Abstract In this paper, we sought to determine the prevalence of arthritis mutilans in a single cohort of Brazilian psoriatic arthritis patients followed at a tertiary university reference center. Our study demonstrated a high prevalence of arthritis mutilans associated to comorbidities and biologic therapy. In addition, our data suggest that axial involvement may be an intriguing aspect of psoriatic arthritis mutilans and that rheumatologists should be aware of axial disease, even if the phenotype is marked by peripheral joint severity.

Abstract Background: Despite the criteria already established for the classification of knee osteoarthritis (OA), a radiographic and/or clinical knee OA diagnosis usually occurs in cases of fully manifest or more advanced disease, which can make health promotion, prevention, and functional rehabilitation in more advanced stages of the disease less effective. In addition, radiographic knee OA can generate more financial costs for health services. Therefore, developing and validating screening instruments to assess the probability of development and progression of knee OA would be of great value for both clinical practice and science. Objective: To cross-culturally adapt and investigate the measurement properties of the Knee OA Pre-screening Questionnaire Brazilian version. Methods: A total of 250 individuals of both sexes aged between 35 and 92 years [(mean (standard deviation): 63 (11) years old; 74.1 (15.1) kg; 1.59 (0.09) m; 29.38 (5.44) kg/m2] participated in this study. The cross-cultural adaptation and analyses of the measurement properties of the KOPS Brazilian version included: (1) assessment of conceptual and item equivalence; (2) assessment of semantic equivalence; (3) assessment of operational equivalence; and (4) assessment of measurement equivalence, reliability, and validity. Results: Cronbach's alpha for the internal consistency among the six components of the KOPS Brazilian version was 0.71. The test-retest 72 h apart for each component resulted in a coefficient correlation intraclass ranging from 0.74 to 1.00. The probability of an individual randomly chosen from the population having KL ≥ 1 and KOPS Brazilian version ≥ 21 points was 0.74 (area under the curve of the Receiver Operating Characteristic – AUC of ROC); furthermore, the AUC for KL ≥ 2 and the KOPS Brazilian version ≥ 23 points was 0.77. Conclusion: The KOPS Brazilian version is a reliable and valid instrument for early screening of knee OA in individuals aged 35 years and over in the Brazilian context.

Abstract Spondyloarthritis (SpA) is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. Over some decades, nonsteroidal anti-inflammatory drugs (NSAIDs) have been the basis for the pharmacological treatment of patients with axial spondyloarthritis (axSpA). However, the emergence of the immunobiologic agents brought up the discussion about the role of NSAIDs in the management of these patients. The objective of this guideline is to provide recommendations for the use of NSAIDs for the treatment of axSpA. A panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis of randomized clinical trials for 15 predefined questions. The Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations were used, and at least 70% agreement of the voting panel was needed. Fourteen recommendations for the use of NSAIDs in the treatment of patients with axSpA were elaborated. The purpose of these recommendations is to support clinicians’ decision making, without taking out his/her autonomy when prescribing for an individual patient.

Abstract Psoriatic arthritis (PsA) is a chronic and systemic immune disease characterized by inflammation of peripheral and/ or axial joints and entheses in patients with psoriasis (PsO). Extra-articular and extracutaneous manifestations and numerous comorbidities can also be present. These recommendations replace the previous version published in May 2013. A systematic review of the literature retrieved 191 articles that were used to formulate 12 recommendations in response to 12 clinical questions, divided into 4 sections: diagnosis, non-pharmacological treatment, conventional drug therapy and biologic therapy. These guidelines provide evidence-based information on the clinical management for PsA patients. For each recommendation, the level of evidence (highest available), degree of strength (Oxford) and degree of expert agreement (interrater reliability) are reported.

OBJECTIVES: To retrospectively evaluate the performance and distinctive pattern of latent tuberculosis (TB) infection (LTBI) screening and treatment in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) under anti-tumor necrosis factor (TNF) therapy and determine the relevance of re-exposure and other risk factors for TB development. METHODS: A total of 135 and 83 patients with AS and PsA, respectively, were evaluated for LTBI treatment before receiving anti-TNF drugs via the tuberculin skin test (TST), chest radiography, and TB exposure history assessment. All subjects were evaluated for TB infection at 3-month intervals. RESULTS: The patients with AS were more often treated for LTBI than were those with PsA (42% versus 30%, p=0.043). The former also presented a higher frequency of TST positivity (93% versus 64%, p=0.002), although they had a lower frequency of exposure history (18% versus 52%, p=0.027) and previous TB (0.7% versus 6%, p=0.03). During follow-up [median, 5.8 years; interquartile range (1QR), 2.2-9.0 years], 11/218 (5%) patients developed active TB (AS, n=7; PsA, n=4). TB re-exposure was the main cause in seven patients (64%) after 12 months of therapy (median, 21.9 months; IQR, 14.2-42.8 months) and five LTBI-negative patients. TB was identified within the first year in four patients (36.3%) (median, 5.3 months; IQR, 1.2-8.8 months), two of whom were LTBI-positive. There was no difference in the TB-free survival according to the anti-TNF drug type/class; neither synthetic drug nor prednisone use was related to TB occurrence (p>0.05). CONCLUSION: Known re-exposure is the most critical factor for incident TB cases in spondyloarthritis. There are also some distinct features in AS and PsA LTBI screening, considering the higher frequency of LTBI and TST positivities in patients with AS. Annual risk reassessment taking into consideration these peculiar features and including the TST should be recommended for patients in endemic countries.

Abstract Spondyloarthritis is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. The classification axial spondyloarthritis is adopted when the spine and/or the sacroiliac joints are predominantly involved. This version of recommendations replaces the previous guidelines published in May 2013. A systematic literature review was performed, and two hundred thirty-seven studies were selected and used to formulate 29 recommendations answering 15 clinical questions, which were divided into four sections: diagnosis, non-pharmacological therapy, conventional drug therapy and biological therapy. For each recommendation the level of evidence supporting (highest available), the strength grade according to Oxford, and the degree of expert agreement (inter-rater reliability) is informed. These guidelines bring evidence-based information on clinical management of axial SpA patients, including, diagnosis, treatment, and prognosis.

Abstract Background: The aims of this article were to assess the prevalence of nephrolithiasis and the factors associated with nephrolithiasis in Brazilian patients with primary gout. Methods: One hundred twenty-three patients with primary gout were recruited from a tertiary referral hospital in São Paulo, Brazil. All patients underwent ultrasonography and had their clinical and laboratory characteristics assessed. Results: One hundred fifteen (93.5%) patients were male, with a mean age of 62.9 ± 9.4 years. Twenty-three (18.7%) patients had asymptomatic nephrolithiasis (detected only by ultrasonography), 7 (6.0%) had symptomatic nephrolithiasis (detected by ultrasonography and a positive clinical history), and 13 (10.0%) had a history of kidney stones, but ultrasonography at evaluation did not show nephrolithiasis. Therefore, 35.0% of the patients had nephrolithiasis (detected either by ultrasonography and/or a positive clinical history). Nephrolithiasis was associated with male gender (43 [100%] vs 72 [90%], p = 0.049), the use of potassium citrate (13 [30.2%] vs 0, p < 0.001) and the use of medications for diabetes (10 [23.3%] vs 8 [10%], p = 0.047) and dyslipidemia (15 [34.9%] vs 10 [12.5%], p = 0.003); benzbromarone had an inverse association with nephrolithiasis (21 [48.8%] vs 55 [68.8%], p = 0.030). In patients with and without nephrolithiasis, no differences were found in the laboratory and ultrasonography characteristics, including serum uric acid levels, urinary uric acid excretion and urine pH. Conclusions: The prevalence of nephrolithiasis in primary gout was 35.0%, and 18.7% of the patients were asymptomatic. Nephrolithiasis was associated with male gender, diabetes and dyslipidemia. A positive history of nephrolithiasis probably biased the prescription of potassium citrate and benzbromarone.

Abstract Background: Adaptive immune cells, including CD4+CD69+ and CD4+CD25+FoxP3+ regulatory T (Treg) cells, are important for maintaining immunological tolerance. In human systemic lupus erythematosus (SLE), CD4+CD25+FoxP3+ Treg cells are reduced, whereas CD69 expression is increased, resulting in a homeostatic immune imbalance that may intensify autoreactive T cell activity. To analyze the mechanisms implicated in autotolerance failure, we evaluated CD4+CD69+ and CD4+CD25+FoxP3+ T cells and interleukin profiles in a pristane-induced SLE experimental model. Methods: For lupus induction, 26 female Balb/c mice received a single intraperitoneal 0.5 ml dose of pristane, and 16 mice received the same dose of saline. Blood and spleen samples were collected from euthanized mice 90 and 120 days after pristane or saline inoculation. Mononuclear cells from peripheral blood (PBMC), peritoneal lavage (PL) and splenocytes were obtained by erythrocyte lysis and cryopreserved for further evaluation by flow cytometry using the GuavaEasyCyte TM HT. After thawing, cells were washed and stained with monoclonal antibodies against CD3, CD4, CD8, CD25, CD28, CD69, FoxP3, CD14 and Ly6C (BD Pharmingen TM). Interleukins were quantified using Multiplex® MAP. The Mann-Whitney test and the Pearson coefficient were used for statistical analysis, and p < 0.05 considered significant. Results: Compared with the controls, SLE-induced animals presented increased numbers of CD4+CD69+ T cells in the blood on T90 and T120 (p = 0.022 and p = 0.008) and in the spleen on T120 (p = 0.049), but there were decreased numbers in the PL (p = 0.049) on T120. The percentage of Treg was lower in blood (p < 0.005 and p < 0.012) on T90 and T120, in spleen (p = 0.043) on T120 and in PL (p = 0.001) on T90. Increased numbers of CD4+ CD69+ T cells in the PL were positively associated with high IL-2 (p = 0.486) and IFN-γ (p = 0.017) levels, whereas reduced Treg cells in the blood were negatively correlated with TNFα levels (p = 0.043) and positively correlated with TGFβ1 (p = 0.038). Conclusion: Increased numbers of CD4+CD69+ T cells and reduced numbers of CD4+CD25+FoxP3+ Treg cells with an altered interleukin profile suggests loss of autotolerance in pristane-induced lupus mice, which is similar to human lupus. Therefore, this model is useful in evaluating mechanisms of cellular activation, peripheral tolerance and homeostatic immune imbalance involved in human SLE.

Abstract Objective: To determine the clinical and demographic factors associated with disease remission and drug survival in patients with ankylosing spondylitis (AS) on TNF inhibitors. Methods: Data from a longitudinal electronic database of AS patients under anti-TNF therapy between June/2004 and August/2013. Demographic, clinical parameters, disease activity by ASDAS remission (< 1.3) and inactive/low (< 2.1) were analyzed to characterize reasons for drug survival and switching of anti-TNF. Results: Among 117 AS patients, 69 (59%) were prescribed only one anti-TNF, 48 (41%) switched to a second anti-TNF and 13 (11%) to a third anti-TNF. Considering ASDAS-CRP < 1.3, 31 (39%) patients were inactive at the end of the study. Non-switchers (P = 0.04), younger age (P = 0.004), non-smoking (P = 0.016), shorter disease duration (P = 0.047), more frequent use of SSZ (P = 0.037) and lower BASDAI (P = 0.027), BASMI (P = 0.034) and BASFI (P = 0.003) at baseline were associated with remission. In the multivariate analysis younger age (P = 0.016) and lower BASDAI (P = 0.032) remained as remission predictors. Conclusion: This study supports that ASDAS-CRP remission is an achievable goal not only for non-switchers but also for second anti-TNF, particularly in patients with younger age and lower BASDAI at baseline. Comedication and non-smoker status seems to have a beneficial effect in anti-TNF response in this population.

Resumo Objetivo: Avaliar, em um país endêmico, a eficácia em longo prazo do rastreamento à procura de infecção latente por tuberculose (ILTB) e profilaxia primária em pacientes com AIJ em uso de bloqueadores do TNF. Métodos: Trata-se de uma coorte retrospectiva que incluiu pacientes com AIJ elegíveis para a terapia anti-TNF. Os pacientes foram rastreados à procura de ILTB previamente ao uso de anti-TNF por meio do teste tuberculínico (TT), radiografia de tórax e história de exposição à TB. Os indivíduos foram acompanhados regularmente em intervalos de dois meses. Resultados: Incluíram-se 69 pacientes com AIJ com idade atual de 17,4 ± 5,8 anos, com média de duração da doença de 5 ± 4,9 anos; 47 pacientes receberam um único anti-TNF, enquanto 22 foram transferidos para outro anti-TNF uma ou duas vezes: 57 foram tratados com etanercepte, 33 com adalimumabe e três com infliximabe. O rastreamento à procura de ILTB foi positivo em três pacientes: um era TT positivo e tinha história de exposição à TB e dois apenas eram TT positivo. Não foi diagnosticado caso de TB ativa durante o período de estudo (mediana de seguimento de 3,8 anos). Conclusão: A avaliação em longo prazo revelou que o rastreamento à procura de ILTB e a profilaxia primária antes do tratamento com anti-TNF foram eficazes em um país de alto risco para TB e o TT foi o parâmetro mais sensível para identificar esses pacientes.

Abstract Objectives: To evaluate, in an endemic country, the long-term efficacy of latent tuberculosis infection (LTBI) screening and primary prophylaxis in patients with JIA receiving TNF blockers. Methods: This was a retrospective cohort that included JIA patients eligible to anti-TNF therapy. Patients were screened for LTBI prior to anti-TNF using tuberculin skin test (TST), chest X-ray and history of exposure to TB. Subjects were regularly followed at 2-month intervals. Results: Sixty-nine JIA patients with current age of 17.4 ± 5.8 years, mean disease duration of 5.0 ± 4.9 years were included. Forty-seven patients received a single anti-TNF, while 22 patients switched to another anti-TNF once or twice: 57 were treated with etanercepte, 33 patients with adalimumab and 3 infliximab. LTBI screening was positive in three patients: one had TST-positive and history of TB exposure and two had solely TST-positive. No active TB was diagnosed during the study period (median of follow-up was 3.8 years). Conclusion: Long-term evaluation revealed that LTBI screening and primary prophylaxis before anti-TNF treatment was effective in a high-risk country and TST was the most sensitive parameter to identify these patients.

Resumo Objetivo Avaliar a prevalência de infecção pelo vírus da hepatite C (VHC) em pacientes de alto risco com lúpus eritematoso sistêmico de início juvenil (LESJ). Desenho do estudo Foram estudados 40 pacientes de baixa renda com LESJ (6 H: 34 M, com média de 19 ± 4,4 anos; duração média da doença de 6 ± 3,2 anos). Incluíram-se no grupo controle 20 crianças e adolescentes saudáveis pareados por nível socioeconômico. Fizeram-se testes anti-VHC com um ensaio imunoenzimático de micropartículas de terceira geração. O critério de inclusão foi o baixo nível socioeconômico. Resultados As frequências de anticorpos anti-VHC foram baixas e comparáveis entre os grupos LESJ e controle (2,5% versus 0, p = 1). Os pacientes com LESJ tinham significativamente mais fatores de risco para infecção por VHC em comparação com o grupo controle, incluindo tratamento imunossupressor (90% versus 0, p < 0,0001), internação (50% versus 12,5%, p = 0,0006) e procedimentos invasivos (47,5% versus 12,5%, p = 0,001). Conclusões A baixa frequência de anticorpos anti-VHC observada nos pacientes de alto risco com LESJ sugere que esse vírus não parece ter um papel relevante na patogênese dessa doença.

Abstract Objective To evaluate the prevalence of hepatitis C virus (HCV) infection in high risk juvenile systemic lupus erythematosus (JSLE). Study design Forty low income JSLE patients (6M:34F; mean age 19 ± 4.4 yrs; mean disease duration 6 ± 3.2 yrs) were studied. Twenty healthy children and adolescents matched for social economical level were included as controls. Anti-HCV tests were performed using a third generation microparticle enzyme immunoassay. Inclusion criterion was low social economical level. Results The frequencies of anti-HCV antibody were low and comparable between JSLE and control group (2.5% vs. 0, p = 1.0). JSLE patients had significantly more risk factors for HCV infection compared to the control group, including immunosuppressive treatment (90% vs. 0, p < 0.0001), hospitalization (50% vs. 12.5%, p = 0.0006) and invasive procedures (47.5% vs. 12.5%, p = 0.001). Conclusions The observed low frequency of anti-HCV antibodies in high risk JSLE suggests that this virus does not seem to have a relevant role in the pathogenesis of this disease.

A gota axial pode afetar todos os segmentos da coluna vertebral. Ela se manifesta como dor nas costas, dor associada com sintomas neurológicos, e como comprometimento neurológico sem dor em 17,9%, 75,8% e 4,2% dos casos, respectivamente. Essas manifestações foram a primeira apresentação da gota em muitos pacientes. Embora radiografias, bem como tomografia computadorizada e especialmente ressonância magnética, possam ser muito sugestivos, análises histopatológicas, citológicas e pesquisa de cristais são o padrão ouro de diagnóstico. Na maioria dos casos que envolveram manifestações neurológicas, o paciente foi submetido à cirurgia, levando a resultados satisfatórios. Há, no entanto, alguns relatos de recuperação total após o tratamento clínico habitual para gota, o que sugere que esse tratamento pode ser a opção inicial para os indivíduos com histórico de gota e sinais radiológicos de envolvimento axial.

Axial gout can affect all segments of the spine. It is manifested as back pain, as pain associated with neurological symptoms, and as neurological impairment without pain in 17.9%, 75.8% and 4.2% of cases, respectively. These manifestations were the first presentation of gout in many patients. Although x-rays as well as computed tomography and especially magnetic resonance scans can be very suggestive, histopathological, cytological and crystal analyses are the diagnostic gold standard. In most cases involving neurological manifestations, the patient underwent surgery, leading to satisfactory results. There are, however, some reports of full recovery following the usual clinical treatment for gout, suggesting that such treatment may be the initial option for those subjects with a history of gout and radiological findings of axial involvement

OBJETIVO: Conduzir uma adaptação cultural cruzada do Índice Funcional de Espondilite Anquilosante de Bath (BASFI, Bath Ankylosing Spondylitis Functional Index) para o português do Brasil e avaliar suas propriedades de medição. MéTODOS: O BASFI foi traduzido por quatro reumatologistas e três professores de língua inglesa. O questionário traduzido foi aplicado a pacientes com espondilite anquilosante por observadores treinados e autoaplicado em três momentos, dias 1, 2 e 14. A validade foi estimada analisando-se a associação do BASFI e as medidas de capacidade funcional (rotação cervical, distância intermaleolar, teste de Schober e distância occipito-parede). A consistência interna foi testada pelo coeficiente α de Cronbach, e a confiabilidade pelo teste-reteste (coeficiente de correlação intraclasse [CCI]). RESULTADOS: Foram incluídos 60 pacientes com espondilite anquilosante: 85% do gênero masculino, com idade média de 47 ± 12 anos e duração média da doença de 20 ± 11 anos. A confiabilidade intraobservador no teste-reteste (intervalo de duas semanas) revelou alto ICC (0,999; 95% IC: 0,997-0,999), além de alta consistência interna (coeficiente α de Cronbach: 0,86; 95% IC: 0,80-0,90). Considerando-se a validade, os índices do BASFI foram correlacionados com a rotação cervical (0,53; P < 0,001) e a distância intermaleolar (0,50; P < 0,001). CONCLUSÃO: A versão do BASFI para o português do Brasil é confiável e válida para avaliação de pacientes com espondilite anquilosante.

OBJECTIVE: To conduct a cross-cultural adaptation of the Bath Ankylosing Spondylitis Functional Index (BASFI) into Brazilian-Portuguese language and to assess its measurement properties. METHODS: The BASFI was translated by four rheumatologists and three English teachers. The translated questionnaire was applied to ankylosing spondylitis patients by trained observers, and self-administered in three moments: days 1, 2, and 14. The validity was assessed analyzing the association of BASFI and functional capacity measures (cervical rotation, intermalleolar distance, Schober's test and occiput-to-wall distance). The internal consistence was tested by Cronbach's αcoefficient and the reliability by testretest (intraclass correlation coefficient - ICC). RESULTS: A total of 60 patients with ankylosing spondylitis was included: 85% male, mean age 47 ± 12 years, and mean disease duration 20 ± 11 years. The intra-observer test-retest (two-week interval) reliability showed a high ICC (0.999, 95% CI: 0.997-0.999) and a high internal consistency (Cronbach's α coefficient: 0.86, CI 95%: 0.80-0.90). Considering the validity, the BASFI indices were correlated with cervical rotation (0.53, P < 0.001) and with intermalleolar distance (0.50, P < 0.001). CONCLUSION: The BASFI Brazilian-Portuguese version is reliable and valid for assessment of patients with ankylosing spondylitis.

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

Psoriatic arthritis (PsA) is a systemic, polymorphic joint disease with variable presentation and clinical course. The outcome depends on the association with severe comorbidities such as diabetes, hypertension and dyslipidemia. Early diagnosis requires a high degree of clinical suspicion, especially when skin manifestations are subtle and poorly defined. Progressive erosive disease can occur in up to half of patients, associated with anatomical and functional changes in about 20%. Thus, the prognosis of PsA remains unclear, especially if diagnosis and treatment are delayed. Based on extensive literature review (PubMed and Lilacs) and experience of our services, new concepts of immunogenetics, pathophysiology, and clinical and therapeutic aspects are discussed. Factors that reduce the quality of life and life expectancy of patients, as well as new guidelines for treatment, will be emphasized. Control of inflammation, especially in enthesitis and axial forms of PsA, was made possible due to the introduction of anti-TNF biologics. Finally, the role of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) should be emphasized, since it promotes meetings and joint studies between rheumatologists and dermatologists to provide scientific evidence for the sweeping changes in clinical management and treatment of patients with PsA