[Show abstract][Hide abstract] ABSTRACT: The authors review the practical aspects of biological therapy use for rheumatoid arthritis patients, commenting safety issues before and after treatment initiation and the best treatment strategies to optimize efficacy.
[Show abstract][Hide abstract] ABSTRACT: Association between ankylosing spondylitis (AS) and two genes, ERAP1 and IL23R, has recently been reported in North American and British populations. The population attributable risk fraction for ERAP1 in this study was 25%, and for IL23R, 9%. Confirmation of these findings to ERAP1 in other ethnic groups has not yet been demonstrated. We sought to test the association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to AS among a Portuguese population. We also investigated the role of these genes in clinical manifestations of AS, including age of symptom onset, the Bath Ankylosing Spondylitis Disease Activity, Metrology and Functional Indices, and the modified Stoke Ankylosing Spondylitis Spinal Score.
The study was conducted on 358 AS cases and 285 ethnically matched Portuguese healthy controls. AS was defined according to the modified New York Criteria. Genotyping of IL23R and ERAP1 allelic variants was carried out with TaqMan allelic discrimination assays. Association analysis was performed using the Cochrane-Armitage and linear regression tests of genotypes as implemented in PLINK for dichotomous and quantitative variables respectively. A meta-analysis for Portuguese and previously published Spanish IL23R data was performed using the StatsDirect Statistical tools, by fixed and random effects models.
A total of 14 nsSNPs markers (8 for IL23R, 5 for ERAP1, 1 for LN-PEP) were analysed. Three markers (2 for IL23R and 1 for ERAP1) showed significant single-locus disease associations, confirming that the association of these genes with AS in the Portuguese population. The strongest associated SNP in IL23R was rs1004819 (OR=1.4, p=0.0049), and in ERAP1 was rs30187 (OR=1.26, p=0.035). The population attributable risk fractions in the Portuguese population for these SNPs are 11% and 9.7% respectively. No association was seen with any SNP in LN-PEP, which flanks ERAP1 and was associated with AS in the British population. No association was seen with clinical manifestations of AS.
These results show that IL23R and ERAP1 genes are also associated with susceptibility to AS in the Portuguese population, and that they contribute a significant proportion of the population risk for this disease.
Clinical and experimental rheumatology 01/2009; 27(5):800-806. · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In addition to adverse effects on gastroduodenal mucosa, it is recognized that non-steroidal antiinflammatory drugs (NSAIDs) can also induce toxicity to the lower intestinal tract. The diagnostic tools available and the lack of information about its pathogenesis and clinical importance are still limitations for its diagnosis. For their anti-inflammatory and analgesic effects, NSAIDs are largely used to treat musculoskeletal disorders. Increased intestinal permeability and inflammation are the main pathogenic steps in the development of NSAIDs enteropathy which may result in bleeding and protein loss. Selective COX-2 inhibitors, although seem safer, may also induce intestinal lesions. In this article, about NSAIDs damage to the lower intestine, we review aspects about its prevalence, pathogenesis, lesions, clinical spectrum and practical clues to diagnosis and treatment.
[Show abstract][Hide abstract] ABSTRACT: Anaemia is a common clinical feature in patients with rheumatoid arthritis and the coexistence of blood loss may not show an obvious iron deficiency anaemia. The cause may be a cancer or other reason for gastrointestinal bleeding that could be underestimated for being explained as associated with the chronic rheumatic disease. Although less described than gastroduodenal lesions, small bowel damage of non-steroidal anti-inflammatory drugs, used in the treatment of rheumatic diseases, are more common than previously thought. The authors describe a clinical case paradigmatic of the difficulties that may appear in the approach of anaemia in a patient with a chronic rheumatic disease and discuss some features of intestinal toxicity of nonsteroidal anti-inflammatory drugs.