Objectives: Thyroid dysfunction in the setting of systemic sclerosis (SSc) has been described previously. We aimed to determine the prevalence of anti-thyroid antibodies (ATA) in a large SSc cohort ...and to ascertain whether they are associated with distinct clinical phenotypes.
Methods: A total of 138 patients with SSc 46 with diffuse (dSSc) and 92 with limited scleroderma (lSSc) and 100 healthy controls (HC) were tested for the presence of ATA anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies using a commercial enzyme-linked immunosorbent assay (ELISA). Clinical and serological data were recorded.
Results: An increased prevalence of anti-TPO but not anti-Tg antibodies was detected in patients with SSc compared to HC (27.5% vs. 14%, p = 0.016). Of note, a statistically significant increase of anti-TPO was detected only in patients with lSSc compared to HC (32.6% vs. 14%, p = 0.003). No correlations with other clinical features were detected.
Conclusions: An increased prevalence of anti-TPO antibodies was identified in patients with lSSc. We propose that ATA testing should be offered to this subgroup of patients.
Background:Antiphospholipid syndrome (APS) is an autoimmune thrombophilia associated with antibodies against phospholipid binding plasma proteins, mainly β2glycoprotein-I (B2GPI), prothrombin (PT) ...and annexin1. APS is expressed mainly as arterial or venous thrombosis and pregnancy complications. APS may occur as isolated disease (primary APS) or secondary to another autoimmune disease, mainly systemic lupus erythematosus (SLE)2.Objectives:To describe the clinical and serological characteristics of a cohort of Greek patients with Primary APS, to check the performance of the 2023 ACR/EULAR APS classification criteria in this cohort and to highlight the non-criteria clinical phenotypes.Methods:A retrospective study in a Greek cohort of Primary APS. Patient demographics, clinical and serological features were recorded. Comparisons are made between classified and non-classified APS patients by using chi-square and one way ANOVA tests. Significance was set at p < 0.05.Results:Sixty-eight patients with primary APS were included. Median age was 55 years (21-80), 69% female and 29% were active smokers (mean packyears: 32 ± 12). The most often implicated antiphospholipid antibodies were ΙgM and ΙgG anti-cardiolipin (51.5% and 29.4%), anti-β2GPI IgG and IgM (25% and 41.2%) and lupus anticoagulant (48.5%). Clinical manifestations were venous thrombosis in 34 patients (50%) most often deep venous thrombosis (n=20), pulmonary embolism (n=16) and cavernous sinus thrombosis (n=3), arterial thrombosis in 25 patients (36.8%) most often stroke (n=18), and pregnancy morbidity in 18 patients (26.4%). Other manifestations included: livedo racemosa (n=3, 4.4%), APS nephropathy (n=4, 5.8%), cardiac valve disease (n=2, 2.9%), thrombocytopenia (n=19, 27.9%) and catastrophic APS (n=1, 1.4%). The following were considered as non-criteria manifestations: migraine (n=6, 8.8%), multiple-sclerosis-like brain lesions (n=6, 8.8%), skin ulcers (n=5, 7.4%), transverse myelitis (n=4, 5.9%), osteonecrosis (n=3, 4.4%), Raynaud’s phenomenon (n=2, 2.9%), malar rash (n=1, 1.4%) and sensorineural hearing loss (n=1, 1.4%).Fifty-one patients (75%) were classified as APS according to the 2023 ACR/EULAR APS Classification Criteria. The arm of non-classified patients included fewer active smokers (5.9% vs 35%, p=0.027), more patients with a moderate/high anti-cardiolipin IgM titre (76.5% vs 43.1%, p=0.017), less arterial (11.8% vs 45.1%, p=0.014) and venous thromboses (23.5% vs 59%, p=0.012). Characteristics that yielded non-significant differences included: thrombocytopenia, three or more otherwise unexplained consecutive prefetal deaths and moderate/high anti-β2GPI IgM (Figure 1).Conclusion:Our study highlights the different clinical phenotypes of APS. In agreement with the existing literature, a portion of patients do not meet the new classification criteria. Therefore, clinicians should evaluate patients carefully, as there are no diagnostic criteria. It is up to the clinician to interpret the clinical manifestations, antibody profile and other risk factors for the diagnosis of APS.REFERENCES:1 Khamashta MA, Amigo MC. Antiphospholipid syndorme: overview of pathogenesis, diagnosis, and management. In: Rheumatology, 6, Hochberg MC, Silman AJ, Smolen JS, et al (Eds), Elsevier, 2015. Vol 2, p.1144.2 Taraborelli M, Leuenberger L, Lazzaroni MG, et al. The contribution of antiphospholipid antibodies to organ damage in systemic lupus erythematosus. Lupus 2016; 25:1365.Figure 1.Comparisons between classified and non-classified Primary APS patients (2023 ACR/EULAR classification criteria)Figure omitted. See PDFAcknowledgements:NIL.Disclosure of Interests:None declared.
BackgroundBoth epidemiology and planning of health care puts high demands on the ability to record and monitor data. Disease registries have contributed significantly the previous years, however, an ...enormous amount of healthcare data is spread among hospitals, primary care providers, researchers, health insurers, with each of these usually acting as a silo, preventing effective use of data.ObjectivesSince Greece is among the first countries that developed an extensive electronic prescription system, we aimed to identify all patients with prescribed pharmacological treatment for RA, SLE and SSc among 7.742.629 Greek citizens (72% of the population, >99% Caucasians) who were included in the system during the first semester of 2014.MethodsThe database of the electronic prescription platform of the Greek National Organization for Provision of Healthcare Services (EOPYY) was used to provide analytics on these patients (date of birth and gender based on the unique citizens' social security numbers and the relevant ICD-10 codes). Permission for use of anonymized data was obtained by the administration of EOPYY together with the positive recommendation of the General Secretariat for Public Health of the Ministry of Health of Greece, in accordance to the national legislation on the Protection of Individuals and Personal Data.ResultsThis “Big Data” analysis revealed that RA prevalence is 0.84%, SLE prevalence is 0.075% and SSc prevalence is 0.016%. Female:male ratio is approximately 4:1 in RA, and 9:1 in both SLE and SSc, with slight differences across age groups (15-24, 25-34, 35-44, 45-54, 55-64, 65-74, 75+). The peak RA prevalence is observed after the age of 75 years; in contrast, the peak prevalence of SLE and SSc is observed between 45-54 and 55-64 years, respectively, which is compatible with the earlier/higher mortality of these patients compared to RA. The highest female preponderance (94%) is noted in patients older than 74 years with SSc, supporting the previously suspected earlier mortality of men compared to women in SSc.ConclusionsThese data provide reliable estimates of the epidemiology of both common and rare autoimmune rheumatic diseases. Analysis of such large databases overrides any incorrect diagnosis-associated limitations that an electronic prescription system may have. However, a proportion of patients may be missed because of mild disease or not receiving (prescribed) treatment, therefore, the true prevalence is likely to be higher than that calculated. Further analyses of data deriving from the second semester of 2014 which covers 95% of the Greek population should confirm these results and reveal the distinct pharmacological approaches, including biologic agents, as well as the co-morbidities. These analyses are in progress.Disclosure of InterestNone declared
BackgroundExisting guidelines advocate aggressive management of dyslipidemia in rheumatoid arthritis (RA) patients according to cardiovascular disease (CVD) risk scores generated for the general ...population (SCORE). More specific RA scores such as the ERS-RA score have not been extensively studied.ObjectivesTo evaluate the use of lipid-lowering agents for CVD prevention (primary/secondary) in RA patients according to different CVD risk scores (SCORE, ERS-RA).MethodsProspective, multicenter (12 hospitals, 6 private offices), cross-sectional, epidemiological study in Greece (06/2015–01/2016, RA Study Group). Demographics, disease characteristics, treatment and comorbidities were collected and SCORE/ERS-RA were calculated.ResultsAmong 1475 patients, 178 (12%) had CVD (44% coronary artery disease, 44% peripheral vascular disease, 27% stroke) and 43% were not receiving any hypolipidemic therapy. From those on therapy, only 12% achieved an LDL-cholesterol (LDL-C) level <70 mg/dl while 48% had LDL-C<100 mg/dl. 859 patients without CVD, diabetes or hypolipidemic therapy were further analyzed (79% women, mean age 59.5 yrs, mean disease duration 3.4 yrs, mean DAS28-ESR 3.4, mean HAQ 0.45). Complete data for SCORE calculation were available in 225/859 patients (26%). When stratified according to CVD risk, 31.5%, 66%, 2% and 0.5% of patients had a SCORE of <1% (low risk), ≥1 to <5% (moderate), ≥5 to <10% (high) and ≥10% (very high), respectively. In moderate risk (1–5%) patients, 78% had an LDL-C>100 mg/dl while among high or very high risk (≥5%) patients, 100% had an LDL-C>70 mg/dl (target groups for drug therapy). Among 996 patients (40–75 yrs old), without CVD events, there were 99 diabetic patients (10%) and less than half (48%) were on hypolipidemic therapy. For the rest, the ERS-RA score was calculated (619/897, 69% with available data); 50% of them (308/619) had a 10-year risk of ≥7.5% (therapeutic cutoff) but only 40% of patients in this group were being treated.ConclusionsA substantial proportion of RA patients with established CVD or diabetes do not receive lipid-lowering therapy or they do not achieve therapeutic targets. Among those without CVD or diabetes, more than half belong to moderate to high CVD risk groups and are not receiving appropriate hypolipidemic therapy.AcknowledgementSupported by grants from the Hellenic Rheumatology Society and Professional Association of Rheumatologists.Disclosure of InterestNone declared
Background Whether systemic sclerosis (SSc) is differently expressed in men versus women has been debated. This is probably due to the fact that published information mainly derives from multi-ethnic ...cohorts followed at tertiary care centers, which always include patients referred for severe disease. In these cohorts the men/women ratios are higher (1/4-5) compared to ethnic cohorts (1/7-9), suggesting biases in the former cohorts due to under-representation of women with milder forms of SSc. Objectives To search for possible differences in morbidity and mortality between men and women with SSc who belong to an ethnic cohort followed at a single academic centre. Methods Demographic, clinical, and outcome data from all SSc patients who had been examined between 1995 and 2011 in our Department were retrospectively analysed. For the purpose of the present study, non-Greek patients referred to our centre were excluded. In order to identify differences in clinical expression, all disease manifestations present in consecutive 3-year intervals from disease onset were recorded for each patient. Independent sample t-tests and Kaplan-Meier analyses were used to search for possible differences between men and women. Results The men/women ratio was 1/8.7 in a total of 223 patients. At the time of last evaluation the mean±SD age in men and women was 55±15 and 59±14 years, while disease duration was 9±7 and 13±10 years, respectively. Age at SSc onset (46±15 in men; 46±15 in women), diffuse skin involvement (61.3% in men; 46.4% in women) and Scl70 positivity (66.6% in men; 59.2% in women) were not significantly different between genders. Prevalence of interstitial lung disease, upper and lower gastrointestinal disease, echocardiographic findings, including estimation of pulmonary artery pressure, and joint contractures during the first through the fourth 3-year interval from disease onset were also not different. However, vasculopathy occurred earlier in men than women, since in the first three years after disease onset digital ulcers and renal crisis developed in 54 vs 31% (p=0.036) and 17 vs 3% (p=0.006), respectively. After excluding non-SSc related deaths, survival was significantly worse in men compared to women (88 vs 99% at 3 years, p=0.001; 80 vs 98%, at 6 years p=0.001; 67 vs 93%, p=0.003 at 6 years and 58 vs 91% at 12 years, p=0.002, respectively). Kaplan-Meier analysis confirmed the worse survival of men with SSc over women (Mantel-Cox test, p=0.002). No significant differences were identified between men and women regarding social history, including smoking, past medical history, including hypertension, or disease management, including immumomodulatory regimens and endothelin receptor antagonist. Conclusions These results, derived from a patient cohort which is representative of the SSc population in Greece, show that the clinical expression of the disease is more severe in men. Further studies to confirm that SSc-associated vasculopathy may develop earlier in men than women are warranted. Disclosure of Interest None Declared
Autoimmune thyroid disease has been associated with several systemic autoimmune disorders. However, limited data are available regarding the prevalence and clinical associations of thyroid ...autoimmunity in antiphospholipid syndrome (APS). Seventy-five patients with APS, 75 patients with systemic lupus erythematosus (SLE) and 75 healthy controls were tested for the presence of antithyroid antibodies (ATAs) (anti-thyroglobulin and anti-thyroid peroxidase anti-TPO) using commercial ELISA. Clinical data were also recorded. Although no significant differences in the prevalence of ATAs were detected among APS, SLE patient groups and healthy controls, a significant increase of anti-TPO antibodies in patients with APS-SLE was found. An increased prevalence of ATAs in APS population with ischemic central nervous system (CNS) clinical manifestations was also detected. We present novel associations between thyroid autoimmunity and ischemic CNS clinical manifestations in the setting of APS.
Introduction Systemic sclerosis (SSc)-related pulmonary arterial hypertension (PAH) has emerged as a major mortality prognostic factor. Mutations of transforming growth factor beta (TGFβ) receptor ...genes strongly contribute to idiopathic and familial PAH. Objective To explore the genetic bases of SSc–PAH, we combined direct sequencing and genotyping of candidate genes encoding TGFβ receptor family members. Materials and methods TGFβ receptor genes, BMPR2, ALK1, TGFR2 and ENG, were sequenced in 10 SSc–PAH patients, nine SSc and seven controls. In addition, 22 single-nucleotide polymorphisms (SNP) of these four candidate genes were tested for association in a first set of 824 French Caucasian SSc patients (including 54 SSc–PAH) and 939 controls. The replication set consisted of 1516 European SSc (including 219 SSc–PAH) and 3129 controls from the European League Against Rheumatism Scleroderma Trials and Research group network. Results No mutation was identified by direct sequencing. However, two repertoried SNP, ENG rs35400405 and ALK1 rs2277382, were found in SSc–PAH patients only. The genotyping of 22 SNP including the latter showed that only rs2277382 was associated with SSc–PAH (p=0.0066, OR 2.13, 95% CI 1.24 to 3.65). Nevertheless, this was not replicated with the following result in combined analysis: p=0.123, OR 0.79, 95% CI 0.59 to 1.07. Conclusions This study demonstrates the lack of association between these TGFβ receptor gene polymorphisms and SSc–PAH using both sequencing and genotyping methods.
OBJECTIVE To investigate the existence of differences among European referral centres for systemic sclerosis (SSc) in the pattern of attendance and referral and in the clinical and therapeutical ...approaches. METHODS In 1995 the European Scleroderma Study Group initiated a multicentre prospective one year study whose aim was to define the disease activity criteria in SSc. During the study period each participating European centre was asked to enrol consecutive patients satisfying American College of Rheumatology criteria for SSc and to fill out for each of them a standardised clinical chart. Patients from various centres were compared and differences in epidemiological, clinical, and therapeutical aspects were analysed. RESULTS Nineteen different medical research centres consecutively recruited 290 patients. The patients could be divided into two subgroups: 173 with the limited (lSSc) and 117 with the diffuse (dSSc) form of the disease. The clinical and serological findings for the series of 290 patients seemed to be similar to data previously reported. However, when the data were analysed to elicit any differences between the participating centres, a high degree of variability emerged, in both epidemiological and clinical features and in the diagnostic and therapeutic approaches to the disease. CONCLUSIONS The clinical approach to SSc, not only in different countries but also in different centres within the same country, is not yet standardised. To overcome this problem, it will be necessary for the scientific community to draw up a standardised procedure for the management of patients with SSc. This would provide a common research tool for different centres engaged in research on this complex disease.
Background:Psoriatic arthritis (PsA) is a chronic inflammatory arthritis that equally affects males and females, ranging from mild to severe debilitating disease. TNF inhibitors (TNFi) have been for ...many years, the first choice among biologic treatments as additional therapy on classical DMARDs. However, real world data about the long term efficacy of TNFi are scarce.Objectives:The aim of this study is to describe the long-term efficacy of TNFi as first and secondline treatment (cycling) among PsA patients with inadequate response to classical DMARDs.Methods:Medical records from 300 consecutive PsA patients who were followed up in the outpatient Rheumatology clinic of the Department of Pathophysiology for the past 33 years, were carefully reviewed to identify those: i) with inadequate response to classical DMARDs according to physicians’ judgement after at least 3 months administration and ii) have received TNFi as the first adds on biologic agent. All patients fulfilled the CASPAR classification criteria for PsA. Survival rates for secondary inefficacy were calculated after the initiation of the first and second TNFi respectively. Pre-specified risk factors related to PsA arthritis (gender, age at articular disease onset, disease duration from arthritis onset until TNFi initiation, peripheral or axial involvement as well as 6 skin variants of psoriasis including plaque, guttate, pustular, inverse, nail dystrophy and mixed form)were evaluated for the association with secondary inefficacy. Patients who presented primary inefficacy (inadequate response within 3 months after TNFi initiation) or adverse events were excluded from the analysis.Results:One hundred and twenty one and 36 patients received TNFi as first line and second treatment respectively, on top of classical DMARDs. DMARDs included methotrexate, leflunomide or cyclosporine and TNFi infliximab, adalimumab, etanercept, golimumab and certolizumab. Sixty three (52%) of these patients were females, the mean±SD duration of articular disease to first TNFi was 5.9±1.0 years and the mean±SD age at articular disease onset was 39±13.3. In seventy five (62%)patients skin disease preceded the articular manifestations, in 12(12,4%) patients skin rash followed joint involvement while 31 (25,6%) patients had concurrently skin and articular involvement. Seventy five (62%) patients had peripheral arthritis whereas forty six (38%) axial involvement. The most common forms of skin disease were plaque (66%) and guttate (13.2%) psoriasis. Fifty five (45.5%) of 121 patients eventually developed secondary inefficacy after the first TNFi and 20 (55%) of 36 patients after the second TNFi. The median time of exposure to first and second TNFi was 35 (range: 4-144) and 32 months (range: 4-156) respectively. The 5-year survival rate of the first and second TNFi was 62%and 40% respectively. The median survival time was 84 months (range:4-144) and 60 months (range:4-156) respectively. No differences were identified regarding the pre-specified PsA-related risk factors, between patients with and without secondary inefficacy to first or second line TNFi treatment. Subgroup analysis among PsA patients with secondary inefficacy to first TNFi showed that female gender and peripheral involvement were considered independent risk factors for early (<35 months) vs late (>35 months) secondary inefficacy.Conclusion:TNFi display good overall survival rates as first line treatment among PsA with inadequate response to cDMARDs. Female gender and peripheral involvement are independent risk factors for early secondary inefficacy to first TNFi.REFERENCES:NIL.Figure 1.Survival curve of first TNFi as additional therapy in PsA patients with inadequate response to cDMARDs (time is shown in months).Figure omitted. See PDFAcknowledgements:NIL.Disclosure of Interests:None declared.
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