Electrocardiographic changes in spondyloarthritis and use of anti-TNF-α drugs: a retrospective study with 100 patients / Alterações eletrocardiográficas em espondiloartrites e uso de anti-TNF-α: estudo retrospectivo em 100 pacientes

ABSTRACT Objective To investigate the prevalence of electrocardiographic changes in patients with spondyloarthritis and to correlate these changes with use of anti-tumor necrosis factor-alpha (TNF-α) drugs and HLA-B27 positivity. Methods Retrospective study including 100 patients diagnosed with spondyloarthritis according to Assessment of SpondyloArthritis International Society (ASAS) criteria and 50 controls. Epidemiological and clinical features, results of inflammatory activity tests, HLA-B27 positivity, and medication use data were extracted from medical records. Disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). All participants were submitted to electrocardiogram performed using a 12-lead device; rhythm, heart rate, conduction disorders and QT interval corrected using the Bazett formula were analyzed. Results Of 100 patients with spondyloarthritis, 51 were on anti-TNF-α drugs and 49 were not. HLA-B27 was detected in 53.1% of patients in the sample. Patients with spondyloarthritis had lower heart rate (p=0.06), longer QT interval (p<0.0001) and higher prevalence of right bundle branch block (p=0.014) compared to controls. Duration of disease was weakly correlated with heart rate (Rho=0.26; 95%CI: 0.06-0.44; p=0.008). The prevalence of right bundle branch block was positively correlated with HLA-B27 positivity. Use of Anti-TNF-α drugs did not interfere with electrocardiographic parameters. Conclusion Patients with spondyloarthritis had lower heart rate, longer QT interval and a higher prevalence of right bundle branch block compared to controls. HLA-B27 positivity was associated with the prevalence of right bundle branch block. Anti-TNF-α drugs had no impact on electrocardiographic findings.

RESUMO Objetivo Avaliar a prevalência de alterações eletrocardiográficas em pacientes com espondiloartrites, correlacionando-as com o uso de medicações antifator de necrose tumoral alfa (TNF-α) e presença do HLA-B27. Métodos Estudo retrospectivo com 100 pacientes com diagnóstico de espondiloartrites pelo critério Assessment of SpondyloArthritis International Society (ASAS) e 50 controles. Foram coletados nos prontuários dos pacientes, dados epidemiológicos, clínicos, exames de atividade inflamatória, presença do HLA-B27, e uso de medicamentos. A atividade de doença foi avaliada pelo Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Todos foram submetidos a eletrocardiograma realizado com aparelho de 12 derivações, sendo analisados ritmo, frequência cardíaca, distúrbios de condução e intervalo QT corrigido pela fórmula de Bazett. Resultados Dos 100 pacientes com espondiloartrites, 49 não usavam anti-TNF-α e 51 utilizavam este medicamento. O HLA-B27 estava presente em 53,1% da amostra. A frequência cardíaca foi mais baixa (p=0,06), o intervalo QT foi mais prolongado (p<0,0001) e existia mais perturbação de condução do ramo direito (p=0,014) nos pacientes com espondiloartrites do que nos controles. Uma modesta correlação de tempo de doença com frequência cardíaca foi encontrada (Rho=0,26; IC95%: 0,06-0,44; p=0,008). A presença do HLA-B27 aumentou a prevalência de perturbação de condução do ramo direito. Nenhum dos parâmetros eletrocardiográficos analisados alterou-se com uso de anti-TNF-α. Conclusão Pacientes com espondiloartrites tiveram frequência cardíaca menor, maior intervalo QT e prevalência maior de perturbação de condução do ramo direito do que controles. O HLA-B27 influi no aparecimento de perturbação de condução do ramo direito. O uso de anti-TNF-α não influiu nos achados eletrocardiográficos.

Associação entre os níveis séricos de potenciais biomarcadores com a presença de fatores relacionados à atividade clínica e ao mau prognóstico em espondiloartrites / The association between serum levels of potential biomarkers with the presence of factors related to the clinical activity and poor prognosis in spondyloarthritis

INTRODUÇÃO: Biomarcadores séricos, tradicionalmente associados à atividade inflamatória e mau prognóstico em doenças reumáticas, não apresentam a mesma relação nas espondiloartrites. OBJETIVO: Estabelecer uma associação entre os níveis séricos de biomarcadores com a presença de fatores associados com a atividade clínica e com o mau prognóstico nas espondiloartropatias. MÉTODOS: Sessenta e dois pacientes (13 com artrite reativa, 19 com espondilite anquilosante e 30 com espondiloartropatia indiferenciada) foram comparados a 46 controles sadios. Foram realizadas avaliações clínicas, radiológicas e laboratoriais. Os resultados foram analisados de acordo com a presença de uveíte, entesite, lombalgia inflamatória, artrite, HLA-B27 e comprometimento das articulações sacroilíacas. Os biomarcadores utilizados foram: VHS, PCRus, SAA, LBP, FSC-M e MMP-3, além da dosagem dos níveis séricos das citocinas: IL-17, IL-6, IL-1α , TNF-α , IFN-γ, e IL-23. RESULTADOS: Quarenta e três (69,4%) pacientes eram homens. A média de idades foi de 31,9 ± 9,9 anos, enquanto a idade média para o aparecimento dos sintomas foi de 26,9 ± 7,3 anos. HLA-B27 foi positivo em 26 (41,9%) dos pacientes, lombalgia inflamatória esteve presente em 42 (67,7%), artrite em 44 (71,0%) e entesite em 34 (54,8%) pacientes. Os níveis séricos de IL-17, IL-23, TNF-α , IL-6, IL-1α e PCRus foram mais elevados em pacientes com espondiloartropatia em comparação com os controles. Os valores de PCRus (P = 0,04), IL-6 (P = 0,003), IL-1α (P = 0,03), e LBP (P = 0,03) se associaram de maneira significativa com presença de HLA-B27, dor lombar inflamatória e artrite. CONCLUSÃO: O aumento dos níveis séricos de PCRus, IL-6, IL-1α e LBP apresentaram associação com fatores relacionados a atividade clínica e mau prognóstico em pacientes com espondiloartrites.

BACKGROUND: Serum biomarkers traditionally associated with inflammatory activity and a poor prognosis in rheumatic diseases do not show the same relationship in spondyloarthritis. OBJECTIVE: To establish the association between serum levels of potential biomarkers with the presence of factors related to clinical activity and poor prognosis in spondyloarthritis. METHODS: Sixty-two patients were included: 13 with reactive arthritis, 19 with ankylosing spondylitis, and 30 with undifferentiated spondyloarthritis. The results were compared with those from 46 healthy controls. Clinical, radiological, and laboratory characteristics were assessed. The results were analyzed based on the presence of uveitis, enthesitis, inflammatory back pain, arthritis, HLA-B27 and sacroiliac involvement. The analyzed biomarkers included ESR, US-CRP, SAA, LBP, FSC-M, and MMP-3; and cytokine serum levels measured were: IL-17, IL-6, IL-1α , TNF-α , IFN-γ, and IL-23. RESULTS: Forty-three (69.4%) patients were male. The average age was 31.9 ± 9.9 years and the age at the onset of symptoms was 26.9 ± 7.3 years. HLA-B27 was positive in 26 (41.9%) patients, inflammatory back pain in 42 (67.7%), arthritis in 44 (71.0%), and enthesitis in 34 (54.8%). IL-17, IL-23, TNF-α , IL-6, IL-1α , and US-CRP levels were significantly higher in patients with SpA when compared to controls. US-CRP (P = 0.04), IL-6 (P = 0.003), IL-1α (P = 0.03), and LBP (P = 0.03) levels were associated with presence of HLA-B27, inflammatory back pain, and arthritis. CONCLUSION: An increase in serum levels of US-CRP, IL-6, IL-1α , and LBP was correlated with factors associated with clinical activity and poor prognosis in spondyloarthritis.

Patogenia de las artropatías seronegativas / Pathogenesis of seronegative arthropathies

Las espondiloartropatías son un grupo de trastornos inflamatorios crónicos que afectan principalmente el esqueleto axial y las articulaciones; se caracterizan por tener factor reumatoide negativo, además de asociarse, frecuentemente, a HLA B27. Muchas veces se acompañan de manifestaciones extraarticulares. Este grupo esta compuesto por cinco patologías: la espondilitis anquilosante, la artritis psoriática, la espondiloartropatía con enfermedad inflamatoria intestinal, la artritis reactiva, incluyendo la enfermedad de Reiter, y la espondiloartropatía indiferenciada. Estas enfermedades son infrecuentes, estimándose una incidencia de 0,2 a un 1 por ciento; su importancia radica en que con frecuencia la aparición es a temprana edad, pudiendo causar gran invalidez. Hasta el momento se desconoce, con certeza, la patogenia de estas enfermedades, planteándose varias hipótesis, basadas principalmente en la participación de la molécula de histocompatibilidad ya mencionada. Es necesario distinguir entre las distintas patologías que conforman este grupo, ya que muchas veces el tratamiento y el pronóstico son diferentes.

Spondyloarthropathies are a group of chronic inflammatory disorders affecting primarily the axial skeleton and joints; they are characterized by a negative rheumatoid factor, and frequently associated with HLA B27. They are often accompanied by extra-articular manifestations. This group is composed of five diseases: ankylosing spondylitis, psoriatic arthritis, spondylarthropathy with Seronegativasinflammatory bowel disease, reactive arthritis, including Reiter’s disease, and undifferentiated spondylarthropathy. These diseases are rare, with an estimated incidence of 0.2 to 1 percent; importance lies in that often the onset is at an early age and can cause major disability. So far, the pathogenesis of these diseases is not known with certainty, though several hypotheses have been raised, mainly based on the involvement of the histocompatibility molecule mentioned above. It is necessary to distinguish between the different disorders that make up this group, because treatment and prognosis of each are different.

The Comparison Between Behcet's Disease and Spondyloarthritides: Does Behcet's Disease Belong to the Spondyloarthropathy Complex?

This study was to clarify whether Behcet's disease (BD) could be classified into the spondyloarthropathy (SpA) complex. It was undertaken on 58 patients with BD (BD group), 56 patients with SpA (SpA group), and 3 patients who concurrently satisfied the criteria for BD and SpA (BDSpA group). The clinical parameters and known susceptible HLA antigens were compared between BD group and SpA group. In addition, 3 patients in BDSpA group were reviewed. The prevalence of definitive sacroiliitis (SI) in BD group and SpA group was 46.4% and 5.2%, respectively. However, none had a definitive SI in healthy controls. Enthesitis was observed in 3.4% of BD group and in 50% of SpA group. The patterns of eye involvement were different between these two groups. HLA-B27 was negative in all 49 patients of BD group, whereas it was positive in 67.9% of SpA group. The prevalence of HLA-B51 was 51.7% in BD group, and that in SpA group was 21.4%. One patient in BDSpA group was considered to have concurrent BD and ankylosing spondylitis (AS). Another patient was closer to AS, and the third to BD. Conclusively, it seems that BD could not be classified into the SpA complex.