were analyzed; 91.9% (n = 113) were female, with a mean disease duration of 6.2 (±5.3) years and mean age of 60.1 (±12.4) years. PSS-QoL-dryness revealed significant negative correlations with Schirmer's test (r = −0.31, p < 0.05) and SSF-test (r = −0.390, p < 0.01). In contrast, we found no significant correlation between ESSPRI-dryness and any objective dryness test. Lower perceived dryness was associated with higher immunological activity determined by increased levels of IgG, FLC and RF-IgA. Whereas patients with only subjective signs of dryness had lower immunological activity.Discussion: Patients' perception of dryness assessed by PSS-QoL correlates with objective measurements of salivary gland function while ESSPRI-dryness did not. Based on the PSS-QoL and objective measures of dryness two distinct groups of PSS patients could be distinguished, which may have implications in daily practice and future clinical studies.

Background: Tear deficiency due to lacrimal gland (LG) dysfunction is one of the major causes of dry eye disease (DED). Therefore, LG stem cell-based therapies have been extensively reported to regenerate injured lacrimal tissue; however, the number of stem cells in the LG tissue is low, and 2D long-term cultivation reduces the differentiation capacity of stem cells. Nevertheless, 3D LG organoids could be an alternative for a DED therapy because it is capable of prolonged growth while maintaining the characteristics of the LG tissue. Here, we report the development of LG organoids and their application as cell therapeutics. Methods: Digested cells from human LG tissue were mixed with Matrigel and cultured in five different media modified from human prostate/salivary organoid culture media. After organoid formation, the growth, specific marker expression, and histological characteristics were analyzed to authenticate the formation of LG organoids. The secretory function of LG organoids was confirmed through calcium influx or proteomics analysis after pilocarpine treatment. To explore the curability of the developed organoids, mouse-derived LG organoids were fabricated and transplanted into the lacrimal tissue of a mouse model of DED. Results: The histological features and specific marker expression of LG organoids were similar to those of normal LG tissue. In the pilocarpine-treated LG organoid, levels of internal Ca2+ ions and β-hexosaminidase, a lysosomal protein in tear fluid, were increased. In addition, the secreted proteins from pilocarpine-treated lacrimal organoids were identified through proteomics. More than 70% of the identified proteins were proven to exosome through gene ontology analysis. These results indicate that our developed organoid was pilocarpine reactive, demonstrating the function of LG. Additionally, we developed LG organoids from patients with Sjogren's syndrome patients (SS) and confirmed that their histological features were similar to those of SS-derived LG tissue. Finally, we confirmed that the mouse LG organoids were well engrafted in the lacrimal tissue two weeks after transplantation. Conclusion: This study demonstrates that the established LG organoids resemble the characteristics of normal LG tissue and may be used as a therapy for patients with DED. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the relationship between alexithymia and depression, anxiety, quality of life, disease duration, and inflammatory markers in patients with Sjogren's Syndrome (SS). Material-method: The study included 168 individuals with primary SS (pSS) (145 females, 23 males) with a mean age of 51.14 ± 9.42 years. The Turkish Version of the Toronto Alexithymia Scale was used to evaluate alexithymia, the Beck Anxiety and Depression Scale to evaluate anxiety and depression, and the World Health Organization Quality of Life Scale-Short Form to evaluate the quality of life. Results: The average alexithymia of individuals with pSS was found to be 53.83 ± 12.61 points. A low and moderately significant correlation was found between alexithymia with anxiety (r:0.514, p:0.00), depression (r:0.522, p:0.00), mental (r:0.474, p:0.0) and social (r:0.486,p: 0.04) sub-parameters of quality of life and Erythrocyte sedimentation rate (ESR) values (r:0.432, p:0.03). Results: According to the results of this study, as alexithymia increases in individuals with pSS, the levels of depression, anxiety and inflammatory markers increase and the quality of life decreases in terms of mental and social aspects. Our results are twofold. According to the results of our study, considering that alexithymia is mediated by depressive symptoms in pSS, it is recommended that patients should be evaluated in detail in terms of alexithymia, depression and anxiety, and therefore these results support the need for a multidimensional approach to treatment. [ABSTRACT FROM AUTHOR]

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Chikungunya virus (CHIKV) infection is caused by an arbovirus prevalent in various parts of the world. The virus can induce autoantibodies and rheumatic diseases, such as rheumatoid arthritis and spondylarthritis. However, until now, no case of Sjögren syndrome (SS) was described associated with CHIKV. In this article, we describe a 49-year-old female with polyarthralgia and a temporary rash on her trunk and arms. Her physical examination showed polyarthritis of her ankles and wrists. Serologies for CHIKV were interpreted as positive with IgM 6.5 (normal range < 0.8) and negative for IgG. Antinuclear antibodies were positive at a titer of 1:640 as well as anti-Ro/SS-A. The diagnosis of subacute CHIKV infection was determined. The Schirmer test, Rose Bengal, and salivary scintigraphy were positive and the diagnosis of SS was confirmed. She was treated with hydroxychloroquine, methotrexate, and a single dose of betamethasone depot. This is the first report on CHIKV associated with SS. Sequence analysis of the CHIKV proteome versus SS autoantigens showed an extensive peptide sharing between the virus and numerous SS autoantigens, thus supporting the hypothesis that autoimmune cross-reactivity might causally link CHIKV to SS. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the impact of hydroxychloroquine (HCQ) on the perinatal outcomes of pregnancies with immune system disorders that necessitate the use of the drug. Methods: This cohort consisted of 202 pregnancies with poor obstetric history and immune system problems. Patients enrolled in special antenatal care program were administered low‐dose low‐molecular‐weight heparin, low‐dose salicylic acid and low‐dose corticosteroid (prophylaxis protocol) as soon as their pregnancies were confirmed. Pregnancies with systemic lupus erythematosis, Sjogren syndrome and rheumatoid arthritis were additionally administered HCQ 200 mg daily as a part of their routine treatment. Pregnancies using HCQ were included in the study group (n = 39) while the remainders were included in control group (n = 163). We compared the groups in terms of the presence of miscarriage, fetal growth restriction (FGR), preeclampsia and preterm birth, as well as gestational week at birth, birthweight and "APGAR score of <7" at 10th minute. Results: Miscarriage rates were 28.2% and 28.2% while preterm birth rates were 16.6% and 28.2% in the control and study groups, respectively (P = 0.215). Preeclampsia and HCQ‐related side effects were not detected in the groups. There were also no significant differences between the groups in terms of FGR, gestational day at birth, birthweight and the presence of "APGAR score <7" at 10th minute (P = 0.462, P = 0.064, P = 0.273 and P = 0.627, respectively). Conclusion: Low‐dose low‐molecular‐weight heparin, low‐dose salicylic acid and low‐dose corticosteroid prophylaxis together with HCQ seem to be promising in pregnancies with immune system disorders. HCQ seems to be a safe and effective drug in low dosages. [ABSTRACT FROM AUTHOR]

Objective To investigate peripheral lymphopenia, a frequent finding in primary Sjögren's syndrome (pSS) associated with higher disease activity and increased mortality. Methods Prospective, cross-sectional study of consecutive patients with pSS (n  = 66) and healthy controls (n  = 181). Lymphocyte subsets were analysed by flow cytometry, naïve (CD45RA+) and memory (CD45RO+) CD4+ T cells were purified by MACS technology. In vitro proliferation and senescence-associated β-galactosidase (SABG) were assessed by flow cytometry. Telomere length and TCR excision circles (TREC) were measured by real-time PCR. Telomerase activity was analysed according to the telomeric repeat amplification protocols (TRAP). Results In pSS, lymphopenia mainly affected naïve CD4+ T cells. We noted a lower frequency of proliferating naïve CD4+ T cells ex vivo and decreased homeostatic proliferation in response to IL-7 stimulation in vitro. Furthermore, naïve CD4+ T cells exhibited signs of immune cell aging including shortened telomeres, a reduction in IL-7R expression and accumulation of SABG. The senescent phenotype could be explained by telomerase insufficiency and drastically reduced levels of T-cell receptor excision circles (TRECs), indicating a history of extensive post-thymic cell division. TRECs correlated with the number of naïve CD4+ T cells linking the extend of earlier proliferation to the inability to sustain normal cell numbers. Conclusion In pSS, evidence for increased proliferation of naïve CD4+ T cells earlier in life is associated with a senescent phenotype unable to sustain homeostasis. The lack of naïve CD4+ T cells forms the basis of lymphopenia frequently observed in pSS. [ABSTRACT FROM AUTHOR]

Objective: To assess pulmonary function and chronic obstructive pulmonary disease (COPD) development over time in patients with primary Sjögren syndrome (pSS), as well as the association between pulmonary function, radiographic findings, respiratory symptoms, and clinical features of pSS, taking cigarette consumption into account.Methods: Forty patients with pSS (mean age 66 yrs; range 42-81 yrs; 39 women), previously participating in a cross-sectional study on pulmonary involvement in pSS, were reassessed by pulmonary function tests after a mean follow-up time of 6 years. At follow-up, patients were also assessed by high-resolution computed tomography of the chest, as well as for pSS disease activity, respiratory symptoms, and cigarette consumption.Results: Patients with pSS showed significantly decreased percentages of predicted total lung capacity (TLC), residual volume (RV), RV/TLC ratio, and diffusing capacity of the lungs for carbon monoxide, as well as an increase in predicted forced expiratory volume in 1 second/vital capacity (FEV1/VC) ratio from baseline to follow-up. The proportion of COPD in patients with pSS did not change significantly from baseline to follow-up (38% vs 40%, respectively). Radiographic signs of bronchial involvement and interstitial lung disease were each found in 38% of the patients.Conclusion: Both airway and pulmonary parenchymal disease were commonly found in patients with pSS, with a coexistence of both an obstructive and restrictive pulmonary function pattern, where the latter tended to deteriorate over time. COPD was a common finding. Airway and pulmonary involvement may be underdiagnosed in pSS, which is why special attention to clinical assessment of pulmonary involvement in patients with pSS is mandated. [ABSTRACT FROM AUTHOR]