Effect of age at disease onset in the clinical profile of spondyloarthritis: a study of 1424 Brazilian patients

Objectives To analyse demographic and clinical variables in patients with disease onset before and after 40, 45 and 50 years in a large series of Brazilian SpA patients. Methods A common protocol of investigation was prospectively applied to 1424 SpA patients in 29 centres distributed through the main geographical regions in Brazil. The mean age at disease onset was 28.56 +/- 12.34 years, with 259 patients (18.2%) referring disease onset after 40 years, 15.1 (10.6%) after 45 years and 81 (5.8%) after 50 years. Clinical and demographic variables and disease indices (BASDAI, BASFI, BASRI, MASES, ASQoL) were investigated. Ankylosing spondylitis was the most frequent disease (66.3%), followed by psoriatic arthritis (18%), undifferentiated SpA (6.7%), reactive arthritis (5.5%), and enteropathic arthritis (3.5%). Results Comparing the groups according to age of disease onset, those patients with later onset presented statistical association with female gender, peripheral arthritis, dactylitis, nail involvement and psoriasis, as well as negative statistical association with inflammatory low hack pain, alternating buttock pain, radiographic sacroiliitis, hip involvement, positive familial history, HLA-B27 and uveitis. BASDAI, BASFI and quality of life, as well as physicians and patient's global assessment, were similar in all the groups. Radiographic indices showed worse results in the younger age groups. Conclusion There are two different clinical patterns in SpA defined by age at disease onset: one with predominance of axial symptoms in the group with disease onset <= 40 years and another favouring the peripheral manifestations in those with later disease onset.

Developing a provisional definition of flare in patients with established gout

Objective Various nonvalidated criteria for disease flare have been used in studies of gout. Our objective was to develop empirical definitions for a gout flare from patient-reported features. Methods Possible elements for flare criteria were previously reported. Data were collected from 210 gout patients at 8 international sites to evaluate potential gout flare criteria against the gold standard of an expert rheumatologist definition. Flare definitions based on the presence of the number of criteria independently associated with the flare and classification and regression tree approaches were developed. Results The mean +/- SD age of the study participants was 56.2 +/- 15 years, 207 of them (98%) were men, and 54 of them (26%) had flares of gout. The presence of any patient-reported warm joint, any patient-reported swollen joint, patient-reported pain at rest score of >3 (010 scale), and patient-reported flare were independently associated with the study gold standard. The greatest discriminating power was noted for the presence of 3 or more of the above 4 criteria (sensitivity 91% and specificity 82%). Requiring all 4 criteria provided the highest specificity (96%) and positive predictive value (85%). A classification tree identified pain at rest with a score of >3, followed by patient self-reported flare, as the rule associated with the gold standard (sensitivity 83% and specificity 90%). Conclusion We propose definitions for a disease flare based on self-reported items in patients previously diagnosed as having gout. Patient-reported flare, joint pain at rest, warm joints, and swollen joints were most strongly associated with presence of a gout flare. These provisional definitions will next be validated in clinical trials.

Ethnic Influence in Clinical and Functional Measures of Brazilian Patients with Spondyloarthritis

Objective. Spondyloarthritides (SpA) can present different disease spectra according to ethnic background. The Brazilian Registry of Spondyloarthritis (RBE) is a nationwide registry that comprises a large databank on clinical, functional, and treatment data on Brazilian patients with SpA. The aim of our study was to analyze the influence of ethnic background in SpA disease patterns in a large series of Brazilian patients. Methods. A common protocol of investigation was prospectively applied to 1318 SpA patients in 29 centers distributed through the main geographical regions in Brazil. The group comprised whites (65%), African Brazilians (31.3%), and people of mixed origins (3.7%). Clinical and demographic variables and various disease index scores were compiled. Ankylosing spondylitis (AS) was the most frequent disease in the group (65.1%); others were psoriatic arthritis (18.3%), undifferentiated SpA (6.8%), enteropathic arthritis (3.7%), and reactive arthritis (3.4%). Results. White patients were significantly associated with psoriasis (p = 0.002), positive HLA-B27 (p = 0.014), and use of corticosteroids (p < 0.0001). Hip involvement (p = 0.02), axial inflammatory pain (p = 0.04), and radiographic sacroiliitis (p = 0.025) were associated with African Brazilian descent. Sex distribution, family history, and presence of peripheral arthritis, uveitis, dactylitis, urethritis, and inflammatory bowel disease were similar in the 3 groups, as well as age at disease onset, time from first symptom until diagnosis, and use of anti-tumor necrosis factor-a agents (p > 0.05). Schober test and thoracic expansion were similar in the 3 groups, whereas African Brazilians had higher Maastricht Ankylasing Spondylitis Enthesitis Scores (p = 0.005) and decreased lateral lumbar flexion (p = 0.003), while whites had a higher occiput-to-wall distance (p = 0.02). African Brazilians reported a worse patient global assessment of disease (p = 0.011). Other index scores and prevalence of work incapacity were similar in the 3 groups, although African Brazilians had worse performance in the Ankylosing Spondylitis Quality of Life questionnaire (p < 0.001). Conclusion. Ethnic background is associated with distinct clinical aspects of SpA in Brazilian patients. African Brazilian patients with SpA have a poorer quality of life and report worse disease compared to whites, (First Release Nov 1 2011; J Rheumatol 2012;39:141-7; doi:10.3899/jrheum.110372)

Conceitos atuais e relevantes sobre artrite psoriásica

A artrite psoriásica (APs) é uma doença articular sistêmica e polimórfica de apresentação e curso clínico variáveis, associada a comorbidades importantes como diabetes mellitus, hipertensão arterial e dislipidemia. Para o diagnóstico precoce da doença é necessário alto grau de suspeita clínica, sobretudo quando as manifestações cutâneas são sutis e pouco definidas. Doença erosiva progressiva pode ocorrer em até metade dos pacientes, associada a alterações anatômicas e funcionais em cerca de 20%, de modo que o prognóstico da APs permanece obscuro, especialmente se diagnóstico e tratamento forem tardios. Fundamentados em ampla revisão da literatura (PubMed e Lilacs) e experiência dos nossos serviços, novos conceitos de imunogenética, fisiopatologia, aspectos clínicos e terapêuticos serão discutidos. Fatores que reduzem a qualidade e a expectativa de vida dos pacientes e novas diretrizes que norteiam um tratamento mais precoce e efetivo serão enfatizados. O controle do processo inflamatório, especialmente nas formas axiais e entesíticas da APs, tornou-se possível graças à introdução dos medicamentos biológicos anti-TNF. Finalmente, o papel do GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) deve ser ressaltado, já que promove reuniões e estudos conjuntos entre reumatologistas e dermatologistas no sentido de fornecer evidências científicas para as amplas mudanças no manejo clínico e terapêutico de pacientes com APs

Estado nutricional e consumo alimentar de pacientes com psoríase dos tipos sistêmica e artropática sistêmica associada

OBJECTIVE: To identify the nutritional status and food intake of individuals with systemic psoriasis and psoriatic arthritis associated. METHODS: This is an exploratory and cross-sectional study with 34 men aged between 19 and 60 years seen at a Psoriasis Center. Participants were divided into systemic psoriasis group and arthritic-systemic psoriasis associated group. For nutritional assessment we used anthropometry, bioelectrical impedance analysis and whole-body plethysmography. Clinical and nutritional information were assessed using the clinical and nutritional history-taking, and the 24-hour dietary recall. For statistics the general linear model test (p < 0.05) was used. RESULTS: According to the body mass index 29.4% patients (n = 10) were eutrophic, 41.2% (n = 14) overweight and 29% (n = 10) obese. Almost all individuals (60%; n = 21) had body fat percentage above normal levels (> 25%) and a high risk for metabolic complications according to the waist circumference and the obesity index, however, there were no statistically significant differences between groups. The mean food intake, total fat, calories and protein were above recommended levels, being 58.8% for lipids (319.17 ± 241.02 mg of cholesterol and 17.42 ± 11.4 g saturated fatty acids); 29.4% for calories and 67.6% for proteins. Thus, regardless of the psoriasis type, an excessive consumption of calories, lipids, fatty acids, cholesterol and a higher incidence of overweight were found. CONCLUSION: The sample showed an abnormal nutritional condition, an increased risk for chronic diseases related to obesity, worsening of the psoriatic lesions, and poor quality of life.

Autoantibodies in patients with psoriasis on anti-TNFalpha therapy

Introduction: Anti-TNF-alfa therapy has been effective in the treatment of patients with refractory psoriasis and psoriasic arthritis. However, the risk of developing autoantibodies in these patients undergoing this therapy is not clear. Objective: To evaluate the induction of specific autoantibodies after anti-TNFα therapy in patients with psoriasis and psoriasic arthritis and, to evaluate the influence of the use of methotrexate on the values of autoantibodies developed during this therapy. Patients and methods: Serum samples from 120 patients, obtained before(baseline) the introduction of anti-TNF-alpha therapy and approximately each 3-6 months during the therapy.O f these 120 patients, 113 were found negative for autoantibodies before starting anti -TNFalpha therapy, 7 were found positive for ANA. The analysis included detection of antinuclear antibodies (ANA) and anti-dsDNA antibodies (indirect immunofluorescence on Hep-2 cells and Crithidia luciliae, respectively); anti extractable nuclear antigens antibodies( ENA)(ELISA). RESULTS: Infliximab is associated with the highest occurrence rate of ANA, anti-dsDNA, ENA with approximately 69,2%, 11,5%, 7,6% of patients treated testing positive. In comparison, only 20%, 6,6%, 2,2% of patients treated with Adalimumab, and 19%, 2,3%, 2,3% of patients treated with Etanercept were positive for ANA, Anti-dsDNA, ENA respectively. As regard the seven patients who were positive at baseline, six of them (85.7%) in addition to being remained positive during the therapy they have also increased the autoantibodies ’s titers. Conclusion: our study have shown that Infliximab is associated with the highest rate of autoantibodies. The concomitant treatment with methotrexate did not modify the titers of autoantibodies developed during the therapy anti-TNFalph. The incidence of ANA, anti-dsDNA antibodies did not correlate with development of Lupus-like syndromes. The difference in the frequency of autoantibodies between psoriasis and psoriatic arthritis was not statistically significant (p = 0.867).

Valutazione della psoriasi ungueale come fattore di rischio per lo sviluppo di artropatia psoriasica - studio pilota

Scopo della tesi è verificare se i pazienti affetti da psoriasi puramente ungueale sviluppano psoriasi artropatica e se esistono parametri clinici che possano permettere di predire lo sviluppo del danno articolare. Viene inoltre valutato l'impatto che la psoriasi ungueale, associata alla psoriasi artropatica, determina sulla qualità di vita dei nostri pazienti. L'artrite psoriasica è spesso associata a psoriasi ungueale, che è più frequente nei pazienti con artrite psoriasica rispetto ai pazienti con psoriasi cutanea. Vi è una stretta relazione funzionale tra l'unghia e l'articolazione interfalangea distale, i tendini e i legamenti: lo sviluppo di entesite della falange distale è infatti associato ad una infiammazione dell'apparato ungueale. Riportiamo i dati preliminari emersi dal nostro studio pilota, che conferma come siano necessari e doverosi ulteriori studi su popolazioni più ampie per determinare la relazione che sussiste fra psoriasi ungueale e psoriasi artropatica

β-glucan triggers spondylarthritis and Crohn's disease-like ileitis in SKG mice

The spondylarthritides (SpA), including ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, and arthritis associated with inflammatory bowel disease, cause chronic inflammation of the large peripheral and axial joints, eyes, skin, ileum, and colon. Genetic studies reveal common candidate genes for AS, PsA, and Crohn's disease, including IL23R, IL12B, STAT3, and CARD9, all of which are associated with interleukin-23 (IL-23) signaling downstream of the dectin 1 β-glucan receptor. In autoimmune-prone SKG mice with mutated ZAP-70, which attenuates T cell receptor signaling and increases the autoreactivity of T cells in the peripheral repertoire, IL-17-dependent inflammatory arthritis developed after dectin 1-mediated fungal infection. This study was undertaken to determine whether SKG mice injected with 1,3-β-glucan (curdlan) develop evidence of SpA, and the relationship of innate and adaptive autoimmunity to this process.

Alopecia areata universalis elicited during treatment with adalimumab

Adalimumab is a fully humanized recombinant anti-tumour-necrosis-factor (TNF-alpha) monoclonal antibody which has been approved for rheumatoid arthritis, active ankylosing spondylitis, psoriatic arthritis and Crohn's disease. We report a case of alopecia areata (AA) universalis occurring 6 months after administration of adalimumab monotherapy in a patient with a long-standing history of psoriatic arthritis and psoriasis. The diagnosis was confirmed by a scalp biopsy which showed a peribulbar infiltrate of both CD4+ and CD8+ T cells, CD1a+ dendritic cells as well as CD68+ and CD163+ macrophages. In addition, immunofluorescence staining for TNF-alpha was found in the mononuclear cell infiltrate. This case suggests a complex role of TNF-alpha in the induction of AA.

Novel genetic risk markers for ulcerative colitis in the IL2/IL21 region are in epistasis with IL23R and suggest a common genetic background for ulcerative colitis and celiac disease

OBJECTIVES: Recently, a genome-wide association study showed that single-nucleotide polymorphisms (SNPs) in the chromosome 4q27 region containing IL2 and IL21 are associated with celiac disease. Given the increased prevalence of inflammatory bowel disease (IBD) among celiac disease patients, we investigated the possible involvement of these SNPs in IBD. METHODS: Five SNPs strongly associated with celiac disease within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block on chromosome 4q27 and one coding SNP within the IL21 gene were analyzed in a large German IBD cohort. The study population comprised a total of 2,948 Caucasian individuals, including 1,461 IBD patients (ulcerative colitis (UC): n=514, Crohn's disease (CD): n=947) and 1,487 healthy unrelated controls. RESULTS: Three of the five celiac disease risk markers had a protective effect on UC susceptibility, and this effect remained significant after correcting for multiple testing: rs6840978: P=0.0082, P(corr)=0.049, odds ratio (OR) 0.77, 95% confidence interval (CI) 0.63-0.93; rs6822844: P=0.0028, P(corr)=0.017, OR 0.73, 95% CI 0.59-0.90; rs13119723: P=0.0058, P(corr)=0.035, OR 0.75, 95% CI 0.61-0.92. A haplotype consisting of the six SNPs tested was markedly associated with UC susceptibility (P=0.0025, P(corr)=0.015, OR 0.72, 95% CI 0.58-0.89). Moreover, in UC, epistasis was observed between the IL23R SNP rs1004819 and three SNPs in the KIAA1109/TENR/IL2/IL21 block (rs13151961, rs13119723, and rs6822844). CONCLUSIONS: Similar to other autoimmune diseases such as celiac disease, rheumatoid arthritis, type 1 diabetes, Graves' disease, and psoriatic arthritis, genetic variation in the chromosome 4q27 region predisposes to UC, suggesting a common genetic background for these diseases.

Dactilite na artrite psoriática

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Science of assessment

Psoriatic arthritis is a multisystem disorder which, from a measurement standpoint, demands consideration of its cutaneous manifestations and both axial and peripheral musculoskeletal involvement. Measurements of various aspects of impairment, ability/disability, and participation/ handicap are feasible using existing measurement techniques, which are for the most part valid, reliable, and responsive. Nevertheless, there remain opportunities for the further development of consensus around core set measures and responder criteria, as well as for instrument development and refinement, standardised assessor training, cross-cultural adaptation of health status questionnaires, electronic data capture, and the introduction of standardised quantitative measurement into routine clinical care.

Tumour necrosis factor inhibitors

The cytokine, tumour necrosis factor-alpha (TNF-alpha) plays a key role in the pathogenesis of many chronic inflammatory and rheumatic diseases, in particular, Crohn's disease, rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Controlled trials have shown that the TNF inhibitors (etanercept, infliximab and adalimumab) significantly reduce symptoms and signs, improve function and quality of life, and reduce radiologically evident damage in patients with rheumatoid diseases. For reasons that are not entirely clear, etanercept does not work in Crohn's disease. Injection site and intravenous reactions and increased risk of infection (in particular, reactivation of tuberculosis) are associated with the use of these agents. Increased risk of lymphoproliferative disease, the development of lupus-like syndromes and demyelination, including optic neuritis and reactivation of multiple sclerosis, are under evaluation in long-term follow-up studies. The TNF inhibitors are expensive (about $18000 per year), and in some patients need to be given continuously to maintain benefit, even in the presence of other immunosuppressive therapy.

Seronegative spondyloarthropathies: To lump or split?

The advent of novel biological therapies for the treatment of rheumatic disease has renewed interest in the seronegative spondyloarthropathies (SpAs). International efforts are redefining disease classification and measures of disease activity, outcome, metrology, and imaging. However, opinion is divided between those who propose that the SpA group represents the same disease with variable expression (the lumpers) and those who consider these to be separate diseases with shared clinical features (the splitters). This review presents the evidence for both approaches.

Non-major-histocompatibility-complex genetics of ankylosing spondylitis

There is strong evidence from twin and family studies indicating that a substantial proportion of the heritability of susceptibility to ankylosing spondylitis (AS) and its clinical manifestations is encoded by non-major-histocompatibility-complex genes. Efforts to identify these genes have included genomewide linkage studies and candidate gene association studies. One region, the interleukin (IL)-I gene complex on chromosome 2, has been repeatedly associated with AS in both Caucasians and Asians. It is likely that more than one gene in this complex is involved in AS, with the strongest evidence to date implicating IL-IA. Identifying the genes underlying other linkage regions has been difficult due to the lack of obvious candidates and the low power of most studies to date to identify genes of the small to moderate magnitude that are likely to be involved. The field is moving towards genomewide association analysis, involving much larger datasets of unrelated cases and controls. Early successes using this approach in other diseases indicates that it is likely to identify genes in common diseases like AS, but there remains the risk that the common-variant, common-disease hypothesis will not hold true in AS. Nonetheless, it is appropriate for the field to be cautiously optimistic that the next few years will bring great advances in our understanding of the genetics of this condition.