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Aim: Sjögren's syndrome (SS) is a chronic, multisystem autoimmune disease characterized by inflammation of the glandular tissues. SS can manifest with various extraglandular involvements, including hematologic complications. The aim of our study is to evaluate the relationship between hematologic and pathological data, specifically focusing on the Focus Score (FS) and the Mas on Chisholm Score (MS), in SS patients. Patients and Methods: The study included 101 patients with Sjögren's syndrome (SS) and 91 individuals in the control group. All SS patients were newly diagnosed according to the 2016 ACR/EULAR criteria. Patients with comorbidities that could lead to hematological di sorders were excluded from the study. Results: The neutrophil, monocyte, and platelet values were found to be statistically significantly lower (p=0.000, p=0.002, p=0.016), while lymphocyte and hemoglobin values, although lower in the SS group compared to the control group, did not reach statistical significance (p=0.053, p=0.685). Correlation analysis revealed a negative correlation between both the FS and MS scores and neutrophil (r=-0.329, p<0.01), lymphocyte (r=-0.264, p<0.01), monocyte (r=-0.306, p<0.01), and platelet (r=-0.220, p<0.01) values. Conclusion: SS can potentially induce cytopenias in the hemogram, with neutropenia, anemia, and thrombocytopenia displaying a negative correlation with FS and MS. Consequently, in patients with elevated FS and MS scores at the time of diagnosis, it is crucial to exercise caution regarding hematological involvement. Even if patients meet the SS diagnostic criteria, a minor salivary gland biopsy should be considered. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper characterizes the immunotherapy-related adverse effects in the oral tissues, in a large series of patients. This includes a description of the severity of oral symptoms, immediate clinical presentation, treatment, chronicity despite holding the immunotherapy, and the development of oral cancer. The management of these patients exemplified new diagnostic tools, detailed clinical presentation that may assist to differentiate between various oral irAEs and outlines unique adjustments in the topical treatment and inclusion of a new treatment modality for these irAEs. Lastly, this paper raises the awareness for second primary oral cancer and possible risk for oral malignant transformation. (1) Background: Immunotherapy-related adverse effects (irAEs) have been reported to manifest in oral tissues, mainly as lichenoid and non-lichenoid lesions and salivary gland dysfunction; however, the characterization of oral irAEs and their clinical impact is limited. (2) Methods: This is a retrospective clinical chart review of 14 patients with oral irAEs, describing the impact of the oral irAEs in terms of the immediate effect, treatment, chronicity of the irAEs and the development of oral cancer. (3) Results: Common symptoms were pain and dry mouth, causing no-to-severe pain and/or dry mouth sensation. The immediate sequala ranged from sensitivity to certain foods up to elimination of oral intake. Treatment included conventional palliation techniques with or without systemic steroids. Discontinuation of the immunotherapy agents was required in 6 patients. Innovative treatment modalities included photobiomodulation for oral mucosal pain relief, and salivary gland intraductal irrigations for relief of salivary gland hypofunction. Late sequala included the development of proliferative leukoplakia and oral cancer. (4) Conclusions: Patients treated with immunotherapy may develop debilitating oral irAEs. They should be followed for oral involvement so treatment may be initiated when the symptoms are mild to avoid discontinuation of the immunotherapy. Patients that develop oral lichenoid lesions should receive long-term follow-up, as they may have higher risk for oral cancer. [ABSTRACT FROM AUTHOR]

Hepatitis delta virus (HDV) has been detected in the minor salivary gland (MSG) tissue of Sjögren's disease (SjD) patients in the absence of a hepatitis B virus (HBV) coinfection. Previous research has shown that HDV antigen (HDAg) expression can trigger an SjD-like phenotype in vivo, demonstrating a potential cause-and-effect relationship. We hypothesize that if HDV plays a role in the development of SjD, then HDV profiles may be correlated with disease manifestations. This retrospective study characterized HDV in a cohort of 48 SjD MSG samples collected between 2014 and 2021. Analyses of HDAg expression, including cell type and subcellular localization, in situ hybridization of HDV RNA, and comparative analyses with associated SjD and viral hepatitis clinical features, were conducted. HDAg was detected in MSG acinar, ductal, myoepithelial, and adipose cells and localized with the nuclei, cytoplasm, and mitochondria. In situ hybridization detected HDV genomic RNA localization in the MSG nuclei. A significant negative correlation was found between HDAg intensity and focal lymphocytic inflammation and in patients with both anti-SSA/Ro-52 and anti-SSA/Ro-60. In analyzing autoimmune disease comorbidities with SjD, it was found that SjD patients diagnosed with autoimmune thyroiditis and/or hypothyroidism were significantly more represented in the high HDAg intensity group compared to the negative and moderate HDAg intensity groups. No significant associations were detected between MSG-localized HDAg and liver enzymes or an evident HBV coinfection. This study has further confirmed that there is a nonhepatic reservoir for chronic HDV persistence in SjD-affected salivary gland tissue in a third independent SjD patient cohort. In addition, this study describes the unique colocalization of HDAg with mitochondria. The detection of HDV antigen and sequence within SjD-affected salivary gland tissue, and in the absence of an evident current or past HBV coinfection, warrants further investigation. [ABSTRACT FROM AUTHOR]

Introduction: Influenza A (H3N2) virus is the major cause of morbidity/mortality due to seasonal influenza over 50 years. Data about the safety/immunogenicity of influenza A/Singapore (H3N2) vaccine are scarce in primary Sjögren syndrome (pSS). Methods: Twenty-one consecutive pSS patients and 42 HC (healthy control individuals) were immunized with influenza A/Singapore/INFIMH-16–0019/2016 (H3N2)-like virus. Rates of SP (seroprotection) and SC (seroconversion), GMT (geometric mean titers), FI-GMT (factor increase in GMT), ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index), and adverse events were appraised before and 4 weeks post-vaccination. Results: pSS and HC had similar mean age (51.2 ± 14.2 vs. 50.6 ± 12.1 years, p = 0.886). Pre-vaccination SP rates were high in pSS and HC (90.5% vs. 71.4%, p = 0.114), and GMT were higher in pSS [80.0 (52.4–160.0) vs. 40.0 (20.0–80.0), p = 0.001]. The percentage of influenza vaccination in the preceding two years was elevated and similar in pSS and HC (94.1% vs. 94.6%, p = 1.000). GMT values augmented in both groups four weeks after vaccination and persisted higher in the first group [160.0 (80.0–320.0) vs. 80.0 (40.0–80.0), p < 0.001] with equivalent FI-GMT [1.4 (1.0–2.8) vs. 1.4 (1.0–2.0), p = 0.410]. Both groups had low and similar SC rates (19.0% vs. 9.5%, p = 0.423). ESSDAI values persisted steadily during the study (p = 0.313). No serious adverse events have occurred. Conclusion: The novel demonstration that the influenza A/Singapore (H3N2) vaccine induces a different pattern of immunogenicity from other influenza A constituents in pSS, featured by a desirable high pre- and post-vaccination immunogenicity, is in line with reported differences in immune responses between strains in trivalent vaccines and may be related to pre-existing immunity. Clinicaltrials.gov: #NCT03540823. Key Points • This prospective study demonstrated a robust pre- and post-vaccination immunogenicity to influenza A/Singapore/INFIMH-16–0019/2016 (H3N2)-like virus in primary Sjögren's syndrome (pSS). • This high immunogenicity pattern may be related to pre-existing immunization, or else it is related to immunogenicity differences of each strain. • This vaccine had an adequate safety profile in pSS, with no impact on disease activity. [ABSTRACT FROM AUTHOR]

Objective: The study aims to evaluate the utility of major salivary gland ultrasonography for diagnosis of primary Sjögren's syndrome (pSS) and to assess its concordance with minor salivary gland biopsy (MSGB). Methods: A cross-sectional study of 72 patients with suspected pSS was performed. Demographic, clinical, and serological data were collected. MSGB was performed, as was ultrasonography. The ultrasound technician was blind to clinical, serological, and histological data. The validity of ultrasonography compared with MSGB, the American-European Consensus Group (AECG), and American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria was assessed by calculating the percentage of agreement, sensitivity, specificity, positive and negative predictive values, and area under the curve (AUC). Results: Based on MSGB as the gold standard, the percentage of agreement between both tests was 78% (AUC 0.75). Based on the ACR/EULAR criteria, the percentage of agreement was 83% (AUC 0.78) for ultrasonography and 81% (AUC 0.83) for biopsy. Sensitivity and specificity were 90% and 67%, respectively, for ultrasonography and 76% and 90% for biopsy. The results were similar with the AECG criteria. The intra- and inter-observer variability was good (κ > 0.7). Significant differences were observed for positive anti-Ro52 values and hypergammaglobulinemia in pathological ultrasound scans. Conclusion: Diagnostic ultrasonography is as useful as MSGB in pSS. Therefore, it could be included in the classification criteria. In this cohort, it proved more sensitive than MSGB and could be used as an initial test for patients suspected of having pSS. MSGB could be used in cases where clinical and serological results are inconclusive. Key Points • Major salivary gland ultrasonography adds diagnostic value similar to that of MSGB, thus potentially enabling this invasive procedure to be avoided. • Ultrasonography could be included in the classification criteria for primary Sjögren's syndrome. • Given that ultrasonography is more sensitive and less specific than MSGB, it could be used as an initial diagnostic test in patients with suspected Sjögren's syndrome. • Biopsy should be performed in those cases where ultrasonography, clinical, and serological data are inconclusive. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of pelvic floor training on pain, sexual dysfunction and quality of life in female patients with primary Sjögren syndrome (pSS) and determine whether pelvic floor training was superior to an education program. Methods: Forty‐six pSS patients (all women) with an average age of 47.78 ± 9.18 years were included in the study. Patients were divided into two groups as a pelvic floor training group and control group for 8 weeks. Visual Analog Scale (VAS), Pelvic Pain Impact Questionnaire (PPIQ), Female Sexual Function Scale (FSFI), Health Assessment Questionnaire (HAQ), Pelvic Floor Disability Index‐20 (PFDI‐20), and Pelvic Floor Impact Questionnaire (PFIQ‐7) were used to evaluate the outcomes. All evaluations were performed at baseline and at the end of the 8th week. Results: When the groups were compared before training, there was no significant difference (p >.05). In post‐training comparisons, there were significant differences in VAS, PPIQ, FSFI, PFIQ‐7, and PFDI‐20 in the pelvic floor training group (p values between.02 and.00), and in FSFI‐lubrication, PFIQ‐7, and PFDI‐20 (p values between.00 and.03) in the control group. According to Δ values, the pelvic floor training group was found to be superior in terms of FSFI orgasm, pain, and lubrication scores (p =.00) and all sub‐parameters of PFDI‐20 (p =.00). Conclusion: Pelvic floor training has a positive effect on the sexual dysfunction and discomfort caused by pelvic symptoms in patients with pSS. Pelvic floor training should be included in rehabilitation programs to improve sexual function and pelvic floor dysfunctions for patients with pSS. [ABSTRACT FROM AUTHOR]

Type I interferon (IFN-I) is thought to play a role in many systemic autoimmune diseases. IFN-I pathway activation is associated with pathogenic features, including the presence of autoantibodies and clinical phenotypes such as more severe disease with increased disease activity and damage. We will review the role and potential drivers of IFN-I dysregulation in 5 prototypic autoimmune diseases: systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, primary Sjögren syndrome, and systemic sclerosis. We will also discuss current therapeutic strategies that directly or indirectly target the IFN-I system. [ABSTRACT FROM AUTHOR]

Tomas Loureiro,1 Sandra Rodrigues-Barros,1 Ana Rita Carreira,1 Filipe Gouveia-Moraes,1 Pedro Carreira,1 Ana Vide Escada,1 Paul Campos,1 Ines Machado,1 Nuno Campos,1 Renato Ambrosio Jr,2 Timothy J Archer,3 Dan Z Reinstein3 1Ophthalmology Department, Hospital Garcia de Orta, Almada, Portugal; 2Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil; 3London Vision Clinic, London, UKCorrespondence: Tomas Loureiro, Ophthalmology Department, Hospital Garcia de Orta, Avenida Torrado da Silva, Almada, 2805-267, Portugal, Tel +351 913 513 175, Email loureiro.tomas@gmail.comPurpose: To evaluate the changes on epithelial thickness before and after topical treatment in primary Sjögren syndrome-associated dry eye disease (SS-DED).Methods: This was a prospective study that included referred women with SS-DED and healthy age-matched controls. Corneal epithelial thickness was evaluated using high-definition anterior segment optical coherence tomography (Cirrus 5000 HD-OCT) in the baseline first consultation, and four weeks after treatment with preservative free 1mg/1mL sodium hyaluronate. Schirmer test 1 (ST1), tear break-up time (TBUT), tear meniscus height (TMH), SICCA Ocular Surface Score (SICCA OSS) and Ocular Surface Disease Index (OSDI) were evaluated. Statistical significance was defined as p-value < 0.05.Results: The study included 40 eyes, 20 with SS-DED and 20 controls. At baseline, SS-DED patients had lower ST1 (11.1 ± 2.2mm vs 14.1 ± 3.1mm, p< 0.01), faster TBUT (9.1 ± 1.8s vs 13.2 ± 1.1s, p< 0.01) and lower TMH (211.2 ± 68.4 μm vs 217.2 ± 60.1μm; p< 0.01) than the control group, whereas SICCA OSS and OSDI were higher (p< 0.01). The superior epithelium was thinner in SS-DED group (41.1 ± 3.2 μm vs 43.1± 2.3 μm, p< 0.01). After treatment, ST1, TBUT, TMH, SICCA OSS, and OSDI improved (p< 0.01), and superior epithelium thickened (p< 0.01) in the SS-DED group.Conclusion: Treatment with sodium hyaluronate improved ST1, TBUT, TMH, SICCA-OSS, and OSDI score. Superior epithelium tends to be thinner in SS-DED but becomes thicker with treatment. Our results seem to illustrate the morphological changes in the corneal epithelium in DED, which could be further recognized as a clinical biomarker of SS-DED.Keywords: dry eye disease, Sjogren’s syndrome, epithelial thickness, AS-OCT

Sjogren’s syndrome (SSj) is a chronic autoimmune disease mainly targeting the exocrine glands, but sometimes associating extra-glandular manifestations. Xerosis, purpura, Raynaud’s phenomenon, cutaneous vasculitis, annular erythema are the main forms of skin involvement. A 26-year-old female patient was admitted for diffuse erythematous rash and angioedema, xerophthalmia and symmetrical arthralgia of hand joints. Anti-nuclear antibodies, anti-SSA and anti-Ro52 antibodies were identified, Schirmer’s test was positive, thus the diagnoses of primary SSj and associated urticarial vasculitis were established. Treatment with oral methylprednisolone, azathioprine and hydroxychloroquine was initiated, with favourable response over the next week. Patients with primary SSj that develop cutaneous vasculitis, lymphadenopathies or lymphopenia may be at risk for additional extra-glandular manifestations, including non-Hodgkin lymphoma.

This article discusses a rare case of a patient with Sjögren syndrome (SS) and psoriasis who was successfully treated with the Janus kinase inhibitor, tofacitinib. The patient presented with symptoms such as xerostomia, xerophthalmia, blurred vision, itching skin rash, scaly plaques, muscle weakness, and weight loss. Laboratory results showed abnormalities in potassium levels, CO2 combining power, blood urea nitrogen, creatinine, and inflammatory markers. Treatment with tofacitinib, along with other medications, resulted in significant improvement in symptoms and laboratory values without any adverse events. The article highlights the potential of targeted synthetic drugs like tofacitinib in the treatment of autoimmune diseases. [Extracted from the article]

A 65-year-old woman operated on for cataract was discharged from hospital with a routine prescription including diclofenac. One week later she was diagnosed with corneal trophic ulcer in the operated eye. As the non-operated eye suffered from filamentary keratopathy, the hypothesis of a serious adverse event due to diclofenac was considered. Diclofenac was stopped and intensive topical non-preservative tears were administered. No further melting was noticed and epithelialization of the cornea occurred. Diclofenac as a non-steroidal anti-inflammatory drug is known for its anesthetic action on the cornea. This effect contributes to aggravation of the pre-existing dry eye syndrome related to Sjögren syndrome (diagnosed a posteriori) with potential for corneal perforation. Therefore the prescription of diclofenac should be preceded by questioning the patient about the predisposing rheumatoid conditions and careful examination of the eye. [ABSTRACT FROM AUTHOR]

Sjögren syndrome (SjS) is an autoimmune disease characterized by the destruction of the exocrine gland epithelia, causing a dryness of mucosa called sicca symptoms, and whose main life-threatening complication is lymphoma. There is a need for new biomarkers in this disease, notably diagnostic biomarkers for patients with genuine sicca symptoms that do not meet current criteria, and prognostic biomarkers for patients at risk of lymphoma. Plasma extracellular vesicles (EVs) are promising biomarker candidates in several diseases, but their potential has not yet been explored in SjS. In this proof-of-concept study, we characterized EVs from primary SjS patients (pSS, n=12) at the phenotypic and proteomic levels, compared to EVs from healthy donor (HD, n=8) and systemic lupus erythematosus patients (SLE, n=12). Specific plasma EVs subpopulations, derived from neutrophils, endothelial, and epithelial cells, were found increased in pSS. We also identified a pSS proteomic signature in plasma EVs, including neutrophil-, epithelial-, and endothelial-related proteins, such as integrin alpha M (ITGAM), olfactomedin-4 (OLFM4), Ras-related protein RAB10, and CD36. Overall, our results support the relevance of plasma EVs as biomarkers in SjS. [ABSTRACT FROM AUTHOR]

Background: Tubulointerstitial nephritis with IgM-positive plasma cells (IgMPC-TIN) is a newer disease about which there are many unclear points. Glucocorticoid therapy is effective in many cases of IgMPC-TIN; however, relapse during glucocorticoid tapering has been reported. Relapse and its treatment are poorly defined. Case Presentation: Case 1 was a 61-year-old man with renal dysfunction and proteinuria. Tubulointerstitial nephritis and IgM-positive plasma cells were observed in a renal biopsy. He was diagnosed with IgMPC-TIN accompanied by Fanconi syndrome and distal renal tubular acidosis (d-RTA). Prednisolone (PSL; 30 mg daily, 0.45 mg/kg/day) treatment was highly effective, and PSL was gradually tapered and discontinued after 1 year. However, 1 month after PSL discontinuation, therapeutic markers were elevated. Therefore, PSL (10 mg daily, 0.15 mg/kg/day) was administered, and the markers indicated improvement. Case 2 was a 43-year-old woman referred for renal dysfunction and proteinuria. Laboratory data revealed that she had primary biliary cholangitis (PBC), d-RTA, and Fanconi syndrome. A renal biopsy showed accumulation of IgM-positive plasma cells in the tubulointerstitium without any glomerular changes. A diagnosis of IgMPC-TIN was made and the patient was started on PSL (35 mg daily, 0.6 mg/kg/day). Therapeutic markers decreased immediately and PSL was discontinued after 1 year. Three months later, the proteinuria and Fanconi syndrome worsened. PSL treatment was restarted (20 mg daily, 0.35 mg/kg/day) and markers indicated improvement. Case 3 was a 45-year-old woman with renal dysfunction and proteinuria. Tubulointerstitial nephritis and IgM-positive plasma cells were observed in a renal biopsy. The patient had PBC, Sjögren syndrome, d-RTA, and Fanconi syndrome, and the diagnosis of IgMPC-TIN was made. The patient was started on PSL (30 mg daily, 0.4 mg/kg/day) and disease markers decreased immediately. However, when PSL was tapered to 15 mg daily (0.2 mg/kg/day), the patient's serum IgM levels increased; therefore, we maintained the PSL at 15 mg daily (0.2 mg/kg/day). Conclusion: We report three cases of relapsed IgMPC-TIN associated with reduction or discontinuation of glucocorticoid therapy. In these cases, elevation of serum IgM preceded that of other markers such as urinary β2-microglobulin, proteinuria, and glycosuria. We recommend monitoring serum IgM levels while tapering glucocorticoids; a maintenance dose of glucocorticoid should be considered if relapse is suspected or anticipated. [ABSTRACT FROM AUTHOR]

This study aimed to compare tear film viscosity (TFV) in Sjögren and non-Sjögren dry eye diseases (DEDs). This was a cross-sectional observational study. A total of 68 DED patients were enrolled, including 32 patients with Sjögren syndrome (SS) and 36 without SS. TFV was assessed by a tear film analyzer and determined by the momentary moving speed (MMS; MMS (t) = α × t−β, t = time (s)) with its power-law fitting-derived parameters (α and β). Among the four indices of TFV (MMS (0.1 s), MMS (2.0 s), α, and β), the SS-DED patients had significantly lower MMS (0.1 s) (p = 2.01 × 10−5), α (p = 0.0375), and β (p = 0.0076). The SS-DED group also had significantly higher OSDI, lower central and nasal tear meniscus height (TMH), and higher OSS. MMS (0.1 s) was significantly correlated with nasal TMH and OSS (ρ = 0.2520, p = 0.0381 in nasal TMH; ρ = −0.3487, p = 0.0036 in OSS). Index β was not correlated with any non-TFV tests. In conclusion, MMS (0.1 s), α, and β are promising TFV indices in distinguishing SS-DED from non-SS-DED patients early. Among these TFV indices, lower MMS is the best alternative clue for detecting SS-DED. [ABSTRACT FROM AUTHOR]

Anti-aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) and Sjögren syndrome (SS) are likely comorbidities. However, the exact effects of age and disease duration on the positivity rates of serum anti-Ro/SSA and anti-La/SSB (anti-SSA/SSB) antibodies and the presence of sicca symptoms in patients with AQP4-IgG remain unknown. In the present study, we evaluated the data from patients with suspected NMOSD who had neurological episodes and tested for serum AQP4-IgG. Associations between the presence of serum AQP4-IgG and SS-related findings were evaluated. The presence of anti-SSA/SSB antibodies [odds ratio (OR), 7.34; 95% confidence interval (CI), 5.71-9.43; p < 0.0001] and that of sicca symptoms (OR, 2.08; 95% CI, 1.67-2.58; p < 0.0001) were both higher in patients with AQP4-IgG (n = 1,651) than in those without AQP4-IgG (n = 2,796). Meanwhile, neither age nor the elapsed time from neurological onset was linked to the prevalence of anti-SSA/SSB antibodies or sicca symptoms, and the prevalence rates of the SS-related factors were elevated since the onset of neurological episodes in those with AQP4-IgG. The frequency of sicca symptoms among those with anti-SSA/SSB antibodies was irrespective of AQP4-IgG (OR, 1.11; 95% CI, 0.67-1.85; p = 0.6892). The measured AQP4-IgG titers did not differ significantly according to the presence of anti-SSA/SSB antibodies (p = 0.2386; Mann-Whitney U test). In summary, age and duration of NMOSD were not the factors producing an elevated prevalence of anti-SSA/SSB antibodies and sicca symptoms in patients with AQP4-IgG, implying that the occurrence of comorbid SS is likely to temporarily precede or synchronize with the onset of AQP4-IgG-positive NMOSD. [ABSTRACT FROM AUTHOR]

Autoimmune diseases triggered by coronavirus disease 2019 (COVID‐19) mRNA vaccination have been emerging. Here, we report the case of a 27‐year‐old Japanese man with autoimmunity‐related neutrophilic dermatosis, occurring as an initial cutaneous manifestation of systemic lupus erythematosus with Sjögren syndrome after the second dose of the Pfizer/BioNTech COVID‐19 vaccination. The patient presented with urticarial erythema and partially annular erythema on the trunk and extremities with severe pruritus. Histopathological analysis showed vacuolar degeneration at the dermo‐epidermal junction and interstitial neutrophil infiltration. We reviewed eight patients, including the aforementioned patient, with exacerbation or new‐onset of SLE after COVID‐19 vaccination and found the patient had relatively mild symptoms, itchy annular erythema, and positive anti‐SS‐A/SS‐B antibodies. COVID‐19 mRNA vaccination can induce the production of type‐I interferon, which plays a crucial role in the pathogenesis of SLE and may cause autoimmunity‐related neutrophilic dermatosis in susceptible individuals. In the case that itchy annular erythema develops approximately 2 weeks after the vaccination, the possibility of systemic or cutaneous lupus erythematosus should be considered. For an accurate diagnosis, dermatologists should obtain a recent vaccination history and perform complete antibody profiling and skin biopsy for patients presenting with annular or erythema multiforme‐like lesions. [ABSTRACT FROM AUTHOR]

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

Purpose: The objective of the study was to compare the efficacy and safety of two concentration of autologous serum (AS) 20% vs 50% in recalcitrant moderate-to-severe dry eye patients. Methods: A double-blind prospective, interventional, and randomized study was done on 44 patients (80 eyes) clinically diagnosed with moderate-to-severe dry eye disease (DED) that was refractory to conventional treatment, and all patients were treated with AS20% or AS50% for 12 weeks. We documented Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), OXFORD corneal staining score (OSS), and Schirmer test (ST) at baseline, 2,4,8, and 12 weeks. These parameters were compared in both groups and between the groups by using Student's t-test. The study included 11 males and 33 females. Results: Out of 80 eyes, 33 eyes had moderate and 47 had severe DED. The age of patients in AS20% was 44.73 ± 14.37 years, and in AS50% was 46.41 ± 14.47 years. The most common etiology associated with DED was secondary Sjogren syndrome. In moderate DED, both the groups showed significant improvement in both subjective and objective parameters. But in severe DED, the AS20% group failed to show any significant improvement objectively, though subjective improvement was present. Conclusion: In refractory severe DED patients, AS50% is better option for treatment and in moderate DED both concentrations of autologous serum are effective.

Sjogren syndrome is a slowly progressive autoimmune disease with lymphocytic infiltration of exocrine glands, peri-epithelial and extra-epithelial tissues. In light of better diagnostic modalities and improved treatment options, patients with Sjogren syndrome are now commonly encountered by anaesthetist for various surgeries. Here, we would like to describe an anaesthetic management of a parturient with bad obstetric history who was diagnosed with Sjogren syndrome and was planned for caesarean delivery. This article also reviewed anaesthetic problems faced due to inherent disease pathology and concurrent alterations in treatment modalities.

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

About 2% of mothers with Sjögren’s syndrome and about 1% of mothers with systemic lupus erythematosus deliver a baby with a congenital heart block (CHB). This is thought to be as a result of the maternal autoantibodies that cross the placenta and cause congenital lupus in the fetus/neonate. Among patients with a 2nd or 3rd degree atrioventricular block, the mortality rate in the neonatal period is about 10%, and most neonates who survive require a pacemaker into adulthood. Despite the compelling mortality and morbidity, the data on the optimal preventive treatments are meager and not well-established. In addition to pharmaceutical therapy, one potentially effective therapy is plasmapheresis. Plasmapheresis is safe in pregnancy, well tolerated, and is effective in removing the offending substances in the serum which may cause disease. We review this literature, in order to educate the reader and to motivate interest in studying this condition in the future.

HIGHLIGHTS 1. Sjögren’s syndrome is a chronic autoimmune disease that attacks the exocrine glands, especially lacrimal and salivary glands. 2. Comprehensive management of pregnant women with Sjögren’s syndrome was described. 3. Clinical and laboratory examination, risk assessment and also preconception counseling before planning pregnancy are needed by women with Sjögren’s syndrome. ABSTRACT Objective: To illustrate the comprehensive management of pregnant women with Sjögren syndrome. Case Report: A 24 years old women came to Dr. Soetomo General Academic Hospital, Surabaya, Indonesia, due to Sjögren syndrome in 35/36 weeks of gestasional age for routine examination. She was first diagnosed with Sjögren syndrome in February 2018 because she complained of dry eyes and hair fall out. This was her first pregnancy. Laboratory result showed positive ANA test. The patient had hypertension with controlled blood preasure and dry eyes. The patient was diagnosed with primigravida 35-36 weeks of pregnancy, single live intrauterine, head presentation, IUGR, screening preeclampsia was positive, and there was complication with Sjögren’s syndrome. The patient was treated by multidisciplinary team consisting of obstetricians, internists, ophthalmologists and neonatologists. Conclusion: Sjögren’s syndrome is a chronic autoimmune disease that attacks the exocrine glands, especially lacrimal and salivary glands. The exact cause of Sjögren's syndrome is still not known. Women with Sjögren’s syndrome should have clinical and laboratory examination, risk assessment and also preconception counseling before planning pregnancy because Sjögren syndrome was a rare case during pregnancy. Close monitoring and proper management was imperative to detect the early complication.

Abstract Background Primary Sjögren Syndrome is a rare autoimmune systemic disease characterized by impaired secretory functions of the exocrine gland. One of the main clinical features is dry mouth and subsequent oral diseases, which are also found in patients with Sicca. This leads to a marked deterioration in the quality of life and the patient’s search for information and solutions. Many patients turn to patients’ associations that offer moments of sharing to their members, especially through online discussion forums. Today, these forums represent quality material for a sociological or biomedical analysis of patients' concerns, as close as possible to their daily lives. Our objective is to analyze the concerns of patients with SS or Sicca regarding their dry mouth especially dental care. Methods In this cross-sectional observation study, a quantitative analysis of the Mouth-Nose online forum discussion of the French Association of Patients with Gougerot-Sjögren’s Syndromes and Dryness have been performed. After reading and re-reading, initial request themes, topics, and subtopics were established and coding was performed. Then, the 885 threads were classified depending the initial request, pragma-linguistic indices and the main topic discussed in the thread. After identifying the threads dealing with dental care, we looked at which types of care were most discussed and classified the discussions according to whether or not the patient was satisfied with their care at the dentist. Results The majority of the initial requests are posts for experiences sharing and/or advice. The topic of “dental care” is one of the main concerns of the forum users. Among the threads that concern dental care, requests to share experience with implants are in the majority. Finally, the majority of the posts on dental care relate to care in private dental practice, deals with dental implants and prevention and resulted mainly in patient satisfaction. Conclusions Analysis of the forum reveals importance of patient concerns about prevention, and care costs due to implant treatment, which add to disease burden. Most of messages relate favorable experiences with their dentists, which is in line with the approach of sharing experiences and support characteristic of a forum.

Xerostomia is the phenomenon of dry mouth and is mostly caused by hypofunction of the salivary glands. This hypofunction can be caused by tumors, head and neck irradiation, hormonal changes, inflammation or autoimmune disease such as Sjögren's syndrome. It is associated with a tremendous decrease in health-related quality of life due to impairment of articulation, ingestion and oral immune defenses. Current treatment concepts mainly consist of saliva substitutes and parasympathomimetic drugs, but the outcome of these therapies is deficient. Regenerative medicine is a promising approach for the treatment of compromised tissue. For this purpose, stem cells can be utilized due to their ability to differentiate into various cell types. Dental pulp stem cells are adult stem cells that can be easily harvested from extracted teeth. They can form tissues of all three germ layers and are therefore becoming more and more popular for tissue engineering. Another potential benefit of these cells is their immunomodulatory effect. They suppress proinflammatory pathways of lymphocytes and could therefore probably be used for the treatment of chronic inflammation and autoimmune disease. These attributes make dental pulp stem cells an interesting tool for the regeneration of salivary glands and the treatment of xerostomia. Nevertheless, clinical studies are still missing. This review will highlight the current strategies for using dental pulp stem cells in the regeneration of salivary gland tissue. [ABSTRACT FROM AUTHOR]

Background: Inclusion body myositis (IBM) is a slowly progressive inflammatory myopathy that typically affects the quadriceps and finger flexors. Sjögren's syndrome (SS), an autoimmune disorder characterized by lymphocytic infiltration of exocrine glands has been reported to share common genetic and autoimmune pathways with IBM. However, the exact mechanism underlying their commonality remains unclear. In this study, we investigated the common pathological mechanisms involved in both SS and IBM using a bioinformatic approach. Methods: IBM and SS gene expression profiles were obtained from the Gene Expression Omnibus (GEO). SS and IBM coexpression modules were identified using weighted gene coexpression network analysis (WGCNA), and differentially expressed gene (DEG) analysis was applied to identify their shared DEGs. The hidden biological pathways were revealed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Furthermore, protein -protein interaction (PPI) networks, cluster analyses, and hub shared gene identification were conducted. The expression of hub genes was validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). We then analyzed immune cell abundance patterns in SS and IBM using single-sample gene set enrichment analysis (ssGSEA) and investigated their association with hub genes. Finally, NetworkAnalyst was used to construct a common transcription factor (TF)-gene network. Results: Using WGCNA, we found that 172 intersecting genes were closely related to viral infection and antigen processing/presentation. Based on DEG analysis, 29 shared genes were found to be upregulated and enriched in similar biological pathways. By intersecting the top 20 potential hub genes from the WGCNA and DEG sets, three shared hub genes (PSMB9, CD74, and HLA-F) were derived and validated to be active transcripts, which all exhibited diagnostic values for SS and IBM. Furthermore, ssGSEA showed similar infiltration profiles in IBM and SS, and the hub genes were positively correlated with the abundance of immune cells. Ultimately, two TFs (HDGF and WRNIP1) were identified as possible key TFs. Conclusion: Our study identified that IBM shares common immunologic and transcriptional pathways with SS, such as viral infection and antigen processing/presentation. Furthermore, both IBM and SS have almost identical immune infiltration microenvironments, indicating similar immune responses may contribute to their association. [ABSTRACT FROM AUTHOR]

Objective Parotid swelling (PSW) is a major predictor of non-Hodgkin's lymphoma (NHL) in primary SS (pSS). However, since detailed information on the time of onset and duration of PSW is scarce, this was investigated to verify whether it may lead to further improved prediction. NHL localization was concomitantly studied to evaluate the role of the parotid gland microenvironment in pSS-related lymphomagenesis. Methods A multicentre study was conducted among patients with pSS who developed B cell NHL during follow-up and matched controls that did not develop NHL. The study focused on the history of salivary gland and lachrymal gland swelling, evaluated in detail at different times and for different durations, and on the localization of NHL at onset. Results PSW was significantly more frequent among the cases: at the time of first referred pSS symptoms before diagnosis, at diagnosis and from pSS diagnosis to NHL. The duration of PSW was evaluated starting from pSS diagnosis, and the NHL risk increased from PSW of 2–12 months to >12 months. NHL was prevalently localized in the parotid glands of the cases. Conclusion A more precise clinical recording of PSW can improve lymphoma prediction in pSS. PSW as a very early symptom is a predictor, and a longer duration of PSW is associated with a higher risk of NHL. Since lymphoma usually localizes in the parotid glands, and not in the other salivary or lachrymal glands, the parotid microenvironment appears to be involved in the whole history of pSS and related lymphomagenesis. [ABSTRACT FROM AUTHOR]

Purpose: The objective of the study was to compare the efficacy and safety of two concentration of autologous serum (AS) 20% vs 50% in recalcitrant moderate‑to‑severe dry eye patients. Methods: A double‑blind prospective, interventional, and randomized study was done on 44 patients (80 eyes) clinically diagnosed with moderate‑to‑severe dry eye disease (DED) that was refractory to conventional treatment, and all patients were treated with AS20% or AS50% for 12 weeks. We documented Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), OXFORD corneal staining score (OSS), and Schirmer test (ST) at baseline, 2,4,8, and 12 weeks. These parameters were compared in both groups and between the groups by using Student’s t‑test. The study included 11 males and 33 females. Results: Out of 80 eyes, 33 eyes had moderate and 47 had severe DED. The age of patients in AS20% was 44.73 ± 14.37 years, and in AS50% was 46.41 ± 14.47 years. The most common etiology associated with DED was secondary Sjogren syndrome. In moderate DED, both the groups showed significant improvement in both subjective and objective parameters. But in severe DED, the AS20% group failed to show any significant improvement objectively, though subjective improvement was present. Conclusion: In refractory severe DED patients, AS50% is better option for treatment and in moderate DED both concentrations of autologous serum are effective. [ABSTRACT FROM AUTHOR]

We present the case of a 28-year-old African man with multiple hospitalizations during the past two years due to worsening shortness of breath. The initial work-up revealed recurrent pulmonary embolism and interstitial lung disease (ILD). The diagnosis of primary Sjogren syndrome was established and a lung biopsy demonstrated cellular non-specific interstitial pneumonia (NSIP). Proper treatment of NSIP was partially effective and respiratory failure persisted, implying additional pathology to NSIP. Further evaluation revealed pulmonary hypertension that required treatment with pulmonary vasodilators. [ABSTRACT FROM AUTHOR]

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

Background: We aimed to explore the underlying mechanism of the total glucoside of peony (TGP) in treating Sjogren syndrome (SS) using the network pharmacology approach. Methods: The protein targets of TGP and SS were identified by database search. Then, the intersection of the two groups was studied. The drug--target network between TGP and the overlapping genes was constructed, visualized, and analyzed by Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment were performed to analyze these genes. Finally, the predictions of potential targets were evaluated by docking study. Results: Forty-six overlapping genes were discovered. The results suggested that TGP used in the treatment of SS is associated with cellular tumor antigen p53, neurotrophic tyrosine kinase receptor type 1, and epidermal growth factor receptor, as well as their related 3372 protein networks, which regulate intrinsic apoptotic signaling pathway, cellular response to oxidative stress, rhythmic process, and other processes. Molecular docking analysis proved that hydrogen bonding is the main form of interaction. Conclusion: Our research provided the protein targets affected by TGP in SS treatment. The key targets (caspase 3, vascular endothelial growth factor A, glyceraldehyde-3-phosphate dehydrogenase, etc.), which involve 3372 proteins, are the multitarget mechanism of TGP in SS treatment. [ABSTRACT FROM AUTHOR]

Interstitial lung disease associated with Sjögren syndrome belongs to the category of “arthralgia caused by dryness pathogen ” in traditional Chinese medicine, and it is generally believed that its pathogenesis is centered on internal dryness, which is caused by internal heat and burning of body fluid due to the lack of innate endowment or external dryness. The metabolism of water and grain essence is slow, and excessive accumulation of grain essence or abnormal transportation and transformation can lead to turbidity, and the accumulation of turbidity is the basis for the development of turbid poison. Turbid poison has the characteristics of poisonous evil, its nature is harsh, it is more likely to consume qi and blood, and it has the characteristics of agglutination, stagnation and filth. Turbid poison can be classified as a class of original poison. The original base of its transformation is turbidity from the grain essence. If the grain essence is transformed into a mellow and moist essence, alienation is brewed into the turbidity of corruption. The formation of turbid poison caused by spleen deficiency is a process of gradual accumulation, which can damage the internal organs and is complex and easily recurring. We believe that deficiency of the spleen and stomach is the source of dryness and that turbid poison with phlegm and blood stasis in the middle jiao and lung channels is the key factor aggravating the dryness. The theory of turbid poison of spleen and stomach covers the whole disease process. In the early stage, the spleen and stomach are deficient and the turbidity gathers at the beginning, which hinders qi and injures body fluid. In the middle stage, the turbidity breeds turbid poison, which leads to heat with phlegm and blood stasis. In the late stage, the turbid poison accumulates to form a mass, which can damage various organs. Clinical treatment should be based on the degree of turbid poison, blocking the source of turbid poison in the early stage, paying attention to the protection of body fluid, dredging the meridians by detoxification in the middle and late stage and taking in energy to restore the vital qi. The symptoms and signs of interstitial lung disease associated with Sjögren syndrome are consistent with the characteristics of turbid poison invading the human body. The theory of turbid poison of spleen and stomach can provide a new idea for the differentiation and treatment of this disease in traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Sjögren syndrome, a systemic autoimmune disease that is characterized by dry mouth and eyes, on which treatment decision remain challenging, while traditional Chinese medicine ( TCM) has advantages and is widely used in China. However, the lack of consensus on standardized TCM patterns diagnosis and treatment based on evidence-based evidence, limits the further improvement of clinical efficacy and scientific research level. Rheumatology Branch, Chinese Academy of Chinese Medicine organized more than 50 experts from 48 hospitals across the country to form Expert Consensus for TCM Patterns of Sjögren Syndrome: (ⅰ) pattern of yin deficiency and depletion of fluid; (ⅱ) pattern of deficiency of both qi and yin; (ⅲ) pattern of endogenous heat due to yin deficiency ( pattern of yin deficiency and heat-poison, included); (ⅳ) pattern of intermingled dryness and blood stasis; (ⅴ) pattern of intermingled dryness and dampness. According to the patterns, principles of treatment and prescriptions are also on the same page. The formation and promotion of this consensus is of importance in the TCM course of diagnosis and treatment of Sjögren syndrome. [ABSTRACT FROM AUTHOR]

Sjögren syndrome (SjS) is an autoimmune disease characterized by the destruction of the exocrine gland epithelia, causing a dryness of mucosa called sicca symptoms, and whose main life-threatening complication is lymphoma. There is a need for new biomarkers in this disease, notably diagnostic biomarkers for patients with genuine sicca symptoms that do not meet current criteria, and prognostic biomarkers for patients at risk of lymphoma. Plasma extracellular vesicles (EVs) are promising biomarker candidates in several diseases, but their potential has not yet been explored in SjS. In this proof-of-concept study, we characterized EVs from primary SjS patients (pSS, n=12) at the phenotypic and proteomic levels, compared to EVs from healthy donor (HD, n=8) and systemic lupus erythematosus patients (SLE, n=12). Specific plasma EVs subpopulations, derived from neutrophils, endothelial, and epithelial cells, were found increased in pSS. We also identified a pSS proteomic signature in plasma EVs, including neutrophil-, epithelial-, and endothelial-related proteins, such as integrin alpha M (ITGAM), olfactomedin-4 (OLFM4), Ras-related protein RAB10, and CD36. Overall, our results support the relevance of plasma EVs as biomarkers in SjS.

Summary: Background: What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score. Methods: In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables. Findings: Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27–2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22–2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01–1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22–1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16–2) were independent predictors of SjS-related death. Interpretation: The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS. Funding: Novartis.

Qi Tang, Jiafen Liao, Xi Xie Department of Rheumatology and Immunology, the Second Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Xi Xie, Department of Rheumatology and Immunology, the Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China, Tel/Fax +86 0731 8529 5255, Email Hsixie1997@csu.edu.cnAbstract: To strengthen the understanding of rheumatic diseases (RDs) as the most common underlying conditions associated with acquired hemophilia (AH), a potentially fatal bleeding condition due to the development of autoantibodies or inhibitors to coagulation factor VIII, and rarely to factor IX, here we presented two cases of RDs associated AH to elucidate the disease progression, treatment, and prognosis. The presented 2 cases showed good responses to glucocorticoid (GC) and immunosuppressive agents. And then, a case-based systematic review was conducted to better understand the clinically practiced diagnosis and treatment of RDs associated AH. A total of 14 articles were included in the final literature review. All the identified 14 patients with underlying RDs and AH presented with bleeding symptoms, increased APTT, decreased FVIII activity, and positive FVIII inhibitors. Twelve of the 14 patients (85.7%) started an eradication of autoantibodies treatment with GC and immunosuppressive agents. Among which six patients achieved partial or complete remission, and four patients (28.6%) switched to Rituximab and responded well. Nine of the 14 patients received hemostasis therapy, including recombinant human FVIIa (rFVIIa). Two patients (14.3%) died due to mass bleeding and key organ failure. AH should be highly suspected in patients with RDs presenting spontaneous mucocutaneous or internal bleeding and an isolated prolonged APTT. Given the high morbidity of AH, it is important to facilitate efficient and proper management.Keywords: acquired hemophilia, systemic lupus erythematosus, Sjogren syndrome, rheumatoid arthritis, connective tissue disease

Abstract 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

In sicca syndrome patients the xerostomia, xerophthalmia and the serological findings may strongly suggest the autoimmune Sjögren’s syndrome, but the histological findings in the labial salivary gland biopsies do not always justify the suspected diagnosis. The aim of this study was to compare the histomorphological changes and the clinical findings in patients with pathologically established Sjögren’s syndrome and in cases with negative histology. A total of 133 labial biopsies have been retrospectively evaluated from 2015 to May 2022, and the characteristic Sjögren’s lesions were found in 67 cases. According to the clinical data, 34 cases proved to be primary, and 33 were associated (“secondary”) forms. In 66 cases, the histology did not justify Sjögren’s syndrome; a significant acinar loss, fibrolipomatous infiltration, and mild sialadenitis had led to the clinical symptoms. In Sjögren’s histologies, the acinar loss was detected in just 31.8% of cases, which might indicate that the diminished saliva production represents immune-mediated hypofunction rather than direct damage of the acini. This is the first systemic study in Hungary investigating the correlation between pathological alterations and clinical findings.

Primary Sjögren syndrome (pSS) is a systemic autoimmune inflammatory disease. Up to now, the role of regulatory T cells (Tregs) and their subgroups in pSS is still in controversial. In this study we tried to elucidate the roles of Tregs and its subgroups in pSS. Total 43 pSS patients and 23 health persons as control were enrolled in this study. We grouped the pSS patients according to the anti-SSa/SSb and the EULAR Sjögren's syndrome disease activity index (ESSDAI). Among the 43 pSS patients, 14 patients were followed after treatment. The percentage of rTregs (resting Treg cells) among Tregs was increased in the pSS group, and decreased after treatment. In the high disease activity subpopulation (ESSDAI ≥ 5), the percentage of rTregs among Tregs decreased after treatment. On the contrary, the percentage of aTregs (activated Treg cells) increased after treatment. It was in an inverse correlation between the percentage of aTreg and rTreg in pSS patients. The Tregs are co-cultured with responder T cells. Tregs from pSS patients showed poorer proliferation inhibitory function. Our results show that the percentages of Tregs and their subgroups altered in pSS patients. The percentage of aTreg and the percentage of rTreg have an inverse correlation in pSS patients. Compared to the control group, the percentage of rTregs among Tregs was increased in the pSS patients and decreased after the treatment. Our study also showed that The Tregs from pSS patients may have poorer inhibitory functions.

Introduction: Sjögren syndrome (SS) is an autoimmune disease characterized by salivary gland (SG) destruction leading to loss of secretory function. A hallmark of the disease is the presence of focal lymphocyte infiltration in SGs, which is predominantly composed of T cells. Currently, there are no effective therapies for SS. Recently, we demonstrated that a newly developed therapy using effective-mononuclear cells (E-MNCs) improved the function of radiation-injured SGs due to anti-inflammatory and regenerative effects. In this study, we investigated whether E-MNCs could ameliorate disease development in non-obese diabetic (NOD) mice as a model for primary SS.Methods: E-MNCs were obtained from peripheral blood mononuclear cells (PBMNCs) cultured for 7 days in serum-free medium supplemented with five specific recombinant proteins (5G culture). The anti-inflammatory characteristics of E-MNCs were then analyzed using a co-culture system with CD3/CD28-stimulated PBMNCs. To evaluate the therapeutic efficacy of E-MNCs against SS onset, E-MNCs were transplanted into SGs of NOD mice. Subsequently, saliva secretion, histological, and gene expression analyses of harvested SG were performed to investigate if E-MNCs therapy delays disease development.Results: First, we characterized that both human and mouse E-MNCs exhibited induction of CD11b/CD206-positive cells (M2 macrophages) and that human E-MNCs could inhibit inflammatory gene expressions in CD3/CD28- stimulated PBMNCs. Further analyses revealed that Msr1-and galectin3-positive macrophages (immunomodulatory M2c phenotype) were specifically induced in E-MNCs of both NOD and MHC class I-matched mice. Transplanted E-MNCs induced M2 macrophages and reduced the expression of T cell-derived chemokine-related and inflammatory genes in SG tissue of NOD mice at SS-onset. Then, E-MNCs suppressed the infiltration of CD4-positive T cells and facilitated the maintenance of saliva secretion for up to 12 weeks after E-MNC administration.Discussion: Thus, the immunomodulatory actions of E-MNCs could be part of a therapeutic strategy targeting the early stage of primary SS.

Sjögren syndrome (SS) is a multisystem autoimmune disease, primarily targeting salivary and lacrimal glands; skin, nasal and vaginal dryness, along with musculoskeletal pain and fatigue are the most commonly reported symptoms. Hearing loss is hypothesized to be frequent as well. The purpose of this systematic review was to estimate the prevalence of Hearing loss and its different subtypes in patients with Sjögren syndrome. PRISMA guidelines were followed to ensure highest quality for our systematic review. A random effects model meta-analysis and meta-regression was conducted using I2 as heterogeneity indicator. Eleven observational studies were included in this systematic review. Ten of them were cross-sectional, while one study was case–control. Studies were assessed for risk of bias: all were rated to a moderate level, except for two rated to a low level. Pooled prevalence of any type of hearing loss was 52.2%. After excluding studies rated to moderate bias, the pooled prevalence of hearing loss was 36.7%. We also conducted a subgroup analysis depending on type of hearing loss. Pooled prevalence of sensorineural hearing loss was 42.6%., while pooled prevalence of conductive hearing loss and mixed hearing loss were 5% and 2.3%, respectively. Meta-regression was conducted in an effort to identify possible variables capable to explain high heterogeneity between studies. Sample size and year of study were separately found to account for a portion of heterogeneity between studies of sensorineural hearing loss. Year of study was also found to account for a portion of heterogeneity between studies of conductive hearing loss. In conclusion, sensorineural hearing loss, is highly prevalent in patients with Sjögren syndrome. On this basis, early screening and follow-up of patients with Sjögren syndrome by pure tone audiometry is important. [ABSTRACT FROM AUTHOR]

10% of rheumatoid arthritis (RA) cases are associated to so-called secondary Sjögren's syndrome (SS). These RA cases have higher DAS, fewer remissions. Is this linked to a poor response to DMARDs (disease-modifying anti-rheumatic drugs)? No study has addressed this question to date. Does the association between secondary Sjögren's syndrome (SS) and rheumatoid arthritis (RA) affect the therapeutic response to DMARDs and long-term prognosis? We conducted a retrospective case–control study: 39 RA associated with SS was (anti-SSA antibodies and/or Chisolm stage III or IV) were compared to 39 isolated cases of erosive RA matched by age, duration of progression and gender. The DAS CRP was higher in the RA + SS group in patients with disease progression of 16 years: 2.6 (1.5–4.5) compared to the RA group: 1.6 (1.3–2.8) (p = 0.0001) while fewer patients were in remission: 61 vs. 92% (p = 0.002). A higher number of B DMARDs have been prescribed: RA + SS = 3.04 (1–7); RA = 1.7 (1–5) (p = 0.004). Anti-TNFs are less effective when RA is associated with SS: 30 vs. 70%. Conversely, Rituximab is more effective when RA is associated with SS: 80 vs. 30%. Erosive RA-related SS exacerbates the clinical course of the condition: higher DAS, fewer remissions. This is linked to reduced treatment efficacy: higher number of DMARDs prescribed, reduced efficacy of anti-TNF drugs. RA-related SS could modify sensitivity to biotherapies: lower percentage of remissions and resistance to anti-TNF drugs. [ABSTRACT FROM AUTHOR]

Objectives: Sjögren syndrome (SS) features salivary gland architectural changes such as ductal deformities and fat deposition secondary to inflammatory cell infiltrates; however, the anatomical and pathophysiological correlations of SS remain to be determined. This study aimed to determine the correlations of imaging findings based on the magnetic resonance (MR) sialography with the clinical and laboratory aspects of SS patients. Methods: We evaluated the MR sialographic findings of two pairs of parotid glands (PGs) and submandibular glands (SMGs) from 41 SS patients. The distinct MR sialographic features were then compared with the clinical symptoms, biological (anti‐SSA/Ro antibody positivity), histological (labial gland focus score), and functional (salivary flow and scintigraphy) data. Results: Ductal deformities such as sialectasis in the PG ducts were exclusively observed in SS, and fat replacement in SMGs was more distinct in patients with SS than in non‐SS sicca patients. Of the 82 PGs and SMGs from 41 SS patients, the grade of sialectasis in PGs on MR sialographic images and fat stage in SMGs showed strong correlations with anti‐SSA/Ro‐positivity. PG sialectasis was found more frequently in patients with dry mouth and decreased salivary gland function. A significant correlation was found between fat deposition in PGs and SMGs and decreased salivary gland function. Conclusion: These results suggest that MR sialography is a reliable, adjunctive anatomical and functional study to assess SS. Detail aspects of sialectasis and fat accumulation encountered on MR sialography in SS patients can help physicians assume the disease status in SS. Level of Evidence: 3 Laryngoscope, 133:307–316, 2023 [ABSTRACT FROM AUTHOR]

Sjögren's syndrome is a chronic and insidious auto-immune disease characterized by lymphocyte infiltration of exocrine glands. The patients typically present with ocular surface diseases related to dry eye and other systemic manifestations. However, due to the high prevalence of dry eye disease and the lack of objective and clinically reliable diagnostic tools, discriminating Sjögren's syndrome dry eye (SSDE) from non-Sjögren's syndrome dry eye (NSSDE) remains a challenge for clinicians. Diagnosing SS is important to improve the quality of life of patients through timely referral for systemic workups, as SS is associated with serious systemic complications such as lymphoma and other autoimmune diseases. The purpose of this article is to describe the current molecular understanding of Sjögren's syndrome and its implications for novel diagnostic modalities on the horizon. A literature review of the pre-clinical and clinical studies published between 2016 and 2022 was conducted. The SSDE pathophysiology and immunology pathways have become better understood in recent years. Novel diagnostic modalities, such as tear and saliva proteomics as well as exosomal biomarkers, provide hope on the horizon. [ABSTRACT FROM AUTHOR]

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BACKGROUND: Amyloidosis is an uncommon disorder characterized by the extracellular deposition of amorphous and insoluble proteins in an abnormal fibrillary configuration. Mammary amyloidosis is an unusual and easily overlooked diagnosis with an ambivalent presentation that could mimic breast cancer. CASE REPORT: We here report the case of 60-year-old Caucasian woman who presented to our surgical oncology department for clinically and radiologically suspicious breast mass. A fine needle biopsy was irrelevant, so we performed a lumpectomy. Final histology revealed an amyloid deposit and further workup was consistent with nodular cutaneous and breast AL amyloidosis associated with Sjögren's syndrome. CONCLUSION: Although rare, an awareness of the clinicopathologic characteristics of this easily overlooked entity is of great importance for breast surgeons. [ABSTRACT FROM AUTHOR]

Background and aims: RFC1-CANVAS and primary Sjögren syndrome (pSS) are among the most frequent causes of sensory ganglionopathy (SG) and can present simultaneously in a given patient, sharing confounding signs and symptoms. We describe the clinical characteristics of patients with SG due to CANVAS who were suspected of having or had received a previous diagnosis of pSS. Methods: Patients with SG and a genetically confirmed RFC1-CANVAS followed in our centre were ascertained and their personal history of pSS was collected. Results: Among the 71 patients with CANVAS, six patients (all females) had been diagnosed with pSS by their clinicians. In these six patients, the mean age at onset of the SG was 61 years, four patients describing gait instability and positive sensory symptoms, one only gait instability and one only positive sensory symptoms. Five patients had a history of chronic cough; signs at examination included a cerebellar syndrome (n = 3), vestibulopathy (n = 2), pes cavus (n = 3) and dysautonomia (n = 2). On neurophysiological examination, SG was generally severe and symmetrical. All patients presented a sicca syndrome, but only four patients had a confirmed pSS as per 2016 ACR-EULAR classification criteria. Four patients were treated but did not respond to immunosuppressive therapy, one suffering from side effects. Interpretation: The suspicion or diagnosis of pSS in a patient with SG should not exclude RFC1 expansion analysis, as a CANVAS diagnosis may dissuade the clinician from initiating or continuing immunosuppressive therapy, especially in unconfirmed pSS patients. Importantly, a sicca syndrome may lead to pSS misdiagnosis. [ABSTRACT FROM AUTHOR]

Sjögren's syndrome is a chronic and insidious autoimmune disease characterized by lymphocyte infiltration of exocrine glands. Patients typically present with dry eye, dry mouth, and other systemic manifestations. Currently, the available molecules and drug-delivery systems for the treatment of Sjögren's syndrome dry eye (SSDE) have limited efficacy since they are not specific to SSDE but to dry eye disease (DED) in general. The current treatment modalities are based on a trial-and-error approach using primarily topical agents. However, this approach gives time for the vicious cycle of DED to develop which eventually causes permanent damage to the lacrimal functional unit. Thus, there is a need for more individualized, specific, and effective treatment modalities for SSDE. The purpose of this article is to describe the current conventional SSDE treatment modalities and to expose new advances in ocular drug delivery for treating SSDE. A literature review of the pre-clinical and clinical studies published between 2016 and 2022 was conducted. Our current understanding of SSDE pathophysiology combined with advances in ocular drug delivery and novel therapeutics will allow the translation of innovative molecular therapeutics from the bench to the bedside. [ABSTRACT FROM AUTHOR]