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- Retamozo, S., et al.
(author)
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Influence of the age at diagnosis in the disease expression of primary Sjogren's syndrome : Analysis of 12,753 patients from the Sjogren Big Data Consortium
- 2021
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In: Clinical and Experimental Rheumatology. - : CLINICAL & EXPER RHEUMATOLOGY. - 0392-856X .- 1593-098X. ; 39:6, s. S166-S174
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Journal article (peer-reviewed)abstract
- Objective. To analyse how the main components of the disease phenotype (sicca symptoms, diagnostic tests, immunological markers and systemic disease) can be driven by the age at diagnosis of primary Sjogren's syndrome (pSS).Methods. By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression.Results. There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of <90% in patients diagnosed at the youngest ages and >95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R-2 0.87) and the frequency of abnormal oral tests (adjusted R-2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.18%), and constitutional, cutaneous, and haematological involvements (the frequency decreased by 0.09% for each 1-year increase). In contrast, other domains showed an ascending pattern, especially pulmonary involvement (for each 1-year increase in the age at diagnosis, the frequency of activity increased by 0.22%), and peripheral nerve involvement (the frequency increased by 0.09% for each 1-year increase).Conclusion. The influence of the age at diagnosis on the key phenotypic features of pSS is strong, and should be considered critical not only for designing a personalised diagnostic approach, but also to be carefully considered when analysing the results of diagnostic tests and immunological parameters, and when internal organ involvement is suspected at diagnosis.
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- Brito-Zeron, P., et al.
(author)
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How immunological profile drives clinical phenotype of primary Sjögren's syndrome at diagnosis : analysis of 10,500 patients (Sjögren Big Data Project)
- 2018
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In: Clinical and Experimental Rheumatology. - : CLINICAL & EXPER RHEUMATOLOGY. - 0392-856X .- 1593-098X. ; 36:3, s. S102-S112
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Journal article (peer-reviewed)abstract
- Objective: To evaluate the influence of the main immunological markers on the disease phenotype at diagnosis in a large international cohort of patients with primary Sjogren's syndrome (SjS).Methods: The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014. As a first step, baseline clinical information from leading centres on clinical research in SjS of the 5 continents was collected. The centres shared a harmonised data architecture and conducted cooperative online efforts in order to refine collected data under the coordination of a big data statistical team. Inclusion criteria were the fulfillment of the 2002 classification criteria. Immunological tests were carried out using standard commercial assays.Results: By January 2018, the participant centres had included 10,500 valid patients from 22 countries. The cohort included 9,806 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years, mainly White (78%) and included from European countries (71%). The frequency of positive immunological markers at diagnosis was 79.3% for ANA, 73.2% for anti-Ro, 48.6% for RF, 45.1% for anti-La, 13.4% for low C3 levels, 14.5% for low C4 levels and 7.3% for cryoglobulins. Positive autoantibodies (ANA, Ro, La) correlated with a positive result in salivary gland biopsy, while hypocomplementaemia and especially cryoglobulinaemia correlated with systemic activity (mean ESSDAI score of 17.7 for ctyoglobulins, 11.3 for low C3 and 9.2 for low C4, in comparison with 3.8 for negative markers). The immunological markers with a great number of statistically-significant associations (p<0.001) in the organ-by-organ ESSDAI evaluation were cryoglobulins (9 domains), low C3 (8 domains), anti-La (7 domains) and low C4 (6 domains).Conclusion: We confirm the strong influence of immunological markers on the phenotype of primary SjS at diagnosis in the largest multi-ethnic international cohort ever analysed, with a greater influence for cryoglobulinaemic-related markers in comparison with Ro/La autoantibodies and ANA. Immunological patterns play a central role in the phenotypic expression of the disease already at the time of diagnosis, and may guide physicians to design a specific personalised management during the follow-up of patients with primary SjS.
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- Bertsias, GK, et al.
(author)
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EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs
- 2010
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 69:12, s. 2074-2082
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Journal article (peer-reviewed)abstract
- To develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations.MethodsThe authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design.ResultsSystemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence >5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1–5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fivefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fluid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD.ConclusionsNeuropsychiatric manifestations in SLE patients should be first evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly.
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- Brito-Zeron, P., et al.
(author)
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Exposure to air pollution as an environmental determinant of how Sjögren's disease is expressed at diagnosis
- 2023
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In: Clinical and Experimental Rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 41:12, s. 2448-2457
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Journal article (peer-reviewed)abstract
- ObjectiveTo analyse how the potential exposure to air pollutants can influence the key components at the time of diagnosis of Sjogren's phenotype (epidemiological profile, sicca symptoms, and systemic disease). MethodsFor the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Air pollution indexes per country were defined according to the OECD (1990-2021), including emission data of nitrogen and sulphur oxides (NO/SO), particulate matter (PM2.5 and 1.0), carbon monoxide (CO) and volatile organic compounds (VOC) calculated per unit of GDP, Kg per 1000 USD.ResultsThe results of the chi-square tests of independence for each air pollutant with the frequency of dry eyes at diagnosis showed that, except for one, all variables exhibited p-values <0.0001. The most pronounced disparities emerged in the dry eye prevalence among individuals inhabiting countries with the highest NO/SO exposure, a surge of 4.61 percentage points compared to other countries, followed by CO (3.59 points), non-methane (3.32 points), PM2.5 (3.30 points), and PM1.0 (1.60 points) exposures. Concerning dry mouth, individuals residing in countries with worse NO/SO exposures exhibited a heightened frequency of dry mouth by 2.05 percentage points (p<0.0001), followed by non-methane exposure (1.21 percentage points increase, p=0.007). Individuals inhabiting countries with the worst NO/SO, CO, and PM2.5 pollution levels had a higher mean global ESSDAI score than those in lower-risk nations (all p-values <0.0001). When systemic disease was stratified according to DAS into low, moderate, and high systemic activity levels, a heightened proportion of individuals manifesting moderate/severe systemic activity was observed in countries with worse exposures to NO/SO, CO, and PM2.5 pollutant levels. ConclusionFor the first time, we suggest that pollution levels could influence how SjD appears at diagnosis in a large international cohort of patients. The most notable relationships were found between symptoms (dryness and general body symptoms) and NO/SO, CO, and PM2.5 levels.
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- Bertsias, G., et al.
(author)
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EULAR recommendations for the management of systemic lupus erythematosus. Report of a task force of the EULAR standing committee for international clinical studies including therapeutics
- 2008
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 67:2, s. 195-205
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Research review (peer-reviewed)abstract
- Objective: Systemic lupus erythematosus (SLE) is a complex disease with variable presentations, course and prognosis. We sought to develop evidence-based recommendations addressing the major issues in the management of SLE. Methods: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Key questions for the management of SLE were compiled using the Delphi technique. A systematic search of PubMed and Cochrane Library Reports was performed using McMaster/Hedges clinical queries' strategies for questions related to the diagnosis, prognosis, monitoring and treatment of SLE. For neuropsychiatric, pregnancy and antiphospholipid syndrome questions, the search was conducted using an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence, and agreement on the statements was measured across the 19 specialists. Results: Twelve questions were generated regarding the prognosis, diagnosis, monitoring and treatment of SLE, including neuropsychiatric SLE, pregnancy, the antiphospholipid syndrome and lupus nephritis. The evidence to support each proposition was evaluated and scored. After discussion and votes, the final recommendations were presented using brief statements. The average agreement among experts was 8.8 out of 10. Conclusion: Recommendations for the management of SLE were developed using an evidence-based approach followed by expert consensus with high level of agreement among the experts.
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| 24. |
- Bertsias, G. K., et al.
(author)
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EULAR points to consider for conducting clinical trials in systemic lupus erythematosus: literature based evidence for the selection of endpoints
- 2009
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:4, s. 477-483
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Research review (peer-reviewed)abstract
- Objective: To assess available evidence on the use of end-points ( outcome measures) in clinical trials in systemic lupus erythematosus (SLE), as a part of the development of evidence-based recommendations for points to consider in clinical trials in SLE. Methods: The European League Against Rheumatism (EULAR) Task Force on SLE comprised 19 specialists, a clinical epidemiologist and a research fellow. Key questions addressing the evidence for clinical trial end-points in SLE were compiled using the Delphi technique. A systematic search of the PubMed and Cochrane Library databases was performed using McMaster/Hedges clinical query strategies and an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence and agreement on the statements was measured across the 19 specialists. Results: Eight questions were generated regarding end-points for clinical trials. The evidence to support each proposition was evaluated. The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not been formally validated in clinical trials, although some indirect validation has been undertaken. Conclusion: This systematic literature review forms the evidence base considered in the development of the EULAR recommendations for end-points in clinical trials in SLE.
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| 25. |
- Flores-Chavez, A., et al.
(author)
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Influence of exposure to climate-related hazards in the phenotypic expression of primary Sjögren's syndrome
- 2023
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In: Clinical and Experimental Rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 41:12, s. 2437-2447
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Journal article (peer-reviewed)abstract
- Objective To analyse how the key components at the time of diagnosis of the Sjogren's phenotype (epidemiological profile, sicca symptoms, and systemic disease) can be influenced by the potential exposure to climate-related natural hazards. Methods For the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Climate-related hazards per country were defined according to the OECD and included seven climate-related hazard types: extreme temperature, extreme precipitation, drought, wildfire, wind threats, river flooding, and coastal flooding. Climatic variables were defined as dichotomous variables according to whether each country is ranked among the ten countries with the most significant exposure. Results After applying data-cleaning techniques and excluding people from countries not included in the OECD climate rankings, the database study analysed 16,042 patients from 23 countries. The disease was diagnosed between 1 and 3 years earlier in people living in countries included among the top 10 worst exposed to extreme precipitation, wildfire, wind threats, river flooding, and coastal flooding. A lower frequency of dry eyes was observed in people living in countries exposed to wind threats, river flooding, and coastal flooding, with a level of statistical association being classified as strong (p<0.0001 for the three variables). The frequency of dry mouth was significantly lower in people living in countries exposed to river flooding (p<0.0001) and coastal flooding (p<0.0001). People living in countries included in the worse climate scenarios for extreme temperature (p<0.0001) and river flooding (p<0.0001) showed a higher mean ESSDAI score in comparison with people living in no-risk countries. In contrast, those living in countries exposed to worse climate scenarios for wind threats (p<0.0001) and coastal flooding (p<0.0001) showed a lower mean ESSDAI score in comparison with people living in no-risk countries. Conclusion Local exposure to extreme climate-related hazards plays a role in modulating the presentation of Sjogren across countries concerning the age at which the disease is diagnosed, the frequency of dryness, and the degree of systemic activity.
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