RESUMEN
Objective: To examine lymphoma subtypes, clinical characteristics, and gender differences in patients with primary Sjögren's syndrome (pSS) and lymphoma in a population-based setting.Method: Patients with Sjögren's syndrome and lymphoma diagnoses were identified by linkage of the Swedish Patient Register 1964-2007 with the Cancer Register 1990-2007. Clinical data were collected from medical records and lymphoma tissues were re-examined. The lymphoma subtype distribution was compared with the Swedish Lymphoma Register.Results: We identified 105 pSS patients with lymphoma. Diffuse large B-cell lymphoma (DLBCL) (32%) and marginal zone lymphoma [MZL including mucosa-associated lymphoid tissue (MALT) lymphoma] (31%) were the most common lymphoma subtypes. The proportion of DLBCL was not increased compared to the general population reference (32%, p = 1), in contrast to MZL (general population 5%, p < 0.0001). Compared to DLBCL, MALT lymphoma was diagnosed at a younger age (55 vs 67 years, p = 0.0001), and earlier after patient-reported sicca onset (7 vs 18 years, p = 0.0001) and pSS diagnosis (2 vs 9 years, p = 0.0005). Sixteen of the pSS-lymphoma cases were men (15%), twice the proportion in general pSS populations. Compared to women, men had a shorter median time from pSS diagnosis to lymphoma diagnosis (1 vs 8 years, p = 0.0003) and more often had lymphoma in the salivary glands (56% vs 29%, p = 0.04).Conclusion: DLBCL and MZL are common in pSS patients, but only MZL/MALT lymphoma occurs at an increased relative frequency in pSS compared to the general population. The study supports increased awareness of signs of lymphoma in men in the first years after pSS diagnosis.
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Linfoma de Células B de la Zona Marginal/epidemiología , Linfoma de Células B Grandes Difuso/epidemiología , Neoplasias de las Glándulas Salivales/epidemiología , Síndrome de Sjögren/epidemiología , Adolescente , Adulto , Distribución por Edad , Edad de Inicio , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Infecciones por Virus de Epstein-Barr/epidemiología , Femenino , Humanos , Linfoma/epidemiología , Linfoma Folicular/epidemiología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/epidemiología , Plasmacitoma/epidemiología , Distribución por Sexo , Síndrome de Sjögren/diagnóstico , Suecia/epidemiología , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: To assess the risk of incident cardiovascular disease in patients with primary Sjögren's syndrome, overall and stratified by Ro/SSA and La/SSB autoantibody status. METHODS: A cohort of patients with primary Sjögren's syndrome in Sweden (n = 960) and matched controls from the general population (n = 9035) were included, and data extracted from the National Patient Register to identify events of myocardial infarction, cerebral infarction and venous thromboembolism. Hazard ratios were estimated using cox proportional hazard regressions. RESULTS: During a median follow-up of 9.5 years, the overall hazard ratio (HR) was 1.6 (95% CI 1.2-2.1) for myocardial infarction, 1.2 (95% CI 0.9-1.7) for cerebral infarction and 2.1 (95% CI 1.6-2.9) for venous thromboembolism. Patients positive for both Ro/SSA and La/SSB autoantibodies had a substantially higher risk of cerebral infarction (HR 1.7, 95% CI 1.0-2.9) and venous thromboembolism (HR 3.1, 95% CI 1.9-4.8) than the general population. These risks were not significantly increased in Ro/SSA- and La/SSB-negative patients. Among autoantibody-positive patients, the highest HR of cerebral infarction was seen after ≥10 years disease duration (HR 2.8, 95% CI 1.4-5.4), while the HR for venous thromboembolism was highest 0-5 years after disease diagnosis (HR 4.7, 95% CI 2.3-9.3) and remained high throughout disease duration. CONCLUSIONS: Primary Sjögren's syndrome is associated with a markedly increased risk of cardiovascular disease and the presence of Ro/SSA and La/SSB autoantibodies identify the subgroup of patients carrying the highest risk. These findings suggest that monitoring and prevention of cardiovascular disease in this patient group should be considered.
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Anticuerpos Antinucleares/sangre , Infarto Cerebral/etiología , Infarto del Miocardio/etiología , Síndrome de Sjögren/complicaciones , Tromboembolia Venosa/etiología , Biomarcadores/sangre , Estudios de Casos y Controles , Infarto Cerebral/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/inmunología , Factores de Riesgo , Síndrome de Sjögren/inmunología , Suecia , Tromboembolia Venosa/inmunologíaRESUMEN
OBJECTIVE: In the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome (pSS), pre-existing lymphoma is not an exclusion criterion for pSS diagnosis, as in earlier criteria. We aimed to explore whether there are differences between pSS patients with and without pre-existing lymphoma at pSS diagnosis. METHOD: Patients with ICD-7-10 codes for Sjögren's syndrome (SS) and a diagnosis of malignant lymphoma before or after SS diagnosis were identified by linking the Swedish Patient Register 1964-2007 with the Cancer Register 1990-2007 (n = 224). Clinical data were collected from medical records. Lymphoma diagnoses were evaluated by tissue review. Characteristics of pSS patients with and without pre-existing lymphoma were compared. RESULTS: We identified 107 patients with pSS as the reason for an SS diagnosis code and a verified lymphoma. Of these, 18 (17%) had a pre-existing lymphoma at pSS diagnosis, defined as lymphoma diagnosed before or within 6 months of pSS diagnosis. Male gender (39% vs 10%, p = 0.006), enlarged lymph nodes during the pSS disease (61% vs 27%, p = 0.01), mucosa-associated lymphoid tissue (MALT) lymphoma (50% vs 22%, p = 0.02), and salivary gland lymphoma (61% vs 26%, p = 0.006) were more common in patients with a pre-existing lymphoma at pSS diagnosis. Other pSS characteristics were similar. CONCLUSION: In a substantial proportion of patients, particularly in men, pSS remains undiagnosed until after lymphoma diagnosis. The study highlights the importance of pSS investigation in patients with lymphoma, especially MALT lymphoma, in the salivary glands.
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Ganglios Linfáticos/patología , Linfoma , Glándulas Salivales/patología , Síndrome de Sjögren , Adulto , Femenino , Humanos , Clasificación Internacional de Enfermedades , Linfoma/complicaciones , Linfoma/diagnóstico , Linfoma de Células B de la Zona Marginal/epidemiología , Masculino , Persona de Mediana Edad , Factores Sexuales , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/epidemiología , Suecia/epidemiologíaRESUMEN
OBJECTIVES: Heterophilic antibodies, such as rheumatoid factor (RF), are known to interfere with enzyme-linked immunosorbent assays (ELISAs). Treatment of rheumatoid arthritis (RA) with tumour necrosis factor (TNF)-α blockers is well established. The aims of this study were to develop a protocol for blocking the interaction of present heterophilic antibodies and to validate this procedure by evaluating the effect on correlations of cytokine levels to clinical response in RA patients treated with adalimumab. METHOD: Fourteen patients with active RA were evaluated at baseline and 3 months after starting adalimumab treatment. Cytokines were analysed with a commercial 12-plex bead ELISA. To block interference by RF, a commercial blocker (HeteroBlock) was used. To determine the optimal concentration of HeteroBlock, patient sera were analysed with different concentrations of HeteroBlock. Subsequently, baseline and follow-up sera from the 14 patients were analysed and correlated with clinical outcome. RESULTS: Measured cytokine levels were reduced in the majority of samples when adding the blocker. The optimal concentration of HeteroBlock was 1600 µg/mL of serum. Sera with high RF levels were more prone to produce false positive values, although some RF-negative sera also demonstrated evidence of interference. HeteroBlock did not interfere with the analysis. In RA patients treated with adalimumab, changes in interleukin (IL)-6 levels between baseline and follow-up correlated with changes in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in sera with added HeteroBlock. CONCLUSIONS: When analysing sera from patients with RA with multiplex bead ELISA, the assay should be evaluated for interference by heterophilic antibodies, and if present corrected with, for example, HeteroBlock.
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Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Citocinas/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Factor Reumatoide , Adalimumab/uso terapéutico , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/métodosRESUMEN
OBJECTIVES: To study signs of obstructive airway disease (OAD) in patients with primary Sjögren's syndrome (pSS) using the forced oscillation technique (FOT). METHOD: Thirty-seven female pSS patients (median age 64, range 38-77 years) without previous physician-diagnosed OAD, participating in a longitudinal follow-up study of pulmonary function, and 74 female population-based controls (median age 64, range 47-77 years), also without physician-diagnosed OAD, and matched with regard to age, height, weight, and tobacco consumption, were included in the study. The pSS patients and controls were studied by the FOT, evaluating resistance and reactance of the respiratory system. RESULTS: pSS patients had significantly increased resistances at 5-25 Hz, decreased reactance at 10-35 Hz, and an increased resonant frequency (Fres) in comparison with controls. Resistance was correlated negatively and reactance positively to the vital capacity (VC), the forced expiratory volume in 1 s (FEV1), and the diffusing capacity for carbon monoxide (DLCO). Compared with controls, pSS patients with (n = 14) and without OAD (n = 21), as determined by spirometry, had significantly increased resistances at 5-25 Hz and decreased reactances at 10-35 Hz. In never-smoking subjects, identical FOT signs were found. CONCLUSIONS: pSS patients showed FOT signs of obstruction affecting both peripheral and central airways. pSS patients without spirometric signs of OAD and never-smoking pSS patients also showed clear FOT signs of obstruction. FOT therefore seems to be a sensitive method for detecting obstruction in pSS patients.
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Enfermedades Pulmonares Obstructivas/diagnóstico , Pruebas de Función Respiratoria/métodos , Síndrome de Sjögren/diagnóstico , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Enfermedades Pulmonares Obstructivas/fisiopatología , Persona de Mediana Edad , Ventilación Pulmonar/fisiología , Síndrome de Sjögren/fisiopatología , EspirometríaRESUMEN
The genetic background of primary Sjögren's syndrome (pSS) is partly shared with systemic lupus erythematosus (SLE). Immunoglobulin G Fc receptors are important for clearance of immune complexes. Fcγ receptor variants and gene deletion have been found to confer SLE risk. In this study, four Fcγ receptor single-nucleotide polymorphisms (SNPs) and one copy number variation (CNV) were studied. Swedish and Norwegian pSS patients (N=527) and controls (N=528) were genotyped for the Fcγ receptor gene variant FCGR2A H131R (rs1801274) by the Illumina GoldenGate assay. FCGR3A F158V (rs396991) was analysed in 488 patients and 485 controls, FCGR3B rs447536 was analysed in 471 patients and 467 controls, and FCGR3B rs448740 was analysed in 478 cases and 455 controls, using TaqMan SNP genotyping assays. FCGR3B CNV was analysed in 124 patients and 139 controls using a TaqMan copy number assay. None of the SNPs showed any association with pSS. Also, no FCGR3B CNV association was detected. The lack of association of pSS with Fcγ receptor gene variants indicates that defective immune complex clearance may not be as important in pSS pathogenesis as in SLE, and may point to important differences between SLE and pSS.
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Receptores de IgG/genética , Síndrome de Sjögren/genética , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Eliminación de Gen , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Noruega , Polimorfismo de Nucleótido Simple , SueciaRESUMEN
OBJECTIVE: We sought to determine whether the serological response towards lytic cycle antigens of Epstein-Barr virus (EBV) is altered in systemic lupus erythematosus (SLE) patients. METHOD: We used enzyme-linked immunosorbent assay (ELISA) to investigate the prevalence of EBV early antigen diffuse (EBV-EA/D) antibodies in sera from 60 patients with SLE, 40 with scleroderma (SSc), 20 with primary Sjögren's syndrome (pSS), 20 with rheumatoid arthritis (RA), 20 healthy controls, and also subjects with various circulating autoantibodies. Samples from patients were obtained from clinics specialized within the diseases in Denmark and Sweden and samples from healthy controls were obtained from volunteers. RESULTS: A significant elevated titre of immunoglobulin (Ig)A, IgG, and IgM EBV-EA/D antibodies was found in SLE patients compared to healthy controls, a finding not explained by immunosuppressive treatment or disease activity. The largest difference was observed for IgA EBV-EA/D antibodies (p = 0.0013) with a seropositive rate of 58% in SLE patients and 0% in healthy controls. RA and SSc patients and individuals seropositive for anti-Scl-70 were additionally found to have elevated titres of IgA EBV-EA/D antibodies (40%, p = 0.014; 60%, p = 0.015; and 38.5%, p = 0.045, respectively). However, the titres were generally lower than in SLE patients. CONCLUSION: Our findings support an association between EBV and SLE. The elevated titre of EBV-EA/D-directed IgA antibodies found in SLE patients could suggest reactivation of EBV in epithelial cells or reinfection of epithelial cells after reactivation in B cells, indicating lack of control of the latent infection.
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Antígenos Virales/inmunología , Inmunoglobulina A/sangre , Lupus Eritematoso Sistémico/inmunología , Adulto , Anciano , Antígenos Virales/sangre , Femenino , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/virología , Masculino , Persona de Mediana EdadRESUMEN
We performed a candidate gene association study in 540 patients with primary Sjögren's Syndrome (SS) from Sweden (n=344) and Norway (n=196) and 532 controls (n=319 Swedish, n=213 Norwegian). A total of 1139 single-nucleotide polymorphisms (SNPs) in 84 genes were analyzed. In the meta-analysis of the Swedish and Norwegian cohorts, we found high signals for association between primary SS and SNPs in three gene loci, not previously associated with primary SS. These are the early B-cell factor 1 (EBF1) gene, P=9.9 × 10(-5), OR 1.68, the family with sequence similarity 167 member A-B-lymphoid tyrosine kinase (FAM167A-BLK) locus, P=4.7 × 10(-4), OR 1.37 and the tumor necrosis factor superfamily (TNFSF4=Ox40L) gene, P=7.4 × 10(-4), OR 1.34. We also confirmed the association between primary SS and the IRF5/TNPO3 locus and the STAT4 gene. We found no association between the SNPs in these five genes and the presence of anti-SSA/anti-SSB antibodies. EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS.
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Ligando OX40/genética , Proteínas Tirosina Quinasas/genética , Síndrome de Sjögren/genética , Síndrome de Sjögren/inmunología , Transactivadores/genética , Linfocitos B/inmunología , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Humanos , Factores Reguladores del Interferón/genética , Interleucina-6/genética , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Noruega , Polimorfismo de Nucleótido Simple , Factor de Transcripción STAT4/genética , Síndrome de Sjögren/enzimología , SueciaRESUMEN
The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.
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Bloqueo Atrioventricular/epidemiología , Bloqueo Atrioventricular/inmunología , Enfermedades Autoinmunes , Hijo de Padres Discapacitados , Madres , Grupos de Población , Adolescente , Bloqueo Atrioventricular/sangre , Bloqueo Atrioventricular/complicaciones , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Niño , Hijo de Padres Discapacitados/estadística & datos numéricos , Preescolar , Epítopos/inmunología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Madres/estadística & datos numéricos , Grupos de Población/estadística & datos numéricos , Prevalencia , SueciaRESUMEN
Primary Sjögren's syndrome (SS) shares many features with systemic lupus erythematosus (SLE). Here we investigated the association of the three major polymorphisms in IRF5 and STAT4 found to be associated with SLE, in patients from Sweden and Norway with primary SS. These polymorphisms are a 5-bp CGGGG indel in the promoter of IRF5, the single nucleotide polymorphism (SNP) rs10488631 downstream of IRF5 and the STAT4 SNP rs7582694, which tags the major risk haplotype of STAT4. We observed strong signals for association between all three polymorphisms and primary SS, with odds ratios (ORs) >1.4 and P-values <0.01. We also found a strong additive effect of the three risk alleles of IRF5 and STAT4 with an overall significance between the number of risk alleles and primary SS of P=2.5 x 10(-9). The OR for primary SS increased in an additive manner, with an average increase in OR of 1.78. For carriers of two risk alleles, the OR for primary SS is 1.43, whereas carriers of five risk alleles have an OR of 6.78. IRF5 and STAT4 are components of the type I IFN system, and our findings emphasize the importance of this system in the etiopathogenesis of primary SS.
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Alelos , Factores Reguladores del Interferón/genética , Factor de Transcripción STAT4/genética , Síndrome de Sjögren/genética , Anciano , Pueblo Asiatico/genética , Pueblo Asiatico/estadística & datos numéricos , Estudios de Casos y Controles , Estudios de Cohortes , Intervalos de Confianza , Femenino , Frecuencia de los Genes , Haplotipos , Heterocigoto , Humanos , Factores Reguladores del Interferón/inmunología , Modelos Lineales , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Noruega , Oportunidad Relativa , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Probabilidad , Factores de Riesgo , Factor de Transcripción STAT4/inmunología , Síndrome de Sjögren/inmunología , Suecia , Población Blanca/genética , Población Blanca/estadística & datos numéricosRESUMEN
A subgroup of patients suffering from primary Sjögren's syndrome (pSS) display unexplained low levels of complement components C3 and/or C4 which is associated with increased risk of non-Hodgkin's lymphoma. C4b-binding protein (C4BP) is a major fluid-phase complement inhibitor which can influence C4 and C3 levels. Therefore we analysed C4BP levels in the sera of patients with pSS to better understand the disturbances in complement in pSS. Associations with other disease markers were also investigated to define a possible role of C4BP as marker of high-risk disease course. Plasma levels of C4BP were analysed in pSS patients (n=86) and in controls (n=68) by ELISA. C4BP levels from 49 patients were correlated to disease activity markers and autoantibody profiles. We found that total C4BP plasma levels were significantly higher in pSS patients compared with controls. C4BP levels correlated to the acute phase response, to levels of C4 and C3 as well as to the CD4+/CD8+ T-cell ratio. C4BP levels were inversely related to IgG levels, extent of autoantibody production and global disease activity. C3dg levels, a marker of complement activation, displayed a negative correlation to C4 levels but interestingly not to C4BP levels. In conclusion, C4BP levels are increased in patients suffering from pSS proportional to their acute phase response. However, in the most active cases, with the most widespread autoantibody production, C4BP levels were decreased in parallel with levels of C3 and C4 and CD4+ T cells, suggesting that disturbed complement regulation may contribute to pathogenicity in pSS.
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Biomarcadores/sangre , Antígenos de Histocompatibilidad/sangre , Síndrome de Sjögren/sangre , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Complemento C3/análisis , Complemento C3/inmunología , Complemento C4/análisis , Complemento C4/inmunología , Proteína de Unión al Complemento C4b , Ensayo de Inmunoadsorción Enzimática , Femenino , Antígenos de Histocompatibilidad/inmunología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Síndrome de Sjögren/inmunologíaRESUMEN
Coeliac disease (CD) is becoming a model for understanding the pathogenesis of autoimmune disorders. In CD, antibodies against transglutaminase 2 (TG2) and specific residues of gliadins have been identified. A similar situation is seen in rheumatoid arthritis (RA) with both anti-citrullinated protein antibodies (ACPA) and auto-antibodies against the citrullinating enzyme, peptidylarginine deiminase (PAD). Previously, we have suggested that a complex between an enzyme and its modified substrate constitutes the neoantigen in autoimmune diseases. Our hypothesis is challenged by findings in patients of primary Sjögren's syndrome (pSS) who do not express ACPA, but who have been reported to carry anti-PAD. The aims of our investigation were to reproduce the study claiming the presence of anti-PAD in pSS and screen for ACPA and antibodies against TG2 and PAD in pSS (n = 78), multiple sclerosis (MS) (n = 85) and Alzheimer's disease (AD) (n = 79) using ELISA. With blood donors (n = 100) as controls, no increased occurrence of autoantibodies was found among the patient groups tested. Contrary to what has been published previously, patients with pSS do not express anti-PAD. The hypothesis of a complex between an enzyme and its modified substrate constituting the neoantigen in autoimmune diseases is still valid. The prevalence of anti-PAD, anti-TG2 and ACPA is comparatively restricted. PAD and TG2 do not seem to be involved directly in autoimmune mechanisms in pSS, MS or AD.
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Enfermedad de Alzheimer/sangre , Autoanticuerpos/sangre , Enfermedades Autoinmunes/fisiopatología , Citrulina/inmunología , Proteínas de Unión al GTP/inmunología , Hidrolasas/inmunología , Esclerosis Múltiple/sangre , Síndrome de Sjögren/sangre , Transglutaminasas/inmunología , Enfermedades Autoinmunes/sangre , Citrulina/metabolismo , Ensayo de Inmunoadsorción Enzimática , Humanos , Proteína Glutamina Gamma Glutamiltransferasa 2 , Desiminasas de la Arginina Proteica , Proteínas/metabolismoRESUMEN
UNLABELLED: Esophageal involvement is common in systemic sclerosis, and esophageal scintigraphy can be used to detect and follow esophageal dysfunction. This study assesses the value of visual and quantitative analysis of esophageal scintigraphy performed as a multiple swallow test in normals and patients with systemic sclerosis. METHODS: Forty patients with systemic sclerosis and 40 sex- and age-matched healthy subjects (controls) were studied. A multiple swallow technique was used and both quantitative and qualitative analyses were performed. Visual analysis of condensed images was performed independently by two physicians. Each swallow was assigned a score on a scale from 1 to 4. In the quantitative analysis, time-activity curves based on the mean condensed images were used to calculate the following 3 parameters: residual activity 12 or 25 sec after the beginning of the swallow, measured with or without baseline correction, respectively, and time from onset of swallow to 50% of peak activity. RESULTS: Both visual and quantitative analysis showed a highly significant (p < 0.001) difference between the patient group and the control group. Visual analysis was best reflected by the residual activity 25 sec after the beginning of the swallow without correction for background. Receiver operating characteristic curves were used to study the ability to separate the two groups using visual or quantitative analysis. A high rate of positive tests in the patient group was achieved only at the cost of a relatively high rate of positive tests in the control group. CONCLUSION: Our results indicate high variability in esophageal motility in controls. This variability impairs the possibilities of developing a screening test to identify asymptomatic patients early in the disease course.
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Esófago/diagnóstico por imagen , Esclerodermia Sistémica/diagnóstico por imagen , Adulto , Anciano , Deglución , Enfermedades del Esófago/diagnóstico por imagen , Esófago/fisiopatología , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Cintigrafía , Esclerodermia Sistémica/fisiopatologíaRESUMEN
OBJECTIVE: To study the seroprevalence of Helicobacter pylori (H. pylori) infection in patients with primary Sjögren's syndrome (SS), fulfilling the 1993 European classification criteria compared with three different control groups. METHODS: Serological tests investigating the presence of antibodies against H. pylori were performed by Enzyme Immuno Assay (EIA) and confirmed by immunoblot (IB). The samples were tested for antibodies against cytotoxin-associated-protein A (CagA). The three control groups included were: one simultaneously collected age-matched group of orthopaedic outpatients without rheumatological disease, a random primary care patient sample from the same geographic region and a group of age-matched blood donors. RESULTS: 45% of the SS patients (n = 164) were EIA-positive for H. pylori and 30% were positive in the confirming IB assay. 23% had antibodies to the CagA protein. We found a clear and statistically significant increase in seroprevalence with increasing age. These estimates were lower compared to the control group of orthopaedic patients but similar to those in the other two control groups, thus showing the importance of multiple control groups in case control studies. In the group of SS patients there were no significant associations between a positive EIA, IB or CagA for H. pylori and the presence of abnormal serum levels of autoantibodies (ANA, anti-SSA, anti-SSB, rheumatoid factor (RF)) or an abnormal lip biopsy. CONCLUSION: Swedish patients with primary SS do not have higher H. pylori seroprevalence rates than controls. Neither was H. pylori seropositivity associated with the presence of immunological markers of SS such as circulating autoantibodies or a lip biopsy with abnormal focus score.
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Antígenos Bacterianos , Infecciones por Helicobacter/complicaciones , Síndrome de Sjögren/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Bacterianas/sangre , Proteínas Bacterianas/inmunología , Femenino , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Helicobacter pylori/aislamiento & purificación , Humanos , Immunoblotting , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Estudios Seroepidemiológicos , Síndrome de Sjögren/epidemiología , Síndrome de Sjögren/inmunología , Suecia/epidemiologíaRESUMEN
OBJECTIVE: To investigate the effect of a moderate to high intensive exercise program on two primary outcomes (aerobic capacity, fatigue), and three secondary outcomes [anxiety, depression and health-related quality of life (HRQoL)] in women with primary Sjögren's syndrome (primary SS). METHODS: Twenty-one women with primary SS were ranked according to degree of fatigue and allocated to an exercise group (TG; n = 11) or a control group (CG; n = 10). The exercise method was Nordic walking for 45 min three times a week for 12 weeks. Outcome measures assessed at baseline and after 12 weeks were aerobic capacity, fatigue, ratings of perceived exertion (RPE), anxiety, depression and HRQoL. RESULTS: Nine women in the TG and 10 women in the CG completed the study. Analysis showed significant differences between the groups regarding aerobic capacity (P = 0.03), fatigue (P = 0.03), RPE (P = 0.03), and depression (P = 0.02) with the better values for the TG. There were no differences in anxiety or HRQoL. CONCLUSION: Our findings support the use of appropriate aerobic exercise in the treatment of primary SS.
Asunto(s)
Terapia por Ejercicio/métodos , Fatiga/rehabilitación , Consumo de Oxígeno , Síndrome de Sjögren/rehabilitación , Adulto , Anciano , Ansiedad/etiología , Ansiedad/rehabilitación , Depresión/etiología , Depresión/rehabilitación , Femenino , Humanos , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Psicometría , Calidad de Vida , Índice de Severidad de la Enfermedad , Síndrome de Sjögren/fisiopatología , Síndrome de Sjögren/psicología , Resultado del TratamientoRESUMEN
OBJECTIVES: To assess the risk of lymphoproliferative disease or other malignancy (standardised incidence ratios (SIRs)), in patients with primary Sjögren's syndrome according to the American-European Consensus Criteria (AECC), compared with patients with sicca syndrome (non-AECC) and the background population. To identify predictors of malignancy and describe lymphoma types and survival probabilities. METHODS: A linked register study using information from the Malmö Primary SS Register, Swedish Cancer Register, and Cause-of-Death Register for calculation of SIRs was carried out. Detected lymphomas were reclassified according to the WHO classification. Cox regression analysis was used to study the predictive value of clinical, laboratory, and histological findings at the time of diagnosis. RESULTS: 507 patients with a median follow up of 8 years (range 1 month to 19 years) were included. SIRs (95% confidence interval (CI)) for malignancies in total and for non-Hodgkin's lymphomas (NHL) were 1.42 (0.98 to 2.00) and 15.57 (7.77 to 27.85), respectively, in those fulfilling the AECC (n = 286). In non-AECC sicca patients (n = 221) SIR for malignancy of any kind was 0.77 (0.41 to 1.32); no lymphoproliferative neoplasms were detected. Significant predictors of lymphoproliferative disease were purpura/skin vasculitis (hazard ratio (HR) = 4.64, 95% CI 1.13 to 16.45), low complement factor C3 (HR = 6.18, 95% CI 1.57 to 24.22), low C4 (HR = 9.49, 95% CI 1.94 to 46.54), CD4+ T lymphocytopenia (HR = 8.14, 95% CI 2.10 to 31.53), and a low CD4+/CD8+ T cell ratio < or = 0.8 (HR = 10.92, 95% CI 2.80 to 41.83). 7/12 (58%) NHLs were diffuse large B cell lymphomas. CONCLUSION: A 16-fold increased risk for development of NHL was found. CD4+ T lymphocytopenia is an additional strong risk factor for developing lymphoma.
Asunto(s)
Linfoma/complicaciones , Síndrome de Sjögren/complicaciones , Anciano , Femenino , Neoplasias Hematológicas/complicaciones , Humanos , Incidencia , Masculino , Registro Médico Coordinado , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , SueciaRESUMEN
OBJECTIVE: To translate the disease-specific Profile of Fatigue (ProF) into Swedish and to evaluate the reliability and validity of the Swedish version. METHODS: Forward and back translations were performed. Seventy patients with primary Sjögren's syndrome (PSS), 48 control persons, and two rheumatologists participated. Test-retest reliability, internal consistency, content, construct and discriminant validity were investigated. RESULTS: The translation was accepted without modifications. The test-retest reliability varied between moderate and good (weighted Kappa = 0.51-0.63). Internal consistency was high (Cronbach's alpha = 0.97). Construct validity was proved by significant correlations of the questionnaire items with the Visual Analogue Scale (VAS) for fatigue (r(s) = 0.55-0.70), and the Physical Function (PF) (r(s) = -0.20 to -0.41) and Vitality (VT) scales (r(s) = -0.60 to -0.77) of the MOS 36-Item Short-Form Health Survey (SF-36). Content validity was mainly judged as good. A significant difference between the scorings of the patients and the scorings of the control group was seen (mean difference 1.6, p<0.005). CONCLUSION: The Swedish version of the ProF is a relatively reliable and valid instrument for the measurement of fatigue in patients with PSS.
Asunto(s)
Fatiga/diagnóstico , Perfil de Impacto de Enfermedad , Síndrome de Sjögren/diagnóstico , Adulto , Fatiga/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Síndrome de Sjögren/epidemiología , Encuestas y Cuestionarios , Suecia , TraduccionesRESUMEN
A 55-year old woman with a diagnosis of primary Sjögren's Syndrome suddenly developed AV-block III. A diagnostic procedure finally revealed sarcoidosis with multiorgan involvement.
Asunto(s)
Bloqueo Cardíaco/etiología , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico , Síndrome de Sjögren/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana EdadRESUMEN
During the last decades different sets of criteria have been used for defining primary Sjögren's syndrome. Using these criteria prevalence estimates have varied between 0.04%-4.8%. This hundred-fold distribution in estimated frequency is partly due to differences in age groups studied, classification criteria used and methods used for objective evaluation of lachrymal and salivary gland hypofunction. Another problem which makes comparison between studies difficult is that workshop recommendations for the various objective tests are very often not strictly followed. Population based studies tend to identify cases with less severe disease and higher prevalence rates. Furthermore, there seems to be little correlation between dryness symptoms reported by subjects and objective hypofunction of lachrymal and/or salivary glands. Possible explanations to these findings include selection bias towards more severe cases in clinical (university) studies and a low predictive value for some criteria in population studies.