RESUMEN
BACKGROUND: Patients with autoimmune diseases can develop multiple autoimmune diseases over a long period of time, and the presence of more than one autoimmune disease in a single patient is defined as polyautoimmunity. Polyautoimmunity may be clinical evidence that autoimmune diseases share similar immunological mechanisms. CASE PRESENTATION: We report a 30-year-old woman with a unique combination of autoimmune diseases predominantly affecting the central nervous system, with hypoparathyroidism, hypophysitis, medulla involvement, and pons and temporal lobe involvement associated with primary Sjögren's syndrome (pSS), occurring independently over a long period. The patient who had a history of muscle cramps and one seizure incident, presented with vomiting and blurred vision. She was diagnosed with hypophysitis and hypoparathyroidism with calcifications in the basal ganglia and cerebellum. She recovered after four months of corticosteroid treatment for hypophysitis and was started on treatment for hypoparathyroidism. Eight months later, she developed vomiting, hiccups, vertigo, and ataxia with a focal lesion in the medulla. She recovered with immunosuppressive treatment for 2 years. Fifty-eight months after the onset of hypophysitis, she developed diplopia and dry mouth and eyes. MRI showed infiltrative lesions in the left pons and left temporal lobe. Based on positive anti-Sjögren's syndrome-related antigen A antibodies and low unstimulated whole salivary flow rate, pSS was diagnosed. She received corticosteroids and continued mycophenolate mofetil treatment with recovery of neurological symptoms. CONCLUSION: This case highlights the need for long-term follow-up to detect autoimmune disease processes involving various organs.
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Hipoparatiroidismo , Síndrome de Sjögren , Humanos , Femenino , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/tratamiento farmacológico , Adulto , Hipoparatiroidismo/complicaciones , Hipoparatiroidismo/diagnóstico , Hipofisitis/complicacionesRESUMEN
AIM: This study aimed to evaluate the long-term survival, causes of death, and prognostic factors in Chinese patients with primary Sjögren syndrome (pSS). METHODS: We included patients with pSS registered in the Chinese Rheumatism Data Centre between May 2016 and December 2021, and collected baseline clinical, laboratory, and treatment data. Survival and standard mortality rates were calculated using general population mortality data. Factors related to mortality were identified using Cox proportional hazards regression. RESULTS: Among the 8588 patients included, 274 died during a median follow-up of 4.0 years. The overall standardized mortality ratio was 1.61 (95% CI: 1.43-1.81). Overall survival rates were 98.2% at 5 years and 93.8% at 10 years. The predominant causes of death were comorbidities, including cardiovascular diseases, tumors, and infections, while the most frequent pSS-related causes of death were interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). Male sex, older age, ILD, PAH, and high EULAR Sjögren's syndrome disease activity index (ESSDAI), thrombocytopenia, anemia, high immunoglobulin A (IgA) level, and glucocorticoid treatment independently increased the mortality risk, while using hydroxychloroquine was a protective factor. CONCLUSION: Mortality rates have significantly increased in Chinese patients with pSS. Comorbidities, rather than pSS-related organ damage, were the main causes of death. All-cause mortality was associated with male sex, older age, ILD, PAH, high ESSDAI, thrombocytopenia, anemia, high IgA level, and glucocorticoid treatment, whereas hydroxychloroquine use might improve the long-term survival.
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Causas de Muerte , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/mortalidad , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , China/epidemiología , Factores de Tiempo , Adulto , Factores de Riesgo , Anciano , Pronóstico , Medición de Riesgo , ComorbilidadRESUMEN
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease that causes dysfunction of salivation and harmful oral conditions. The association between periodontal disease (PD) and pSS with or without geniquin therapy remains controversial. This study evaluated the association between geniquin therapy and the risk of subsequent development of PD in pSS patients. From Taiwan's National Health Insurance Research Database, we selected a control cohort of 106,818 pSS patients, followed up from 2000 to 2015, matched (1:4) by age and index year with 427,272 non-pSS patients. We also analyzed 15,149 pSS patients receiving geniquin therapy (cohort 1) and 91,669 pSS patients not receiving geniquin therapy (cohort 2). After adjusting for confounding factors, multivariate Cox proportional hazards regression analysis was used to compare the risk of PD over the 15-year follow-up. In the control cohort, 11,941 (11.2%) pSS patients developed PD compared to 39,797 (9.3%) non-pSS patients. In cohorts 1 and 2, 1,914 (12.6%) pSS patients receiving geniquin therapy and 10,027 (10.9%) pSS patients not receiving geniquin therapy developed PD. The adjusted hazard ratio (HR) for subsequent PD in pSS patients was 1.165 (95% confidence interval [CI] = 1.147-1.195, p < 0.001) and in pSS patients receiving geniquin therapy was 1.608 (95% CI = 1.526-1.702, p < 0.001). The adjusted HR for PD treatment was 1.843. Patients diagnosed with pSS showed an increased risk of developing subsequent PD and receiving PD treatment than patients without pSS, while pSS patients receiving geniquin therapy showed even higher risks.
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Enfermedades Periodontales , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/epidemiología , Síndrome de Sjögren/tratamiento farmacológico , Taiwán/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Enfermedades Periodontales/complicaciones , Enfermedades Periodontales/epidemiología , Estudios de Cohortes , Anciano , Factores de Riesgo , Modelos de Riesgos ProporcionalesRESUMEN
Amidst the COVID-19 pandemic, hydroxychloroquine (HCQ) was widely administered despite limited data on its safety and efficacy. This study assesses the acute and chronic impacts of HCQ on electrocardiography (ECG) parameters alongside the effects of azithromycin and levofloxacin coadministration in patients with COVID-19. A comprehensive analysis was conducted on 109 COVID-19 patients receiving HCQ, with or without Azithromycin and/or Levofloxacin, and 51 long-term HCQ-treated Sjogren's syndrome (SS) patients. ECG parameters, including QTc interval, were meticulously evaluated against a control group of 109 COVID-19 patients without HCQ treatment. HCQ monotherapy, in combination with Levofloxacin, significantly prolonged the QTc interval in COVID-19 patients compared to controls. Notably, the combination of HCQ and Azithromycin demonstrated a mitigated impact on QTc prolongation. Long-term HCQ use in SS patients did not significantly affect QTc intervals, illustrating a distinct safety profile from short-term use in COVID-19 treatment. HCQ's impact on QTc prolongation is influenced by therapeutic context, coadministered drugs, and patient demographics. The findings underscore the necessity of cautious HCQ use, particularly in acute settings like COVID-19, where monitoring and consideration of drug interactions and patient-specific factors are critical.
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Azitromicina , Tratamiento Farmacológico de COVID-19 , Electrocardiografía , Hidroxicloroquina , Síndrome de QT Prolongado , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Hidroxicloroquina/administración & dosificación , Electrocardiografía/efectos de los fármacos , Femenino , Masculino , Persona de Mediana Edad , Azitromicina/uso terapéutico , Azitromicina/efectos adversos , Azitromicina/administración & dosificación , Síndrome de QT Prolongado/inducido químicamente , Anciano , Síndrome de Sjögren/tratamiento farmacológico , Quimioterapia Combinada , Levofloxacino/uso terapéutico , Levofloxacino/administración & dosificación , Levofloxacino/efectos adversos , Adulto , SARS-CoV-2 , COVID-19RESUMEN
BACKGROUND: Sjögren's disease is a chronic autoimmune disease with an unmet need for targeted therapies. The aim of the TWINSS study is to evaluate the safety and efficacy of iscalimab, a monoclonal antibody against CD40, in patients with active Sjögren's disease. METHODS: This randomised, double-blind, placebo-controlled, phase 2b study, conducted at 71 sites in 23 countries, enrolled patients aged 18 years or older fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology (EULAR) 2016 criteria. In the dose-ranging cohort 1, patients with a EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score of 5 or higher and a EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score of 5 or higher were randomly assigned (1:1:1:1) to subcutaneous iscalimab 150 mg, 300 mg, 600 mg, or placebo. In the proof-of-concept cohort 2, patients with an ESSDAI score of less than 5, ESSPRI (dryness or fatigue) score of 5 or higher, and Impact of Dry Eye on Everyday Life score of 30 or higher were randomly assigned (1:1) to iscalimab 600 mg or placebo. The sponsor, investigator, site personnel, and patients were masked to the treatment assignment. The primary objectives were to demonstrate a dose-response relationship of iscalimab based on the change in ESSDAI from baseline to week 24 in cohort 1 by Multiple Comparison Procedure-Modelling (MCP-Mod), and to assess the effect of iscalimab 600 mg on ESSPRI at week 24 in cohort 2. All the efficacy analyses included all patients who were randomly assigned, and safety analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT03905525), and is complete. FINDINGS: Between Oct 1, 2019, and Feb 28, 2022, 460 patients were screened; 173 patients were assigned to cohort 1 (44 to iscalimab 150 mg, 43 to 300 mg, 43 to 600 mg, and 43 to placebo) and 100 to cohort 2 (50 to each group). In cohort 1, the MCP step showed a significant dose-response relationship for placebo-adjusted ESSDAI change from baseline in one of four models (Linlog model, one-sided p=0·0041). ESSDAI decreased from baseline to week 24 with all three doses of iscalimab; 150 mg and 600 mg doses showed statistically significant improvement (placebo-adjusted least squares [LS] mean difference -3·0 [95% CI -4·9 to -1·1]; p=0·0025 for 150 mg and -2·9 [-4·9 to -1·0]; p=0·0037 for 600 mg). In cohort 2, ESSPRI showed a trend towards improvement with iscalimab 600 mg (placebo-adjusted LS mean change from baseline -0·57 points [95% CI -1·30 to 0·15]; p=0·12). Serious adverse events were reported in nine patients in cohort 1 (one [2%] of 43 in the placebo group, one [2%] of 44 in the iscalimab 150 mg group, three [7%] of 42 in the 300 mg group, four [9%] of 44 in the 600 mg group) and four patients in cohort 2 (two [4%] of 50 in each group). No deaths occurred over the 24-week period. INTERPRETATION: The study met the primary objective of demonstrating a significant dose-response relationship with iscalimab in terms of disease activity at week 24. Iscalimab was well tolerated and showed initial clinical benefit over placebo in two distinct populations of patients with Sjögren's disease, to be confirmed in larger trials. FUNDING: Novartis Pharma.
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Relación Dosis-Respuesta a Droga , Síndrome de Sjögren , Humanos , Método Doble Ciego , Femenino , Masculino , Persona de Mediana Edad , Síndrome de Sjögren/tratamiento farmacológico , Inyecciones Subcutáneas , Adulto , Resultado del Tratamiento , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anciano , Índice de Severidad de la Enfermedad , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéuticoRESUMEN
BACKGROUND: Motor neuron disease (MND) is a chronic and progressive neurodegenerative disorder with an unknown cause. The development of amyotrophic lateral sclerosis (ALS) is believed to be linked to an immune response. Monocytes/macrophages and T cells are key players in the disease's advancement. Monitoring levels of cytokines in the blood can help forecast patient outcomes, while immunotherapy shows promise in alleviating symptoms for certain individuals. CASE PRESENTATION: A 56-year-old male patient was admitted to the hospital due to progressive limb weakness persisting for eight months. The neurological examination revealed impairments in both upper and lower motor neurons, as well as sensory anomalies, without corresponding signs. Electrophysiological examination results indicated extensive neuronal damage and multiple peripheral nerve impairments, thereby the diagnosis was ALS. One month ago, the patient began experiencing symptoms of dry mouth and a bitter taste. Following tests for rheumatic immune-related antibodies and a lip gland biopsy, a diagnosis of Sjögren's syndrome (SS) was proposed. Despite treatment with medications such as hormones (methylprednisolone), immunosuppressants (hydroxychloroquine sulfate), and riluzole, the symptoms did not significantly improve, but also did not worsen. CONCLUSION: It is recommended to include screening for SS in the standard assessment of ALS. Furthermore, research should focus on understanding the immune mechanisms involved in ALS, providing new insights for the diagnosis and treatment of ALS in conjunction with SS.
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Esclerosis Amiotrófica Lateral , Síndrome de Sjögren , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Amiotrófica Lateral/complicaciones , Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/patología , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/tratamiento farmacológico , Síndrome de Sjögren/patologíaRESUMEN
Yellow nail syndrome (YNS) is a rare, acquired condition, characterised by at least two of the three clinical criteria: nail changes, respiratory tract disease and lymphoedema. Currently, the aetiology of YNS remains unknown; however, it is believed to be caused by impaired lymphatic drainage. Currently, there remain no definitive treatment options available and no prospective trials evaluating this. Management includes supportive care and symptomatic treatment. The presence of YNS has been described alongside various conditions, including autoimmune diseases, malignancies and drug exposures. To strengthen the literature on this topic, we present the case of a female patient with a history of anti-SSA and anti-SSB positive primary Sjögren's syndrome, who developed YNS in the immediate postpartum period.
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Síndrome de Sjögren , Síndrome de la Uña Amarilla , Humanos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/tratamiento farmacológico , Síndrome de Sjögren/diagnóstico , Femenino , Síndrome de la Uña Amarilla/diagnóstico , Adulto , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunologíaRESUMEN
Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase, plays a remarkable role in the transmission and amplification of extracellular signals to intracellular signaling pathways. Various types of cells use the BTK pathway to communicate, including hematopoietic cells particularly B cells and T cells. The BTK pathway plays a role in controlling the proliferation, survival, and functions of B cells as well as other myeloid cells. First, second, and third-generation BTK inhibitors are currently being evaluated for the treatment of immune-mediated diseases in addition to B cell malignancies. In this article, the available evidence on the action mechanisms of BTK inhibitors is reviewed. Then, the most recent data obtained from preclinical studies and ongoing clinical trials for the treatment of autoimmune diseases, such as pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, systemic lupus erythematosus, Sjögren's disease, rheumatoid arthritis, systemic sclerosis, multiple sclerosis, myasthenia gravis, and inflammatory diseases such as psoriasis, chronic spontaneous urticaria, atopic dermatitis, and asthma are discussed. In addition, adverse effects and complications associated with BTK inhibitors as well as factors predisposing patients to BTK inhibitors complications are discussed.
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Agammaglobulinemia Tirosina Quinasa , Enfermedades Autoinmunes , Pénfigo , Inhibidores de Proteínas Quinasas , Transducción de Señal , Humanos , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Enfermedades Autoinmunes/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pénfigo/tratamiento farmacológico , Pénfigo/inmunología , Pirimidinas/uso terapéutico , Piperidinas/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Miastenia Gravis/tratamiento farmacológico , Esclerosis Múltiple/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirazoles/farmacología , Nitrilos/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Adenina/análogos & derivados , Adenina/uso terapéutico , Asma/tratamiento farmacológico , Linfocitos B/inmunología , Síndrome de Sjögren/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Esclerodermia Sistémica/tratamiento farmacológico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Benzamidas , Imidazoles , PirazinasRESUMEN
Purpose: CD25KO mice are a model of Sjögren disease (SjD) driven by autoreactive T cells. Cathepsin S (CTSS) is a protease crucial for major histocompatibility complex class II presentation that primes T cells. We investigated if a diet containing CTSS inhibitor would improve autoimmune signs in CD25KO mice. Methods: Four-week female CD25KO mice were randomly chosen to receive chow containing a CTSS inhibitor (R05461111, 262.5 mg/kg chow) or standard chow for 4 weeks. Cornea sensitivity was measured. Inflammatory score was assessed in lacrimal gland (LG) histologic sections. Flow cytometry of LG and ocular draining lymph nodes (dLNs) investigated expression of Th1 and Th17 cells. Expression of inflammatory, T- and B-cell, and apoptotic markers in the LG were assessed with quantitative PCR. The life span of mice receiving CTSS inhibitor or standard chow was compared. CD4+ T cells from both groups were isolated from spleens and adoptively transferred into RAG1KO female recipients. Results: Mice receiving CTSS inhibitor had better cornea sensitivity and improved LG inflammatory scores. There was a significant decrease in the frequency of CD4+ immune cells and a significant increase in the frequency of CD8+ immune cells in the dLNs of CTSS inhibitor mice. There was a significant decrease in Th1 and Th17 cells in CTSS inhibitor mice in both LGs and dLNs. Ifng, Ciita, and Casp8 mRNA in CTSS inhibitor mice decreased. Mice that received the CTSS inhibitor lived 30% longer. Adoptive transfer recipients with CTSS inhibitor-treated CD4+ T cells had improved cornea sensitivity and lower inflammation scores. Conclusions: Inhibiting CTSS could be a potential venue for the treatment of SjD in the eye and LG.
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Catepsinas , Modelos Animales de Enfermedad , Citometría de Flujo , Aparato Lagrimal , Ratones Noqueados , Síndrome de Sjögren , Animales , Ratones , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/tratamiento farmacológico , Femenino , Catepsinas/antagonistas & inhibidores , Catepsinas/metabolismo , Catepsinas/genética , Aparato Lagrimal/patología , Aparato Lagrimal/metabolismo , Ratones Endogámicos C57BL , Traslado Adoptivo , Células Th17/inmunología , Reacción en Cadena en Tiempo Real de la Polimerasa , Células TH1/inmunología , Subunidad alfa del Receptor de Interleucina-2RESUMEN
The present study aimed at investigating whether the hydroxychloroquine (HCQ) treatment would impact the neutralizing antibody production, viremia levels and the kinetics of serum soluble mediators upon planned 17DD-Yellow Fever (YF) primovaccination (Bio-Manguinhos-FIOCRUZ) of primary Sjögren's syndrome (pSS). A total of 34 pSS patients and 23 healthy controls (HC) were enrolled. The pSS group was further categorized according to the use of HCQ (HCQ and Non-HCQ). The YF-plaque reduction neutralization test (PRNT ≥1:50), YF viremia (RNAnemia) and serum biomarkers analyses were performed at baseline and subsequent time-points (Day0/Day3-4/Day5-6/Day7/Day14-D28). The pSS group showed PRNT titers and seropositivity rates similar to those observed for HC (GeoMean = 238 vs 440, p = .11; 82% vs 96%, p = .13). However, the HCQ subgroup exhibited lower seroconversion rates as compared to HC (GeoMean = 161 vs 440, p = .04; 69% vs 96%, p = .02) and Non-HQC (GeoMean = 161 vs 337, p = .582; 69% vs 94%, p = .049). No differences in YF viremia were observed amongst subgroups. Serum biomarkers analyses demonstrated that HCQ subgroup exhibited increased levels of CCL2, CXL10, IL-6, IFN-γ, IL1-Ra, IL-9, IL-10, and IL-2 at baseline and displayed a consistent increase of several biomarkers along the kinetics timeline up to D14-28. These results indicated that HCQ subgroup exhibited a deficiency in assembling YF-specific immune response elicited by 17DD-YF primovaccination as compared to Non-HCQ subgroup. Our findings suggested that hydroxychloroquine is associated with a decrease in the humoral immune response after 17DD-YF primovaccination.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Hidroxicloroquina , Seroconversión , Síndrome de Sjögren , Fiebre Amarilla , Humanos , Hidroxicloroquina/uso terapéutico , Síndrome de Sjögren/tratamiento farmacológico , Síndrome de Sjögren/inmunología , Femenino , Persona de Mediana Edad , Masculino , Adulto , Fiebre Amarilla/inmunología , Fiebre Amarilla/prevención & control , Anticuerpos Antivirales/sangre , Anticuerpos Neutralizantes/sangre , Vacuna contra la Fiebre Amarilla/inmunología , Anciano , Viremia/tratamiento farmacológico , Viremia/inmunología , Virus de la Fiebre Amarilla/inmunología , Citocinas/sangre , Biomarcadores/sangreRESUMEN
BACKGROUND: This study explored similarities and differences among Chinese patients and rheumatologists in their attitudes towards and perceptions of traditional Chinese medicine (TCM) for Sjögren's syndrome (SS), including analyzing factors that influenced their decision making. METHODS: An anonymous questionnaire was used to conduct a multicenter survey among patients with SS at three tertiary care medical centers in Beijing and among rheumatology clinicians at several hospitals across China. Results were analyzed using descriptive statistics. RESULTS: There were 942 valid questionnaires from patients from 31 provinces and cities in China, with a male-to-female ratio of approximately 1:14, a mean age of 48.81 years, and a median disease duration of 7 (4, 10) years. There were 320 valid questionnaires from rheumatologists, covering 30 provinces and cities in China, with a male-to-female ratio of approximately 0.87:1, a mean age of 48 years, and a median work duration of 10.5 (6, 15) years. The rheumatologists treated a median of 15 (11, 50) SS cases per month, and the median proportion of SS to all rheumatic diseases was 6.66% (6-10%). Many patients believed TCM could cure the root of the disease, and the most expected TCM therapies were TCM patent prescriptions and medicinal teas. Conversely, rheumatologists placed high value on the efficacy of TCM, and most commonly prescribed Chinese herbal decoctions. Most doctor-patient groups were positive about TCM treatment, citing the low side effects as the major advantage. Regression analysis showed that for patients over 40 years old with a course of disease > 4 years, the probability of using TCM has increased by 1-6 times; the probability of recommending TCM in clinical work of doctors who have worked for more than 15 years, TCM and integrated traditional Chinese and western medicine has increased 1-2 times. CONCLUSIONS: TCM has become widely accepted and earned attention from doctor-patient groups, especially among older patients and experienced rheumatologists. However, negative prejudices and absence of accurate information about TCM treatments and SS itself require improvement. The contradiction between TCM dosage form and efficacy is a major problem, and patient demand for convenient and efficient TCM patent preparations suggests future work should focus on developing TCM patent preparations with clear compositions and mechanisms.
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Medicina Tradicional China , Reumatólogos , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , China , Encuestas y Cuestionarios , Adulto , Reumatólogos/psicología , Conocimientos, Actitudes y Práctica en Salud , Actitud del Personal de SaludRESUMEN
ABSTRACT: A 65-year-old woman presented with unexplained weight loss, recurrent fever, and a dermatosis with painful nodules on the extremities. Biopsies showed focal lobular panniculitis with neutrophilic microgranulomas. Comprehensive investigations ruled out infection and hematologic and solid organ neoplasms. Laboratory results showed anti-Ro/SSA and anti-La/SSB antibody positivity, and elevated inflammatory markers. Dry mouth and eye were confirmed. The diagnosis of Sjögren syndrome with cutaneous panniculitis was established. Prednisone treatment with 30 mg/d resulted in remission of fever and pain improvement. This case emphasizes Sjögren syndrome as an autoimmune disease with multiple cutaneous manifestations and highlights its association with granulomatous panniculitis.
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Paniculitis , Síndrome de Sjögren , Humanos , Femenino , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/tratamiento farmacológico , Anciano , Paniculitis/patología , Paniculitis/etiología , Prednisona/uso terapéutico , Granuloma/patología , Resultado del Tratamiento , BiopsiaRESUMEN
Background: Targeted therapy for Sjögren's syndrome (SS) has become an important focus for clinicians. Multi-omics-wide Mendelian randomization (MR) analyses have provided new ideas for identifying potential drug targets. Methods: We conducted summary-data-based Mendelian randomization (SMR) analysis to evaluate therapeutic targets associated with SS by integrating DNA methylation, gene expression and protein quantitative trait loci (mQTL, eQTL, and pQTL, respectively). Genetic associations with SS were derived from the FinnGen study (discovery) and the GWAS catalog (replication). Colocalization analyses were employed to determine whether two potentially relevant phenotypes share the same genetic factors in a given region. Moreover, to delve deeper into potential regulation among DNA methylation, gene expression, and protein abundance, we conducted MR analysis to explore the causal relationship between candidate gene methylation and expression, as well as between gene expression and protein abundance. Drug prediction and molecular docking were further employed to validate the pharmacological activity of the candidate drug targets. Results: Upon integrating the multi-omics data, we identified three genes associated with SS risk: TNFAIP3, BTN3A1, and PLAU. The methylation of cg22068371 in BTN3A1 was positively associated with protein levels, consistent with the negative effect of cg22068371 methylation on the risk of SS. Additionally, positive correlations were observed between the gene methylation of PLAU (cg04939496) and expression, as well as between expression and protein levels. This consistency elucidates the promotional effects of PLAU on SS risk at the DNA methylation, gene expression, and protein levels. At the protein level, genetically predicted TNFAIP3 (OR 2.47, 95% CI 1.56-3.92) was positively associated with SS risk, while BTN3A1 (OR 2.96E-03, 95% CI 2.63E-04-3.33E-02) was negatively associated with SS risk. Molecular docking showed stable binding for candidate drugs and target proteins. Conclusion: Our study reveals promising therapeutic targets for the treatment of SS, providing valuable insights into targeted therapy for SS. However, further validation through future experiments is warranted.
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Metilación de ADN , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Simulación del Acoplamiento Molecular , Sitios de Carácter Cuantitativo , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/genética , Síndrome de Sjögren/tratamiento farmacológico , Síndrome de Sjögren/metabolismo , Metilación de ADN/efectos de los fármacos , Predisposición Genética a la Enfermedad , Terapia Molecular Dirigida , Polimorfismo de Nucleótido Simple , MultiómicaRESUMEN
OBJECTIVE: This study aimed to evaluate the efficacy and safety of total glucosides of paeony (TGP) in patients with primary Sjögren's syndrome (pSS). PATIENTS AND METHODS: This study included 236 patients with pSS, including 118 TGP users and 118 non-users. Propensity score matching and Binary logistic regression analyses were used to minimize confounding factors and determine the association between TGP treatment and clinical variables. RESULTS: The baseline indexes of TGP users and non-users were basically the same. The median time of follow-up in the two groups was also similar (p < 0.05). Compared with non-users, TGP users showed higher rates of improvement in dry mouth and eyes and musculoskeletal involvement, as well as more significant reductions in serum alanine aminotransferase (ALT) and direct bilirubin (DBIL) levels after treatment. Logistic regression confirmed that the use of TGP was negatively correlated with the increase of ALT and DBIL in pSS patients, and the reduction in these variables was more pronounced after 2 years of treatment. The incidence of adverse reactions in the TGP users was 11.9%, which was compatible with those in non-users. CONCLUSIONS: TGP is often a safe option for treating pSS patients with musculoskeletal features and abnormal ALT levels. Besides, it can help improve dry mouth and dry eyes and decrease DBIL levels.
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Glucósidos , Paeonia , Puntaje de Propensión , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/tratamiento farmacológico , Paeonia/química , Glucósidos/uso terapéutico , Glucósidos/efectos adversos , Persona de Mediana Edad , Femenino , Masculino , Resultado del Tratamiento , Adulto , Extractos Vegetales/uso terapéutico , Extractos Vegetales/efectos adversos , AncianoRESUMEN
BACKGROUND: Autoimmune rheumatic diseases have distinct pathogenic mechanisms and are causes of disability and increased mortality worldwide. In this study, we aimed to examine annual trends in pain management modalities among patients with autoimmune rheumatic diseases. METHODS: We identified newly diagnosed patients with ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, or systemic lupus erythematosus (SLE) in the Merative Marketscan Research Databases from 2007 to 2021. The database includes deidentified inpatient and outpatient health encounters with employment-sponsored health insurance claims in the USA. We found minimal occurrences of multiple overlapping conditions and included only the initial recorded diagnosis for each patient. We determined the annual incidence of patients treated with opioids, anticonvulsants, antidepressants, skeletal muscle relaxants, non-steroidal anti-inflammatory drugs (NSAIDs), topical analgesics, and physical therapy in the year following diagnosis. Logistic regression was used to estimate the association between calendar year and outcomes, adjusted for age, sex, and region. FINDINGS: We included 141 962 patients: 10 927 with ankylosing spondylitis, 21 438 with psoriatic arthritis, 71 393 with rheumatoid arthritis, 16 718 with Sjögren's syndrome, 18 018 with SLE, and 3468 with systemic sclerosis. 107 475 (75·7%) were women and 34 487 (24·3%) were men. Overall, the incidence of opioid use increased annually until 2014 by 4% (adjusted odds ratio [aOR] 1·04 [95% CI 1·03-1·04]) and decreased annually by 15% after 2014 (0·85 [0·84-0·86]). The incidence of physical therapy use increased annually by 5% until 2014 (aOR 1·05 [95% CI 1·04-1·06]), with a slight decrease annually by 1% after 2014 (0·99 [0·98-1·00]). The incidence of anticonvulsant use increased annually by 7% until 2014 (aOR 1·07 [95% CI 1·07-1·08]) and did not significantly change after 2014 (1·00 [0·99-1·00]). Before 2014, the incidence of NSAIDs use increased by 2% annually (aOR 1·02 [95% CI 1·02-1·03]); however, after 2014, the incidence decreased annually by 5% (0·95 [0·95-0·96]). These trends did not differ by sex except for NSAID use before 2014 (pinteraction=0·02) and topical analgesic use after 2014 (pinteraction=0·0100). INTERPRETATION: Since 2014, the use of non-opioid pain management modalities has increased or stabilised, whereas opioid and NSAID use has declined. Future studies are needed to evaluate the effectiveness of these changes, and the effects they have had on outcomes such as quality of life, disability, and function. FUNDING: National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Asunto(s)
Enfermedades Autoinmunes , Manejo del Dolor , Enfermedades Reumáticas , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estados Unidos/epidemiología , Enfermedades Reumáticas/epidemiología , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/terapia , Manejo del Dolor/métodos , Adulto , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/terapia , Anciano , Adulto Joven , Antiinflamatorios no Esteroideos/uso terapéutico , Adolescente , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Analgésicos Opioides/uso terapéutico , Síndrome de Sjögren/epidemiología , Síndrome de Sjögren/tratamiento farmacológico , Síndrome de Sjögren/terapia , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/epidemiología , Analgésicos/uso terapéuticoRESUMEN
Sjögren's disease (SjD) is a chronic, systemic autoimmune disease with no approved disease-modifying therapies. Dazodalibep (DAZ), a novel nonantibody fusion protein, is a CD40 ligand antagonist that blocks costimulatory signals between T and B cells and antigen-presenting cells, and therefore may suppress the wide spectrum of cellular and humoral responses that drive autoimmunity in SjD. This study was a phase 2, randomized, double-blinded, placebo (PBO)-controlled trial of DAZ with a crossover stage in two distinct populations of participants with SjD. Population 1 had moderate-to-severe systemic disease activity and population 2 had an unacceptable symptom burden and limited systemic organ involvement. All participants had a diagnosis of SjD, with 21.6% and 10.1% having an associated connective tissue disease (rheumatoid arthritis or systemic lupus erythematosus) in populations 1 and 2, respectively. The remaining participants would be considered as having primary Sjögren's syndrome. The primary endpoint for population 1 (n = 74) was the change from baseline in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index at day 169. The primary endpoint for population 2 (n = 109) was the change from baseline in the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index at day 169. The primary endpoints (least squares mean ± standard error) were achieved with statistical significance for both population 1 (DAZ, -6.3 ± 0.6; PBO, -4.1 ± 0.6; P = 0.0167) and population 2 (DAZ, -1.8 ± 0.2; PBO, -0.5 ± 0.2; P = 0.0002). DAZ was generally safe and well tolerated. Among the most frequently reported adverse events were COVID-19, diarrhea, headache, nasopharyngitis, upper respiratory tract infection, arthralgia, constipation and urinary tract infection. In summary, DAZ appears to be a potential new therapy for SjD and its efficacy implies an important role for the CD40/CD40 ligand pathway in its pathogenesis. ClinicalTrials.gov identifier: NCT04129164 .
Asunto(s)
Ligando de CD40 , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/tratamiento farmacológico , Ligando de CD40/antagonistas & inhibidores , Ligando de CD40/inmunología , Método Doble Ciego , Femenino , Persona de Mediana Edad , Masculino , Adulto , Anciano , Resultado del TratamientoRESUMEN
Sjögren's syndrome (SS) is an autoimmune disease in which the salivary glands (SGs) and the lacrimal glands (LGs) are affected by lymphocytic infiltration and inflammation. It has been reported that interferon-α (IFN-α) released by plasmacytoid dendritic cells (pDCs) contribute to the pathology of SS, and ART has been shown to effectively ameliorates SS. Despite the current research endeavors, the mechanism of how ART works in the treatment of SS remains to be fully elucidated. Whether ART can treat SS by inhibiting IFN-α remains unclear. This hypothesis was tested both in vivo and in vitro settings during the study. The SS model mice, which were treated with ART, showed amelioration in symptoms related to dryness. RNA-seq analysis revealed strong anti-IFN-α signaling response upon ART treatment. Additional in vitro studies provided further confirmation that the application of ART inhibits the MyD88 protein expression and the nuclear translocation of IRF7. This suggests that the intervention of ART in the TLR-MyD88-IRF7 pathway plays a role in the therapeutic approach for SS. In summary, this study highlighted the therapeutic potential of ART in SS and ART inhibited the IFN-α signaling in pDCs via the TLR-MyD88-IRF7 pathway.
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Artesunato , Células Dendríticas , Factor 7 Regulador del Interferón , Interferón-alfa , Ratones Endogámicos C57BL , Factor 88 de Diferenciación Mieloide , Transducción de Señal , Síndrome de Sjögren , Animales , Síndrome de Sjögren/tratamiento farmacológico , Síndrome de Sjögren/metabolismo , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Interferón-alfa/metabolismo , Interferón-alfa/farmacología , Transducción de Señal/efectos de los fármacos , Factor 7 Regulador del Interferón/metabolismo , Ratones , Artesunato/farmacología , Artesunato/uso terapéutico , Receptores Toll-Like/metabolismo , Femenino , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Primary Sjögren's Syndrome (pSS) is a systemic chronic autoimmune disorder that contributes to dry mouth (xerostomia) and eyes (xerophthalmia). It mainly affects females between 40 and 60 years old. So far, there is no treatment to cure SS; however, there is a list of medications that can ameliorate the symptoms. In addition, there has been no single test until now to detect pSS, but clinical and immunological investigations are applied as diagnostic tools. Therefore, this study aimed to explore the characteristics of pSS in Saudi patients based on the onset of the disease through laboratory findings and pharmaceutical management. METHODOLOGY: This retrospective study examined diagnosed patients with pSS between 2018 and 2023 from the National Guard Hospital, Saudi Arabia. Data of pSS patients was categorized into two groups: early (under 40 years old) and late-onset (40 years old and above). Data on demographic information, mortality rate, and blood tests such as complete blood count (CBC), creatinine, erythrocyte sedimentation rate (ESR), and vitamin levels, in addition to prescribed medications, were collected from the patient's medical record. Chi-square and t-tests were mainly used, and statistical significance was determined at a P-value less than 0.05. RESULTS: A total of 453 patients were included in the study, where the early-onset group comprised 136 and the late-onset group comprised 317 patients. The mean age of the early and late onset was 34.2 and 60.4, respectively. ESR was significantly higher in the early (46.3 mm/hr) and late-onset (49.8 mm/hr). The most common medication used by all pSS patients was hydroxychloroquine. However, artificial tears were mainly observed in the late-onset group. Other medications, such as pilocarpine, methotrexate, and azathioprine, were prescribed to pSS patients to a lesser extent. CONCLUSION: This study suggests that the onset of pSS could occur even before the age of 40 among Saudi citizens. Notably, elevated ESR levels appeared to be a feature of pSS, which was consistent with other previous findings. The variability of some medications between early-onset and late-onset pSS may indicate disease progression. However, further investigations are required to confirm this observation.