Argentine Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Postmenopausal Women and Men Aged 50 Years and Older.

OBJECTIVE: The aim of this study was to provide an evidence-based framework to guide health care professionals treating patients under glucocorticoid (GC) therapy and develop guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis (GIO) in postmenopausal women and men aged ≥50 years. METHODS: An expert panel on bone diseases designed a series of clinically meaningful questions following the PICO (Population, Intervention, Comparator, and Outcome) structure. Using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology, we made a systematic literature review, extracted and summarized the effect estimates, and graded the quality of the evidence. The expert panel voted each PICO question and made recommendations after reaching an agreement of at least 70%. RESULTS: Seventeen recommendations (9 strong and 8 conditional) and 8 general principles were developed for postmenopausal women and men aged ≥50 years under GC treatment. Bone mineral density (BMD), occurrence of fragility fractures, probability of fracture at 10 years by Fracture Risk Assessment Tool, and other screening factors for low BMD are recommended for patient evaluation and stratification according to fragility fracture risk. The treatment of patients under GC therapy should include counseling on lifestyle habits and strict control of comorbidities. The goal of GIO treatment is the nonoccurrence of new fragility fractures as well as to increase or maintain BMD in certain clinical situations. This was considered for the therapeutic approach in different clinical scenarios. CONCLUSIONS: This GIO guideline provides evidence-based guidance for health care providers treating patients.

Multicenter lupus register from Argentina, the RELESSAR database: Influence of ethnicity on disease phenotype.

OBJECTIVE: The objective is to describe the main characteristics of patients with systemic lupus erythematosus (SLE) in Argentina and to examine the influence of ethnicity on the expression of the disease. PATIENTS AND METHODS: RELESSAR is a multicentre register carried out by 106 researchers from 67 rheumatologic Argentine centres. It is a cross-sectional study of SLE (1982/1997 ACR) patients. RELESSAR electronic database includes demographic, cumulative SLE manifestations, SELENA-SLEDAI, SLICC-SDI, Katz's severity and Charlson's comorbidity indexes and treatment patterns. RESULTS: We included 1,610 patients, 91.7% were female with a median age at diagnosis of 28.1 ± 12.8; 96.2% met ≥4 ACR 1982/97 criteria. Frequent manifestations were arthritis (83.5%), malar rash (79.5%), photosensitivity (75.3%), haematological (63.8%) and renal disease (47.4%), antinuclear antibodies (96%), anti-dsDNA (66.5%) and anti-Smith antibodies (29%). The mean Selena-SLEDAI score at last visit was 3.18 (SD 4.3) and mean SDI was 1 (SD 1.3). The accumulated treatments most frequently used were antimalarials (90.4%), corticosteroids (90%), azathioprine (31.8%), intravenous cyclophosphamide (30.2%), mycophenolate mofetil or mycophenolic acid (24.5%), methotrexate (19.3%), belimumab 5.3% and rituximab 5.1%. Refractory lupus was diagnosed in 9.3% of the cases. The main causes of death were lupus activity (25.0%), activity and concomitant infections (25.0%), infections (18.2%), vascular disease (13.6%) and cancer (4.5%). Mortality was associated with higher SLEDAI, Katz, damage indexes and comorbidities. Of the 1610 patients included, 44.6% were Caucasian, 44.5% Mestizo, 8.1% Amerindian and 1.2% Afro-Latin American. Mestizo patients had higher male representation, low socioeconomic status, more inadequate medical coverage, fewer formal years of education and shorter disease duration. Polyadenopathies and Raynaud's phenomenon were more frequent in Caucasians. In the logistic regression analysis higher damage index (OR 1.28, CI 95% 1.02-1.61, p = 0.03) remained associated to mestizo ethnicity. CONCLUSIONS: This study represents the largest number of adult patients with SLE studied in Argentina. Caucasian patients were differentiated by having Raynaud's phenomenon and polyadenopathy more frequently, while patients of Mestizo origin had higher damage indexes.

Rheumatoid arthritis in Latin Americans enriched for Amerindian ancestry is associated with loci in chromosomes 1, 12, and 13, and the HLA class II region.

OBJECTIVE: To identify susceptibility loci for rheumatoid arthritis (RA) in Latin American individuals with admixed European and Amerindian genetic ancestry. METHODS: Genotyping was performed in 1,475 patients with RA and 1,213 control subjects, using a customized BeadArray containing 196,524 markers covering loci previously associated with various autoimmune diseases. Principal components analysis (EigenSoft package) and Structure software were used to identify outliers and define the population substructure. REAP software was used to define cryptic relatedness and duplicates, and genetic association analyses were conducted using Plink statistical software. RESULTS: A strong genetic association between RA and the major histocompatibility complex region was observed, localized within BTNL2/DRA-DQB1- DQA2 (P = 7.6 × 10(-10) ), with 3 independent effects. We identified an association in the PLCH2-HES5-TNFRSF14-MMEL1 region of chromosome 1 (P = 9.77 × 10(-6) ), which was previously reported in Europeans, Asians, and Native Canadians. We identified one novel putative association in ENOX1 on chromosome 13 (P = 3.24 × 10(-7) ). Previously reported associations were observed in the current study, including PTPN22, SPRED2, STAT4, IRF5, CCL21, and IL2RA, although the significance was relatively moderate. Adjustment for Amerindian ancestry improved the association of a novel locus in chromosome 12 at C12orf30 (NAA25) (P = 3.9 × 10(-6) ). Associations with the HLA region, SPRED2, and PTPN22 improved in individuals positive for anti-cyclic citrullinated peptide antibodies. CONCLUSION: Our data define, for the first time, the contribution of Amerindian ancestry to the genetic architecture of RA in an admixed Latin American population by confirming the role of the HLA region and supporting the association with a locus in chromosome 1. In addition, we provide data for novel putative loci in chromosomes 12 and 13.

Chromosome 17p12-q11 harbors susceptibility loci for systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies against intracellular components, the formation of immune complexes, and inflammation in various organs, typically the skin and kidney glomeruli. The etiology of the disease is not well understood but is most likely the result of the interaction between genetic and environmental factors. In order to identify susceptibility loci for SLE, we have performed genome scans with microsatellite markers covering the whole genome in families from Argentina, Italy, and Europe. The results reveal a heterogeneous disease with different susceptibility loci in different family sets. We have found significant linkage to chromosome 17p12-q11 in the Argentine set of families. The maximum LOD score was given by marker D17S1294 in combination with D17S1293, when assuming a dominant inheritance model (Z = 3.88). We also analyzed a repeat in the promoter region of the NOS2A gene, a strong candidate gene in the region, but no association was found. The locus on chromosome 17 has previously been identified in genetic studies of multiple sclerosis families. Several other interesting regions were found at 1p35, 1q31, 3q26, 5p15, 11q23 and 19q13, confirming previously identified loci for SLE or other autoimmune diseases.