Mónica Fernández Castro

A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations

A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this locus in different Caucasian cohorts. We analyzed 10 GWAS-genotyped SNPs in the IL12RB2 region (2309 SSc patients and 5161 controls). We then selected three SNPs (rs3790567, rs3790566 and rs924080) based on their significance level in the GWAS, for follow-up in an independent European cohort comprising 3344 SSc and 3848 controls. The most-associated SNP (rs3790567) was further tested in an independent cohort comprising 597 SSc patients and 1139 controls from the USA. After conditional logistic regression analysis of the GWAS data, we selected rs3790567 [P(MH)= 1.92 × 10(-5) odds ratio (OR) = 1.19] as the genetic variant with the firmest independent association observed in the analyzed GWAS peak of association. After the first follow-up phase, only the association of rs3790567 was consistent (P(MH)= 4.84 × 10(-3) OR = 1.12). The second follow-up phase confirmed this finding (P(χ2) = 2.82 × 10(-4) OR = 1.34). After performing overall pooled-analysis of all the cohorts included in the present study, the association found for the rs3790567 SNP in the IL12RB2 gene region reached GWAS-level significant association (P(MH)= 2.82 × 10(-9) OR = 1.17). Our data clearly support the IL12RB2 genetic association with SSc, and suggest a relevant role of the interleukin 12 signaling pathway in SSc pathogenesis.

Comprehensive Description of Clinical Characteristics of a Large Systemic Lupus Erythematosus Cohort from the Spanish Rheumatology Society Lupus Registry (RELESSER) With Emphasis on Complete Versus Incomplete Lupus Differences

AbstractSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement and pronounced racial and ethnic heterogeneity. The aims of the present work were (1) to describe the cumulative clinical characteristics of those patients included in the Spanish Rheumatology Society SLE Registry (RELESSER), focusing on the differences between patients who fulfilled the 1997 ACR-SLE criteria versus those with less than 4 criteria (hereafter designated as incomplete SLE (iSLE)) and (2) to compare SLE patient characteristics with those documented in other multicentric SLE registries.RELESSER is a multicenter hospital-based registry, with a collection of data from a large, representative sample of adult patients with SLE (1997 ACR criteria) seen at Spanish rheumatology departments. The registry includes demographic data, comprehensive descriptions of clinical manifestations, as well as information about disease activity and severity, cumulative damage, comorbidities, treatments and mortality, using variables with highly standardized definitions.A total of 4.024 SLE patients (91% with ≥4 ACR criteria) were included. Ninety percent were women with a mean age at diagnosis of 35.4 years and a median duration of disease of 11.0 years. As expected, most SLE manifestations were more frequent in SLE patients than in iSLE ones and every one of the ACR criteria was also associated with SLE condition; this was particularly true of malar rash, oral ulcers and renal disorder. The analysis—adjusted by gender, age at diagnosis, and disease duration—revealed that higher disease activity, damage and SLE severity index are associated with SLE [OR: 1.14; 95% CI: 1.08–1.20 (P < 0.001); 1.29; 95% CI: 1.15–1.44 (P < 0.001); and 2.10; 95% CI: 1.83–2.42 (P < 0.001), respectively]. These results support the hypothesis that iSLE behaves as a relative stable and mild disease. SLE patients from the RELESSER register do not appear to differ substantially from other Caucasian populations and although activity [median SELENA-SLEDA: 2 (IQ: 0–4)], damage [median SLICC/ACR/DI: 1 (IQ: 0–2)], and severity [median KATZ index: 2 (IQ: 1–3)] scores were low, 1 of every 4 deaths was due to SLE activity.RELESSER represents the largest European SLE registry established to date, providing comprehensive, reliable and updated information on SLE in the southern European population.

Brief Report: IRF4 Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross-Disease Meta-Analysis of Genome-Wide Association Studies

Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc–RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc–RA loci through an interdisease meta–genome‐wide association (meta‐GWAS) strategy.

SJÖGREN-SER: Registro nacional de pacientes con síndrome de Sjögren primario de la Sociedad Española de Reumatología: objetivos y metodología

OBJECTIVE To describe the objectives and methods of the Spanish Society of Rheumatology primary Sjögren syndrome (pSS) registry (SJOGREN-SER) METHODS: This is a multicenter descriptive transversal study of a cohort of pSS patients fulfilling European/American consensus criteria collected from Rheumatology clinics all over Spain. Patients were included by randomisation from an anonymised list provided by every department. Data were collected by reviewing clinical records and an interviewing the patients. Two hundred and ninety eight variables were investigated: epidemiological, clinical, serological characteristics, treatments and complications. Informed consent was obtained and local ethics committees approved the study. Variables were analysed by descriptive statistical methods, using means, medians, and rates, with their deviations and interquartile ranges (p25-p75). RESULTS A total of 3 rheumatology departments participated in the registry. A total of 437 patients were included. And 95% of them were women, with a median age of 58. Median age at pSS s diagnosis was 50 years. Dryness symptoms (95%) were the most frequent complaint and anti-Ro/SS-A were present in 94% of the cases. Only 27% of the patients fulfilled the new 2012 SICCA-ACR classification criteria. CONCLUSIONS SJOGREN-SER has been designed in order to characterize a representative pSS Spanish cohort, in clinical daily practice, to analyze the magnitude and distribution of its manifestations, activity, accumulated damage and therapeutic management of the disease. This will allow broadening the knowledge of this disease and plan strategies of action in pSS.

Comorbidities in patients with Primary Sjögren's Syndrome and Systemic Lupus Erythematosus: A comparative registries‐based study

To compare the prevalence of the main comorbidities in 2 large cohorts of patients with primary Sjögrens syndrome (SS) and systemic lupus erythematosus (SLE), with a focus on cardiovascular (CV) diseases.

Factors associated with severe dry eye in primary Sjögren’s syndrome diagnosed patients

IntroductionPrimary Sjögren’s syndrome (pSS) is an autoimmune disease, characterized by lymphocytic infiltration of exocrine glands and other organs, resulting in dry eye, dry mouth and extraglandular systemic findings.ObjectiveTo explore the association of severe or very severe dry eye with extraocular involvement in patients diagnosed with primary Sjögren’s syndrome.MethodsSJOGRENSER registry is a multicenter cross-sectional study of pSS patients. For the construction of our main variable, severe/very severe dry eye, we used those variables that represented a degree 3–4 of severity according to the 2007 Dry Eye Workshop classification. First, bivariate logistic regression models were used to identify the effect of each independent variable on severe/very severe dry eye. Secondly, multivariate analysis using regression model was used to establish the independent effect of patient characteristics.ResultsFour hundred and thirty-seven patients were included in SJOGRENSER registry; 94% of the patients complained of dry eye and 16% developed corneal ulcer. Schirmer’s test was pathological in 92% of the patients; 378 patients presented severe/very severe dry eye. Inflammatory articular involvement was significantly more frequent in patients with severe/very severe dry eye than in those without severe/very severe dry eye (82.5 vs 69.5%, p = 0,028). Inflammatory joint involvement was associated with severe/very severe dry eye in the multivariate analysis, OR 2.079 (95% CI 1.096–3.941).ConclusionSevere or very severe dry eye is associated with the presence of inflammatory joint involvement in patients with pSS. These results suggest that a directed anamnesis including systemic comorbidities, such as the presence of inflammatory joint involvement or dry mouth in patients with dry eye, would be useful to suspect a pSS.

Afectación oral en el paciente con síndrome de Sjögren primario. Manejo multidisciplinar entre odontólogos y reumatólogos

Primary Sjögrens syndrome is a chronic systemic autoimmune disease that causes destruction of lacrimal and salivary glands. The most common and earliest symptoms are oral and ocular dryness. Dry mouth makes talking difficult, tasting and chewing properly, impairing quality of life of these patients. The most common oral signs and symptoms are hyposialia with or without xerostomia, tooth decay, fungal infections, traumatic oral lesions, dysphagia, dysgeusia, and inflammation of salivary glands. There are different therapeutic strategies, depending on the severity of each case, and the increase in the amount of saliva, to reduce the number of cavities and oral infections. It is particularly important to establish a close relationship between the dentist and the rheumatologist in order to make an early and correct diagnosis, promoting appropriate dietary and hygiene measures, as well as to treat and prevent potential oral complications.

Tratamiento de fondo del síndrome seco. ¿Qué puede aportar el reumatólogo?

No effective treatment has been documented for the glandular primary Sjögren syndrome (PSS) despite the development of oral and biologic agents that have significant activity against other autoimmune disorders. Some disease-modifying agents have been empirically evaluated for the treatment of PSS. Targeting B cells also seems very promising in SSP because of the B-cell hyperactivity recognized in this desease. This article reviews existing data on the use of disease-modifying therapy for glandular of SSP. To date, published studies and trials of oral DMARDs for the treatment of SSP have shown disappointing results. B-cell modulation is clearly a promising therapy for PSS. Many challenges in trial design and execution are evident from the studies reviewed.

Uso de glucocorticoides en la artritis reumatoide. ¿Cuándo y cómo deben usarse los esteroides en la artritis reumatoide?

provide solid evidence that low-dose GC can inhibit radiographic damage in early RA, and that side effects of GC, when used in that clinical framework, are limited to hyperglycaemia, cataracts, and transient weight gain.Glucocorticoids (GC) are a mainstay of the therapy in rheumatoid arthritis (RA). Currently, and despite their extensive use, the discussion about the benefits and adverse effects of low dose GC in the management of RA persists. In recent years, a number of clinical trials have attempted to establish the benefits of long-term GC use as a disease-modifying antirheumatic drug in RA, and to define their side effects. Results of these clinical trials provide solid evidence that low-dose GC can inhibit radiographic damage in early RA, and that side effects of GC, when used in that clinical framework, are limited to hyperglycaemia, cataracts, and transient weight gain.

Use of glucocorticosteroids in rheumatoid arthritis. How and when should steroids be used in rheumatoid arthritis

Abstract Glucocorticoids (GC) are a mainstay of the therapy in rheumatoid arthritis (RA). Currently, and despite their extensive use, the discussion about the benefits and adverse effects of low dose GC in the management of RA persists. In recent years, a number of clinical trials have attempted to establish the benefits of long-term GC use as a disease-modifying antirheumatic drug in RA, and to define their side effects. Results of these clinical trials provide solid evidence that low-dose GC can inhibit radiographic damage in early RA, and that side effects of GC, when used in that clinical framework, are limited to hyperglycemia, cataracts, and transient weight gain.