Rheumatoid arthritis seems to have DMARD treatment decision influenced by fibromyalgia.

OBJECTIVE: To compare DMARD use in patients with and without FM over time, including overtreatment and undertreatment rates in both groups. METHODS: A prospective cohort study with patients attending an RA outpatient clinic was conducted. Participants were consecutively recruited between March 2006 and June 2007 and were followed through December 2013. Data on DMARD use (prevalences, doses and escalation rates), DAS28, HAQ and radiographic progression were compared among RA patients with FM and without FM. Mistreatment clinical scenarios were allegedly identified and compared between groups. RESULTS: 256 RA patients (32 with FM) were followed for 6.2±2.0 (mean±SD) years comprising 2986 visits. At baseline, RA duration was 11.1±7.4 years. DAS28 and HAQ were greater in RA with FM group, and were closer to RA without FM group towards the end. RA patients with FM used higher doses of tricyclic antidepressants, leflunomide and prednisone, and lower doses of methotrexate. When compared to RA patients without FM, participants with RA and FM used more often tricyclic antidepressants, leflunomide, prednisone, continuous analgesics and less often methotrexate. Groups presented similar 7-year biologic-free survival, and radiographic progression-free survival in Cox regression. RA patients with FM had greater proportions of visits in mistreatment scenarios when compared to RA patients without FM (28.4 vs. 19.8%, p<0.001). CONCLUSIONS: RA patients with FM used more leflunomide and prednisone, and RA mistreatment was more frequent in FM patients. Certainly, RA patients with FM will benefit from a personalized T2T strategy, including ultrasound (when suitable) and proper FM treatment.

Rheumatoid arthritis seems to have DMARD treatment decision influenced by fibromyalgia / As decisões de tratamento com DMARD na artrite reumatoide parecem ser influenciadas pela fibromialgia

Abstract Objective: To compare DMARD use in patients with and without FM over time, including overtreatment and undertreatment rates in both groups. Methods: A prospective cohort study with patients attending an RA outpatient clinic was conducted. Participants were consecutively recruited between March 2006 and June 2007 and were followed through December 2013. Data on DMARD use (prevalences, doses and escalation rates), DAS28, HAQ and radiographic progression were compared among RA patients with FM and without FM. Mistreatment clinical scenarios were allegedly identified and compared between groups. Results: 256 RA patients (32 with FM) were followed for 6.2 ± 2.0 (mean ± SD) years comprising 2986 visits. At baseline, RA duration was 11.1 ± 7.4 years. DAS28 and HAQ were greater in RA with FM group, and were closer to RA without FM group towards the end. RA patients with FM used higher doses of tricyclic antidepressants, leflunomide and prednisone, and lower doses of methotrexate. When compared to RA patients without FM, participants with RA and FM used more often tricyclic antidepressants, leflunomide, prednisone, continuous analgesics and less often methotrexate. Groups presented similar 7-year biologic-free survival, and radiographic progression-free survival in Cox regression. RA patients with FM had greater proportions of visits in mistreatment scenarios when compared to RA patients without FM (28.4 vs. 19.8%, p < 0.001). Conclusions: RA patients with FM used more leflunomide and prednisone, and RA mistreatment was more frequent in FM patients. Certainly, RA patients with FM will benefit from a personalized T2T strategy, including ultrasound (when suitable) and proper FM treatment.

Resumo Objetivo: Comparar o uso de fármacos antirreumáticos modificadores da doença (DMARD) em pacientes com e sem fibromialgia (FM) ao longo do tempo, incluindo as taxas de tratamento excessivo e subtratamento em ambos os grupos. Métodos: Estudo de coorte prospectiva com pacientes atendidos em um ambulatório de artrite reumatoide (AR). Os participantes foram recrutados consecutivamente entre março de 2006 e junho de 2007 e foram seguidos até dezembro de 2013. Compararam-se os dados de uso de DMARD (prevalências, doses e taxas de escalonamento), 28-Joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) e progressão radiográfica entre pacientes com e sem FM. Os cenários clínicos de tratamento supostamente incorreto foram identificados e comparados entre os grupos. Resultados: Seguiram-se 256 pacientes com AR (32 com FM) por 6,2 ± 2,0 (média ± DP) anos, período que abrangeu 2.986 consultas. No início do estudo, a duração da AR era de 11,1 ± 7,4 anos. O DAS28 e o HAQ foram maiores no grupo AR com FM e estavam mais próximos do grupo AR sem FM no fim do estudo. Os pacientes com AR com FM usaram doses mais altas de antidepressivos tricíclicos, leflunomida e prednisona e doses mais baixas de metotrexato. Quando comparados com os pacientes com AR sem FM, os participantes com AR e FM usaram mais frequentemente antidepressivos tricíclicos, leflunomida, prednisona e analgésicos contínuos e menos frequentemente metotrexato. Os grupos apresentaram sobrevida em sete anos sem agentes biológicos e livres de progressão radiográfica semelhantes na regressão Cox. Os pacientes com AR com FM apresentaram uma maior proporção de consultas em cenários de tratamento supostamente incorreto quando comparados com os pacientes com AR sem FM (28,4 vs. 19,8%, p < 0,001). Conclusões: Os pacientes com AR e FM usaram mais leflunomida e prednisona e o tratamento supostamente incorreto na AR foi mais frequente em pacientes com FM. Os pacientes com AR com FM certamente se beneficiarão de uma estratégia personalizada de tratamento por metas (T2 T), incluindo ultrassonografia (quando apropriado) e controle da FM.

Rheumatoid arthritis seems to have DMARD treatment decision influenced by fibromyalgia. / As decisões de tratamento com DMARD na artrite reumatoide parecem ser influenciadas pela fibromialgia.

OBJECTIVE: To compare DMARD use in patients with and without FM over time, including overtreatment and undertreatment rates in both groups. METHODS: A prospective cohort study with patients attending an RA outpatient clinic was conducted. Participants were consecutively recruited between March 2006 and June 2007 and were followed through December 2013. Data on DMARD use (prevalences, doses and escalation rates), DAS28, HAQ and radiographic progression were compared among RA patients with FM and without FM. Mistreatment clinical scenarios were allegedly identified and compared between groups. RESULTS: 256 RA patients (32 with FM) were followed for 6.2±2.0 (mean±SD) years comprising 2,986 visits. At baseline, RA duration was 11.1±7.4 years. DAS28 and HAQ were greater in RA with FM group, and were closer to RA without FM group towards the end. RA patients with FM used higher doses of tricyclic antidepressants, leflunomide and prednisone, and lower doses of methotrexate. When compared to RA patients without FM, participants with RA and FM used more often tricyclic antidepressants, leflunomide, prednisone, continuous analgesics and less often methotrexate. Groups presented similar 7-year biologic-free survival, and radiographic progression-free survival in Cox regression. RA patients with FM had greater proportions of visits in mistreatment scenarios when compared to RA patients without FM (28.4 vs. 19.8%, p<0.001). CONCLUSIONS: RA patients with FM used more leflunomide and prednisone, and RA mistreatment was more frequent in FM patients. Certainly, RA patients with FM will benefit from a personalized T2T strategy, including ultrasound (when suitable) and proper FM treatment.

Ficolin Gene Polymorphisms in Systemic Lupus Erythematosus and Rheumatoid Arthritis.

Systemic lupus erythemathosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune diseases characterized by an immune balance breakdown and by chronic inflammation. Several findings link SLE and RA development with the complement system and ficolin components have emerged as candidates for disease development. Since genetic association studies with ficolin genes in SLE and RA have not yet been conducted in a Brazilian population, the aim of this study was to determine whether polymorphisms of ficolin-1(FCN1) and ficolin-2 (FCN2) genes are associated with SLE and RA susceptibility as well as disease manifestation. Two SNPs within FCN1 (rs2989727 and 1071583) and three in FCN2 (rs17514136, rs3124954, and rs7851696) were studied in 208 SLE and184 RA patients as well as 264 healthy individuals in a Southeast Brazilian population. For SLE patients, the FCN2 rs17514136 SNP was associated with a more severe disease (SLICC) (p = 0.0067). Furthermore, an association between the occurrence of nephritis and the T/T genotype for FCN2 rs3124954 SNP (p = 0.047, OR = 3.17, 95%CI = 1.34-7.5) was observed. No association was observed between the studied polymorphisms and RA development. Thus, our data support involvement of the FCN2 gene in the SLE phenotype.

Experiência da adoção do I e II Consensos Brasileiros de Fator Antinuclear por Imunofluorescência Indireta em Células HEp-2 em um hospital universitário / Experience of an university hospital on the implementation of I and II Brazilian Consensuses for Standardization of ANA in HEp-2 Cells

OBJETIVO: Analisar a prevalência, padrões e títulos do Fator Antinuclear (FAN) por imunofluorescência indireta (IFI) em células HEp-2 em um hospital universitário após a adoção do I e II Consensos Nacional para Padronização dos Laudos de FAN em Células HEp-2. MÉTODO: Foi realizado um estudo transversal, em que foram revisados os laudos de FAN por IFI originários de solicitações encaminhadas ao Serviço de Patologia Clínica do Hospital de Clínicas de Porto Alegre (SPC/HCPA) entre 2002 e 2005. RESULTADOS: Foram analisados 12.095 testes de FAN no período entre 2002 e 2005. As solicitações com resultado reagente foram de 2.577 (21,30 por cento), com média anual de 644±233). Houve um aumento significativo na proporção de resultados reagentes posterior à adoção dos Consensos (p < 0,001). A Reumatologia foi a especialidade que mais solicitou exames por paciente atendido, mas houve um declínio nesse número nos anos posteriores à adoção do Consenso, ocorrido em 2004 (p < 0,001). O padrão de imunofluorescência de FAN mais frequentemente encontrado foi o padrão nuclear pontilhado fino, presente em 52,3 por cento dos resultados reagentes (453/866), e os títulos mais encontrados foram 1/80 e 1/160 (27,8 por cento e 29,4 por cento, respectivamente). CONCLUSÃO: Após a adoção do Consenso Nacional de Padronização de Laudos de FAN, observou-se um aumento de exames com resultados reagentes, na sua maioria, com títulos baixos e padrão nuclear pontilhado fino. Na Reumatologia, observou-se uma diminuição no número de solicitações desse exame. As potenciais causas para essas observações são discutidas, mas seu real impacto sobre a situação clínica do paciente e seu tratamento merece ser mais bem estudado.

OBJECTIVE: To evaluate the prevalence of patterns and titers of antinuclear antibodies (ANA) detected by indirect immunofluorescence (IIF) technique on HEp-2 cells in a university hospital following the introduction of I and II Brazilian Consensuses for Standardization of ANA in HEp-2 Cells. METHODS:A transversal study was performed between 2002 and 2005 during which all ANA orders to Serviço de Hospital de Clínicas de Porto Alegre (SPC/HCPA) and cognate results were reviewed. RESULTS:12.095 tests of ANA were revised. The number of positive results during this period was 2.577 (21.30 percent), annual mean 644 (SD: 233). A marked increase in the number of positive results was observed following the introduction of the Consensuses (p < 0.001). Rheumatology was the medical specialty which requested the highest number of ANA testing per patient although a significant decrease of these numbers was observed after the introduction of the Consensus in 2004 (p < 0,001). Nuclear fine speckled immunofluorescence labeling was the most frequently ANA pattern observed, 52.3 percent (453/866), and low ANA titers (1/80 and 1/160) more commonly detected (27.8 percent and 29.4 percent, respectively). CONCLUSION: Following the introduction of the Brazilian Consensus for standardization of ANA in HEp-2 cells an increased number of positive results was observed, mostly in low titers and with nuclear fine speckled immunofluorescence pattern. Moreover, there were decreasing numbers of ANA orders by rheumatologists in the same period. Potential causes for these observations are discussed but the real impact in the clinical condition of the patient and therapy deserves to be better studied.

Acquired factor XI inhibitor in systemic lupus erythematosus--case report and literature review.

OBJECTIVES: Rare patients with systemic lupus erythematosus (SLE) patients exhibit anticoagulants that interfere in the earlier stages of the intrinsic coagulation pathway, such as those involving factor XI (FXI). The objectives of our study were to describe the presence of an acquired inhibitor to FXI causing a life-threatening bleeding disorder in an SLE patient and to review the association of this coagulopathy with SLE. METHODS: We describe the clinical presentation of an SLE patient with an acquired FXI inhibitor. We reviewed the scientific literature using the MEDLINE database searching the following combinations of terms: "SLE and Factor XI," "SLE and Factor XI inhibitor," and "Factor XI inhibitor," from 1964 to 2007. RESULTS: A 20-year-old woman with a 6-year history of SLE was admitted to the hospital because of severe life-threatening abdominal bleeding due to a ruptured ovarian cyst. This hemorrhagic event was related to the presence of an FXI inhibitor. We reviewed another 13 SLE patients with this condition, 8 of whom had bleeding events. Most patients had manifestations of active SLE, and prednisone was used as the primary treatment. CONCLUSIONS: SLE activity seems to be associated with the production of antibodies directed against FXI, which may cause important coagulopathies, especially bleeding events. The inhibitor disappeared after immunosuppressive therapy for SLE in most cases, suggesting that the appearance of this inhibitor is immune mediated. Although the majority of cases with the FXI inhibitor are not fatal, it should be suspected and investigated in SLE patients, especially those with abnormal clotting tests.

Growth velocity and interleukin 6 concentrations in juvenile idiopathic arthritis.

OBJECTIVE: .To evaluate associations of growth velocity with inflammatory markers and cumulative dose of glucocorticoid in a cohort of patients with juvenile idiopathic arthritis (JIA) followed during 1 year. METHODS: Seventy-nine patients were evaluated. Disease activity was evaluated by a pediatric rheumatologist. Anthropometric data were classified according to the World Health Organization standards. Tanner growth velocity curves were used; values below the Z-score < or = -2 were considered low growth velocity. Serum concentrations of interleukin 6 (IL-6) were measured by ELISA, and values > 1 pg/ml were considered elevated. RESULTS: The prevalence of low growth velocity was 25.3%, and it was associated with active disease on followup visit, elevated IL-6, erythrocyte sedimentation rate and C-reactive protein, and higher cumulative glucocorticoid doses. In the multiple linear regression with growth velocity as the dependent variable, only elevated IL-6 level was independently and negatively associated with growth velocity. CONCLUSION: Low growth velocity is highly prevalent in children with JIA. Elevated IL-6 levels seem to have an important negative influence on growth in these children, while total glucocorticoid exposure appears to be a secondary factor.

Padrões de imunofluorescência do fator antinuclear (FAN) em células HEp-2 de soros reagentes para anti-SSA/Ro / Antinuclear antibodies (ANA) immunofluorescent patterns in HEp-2 cells on samples positive for anti-SSA/Ro

OBJETIVO: avaliar os padrões de imunofluorescência do fator antinuclear (FAN) em soros reagentes para anticorpos anti-SSA/Ro e sua associação clínica. MÉTODO: foi realizado um estudo transversal retrospectivo, no qual foram revisadas as solicitações de anticorpos antiantígenos nucleares extraíveis (anti-ENA) encaminhadas ao SPC/HCPA no período de dois anos. Das solicitações com resultado positivo para anti-ENA identificou-se qual ou quais auto-anticorpos estavam envolvidos (anti-SSA/Ro, anti-SSB/La, anti-RNP, anti-Sm, anti-Scl-70), bem como os padrões de imunofluorescência do FAN e os quadros clínicos dos pacientes anti-SSA/Ro positivo. As técnicas usadas para detecção e identificação foram FAN por imunofluorescência indireta (IFI) em células HEp-2 e anti-ENA por hemaglutinação. RESULTADOS: das 392 solicitações analisadas 90 eram anti-ENA positivo. Houve um predomínio do sexo feminino (94 por cento) (86/91) e a idade média foi de 42 anos. O anti-SSA/Ro foi o mais freqüente (67,8 por cento) (61/90), sendo que todas as amostras anti-SSA/Ro positivas eram positivas para o FAN. O padrão de imunofluorescência nuclear pontilhado fino foi o predominante (68,9 por cento) (42/61) nos pacientes com anti-SSA/Ro positivo, e o quadro clínico mais encontrado foi de lúpus eritematoso sistêmico, em 50,8 por cento (31/61) dos pacientes. CONCLUSÃO: o teste de FAN por IFI utilizando células HEp-2 é um bom método de triagem para detecção de auto-anticorpos anti-SSA/Ro, apresentando maior associação com o padrão nuclear pontilhado fino. Diferente do que tem sido descrito na literatura, não encontramos nenhuma amostra de pacientes com anti-SSA/Ro que tenham apresentado FAN falso-negativo na IFI. Pelo menos na nossa experiência, esses dados questionam o custo-efetividade da solicitação de rotina desse exame em pacientes FAN negativo pelo teste de IFI.

OBJECTIVE: to evaluate the pattern at immunofluorescence of the antinuclear antibodies (ANA) detected by the indirect immunofluorescence (IIF) technique in positive samples for anti-SSA/Ro autoantibody and the clinical associations. METHODS: a retrospective transversal study was performed in a period of two years where the all the solicitations of testing for the presence of anti-extractable nuclear antigen (anti-ENA) antibodies delivered to the SPC/HCPA were analyzed. We selected the positive samples and identified which autoantibodies were involved (anti-SSA/RO, anti-SSB/La, anti-RNP, anti-Sm and anti-Scl70) as well as the immunofluorescence patterns by ANA testing and the clinical associations found in the patients presenting anti-SSA/Ro positive serum. IIF was used for ANA using HEp-2 cells and hemagglutination for anti-ENA antibodies detection. RESULTS: 90 out of the 392 solicitations analyzed were anti-ENA positive, with a predominance of women (86/91 - 94 percent) and the mean age was 42 years old. The most frequent autoantibody was anti-SSA/Ro (61/90 - 67.8 percent) and all samples that were anti-SSA/Ro positive were also ANA positive. Speckled nuclear immunofluorescence was the most frequent ANA pattern (42/61 - 68.9 percent) among the anti-SSA/Ro positive samples and systemic lupus erythematosus was the most common clinical diagnosis (31/61 - 50.8 percent). CONCLUSION: ANA testing by IIF using HEp-2 cells proved to be a good screening test for the detection of anti-SSA/Ro antibodies, that showed a strong positive association to the speckled nuclear IIF pattern. As opposed to what has been described in the literature, there was no ANA negative among the anti-SSA/Ro positive samples. At least in our experience, these data question the cost-effectiveness of performing routine screening for anti-SSA/Ro antibodies in ANA negative samples by IIF testing.

Neuropsychiatric systemic lupus erythematosus: correlation of brain MR imaging, CT, and SPECT.

Systemic lupus erythematosus (SLE) patients frequently present with neuropsychiatric symptoms. We conducted an imaging study with magnetic resonance (MR) imaging, computed tomography (CT), and single photon emission CT (SPECT) in 23 patients with SLE, 13 with major neuropsychiatric symptoms (NPSLE) and 10 without (non-NPSLE). The most frequent brain imaging findings were seen with MR imaging and were more prevalent in NPSLE: high signal intensity focal white matter lesions, infarcts in the cortex and pons, and basal ganglia lesions.

Pregnancy and systemic sclerosis

Objetivo: Avaliar a mútua relaçao entre gravidez e esclerose sistêmica. Métodos: Estudo multicêntrico retrospectivo de 570 pacientes com esclerodermia, de ambos os sexos. Foram incluídas 94 gravidezes, com a finalidade de avaliar os efeitos da gravidez na evoluçao clínica da doença. Os efeitos da esclerose sistêmica na gravidez também foram considerados. Em todas essas pacientes, a gravidez ocorreu após o início da doença. Resultados: Os autores encontraram perda fetal em 28 (29,78 por cento) - aborto (21,27 por cento), morte fetal (4,25 por cento) e prematuridade (8,51 por cento) - diretamente relacionada com a esclerose sistêmica. Quando a gravidez foi avaliada em sua açao sobre a evoluçao clínica da doença, a morte materna ocorreu em 6,38 por cento. Insuficiência renal post-partum foi a causa principal de morte em quatro pacientes. Duas outras tiveram aumento importante de atividade da doença com grave comprometimento cardiorespiratório e evoluçao tumultuada para êxito letal seis a dez meses após o parto. As maes que sobreviveram mostraram aumento da atividade da doença em 18,08 por cento das gestaçoes principalmente relacionada a envolvimento do pulmao e dano vascular. Conclusoes: Toda paciente com esclerose sistêmica deve ser alertada para o fato de que a gravidez geralmente afeta a doença subjacente e também pode complicá-la. O terceiro trimestre é um período perigoso, com risco de início de hipertensao e crise renal. Apesar do risco de prematuridade ou perda fetal, o recém-nato é frequentemente saudável. Em pacientes com comprometimento renal, uma crise renal esclerodérmica deve ser diferenciada da pré-eclâmpsia, através da atividade de renina no plasma, a qual pode estar elevada nas paciente com esclerose sistêmica e normal ou diminuida na pré-eclâmpsia. Infelizmente, até hoje nao há fatores acurados de prognóstico e outras séries de pacientes devem ser estudadas