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OBJECTIVE: Sjögren syndrome (SS) is an autoimmune disorder, affecting about 16,000 individuals in Italy, yet lacking a standardized therapy protocol and a plain inclusion in the reimbursed healthcare services. This raises many controversial issues about how managing the SS patient, to relief pain and discomfort and improve patients' health and social life. The ozone therapy resulted successful in previous reports, and therefore, it was used in this case report. CASE PRESENTATION: A 69-years old female outpatient, showing positivity to Schirmer's test, was previously diagnosed as a primary Sjögren syndrome, who later developed an autoimmune thyroiditis and showed the presence of rheumatoid factors. The patient suffered from a marked ocular dryness, subsequently to a purported endothelitis, alongside with fatigue and pain. Laboratory tests showed a positive ANA 1:320 in a speckled pattern with negative anti-SSA and anti-SSB tests. From December 2020 to January 2021 she underwent 2 routes of three sessions of oxygen-ozone autohemotherapy (O2-O3 AHT), as described below and improved, with only 2 sessions, her symptomatology and clinical outcome, as ocular dryness, fatigue and pain, rapidly disappeared. CONCLUSIONS: The use of ozone in the therapy of SS is a straightforward, affordable and feasible approach to treat primary Sjögren syndrome without significant side effects. [ABSTRACT FROM AUTHOR]

Background: We aimed to assess the efficacy of the injections of platelet rich plasma (PRP) for the treatment of severe dry eye disease (DED).Results: In this retrospecitve interventional clinincal study, we included 28 eyes of 14 patients with severe DED who were diagnosed with Sjogren syndrome. Each patient received unilateral lacrimal gland injection of PRP at days 0, 30, 60 and 90 days while the other eye served as control group who received preservative free eye drops. We objectively assessed parameters at baseline, 1 month, 2 months and 3 months including ocular surface analyzer (OSA) namely; noninvasive tear breakup times (NIBUT), tear meniscus height (TMH), lipid layer thickness (LLT) in addition to the Schirmer test I, corneal fluorescein staining (CFS) and meiboscore. The mean age was 43.4 ± .7.85 years. Comparing different parameters, baseline data showed non-significant difference between injected eye group and control group. After 1 and 3 months of follow up, there were significant differences between both groups regarding NITBUT, TMH, LLT, CFS and Schirmer test, with p <  0.001 in favor of PRP group.Conclusion: Injection of PRP in lacrimal gland is simple, safe, and effective technique in treatment of severe dry eye; proved by improvement of tear film parameters through subjective and objective assessment. Further studies are needed to standardize the technique and to confirm these results. [ABSTRACT FROM AUTHOR]

• Sphingosylphosphorylcholine (SPC) is a sphingolipid with several immunomodulatory functions. • SPC ameliorates disease pathology in an animal model of sjögren syndrome (SS). • SPC increased regulatory B (B reg) cells and salivary secretion-related genes in mouse splenocytes and human submandibular gland (HSG) cells, respectively. • SPC is a new therapeutic target in SS. Sjögren syndrome (SS) is an autoimmune disease in which immune cells infiltrate the exocrine gland. Since SS is caused by a disorder of the immune system, treatments should regulate the immune response. Sphingosylphosphorylcholine (SPC) is a sphingolipid that mediates cellular signaling. In immune cells, SPC has several immunomodulatory functions. Accordingly, this study verifies the immunomodulatory ability and therapeutic effect of SPC in SS. To understand the function of SPC in SS, we treated SPC in female NOD/ShiJcl (NOD) mice. The mice were monitored for 10 weeks, and inflammation in the salivary glands was checked. After SPC treatment, we detected the expression of regulatory B (B reg) cells in mouse splenocytes and the level of salivary secretion-related genes in human submandibular gland (HSG) cells. Salivary flow rate was maintained in the SPC-treated group compared to the vehicle-treated group, and inflammation in the salivary gland tissues was relieved by SPC. SPC treatment in mouse cells and HSG cells enhanced B reg cells and salivary secretion markers, respectively. This study revealed that SPC can be considered as a new therapeutic agent against SS. [ABSTRACT FROM AUTHOR]

Lung involvement in autoimmune diseases (AID) is uncommon, but may precede other organ manifestations. A diagnostic problem is chronicity presenting with lung fibrosis. A new category of interstitial pneumonia with autoimmune features for patients with clinical symptoms of AID and presenting with usual interstitial pneumonia (UIP) enables antifibrotic treatment for these patients. Hypersensitivity pneumonia (HP) and other forms of lung fibrosis were not included into this category. As these diseases based on adverse immune reactions often present with unspecific clinical symptoms, a specified pathological diagnosis will assist the clinical evaluation. We aimed to establish etiology-relevant differences of patterns associated with AID or HP combined with lung fibrosis. We retrospectively evaluated 51 cases of AID, and 29 cases of HP with lung fibrosis, and compared these to 24 cases of idiopathic pulmonary fibrosis (UIP/IPF). Subacute AID and HP most often presented with organizing pneumonia (OP), whereas chronicity was associated with UIP. Unspecified fibrosis was seen in a few cases, whereas NSIP pattern was rare. In 9 cases, the underlying etiology could not be defined. Statistically significant features differentiating chronic AID or HP from UIP/IPF are lymphocytic infiltrations into myofibroblastic/fibroblastic foci. Other features significantly associated with AID and HP were granulomas, isolated Langhans giant cells, and protein deposits, but seen in only a minority of cases. A combination of UIP with one of these features enabled a specific etiology-based diagnosis. Besides the antifibrotic drug regimen, additional therapies might be considered. [ABSTRACT FROM AUTHOR]

Abstract 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.

Jonathan Lilley,1 Erin C O’Neil,1 Vatinee Y Bunya,1 Kennedy Johnson,1 Gui-Shuang Ying,2 Peiying Hua,2 Mina Massaro-Giordano1 1Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; 2Center for Preventive Ophthalmology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USACorrespondence: Mina Massaro-GiordanoDepartment of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, 51 N. 39th Street, Philadelphia, PA, 19104, USATel +1 215-662-9393Email mina@pennmedicine.upenn.eduPurpose: To assess the efficacy and safety of an intranasal tear neurostimulator (ITN) device in Sjögren syndrome (SS) patients.Methods: This was a two-visit prospective, randomized, controlled, same-day crossover study in participants with SS. Inclusion criteria were assessed at a baseline screening visit and included an Ocular Surface Disease Index (OSDI) score ≥ 13, and a Schirmer with anesthesia ≤ 10 mm/5 min (in at least one eye), with a cotton swab stimulation induced increase of ≥ 4 mm in the same eye. Participants returned for the application visit, where they received intranasal and extranasal applications of the ITN in random sequence, separated by at least 60 min. Schirmer scores were measured in both eyes after each application and compared to baseline values. Generalized linear models were performed to compare the change in Schirmer scores from baseline, and generalized estimating equations were used to account for correlations from repeated measurements in the same eye and measurements from two eyes of the same patient.Results: Fifty-five participants were screened and 35 were enrolled (all female), ranging in age from 31 to 72 years (mean, 57 years). The baseline OSDI score ranged from 14 to 91 (mean, 50.5), and the baseline Schirmer score had a mean (SD) of 6.4 (3.5) ranging from 0 to 20 (mm/5min). Improvement in Schirmer scores was significantly greater for intranasal device application (13.5 mm/5min, 95% CI: 10.4, 16.5) compared to extranasal device application (0.8mm/5min, 95% CI: − 0.9, 2.4) (p< 0.0001). The effects of the intranasal device application were significant regardless of the participant’s baseline Schirmer score and systemic SS medication usage (p< 0.05).Conclusion: Intranasal application of the ITN device significantly increased tear production in a subset of SS patients compared to baseline and was more effective than extranasal application. While production of the ITN device was recently discontinued, our findings suggest that other therapies that neurostimulate the lacrimal function unit may be effective in a subset of SS patients.Keywords: Sjögren syndrome, intranasal tear neurostimulation, tear production

Abstract Sarcoidosis is a multisystem disease which rarely involves pleura resulting in various manifestations including pleural effusion, pneumothorax, pleural thickening, hydropneumothorax, trapped lung, hemothorax, or chylothorax. Hemorrhagic Pleural effusion secondary to sarcoidosis is extremely rare. Sarcoidosis is considered to be exclusion criteria for diagnosis of sjogrens syndrome (SS).But there are reports showing coexistence of these two disorders in the past. We present a patient with SS who presented with isolated hemorrhagic pleural effusion due to sarcoidosis.

As the largest salivary gland in oral cavity, the parotid gland plays an important role in initial digesting and lubricating food. The abnormal secretory function of the parotid gland can lead to dental caries and oral mucosal inflammation. In recent years, single-cell RNA sequencing (scRNA-seq) has been used to explore the heterogeneity and diversity of cells in various organs and tissues. However, the transcription profile of the human parotid gland at single-cell resolution has not been reported yet. In this study, we constructed the cell atlas of human parotid gland using the 10× Genomics platform. Characteristic gene analysis identified the biological functions of serous acinar cell populations in secreting digestive enzymes and antibacterial proteins. We revealed the specificity and similarity of the parotid gland compared to other digestive glands through comparative analyses of other published scRNA-seq data sets. We also identified the cell-specific expression of hub genes for Sjögren syndrome in the human parotid gland by integrating the results of genome-wide association studies and bulk RNA-seq, which highlighted the importance of immune cell dysfunction in parotid Sjögren syndrome pathogenesis. [ABSTRACT FROM AUTHOR]

Sjögren syndrome (SS) is a chronic and progressive autoimmune disease characterized by dry mouth and dry eyes, and characteristic autoantibodies. Evidence of altered macroautophagy/autophagy and apoptosis has been associated with SS, but a mechanistic understanding of the gene expression changes associated with these abnormal processes has not been realized. Recently, increased LAMP3 (lysosomal associated membrane protein 3) expression was found in a subset of SS patients and was associated with increased apoptosis and autoantigen accumulation and release. To better understand how LAMP3 expression might modulate apoptosis, cell biology, and biochemical studies were used to examine the effect of LAMP3 expression in minor salivary gland cells. LAMP3 expression resulted in degradation of LAMP1 increasing lysosomal membrane permeabilization and relocalization of cathepsins to the cytoplasm, resulting in destabilizing autophagic flux and caspase activation. These findings highlight the central role of LAMP3 expression in the pathogenesis of SS. A253-control: A253 control for LAMP3 stable overexpression; A253- LAMP3: A253 LAPM3 stable overexpression; CASP1: caspase 1; CASP3: caspase 3; CHX: cycloheximide; CTSB: cathepsin B; CTSD: cathepsin D; CQ: chloroquine; DCs: dendritic cells; ER: endoplasmic reticulum; LGALS3: galectin 3; HCV: hepatitis C virus; HSG-control: HSG control for LAMP3 stable overexpression; HSG-LAMP3: HSG LAMP3 stable overexpression; HSP: heat shock protein; HTLV-1: human T-lymphocyte leukemia virus-1; IXA: ixazomib; LAMP: lysosomal associated membrane protein; MHC: major histocompatibility complex; mAb: monoclonal antibody; OE: overexpression; pepA: pepstatin A; pAb: polyclonal antibody; pSS: primary Sjögren syndrome; qRT-PCR: quantitative real- time reverse transcriptase polymerase chain reaction; SLE: systemic lupus erythematosus; SS: Sjögren syndrome; UPR: unfolded protein response; V-ATPase: vacuolar-type proton- translocating ATPase; Y-VAD: Ac-YVAD-cmk; Z-DEVD; Z-DEVD-fmk; Z-VAD: Z-VAD- fmk [ABSTRACT FROM AUTHOR]

Anti-Ki/SL antibodies were first described in 1981 and have been associated with systemic lupus erythematosus (SLE) and Sicca syndrome. Despite the long history, very little is known about this autoantibody system, and significant confusion persists. Anti-Ki/SL antibodies target a 32 kDa protein (also known as PSME3, HEL-S-283, PA28ƴ, REGƴ, proteasome activator subunit 3), which is part of the proteasome complex. Depending on the assay used and the cohort studied, the antibodies have been reported in approximately 20% of SLE patients with high disease specificity as compared to non-connective tissue disease controls. The aim of this review is to summarize the history and key publications, and to explore future direction of anti-Ki/SL antibodies. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the frequency of connective tissue diseases (CTDs) in patients with chronic spontaneous urticaria (CSU) and to evaluate clinical and laboratory characteristics of CSU accompanied by CTDs. Patients and methods: Between January 2017 and December 2020, a total of 390 CSU patients (120 males, 270 females; mean age: 38.9±13.7 years; range, 18 to 78 years) were included in the study. Clinical and laboratory characteristics of CSU in patients with and without CTD were analyzed. Results: A total of 6.4% patients (n=25) with CSU had CTD, and the rate was found to be 8.9% in female patients (n=24). In these patients, Sjögren syndrome (SS) was seen in 15 (5.5%), rheumatoid arthritis in five (1.85%), undifferentiated connective tissue disease in three (1.11%), and systemic lupus erythematosus in one (0.37%). Anti-thyroglobulin antibody, rheumatoid factor, anti-cyclic citrullinated peptide antibody, antinuclear antibody positivity, low complement 4 level, and erythrocyte sedimentation rate were significantly different between CSU patients with and without CTD (p=0.013, p<0.001, p<0.001, p<0.001, p=0.0182, p<0.001, respectively). Conclusion: Our study results suggest that CSU is associated with CTDs, particularly with Sjögren syndrome. Every patient diagnosed with CSU should be questioned about rheumatic symptoms, particularly female patients and those having later-onset CSU. [ABSTRACT FROM AUTHOR]

L'atteinte articulaire est une des manifestations extra-glandulaires les plus fréquentes dans le syndrome de Sjögren primitif (SSp) ou maladie de Sjögren. On éliminera toujours une PR, un lupus systémique et une spondyloarthrite qui peuvent avoir des présentations cliniques proches et peuvent s'associer au SS. L'atteinte articulaire touche près de la moitié des patients SSp avec des arthrites cliniques pour 16 % d'entre eux. Le plus souvent, il s'agit d'arthrites symétriques, des interphalangiennes proximales, métacarpophalangiennes (MCP) et poignets, touchant moins de 5 articulations. L'échographie met en évidence des synovites de grade 1 ou 2, avec un signal Doppler positif dans moins d'un quart des cas et des ténosynovites, majoritairement des fléchisseurs des doigts. Il n'y a pas d'arthrite érosive radiographique dans le SSp. L'utilisation d'imagerie plus sensible que la radiographie telles que l'échographie et l'IRM montre fréquemment des érosions des MCP et des poignets. Il faudra alors rechercher une polyarthrite rhumatoïde associée à un SS secondaire. Cinq à dix pour cents des patients atteints de SSp ont des anticorps anti-CCP. La présence d'anticorps anti-CCP n'exclut pas forcément le diagnostic de SSp mais doit alerter sur le risque d'un développement ultérieur d'une polyarthrite rhumatoïde et nécessite donc un suivi radiographique même si le SSp évolue depuis de nombreuses années. L'atteinte articulaire est de bon pronostic et semble être un facteur prédictif d'évolution clinique favorable. La prise en charge thérapeutique doit être guidée par le niveau d'activité clinique et reposera sur les AINS ou les corticoïdes ± l'hydroxychloroquine. Les traitements de fond synthétiques seront proposés à visée d'épargne cortisonique. Joint involvement is one of the most common extra-glandular manifestations in primary Sjögren's syndrome (pSS), affecting almost half of the patients with clinical arthritis in 16 %. Most commonly, these are symmetrical arthritis, affecting fewer than 5 joints. Ultrasound shows grade 1 or 2 synovitis, with a positive doppler signal in less than a fourth of cases, and tenosynovitis, mostly of the finger flexors. Radiographs should not show erosion. In presence of erosions on ultrasound or MRI, which may be found on MCP and wrists, RA with secondary SS should be excluded. Five to 10 % of patients with SSp have anti-CCP antibodies. The presence of anti-CCP antibodies does not necessarily exclude the diagnosis of SSp, but it should alert to the risk of further development of RA, therefore requiring radiographic follow-up even if the pSS has been evolving for many years. Joint involvement has a good prognosis and appears to be a predictor of a favourable clinical course. Treatment should be guided by the level of clinical activity and should be based on NSAIDs or corticosteroids ± hydroxychloroquine. Synthetic disease-modifying anti-rheumatic drugs should be offered for corticosteroid sparing. [ABSTRACT FROM AUTHOR]

Le syndrome de Sjögren (SS) primaire ou maladie de Sögren est une pathologie auto-immune à forte prédominance féminine (9/1) avec un pic de fréquence vers 50 ans, mais il existe des formes débutant avant 20 ans. Les formes avec la triade classique « sécheresse, fatigue et douleurs » sont un mode habituel d'entrée dans la maladie et constituent environ 30 % des patients avec SS primitif. Les atteintes systémiques avec une ou plusieurs atteintes viscérales se voient dans environ 70 % des cas. Phénomène de Raynaud tardif, atteinte bronchiolaire, atteinte interstitielle pulmonaire, synovites, neuropathies surtout sensitives, néphrite tubulo-interstitielle, poussées de parotidomégalie sont autant de modes de révélation possibles de la maladie, car le syndrome sec peut être au second plan. Enfin, le SS doit aussi être évoqué en cas de vascularite cryoglobulinémique dont l'expression associe souvent glomérulonéphrite membranoproliférative, purpura, livedo et mononeuropathie multiple. Plus rarement, c'est la découverte d'un lymphome de MALT ou la survenue d'un bloc auriculo-ventriculaire congénital qui fera découvrir un SS associé. Primary Sjögren's syndrome (SS) or Sjögren disease is an autoimmune disorder with a high female ratio (9:1) with a peak of frequency around 50-year-old, but there are also cases with early onset before the age of 20. Forms with the classic triad of dryness, fatigue and pain are a common mode of entry into the disease and account for about 30% of patients with primary SS. Systemic involvement with one or more visceral manifestations is seen in about 70% of cases. Late Raynaud's phenomenon, bronchiolar involvement, interstitial lung disease, synovitis, neuropathies (particularly sensory neuropathies), tubulointerstitial nephritis, and parotid enlargement are all possible entry points to the disease since the dryness may be in the background. Finally, SS should also be considered in cases of cryoglobulinemic vasculitis, which often combines membranoproliferative glomerulonephritis, purpura, livedo and multiple mononeuropathy. More rarely, it is the discovery of a MALT lymphoma or the occurrence of a congenital atrioventricular heart block that will lead to the diagnosis of SS. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to determine the risk of cancer in patients with primary Sjögren syndrome (pSS) from a single center in Turkey. Methods: Clinical data of the subjects with pSS were retrospectively analyzed. The incidence of cancer for general population was obtained from GLOBOCAN 2018. Age- and sex-specific standardized incidence ratios (SIR) of solid and hematological cancers were calculated compared with the general population. Results: Four hundred thirty patients with pSS were included in the study. The majority of the patients were female (n = 396, 92.1%), and the mean age was 58.6 ± 12.0 years. Thirty-four patients (7.9 %) were diagnosed with cancer (26 solid and 8 hematological) during follow-up. The SIR for all cancers was 2.45 (95% CI, 1.625-3.275). The SIR was 2.42 (95% CI, 1.542-3.298) for solid cancers and 8.42 (95% CI, 2.394 - 14.446) for hematological cancers. The most diagnosed malignancies were breast cancer (n = 6), ovarian cancer (n = 6), and non-Hodgkin lymphoma (NHL) (n = 4). There was an increased risk for ovarian cancer (SIR 12.76, 95% CI, 2.545-22.975). The SIR values were 2.08 (95% CI, 0.419-3.741) and 10.81 (95% CI, 0.216-21.404) for breast cancer and NHL, respectively. Conclusion: The risk of hematological and solid cancers was higher in the patients with pSS when compared to general population. In our pSS cohort, the risk for ovarian cancer was found to be increased, which has not been previously reported in the literature. [ABSTRACT FROM AUTHOR]

Sjogren's syndrome is an inflammatory disease affecting many systems. We report a Sjogren case with the presenting feature of an acute motor‐predominant polyneuropathy resembling Guillain–Barre syndrome. Upon further investigation, it was found that the patient had sicca symptoms for months. Scrupulous history should be taken to prevent a missed diagnosis. [ABSTRACT FROM AUTHOR]

Kidney stone disease represents a rare cause of chronic kidney disease (2–3%) but has severe clinical consequences. Type 1 renal tubular acidosis is a strong lithogenic condition mainly related to primary Sjögren syndrome. This study aimed to illustrate an unusual presentation of Sjögren syndrome to improve the knowledge about rare kidney stone diseases, and to provide clues for the diagnostic approach in this specific condition. We report the case of a 35-year-old Indian woman with severe nephrocalcinosis and chronic kidney disease with tubular proteinuria who presented for metabolic assessment. We found advanced chronic kidney disease, low serum bicarbonate, permanent alkaline urine with pH at ~7.1, and severe hypocitraturia corresponding to type 1 renal tubular acidosis. The erythrocyte sedimentation rate was high. Serological screening for HAV, HBV, HCV, HIV, EBV was negative and complement was normal. Autoimmune screening showed antinuclear antibodies (>1/1.280) with anti-SSA, anti-SSA/Ro52 and anti-SSB antibodies. Genetic testing excluded an inherited cause of renal tubular acidosis. A renal biopsy showed moderate chronic tubulo-interstitial nephritis without any glomerular involvement. Primary Sjögren syndrome with significant renal involvement was considered, and corticosteroids were then subsequently initiated in combination with potassium citrate with vitamin D substitution. Only partial improvement was observed in electrolytes disturbance. After 15 months, her renal function remained stable. In conclusion, nephrocalcinosis could be the first manifestation of severely impacting diseases such as primary Sjögren syndrome. Chronic kidney disease, bilateral nephrocalcinosis, and metabolic acidosis can be linked through type 1 renal tubular acidosis. Therefore, autoimmune screening for Sjögren syndrome should be considered in such cases. [ABSTRACT FROM AUTHOR]

Objective: Sjögren syndrome (SS) has a significant impact on health-related quality of life (HRQOL). We sought to evaluate how the Patient Reported Outcome Measurement Information System (PROMIS) domains in SS may supplement the European League Against Rheumatism (EULAR) Sjögren Syndrome Patient Reported Index (ESSPRI).Methods: A cross-sectional evaluation was performed on consecutive adult patients during visits to an SS clinic between March 2018 and February 2020. Each patient completed PROMIS short forms related to HRQOL and the ESSPRI, and had a clinical assessment. Patients were either classified as SS by 2016 American College of Rheumatology (ACR)/EULAR criteria, or as "sicca not otherwise specified (NOS)" and used as a comparison group. Univariable and multivariable linear regression models were used to evaluate predictors of PROMIS fatigue (-F), pain interference (-PI), and ability to participate in social roles and activities (-APS).Results: Two hundred twenty-seven patients with SS and 85 with sicca NOS were included and did not differ in ESSPRI domains; 26% of the SS and 20% of the sicca NOS group had concurrent autoimmune disease. In SS, PROMIS-PI, PROMIS-F, and PROMIS physical function were at least one-half SD worse than US population normative values. PROMIS-PI (r = 0.73) and PROMIS-F (r = 0.80) were highly correlated with ESSPRI pain and fatigue subdomains. Fatigue and pain interference, but not dryness or mood disturbance, were the strongest predictors of social participation in multivariable analysis.Conclusion: In our SS cohort, PROMIS instruments identified a high disease burden of pain interference, fatigue, and physical function. PROMIS-F strongly predicted PROMIS-APS. PROMIS-PI and PROMIS-F scores correlated highly with their respective ESSPRI domains. PROMIS instruments should be considered to identify relevant HRQOL patterns in SS. [ABSTRACT FROM AUTHOR]

Abstract 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 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.

Immune-mediated eye diseases(IMED)represent a kind of autoimmune eye diseases, such as thyroid-associated ophthalmopathy, autoimmune uveitis and Sjögren syndromes. Owning to its complicated pathophysiological mechanisms, the efficacies of current therapeutic strategies for IMED are unsatisfactory, which may ultimately result in severe visual impairment. Exosomes are lipid bilayer vesicles secreted by cells that play an important role in cell-to-cell communication and immune regulation. Recent studies have shown that exosomes secreted by cells under pathological conditions are closely associated with the development and progression of IMED, and the exosomes derived from certain cells(such as mesenchymal stem cells)are deemed as promising therapy for IMED. Hence, we review the recent advances of exosomes in IMED.

We present the case of woman in her 50s who developed numerous red-brown telangiectatic macules on her trunk and extremities, as well as persistent dry eyes and dry mouth. Skin biopsy was consistent with telangiectasia macularis eruptiva perstans (TMEP). Serum tryptase was elevated suggesting systemic involvement. Anti-Ro and La were negative. ANA was positive. Salivary gland biopsy revealed a focus score of 3 and immunostains revealed infiltrates of aberrant CD117 positive mast cells. This case suggests a mechanistic role of mastocytosis in salivary compromise.

The purpose of this study was to investigate the changes in E-FABP in the salivary and lacrimal glands of the Sjögren syndrome (SS) model non-obese diabetic mice (NOD). Cotton thread and ocular vital staining tests were performed on 10-week NOD male mice (n = 24) and age- and sex-matched wild-type (WT) mice (n = 25). Tear and saliva samples were collected at sacrifice for E-FABP ELISA assays. Salivary and lacrimal gland specimens underwent immunohistochemistry stainings for E-FABP. Real-time RT-PCR was also performed for the quantification of mRNA expression levels in the salivary and lacrimal glands. Corneal vital staining scores in the NOD mice were significantly higher compared with those for the wild-type mice (p = 0.0001). The mean tear E-FABP level showed a significantly lower concentration in the NOD mice (p = 0.001). The mean saliva E-FABP level also showed a significantly lower concentration in the NOD mice (p = 0.04). Immunohistochemistry revealed intense E-FABP staining in the LG acinar epithelium and less intense staining in the acinar epitheliae of the SGs in the NOD mice compared to the WT mice. Real-time RT-PCR for the mRNA expression of E-FABP showed a significantly decreased expression in the SG and a significant increase in the LG of the NOD mice compared to the WT mice. In conclusion, the E-FABP showed marked alterations in the tear film, saliva, lacrimal, and salivary glands of the NOD mouse, which may help explain the ocular surface changes in relation to the dry eye disease in this SS model mouse and keratoconjunctivitis sicca in SS patients. [ABSTRACT FROM AUTHOR]

The MDS Video Challenge continues to be the one of most widely attended sessions at the International Congress. Although the primary focus of this event is the presentation of complex and challenging cases through videos, a number of cases over the years have also presented an unusual or important neuroimaging finding related to the case. We reviewed the previous Video Challenge cases and present here a selection of those cases which incorporated such imaging findings. We have compiled these "imaging pearls" into two anthologies. The first focuses on pearls where the underlying diagnosis was a genetic condition. This second anthology focuses on imaging pearls in cases where the underlying condition was acquired. For each case we present brief clinical details along with neuroimaging findings, the characteristic imaging findings of that disorder and, finally, the differential diagnosis for the imaging findings seen. [ABSTRACT FROM AUTHOR]

Giant cell arteritis (GCA) is an autoimmune vasculitis involving large and medium arteries. GCA is rarely associated with autoimmune diseases, such as Sjögren's syndrome. Glucocorticoids (GC) are the cornerstone of the treatment of GCA as they are very effective but are often given for 1 year to avoid relapses. Here we report a rare case of GCA overlapping with Sjögren's syndrome along with the management. [ABSTRACT FROM AUTHOR]

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This study aimed to describe a patient with Sjögren syndrome who developed Plummer-Vinson syndrome, and to review the literature and describe shared aspects of this rare association. A systematic screening of articles was conducted in PubMed/MEDLINE, LILACS, SciELO, Scopus, Web of Science, and Cochrane, dating 1940 to 2020. All the articles included the association between Sjögren syndrome and Plummer-Vinson syndrome. No language restriction was applied. The following terms were used: "Sjögren syndrome" or "sicca syndrome" and "Plummer-Vinson syndrome" or "Paterson-Kelly syndrome." We performed our analysis by adding our present case, with a total of 4 cases. Three out of four were female (75%), age varied from 56 to 58 years old. In 2 cases, Sjögren syndrome preceded Plummer-Vinson syndrome diagnosis, and in 1 report, Plummer-Vinson syndrome appeared before Sjögren syndrome. Disease duration varied from 7 to 20 years. In two cases, autoantibodies were available, and antinuclear antibodies and anti-Ro/SS-A were positive in both, and anti-La/SS-B in one of them was associated with anti-dsDNA; however, no data regarding lupus was available in the article. Treatment involved iron supplementation in 3/3. Two out of three received parenteral iron supplementation, and in these two cases, mechanical esophageal dilatation was needless. In the other case, an additional endoscopic esophageal dilatation was necessary to receive the oral iron supplement. All 3 cases had a good outcome. This case illustrates a patient with Sjögren syndrome who developed the rare Plummer-Vinson syndrome. In Sjögren syndrome, the presence of iron-deficiency anemia, dysphagia, and weight loss should alert the physician to search for associated Plummer-Vinson syndrome. Highlights: Plummer-Vinson syndrome (PVS) is a sporadic disease characterized by the triad of dysphagia, iron-deficient anemia, and webs on the esophagus. There are only three previous cases of PVS in Sjögren syndrome. The parenteral iron supplementation treats PVS adequately and seems to preclude the need for endoscopic esophageal dilatation. [ABSTRACT FROM AUTHOR]

Kuru göz, yaşlı popülasyonda en sık görülen oküler hastalıklardan biridir ve önemi giderek artmaktadır. Yaşlanma, azalmış hormonlar ve sistemik otoimmünite kuru göz hastalığının yaygın nedenleri arasındadır. Kuru göz etiyolojisi değişebilse de ana nedenin hem lakrimal bezlerde hem de oküler yüzeylerde inflamasyon olduğu bilinmektedir. Kuru gözün tedavisinde immün modülatör bir ajan olan topikal siklosporin A (CsA) % 0,05'in etkinliğini değerlendirmek için toplam 51 kuru göz sendromu hastası çalışmaya dahil edildi. Hastaların 41'i kadın, 5'i erkekti. Hastaların ortalama ilaç kullanım süresi 8.72 ± 3.59 ay (6-16 ay) idi. Tedavi öncesi Schirmer skorları ile Sjögren ve Sjögren olmayan grupların 1., 6. ve son kontrollerinde bulunan Schirmer skorları arasında istatistiksel olarak anlamlı bir fark gözlendi (p 0.05). Sonuç olarak hem Sjögren hem de Sjögren olmayan grupların Schirmer ve floresein TBUT skorlarında ve gözyaşı menisküs yüksekliğinde anlamlı bir artış olduğu bulundu.

Pulmonary involvement in Sjogren syndrome (SS) could manifest as cystic lung disease (CLD). CLD in SS includes lymphocytic interstitial pneumonia (LIP) and pulmonary amyloidosis. Differential diagnosis usually requires surgical lung biopsy, whereas CT-guided percutaneous fine needle aspiration biopsy (CT-FNAB) has not yet explored. We describe the case of a 63-year-old never smoker Caucasian female with a SS diagnosis who displayed a newly detected diffuse CLD at high-resolution computed tomography, though totally asymptomatic. Given the favorable location of one big lesion at the superior left lobe, a CT-FNAB was proposed instead of a more invasive SLB. At histology examination a diagnosis of pulmonary nodular AL kappa amyloidosis in the context of SS was established. In conclusion, CT-FNAB might represent an alternative and less invasive diagnostic procedure than SLB in the differential diagnosis of CLD, even if further research is needed. Moreover, this case presents an unusual association between SS and pulmonary nodular AL kappa amyloidosis, with pulmonary nodules and cysts without systemic manifestations.

Soft tissue calcifications associated with various connective tissue diseases such as dermatomyositis and scleroderma have been well documented Plaque-like sheets of subcutaneous calcifications presenting as an indurated soft tissue mass in a patient with primary Sjogren syndrome have been rarely documented in the literature. We present the magnetic resonance and conventional radiographic findings of calcinosis cutis and calcinosis circumscripta of a 47-year-old woman with biopsy proven Sjogren syndrome. We also delineate various types of soft tissue calcification, histopathology of calcinosis cutis, and current treatment options. Recognizing the magnetic resonance characteristics of this phenomenon may prove useful to radiologists, especially in the absence of clinical history and conventional radiographs.

Abstract Only proven pathogenic mutations associated with myeloid neoplasms are key to establish the clonal nature of the bone marrow fibrosis. In cases with genetic variants of uncertain meaning, the clinical picture may be required to rule out secondary causes.

Katastrofik antifosfolipid sendromu; nadir görülen hızlı seyirli mortalitesi yüksek antifosfolipid antikor sendromunun ciddi bir formudur. Sendrom, yaygın mikro trombozlara bağlı olarak multiorgan yetmezliğine neden olur. Bu olguda; 58 yaşında kadın hasta da alt extremite distal bölgeden başlayan ekimozlar üst bacak bölgesine ve üst extremiteye yayılan lezyonlar hızlı seyir göstererek nekrotik alanlara dönüştü. Histopatolojik incelemede dermiste intravasküler trombüsler tespit edilen hastanın laboratuvar bulgularında IgM anti-kardiyolipin antikor ve Lupus antikoagülan’ı pozitifti. Klinik seyir çok hızlı ilerleyen hastada akciğer ve böbrek tutulumu da eşlik etti. Mevcut bulgularla hastaya katastrofik antifosfolipid sendromu tanısı konuldu. Katastrofik antifosfolipid sendromu vakalarının üçte ikisin de, en sık enfeksiyonların tetiklemesine sekonder olarak gelişmektedir. Katastrofik antifosfolipid sendromu’na otoimmün hastalıklar özellikle sistemik lupus eritematozus eşlik etmektedir. Olgumuz; Sjögren sendromunun katastrofik APS etyolojisinde düşünülmesini gerektiğini vurgulamak amacıyla sunulmaktadır.

AIM: To observe the morphological changes of corneal subbasal nerve(SBN)plexus in patients with Sjogren syndrome(SS)by in vivo confocal microscopy(IVCM)study and analyze its correlation with clinical symptoms.METHODS: We collected 22 cases(44 eyes)patients with Sjogren's syndrome(observation group)and 22 cases(44 eyes)healthy people with the same age(control group)for observation of central corneal SBN fibers diameter, number of beads, and tortuosity, and recorded tear film break up time(BUT), Schirmer's Ⅰ test(SⅠt), tear meniscus height(TMH), dendritic cell(DC)density, the results were applied to perform statistical analysis.RESULTS: Under IVCM observation, the diameter of corneal SBN fibers in the observation group became thinner, the number of beads and the degree of nerve fiber tortuosity were increased compared with the control group(Pr=0.472, Pr=0.562, Pr=0.246, P=0.02)and DC density(r=-0.636, Pr=-0.621, Pr=-0.688, Pr=-0.438, Pr=0.528, Pr=-0.634, Pr=-0.713, Pr=-0.384, P< 0.01)and DC density(r=0.604, PCONCLUSION: IVCM can effectively observe the morphology of corneal nerve plexus. In SS patients, the diameter of corneal SBN fibers becomes thinner, the number of beads increases, and the tortuosity of nerve fiber increases. Moreover, the degree of nerve fiber lesions is correlated with the severity of dry eye clinical symptoms.

Five percent of the cancers in the parotid region are non-hodgkin lymphomas. This lymphoma, involving the mucosa-associated lymphoid tissue (MALT), is called MALToma. A chronic autoimmune inflammatory process of the parotid gland, such as Sjogren's syndrome, results in an increased incidence of parotid MALToma. Biopsy of the parotid is essential for appropriate diagnosis; this can then be completed by radiotherapy, chemotherapy or therapy with monoclonal antibodies according to the stage of the disease. This study shows a clinical case of a 50-year-old patient with Sjogren's syndrome who developed a parotid MALToma.

Background: Patients with cancer and an underlying autoimmune disease who are considering immune checkpoint blockers (ICBs) need to know about the benefits and risks of severe immune-related adverse events and flares of the autoimmune condition., Objective: This study aims to develop and alpha test an educational website for patients with cancer., Methods: Learning topics, images, and website architecture (including flow and requirements) were developed and iteratively reviewed by members of a community scientist program, a patient advisory group, and content experts. Alpha testing was performed, measuring the site's usability using the Suitability Assessment of Materials and its acceptability using the Ottawa Acceptability Measure., Results: The website included a home page; general information about ICBs; comprehensive modules on the benefits and risks of ICBs for patients with cancer and preexisting autoimmune diseases; general wellness information; and features such as a quiz, additional resources, and a glossary. For the alpha testing, 9 users assessed the newly developed website. Patient reviewers (n=5) had rheumatoid arthritis, Crohn disease, Sjogren syndrome, or vasculitis. Health care provider reviewers (n=4) were medical oncologists or rheumatologists. The median Suitability Assessment of Materials rating was 75 (IQR 70-79; range 0-100) for patients versus 66 (IQR 57-72; range 0-100) for providers (scores ≥70 indicate no substantial changes needed). Recommendations for improvement, mostly involving navigation and accessibility, were addressed. All participants expressed that the website was acceptable and balanced in terms of discussion of benefits and harms. Because half (2/4, 50%) of the providers suggested we increase the amount of information, we extended the content on the impact of having an autoimmune disease when considering ICB treatment, the probability of flares, and the management of flares in this context., Conclusions: The feedback led to minor revisions to enhance readability, navigation, and accessibility, ensuring the website's suitability as a decision-making aid. The newly developed website could become a supporting tool to facilitate patient-physician discussion regarding ICBs., (©Maria A Lopez-Olivo, Maria E Suarez-Almazor, Gabrielle F Duhon, McKenna Cherry, Huifang Lu, Cassandra Calabrese, Mehmet Altan, Hussain Tawbi, Alexa Meara, Clifton O Bingham, Adi Diab, Viola B Leal, Robert J Volk. Originally published in JMIR Cancer (https://cancer.jmir.org), 25.10.2024.)

Introduction: In patients with Hereditary Angioedema (HAE) related to primary C1 inhibitor deficiency (C1INH), the defective clearance of immune complexes and apoptotic materials along with impairment of normal humoral response potentially leads to autoimmunity. Few studies report evidence on autoimmune diseases in C1INH-HAE, but no large population studies focus on rare connective tissue diseases (RCTDs). We aim at evaluating for the first time prevalence and distribution of RCTDs - Systemic Lupus Erytematosus (SLE), primary Sjogren Syndrome (SjS), primary antiphospholipid syndrome (APS), Systemic Sclerosis (SSc), and mixed connective tissue diseases (MCTD) in a large Italian cohort of C1INH-HAE patients., Methods: A multicenter observational study includes C1INH-HAE patients from ITACA Centers throughout Italy (time frame Sept 2023-March 2024). Inclusion criteria are i. a defined diagnosis of type I or type II C1INH-HAE; ii. age ≥15 years (puberty already occurred); iii. enrollment in the ITACA Registry. The diagnosis of SLE, primary SjS, primary APS, SSc, and MCTD are made in accordance with international classification criteria., Results: Data are collected from a total of 855 C1INH-HAE patients referring to 15 ITACA Centers. Patients with concomitant RCTDs were 18/855 (2.1%) with F:M ratio 3.5 and a prevalent type I C1INH-HAE diagnosis (87.2%). A diagnosis of SLE results in 44.5% of cases (n=8) while the remaining diagnoses are primary SjS (22.2%, n=4), primary APS (16.6%, n=3), SSc (11.2%, n=2), and a single case of MCTD (5.5%). The female gender is prevalent in all the RCTDs. Patients on long term prophylaxis (LTP) are significantly prevalent in RCTDs group than in the whole C1INH-HAE population (p<0.01)., Conclusions: A relevant prevalence of RCTDs is documented in C1INH-HAE patients, mainly SLE. Patients with RCTDs are on LTP in a significant proportion supporting the idea of a bidirectional link between C1INH-HAE and autoimmunity., Competing Interests: PT received speaker/consultancy fees from CSL Behring and Takeda. RS was consultant for Biocryst and Takeda, and received travel grants from Takeda, Biocryst, CSL Behring, Alk Abello and Novartis. FA received consultancy fees or research grants from CSL Behring and Takeda. MG received speaker fees from CSL Behring. DF received speaking fees or research grants from CSL-Behring and Takeda. AZ received speaker/consultancy fees from and/or was a member of advisory boards for BioCryst, CSL Behring, KalVista, Pharming, Pharvaris, and Takeda. MC received travel grants from CSL Behring, Menarini, Novartis, and Shire-Takeda, and consultancy fees from Biocryst, CSL Behring, and Shire-Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision, (Copyright © 2024 Triggianese, Senter, Perego, Gidaro, Petraroli, Arcoleo, Brussino, Giardino, Rossi, Bignardi, Quattrocchi, Brancaccio, Cesoni Marcelli, Accardo, Lo Sardo, Cataudella, Guarino, Firinu, Bergamini, Spadaro, Zanichelli and Cancian.)

Background: Psychiatric disorders, such as major depressive disorder (MDD), anxiety disorder (AD), bipolar disorder (BD), and schizophrenia (SCZ), are disturbances in brain activity that lead to disorders of cognition, behavior, and emotion regulation. Among Sjogren syndrome (SS) patients, psychiatric disorders are more prevalent than in the general population. Identifying associated risk factors can provide new evidence for clinical diagnosis and treatment., Methods: We selected genetic instruments based on published genome-wide association studies (GWASs) to determine predisposition. Then, we conducted a 2-sample bidirectional Mendelian randomization (MR) analysis to explore the potential causal associations between SS and four major psychiatric disorders. The primary analysis was performed using MR with the inverse-variance weighted method. Confirmation was achieved through Steiger filtering and testing to determine the causal direction. Sensitivity analyses were conducted using MR-Egger, MR-PRESSO, and "leave-one-out" method methods., Results: Our study showed that SS was linked to BD and SCZ, indicating that individuals with SS may have a reduced risk of developing BD (IVW: OR = 0.940, P =0.014) and SCZ (IVW: OR = 0.854, P =1.47*10-4), while there was no causal relationship between SS and MDD or AD. MR-Egger regression shows no evidence of pleiotropy (BD: intercept = 0.007, p = 0.774; SCZ: intercept = 0.051, p = 0.209). The same as the MR-PRESSO analysis (BD: global test p = 1.000; SCZ: global test p = 0.160). However, the results from the leave-one-out analysis demonstrated instability. Specifically, after excluding SNP rs3117581, the effects on BD and SCZ were found to be non-significant, suggesting the potential influence of unrecognized confounding factors. The results of the reverse MR show that four major psychiatric disorders had no causal effects on SS., Conclusions: Our research findings demonstrate a causal relationship between SS and SCZ, as well as between SS and BD. There are no causal effects between the four major psychiatric disorders and SS. These findings suggest that SS may have the potential to reduce the risk of both psychiatric disorders. This study provides new insight for their prevention and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pan, Zhou, Wei, Zhao, Wang, Chen, Xiao, Song, Liang, Zou, Li and Xiong.)

Acute interstitial nephritis (AIN) is known to cause acute kidney injury and is characterized by immunocyte infiltration and interstitial fibrosis. Primary etiologies include drugs, infections, and autoimmune disorders. Herein, we presented the case of a 78-year-old woman patient with AIN with anti-centromere antibody (ACA) positivity, secondary to an idiopathic immune system disorder. Her serum creatinine (sCr) was 0.67 mg/dL 2 months prior to consulting us, which increased to 2.79 mg/dL. The renal biopsy revealed an AIN comprising interstitial infiltration with immunocytes and CD138 + cells. Furthermore, all other antibodies tested negative using immunofluorescence on both glomeruli and tubulointerstitial lesions. The ACA was elevated to a level of ≥ 500 U/mL. The ACA positive has been known to be accompanied by worsening kidney function in patients with systemic sclerosis and primary biliary cholangitis. However, any autoimmune disease were not diagnosed. Successful treatment with an initial dose of 30 mg/day of glucocorticoids tapered to 25 mg/day resulted in a decrease in the sCr to 1.53 mg/dL 4 weeks later. Nine months later, glucocorticoids was tapered, based on the threshold of a sCr of 1.03 mg/dL and the titer of ACA of 291 U/mL. In this case, glucocorticoid treatment remarkably improved renal function in AIN containing CD138 + cells accompanied by a reduction of ACA titer. The etiology of ACA-positive AIN was unknown; however, the incidence of ACA-positive AIN should always be deliberated., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: Salivary hypofunction leads to debilitating oral symptoms and has major complications for overall quality of life. Two of the most frequent causes of xerostomia are radiotherapy in the head and neck and Sjögren's syndrome. Only symptomatic treatment is available today. An increasing number of both preclinical and clinical studies have suggested that mesenchymal stem cell (MSC) transplantation treatment can increase the salivary flow rate and ameliorate symptoms of xerostomia. However, both adipose-derived and bone marrow-derived MSCs are used, although they differ in important ways. The primary objective of this study is an indirect comparison of the change in the unstimulated salivary flow rate after intervention between patients treated with adipose-derived or bone marrow-derived MSCs., Methods: This systematic review and network meta-analysis will search for eligible studies in the MEDLINE, EMBASE, and Cochrane CENTRAL register of Controlled Trials. Eligible studies are as follows: clinical studies including human patients with salivary hypofunction due to either radiotherapy or Sjogren's syndrome who were subsequently treated with either adipose-derived MSCs or bone marrow-derived MSCs. Studies with no control group will be excluded. The search phrase has been peer-reviewed following the PRESS guidelines. The primary outcome is the change in the unstimulated salivary flow rate after treatment with either adipose-derived or bone marrow-derived MSCs. Secondary outcomes are as follows: change in patient reported outcomes, methods of intervention administration, number of injected MSCs, and safety. Data from included studies will be pooled and compared with a fixed-effects or random effects model dependent on signs of heterogeneity, presented with a forest plot, and indirectly compared with a meta-regression in a network meta-analysis. Risk of bias will be assessed with the tools ROBINS-I or RoB-2 depending on type of study., Discussion: Both adipose-derived and bone marrow-derived MSCs are used today for experimental treatment of salivary hypofunction in humans as no direct or indirect comparisons have been made. Therefore, an evaluation of the effect of adipose-derived vs bone marrow-derived MSC treatment is needed to support future decision-making on the type of MSC used in a clinical trial., Systematic Review Registration: PROSPERO ID CRD42024527183., (© 2024. The Author(s).)

We report the case of a 74-year-old female, who presented with a two-month history of fever, night sweats, and lymphadenopathy. She was thoroughly investigated, with high clinical suspicion for lymphoma. However, lymph node biopsy results revealed histopathological features of a hyaline vascular variant of Castleman disease. Owing to the involvement of multiple lymph node regions and the presence of systemic symptoms, the patient was diagnosed with multicentric Castleman disease and was started on steroid therapy, as well as anti-interleukin-6 (anti-IL-6) therapy, namely, tocilizumab, for the management of this condition. The patient responded well to the treatment and was discharged home in stable condition., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mansour et al.)

Background: Rheumatological toxicity associated with immunotherapy, particularly Sjögren's syndrome (SjS), has been observed with variable incidence in patients treated with immune checkpoint inhibitors (ICIs). Although SjS is a well-known autoimmune disease, its occurrence as an immune-related adverse event (irAE) during cancer treatment is less well understood. Current literature documents a range of incidence rates and clinical manifestations of SjS in patients undergoing ICI therapy, highlighting the need for early diagnosis and multidisciplinary management., Case Presentation: A 40-year-old woman underwent mammography, which revealed a 43 mm mass in the left breast. Core biopsy confirmed grade 3 infiltrating triple negative ductal carcinoma with high MIB-1. She received neoadjuvant chemotherapy, followed by surgery and radiotherapy. A CT scan in September 2022 showed lung nodules and lymph node involvement. A lung biopsy confirmed breast cancer metastasis. She started treatment with atezolizumab and nab-paclitaxel with evidence of a partial response. Nab-paclitaxel was discontinued due to side effects and atezolizumab was continued as maintenance therapy. After four cycles, the patient developed symptoms consistent with Sjögren's syndrome (SjS), which were confirmed by diagnostic tests. Treatment with prednisone, pilocarpine and hydroxychloroquine was initiated alongside ongoing immunotherapy. The patient continues to receive atezolizumab with stable disease and good quality of life., Conclusion: This case highlights the importance of recognizing SjS as a potential irAE in patients treated with ICIs, particularly those with TNBC. Multidisciplinary collaboration is essential for the prompt diagnosis and effective management of SjS to maintain both cancer control and patient quality of life. Given the recent emergence of these events and the lack of specific guidelines, our case report may provide valuable insights into the management of a little-known adverse event and pave the way for further real-world data collection on the management of these rare but significant toxicities that impact on patient quality of life. Further research is needed to optimize treatment protocols and outcomes for patients experiencing rheumatological irAEs during cancer immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pellegrino, D’Antonio, Ierinò, Onesti, Aschelter, Santini and Mazzuca.)

Introduction: Almost one-quarter of immune checkpoint inhibitor (ICI) recipients experience sicca syndrome, while Sjögren's disease (SjD) is estimated at 0.3-2.5%, possibly underreported., Areas Covered: This narrative review (Medline/Embase until January/31/2024) addresses the pathophysiology, incidence, demographic/clinical features, biomarkers, labial salivary gland biopsy (LSGB), fulfillment of the idiopathic SjD (iSjD) classificatory criteria, differential diagnosis, and management of sicca syndrome/SjD associated with ICIs., Expert Opinion: SjD associated with ICIs is underdiagnosed, since studies that performed the mandatory SjD investigation identified that 40-60% of patients with sicca syndrome associated with ICIs meet the iSjD classificatory criteria. LSGB played a fundamental role in recognizing these cases, as most of them had negative anti-Ro/SS-A antibody. Despite the finding of focal lymphocytic sialoadenitis in LSGB samples mimicking iSjD, immunohistochemical analysis provided novel evidence of a distinct pattern for sicca syndrome/SjD associated with ICIs compared to iSjD. The former has scarcity of B lymphocytes, which are a hallmark of iSjD. Additionally, patients with sicca syndrome/SjD associated with ICIs have demographical/clinical/serological and treatment response dissimilarities compared to iSjD. Dryness symptoms are more acute in the former than in iSjD, with predominance of xerostomia over xerophthalmia, and partial/complete response to glucocorticoids. Dryness symptoms in ICI-treated patients warrant prompt SjD investigation.

Purpose: To evaluate and compare subbasal corneal nerve parameters of the inferior whorl in patients with dry eye disease (DED), neuropathic corneal pain (NCP), and controls using a novel deep-learning-based algorithm to analyze in-vivo confocal microscopy (IVCM) images., Methods: Subbasal nerve plexus (SNP) images of the inferior whorl of patients with DED (n = 49, 77 eyes), NCP (n = 14, 24 eyes), and controls (n = 41, 59 eyes) were taken with IVCM and further analyzed using an open-source artificial intelligence (AI)-based algorithm previously developed by our group. This algorithm automatically segments nerves, immune cells, and neuromas in the SNP. The following parameters were compared between groups: nerve area density, average nerve thickness, average nerve segment tortuosity, junction point density, neuroma density, and immune cell density., Results: 160 eyes of 104 patients (63 % females), aged 56.8 ± 15.4 years, were included. The mean nerve area density was significantly lower in the DED (P = 0.012) and NCP (P < 0.001) groups compared to the control group. The junction point density was lower in the NCP group compared with control (P = 0.001) and DED (P = 0.004) groups. The immune cell density was higher in the DED group compared with controls (P < 0.001)., Conclusions: Deep-learning-based analysis of IVCM images of the corneal SNP inferior whorl distinguished a decreased mean nerve area density in patients with DED and NCP compared with controls and an increased immune cell density in patients with oGVHD- and SS-associated DED. These findings suggest that the inferior whorl could be used as landmark to distinguish between patients with DED and NCP., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mucosa-associated lymphoid tissue (MALT) lymphoma commonly arises from chronic inflammation or autoimmune diseases, such as Sjögren syndrome (SjS). Although rare, amyloid deposition in MALT lymphoma has been reported. We present a rare case of parotid gland MALT lymphoma in a 49-year-old woman, in whom preoperative diagnosis was challenging due to atypical imaging findings resulting from amyloid deposits. MRI showed T2-hypointense and T1-iso- to slightly hyperintense masses in the left parotid gland and right sublingual gland, with predominant marginal contrast enhancement and no significant diffusion restriction. Additionally, atrophy and fatty replacement of the parenchyma were noted in bilateral parotid glands, suggesting SjS. Left superficial parotidectomy was performed and pathological findings confirmed MALT lymphoma with extensive amyloid deposition. Histopathological findings of the resected parotid gland parenchyma also suggested SjS. MALT lymphoma should be considered in the differential diagnosis of multiple salivary gland masses in patients with suspected SjS. If MRI reveals atypical imaging findings for malignant lymphoma, particularly T2-hypointensity with no significant diffusion restriction, the possibility of amyloid deposition in MALT lymphoma should be considered., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Introduction: Sjögren's syndrome is a chronic autoimmune disorder that results in dry eyes and mouth. It is rarely associated with cryoglobulinemia, the agglutination of cryoglobulins at cold temperatures that leads to systemic inflammation and organ damage. We have, herein, presented a case of Cryoglobulinemic Vasculitis (CryoVas), which presents as cryoglobulinemic glomerulonephritis and Central Nervous System (CNS) vasculitis and peripheral neuropathy., Case Report: A 52-year-old woman with a past medical history of Sjögren's syndrome was admitted to the intensive care unit with severe hyponatremia, orthopnea, and progressive lower extremity weakness, and was found to have an intradural extramedullary hematoma with mass effect in the thoracic spine and diffuse hyperintense cord signal abnormality in thoracic spine suggestive of intermixed proteinaceous or hemorrhagic material. Further testing demonstrated that the patient experienced worsening neuropathy, proteinuria, hematuria, declining renal function, and the presence of cryoglobulins in the blood. After a thorough examination and a renal biopsy, the patient was diagnosed with cryoglobulinemic glomerulonephritis and cryoglobulinemic vasculitis of the spine. The patient was treated with rituximab and pulse-dose steroids, with which the patient exhibited improved renal function and resolution of a previously seen intradural hematoma on repeat MRI., Conclusion: We have, herein, discussed a rare case of cryoglobulinemic vasculitis that has led to a rare CNS manifestation and concomitant cryoglobulinemic glomerulonephritis. This suggests that clinicians should consider cryoglobulinemic vasculitis as the etiology that could manifest with multiorgan involvement, especially in patients with underlying rheumatic diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Celiac disease (CeD) is an immune-mediated disorder affecting the small bowel, associated with genetic factors and increasing global prevalence., Aim: This study explores the association between CeD, Systemic Lupus Erythematosus (SLE), primary Sjogren syndrome (pSS), and Systemic Sclerosis (SSc)., Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. Searches across multiple databases yielded 2728 articles, with 15 studies selected. Data extraction included study characteristics, prevalence of CeD and CeD antibodies in SLE, pSS, and SSc. Quality assessment utilized the Newcastle-Ottawa Scale., Results: The meta-analysis revealed a pooled prevalence of biopsy-proven CeD in SLE, pSS, and SSc of approximately 3%. Seroprevalence of any CeD antibody in SLE, pSS, and SSc ranged from 3% to 10%. Notably, pSS exhibited the highest prevalence at 5.59%. High heterogeneity was observed in seroprevalence across autoimmune conditions. Quality assessment indicated robust methodological quality in the selected studies., Conclusion: This study highlights a significantly higher prevalence of CeD, especially pSS, compared to the general population. The findings underscore the importance of recognizing elevated CeD antibodies in patients with SLE, pSS and SSc emphasizing the need for early detection and comprehensive care for gastrointestinal symptoms in these conditions., Competing Interests: Conflict of interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Author names: Renato Beas MD, Euler Altamirano-Farfan MD, Diego Izquierdo-Veraza MD, Dalton A. Norwood MD, Adrian Riva-Moscoso MD, Ambar Godoy MD, Eleazar E. Montalvan-Sanchez MD, Mirian Ramirez BS, Daniel A. Guifarro MD, Emily Kitchin MD, Monika Fischer MD, Satya Kurada MD., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)