BackgroundAdvances in pathophysiology and treatment of ankylosing spondylitis (AS) was recently demonstrated. However, the effect of anti-TNF in the newly described inflammatory pathways involved pathogenesis of this disease remains to be determined. The aim of our study was, therefore, to investigate long-term influence of anti-TNF drugs in IL-23/IL-17 axis of AS patients and their possible correlation with treatment, clinical, laboratory and radiographic parameters.MethodsEighty-six AS anti-TNF naïve patients, 47 referred for anti-TNF therapy (active-AS; BASDAI ≥ 4) and 39 with BASDAI < 4 (control-AS) were included. The active group was evaluated at baseline, 12-months and 24-months after TNF blockade and compared at baseline to control-AS group and to 47 healthy age- and gender-matched controls. Plasma levels of IL-17A, IL-22, IL-23 and PGE2 were measured. Non-steroidal anti-inflammatory drugs (NSAIDs) intake were recorded every 6 months. Radiographic severity and progression was assessed by mSASSS at baseline and 24 months after therapy.ResultsAt baseline, active-AS group presented higher IL-23 and PGE2 levels compared to control-AS group (p < 0.001 and p = 0.008) and to healthy controls (p < 0.001 and p = 0.02). After 24-months of TNF blockade, IL-23 and PGE2 remained elevated with higher levels compared with the healthy group (p < 0.001 and p = 0.03) in spite of significant improvements in all clinical/inflammatory parameters (p < 0.001). Further analysis of 27 anti-TNF-treated patients who achieved a good response (ASDAS-CRP < 2.1,with a drop ≥ 1.1) at 24-months revealed that IL-23 plasma levels remained higher than healthy controls (p < 0.001) and higher than control-AS group with similar disease activity (ASDAS-CRP < 2.1, p = 0.01). In active-AS group (n = 47), there was a strong correlation between IL-23 and IL-17A at baseline, 12-months and 24-months after anti-TNF therapy (p ≤ 0.001).ConclusionThis study provides novel data demonstrating that the IL-23/IL-17 axis is not influenced by TNF blockade in AS patients despite clinical and inflammation improvements and NSAID intake.

The incidence of lung neoplasms is increasing in Brazil and in the world, probably as a result of the increase in smoking. Due to the greater number of cases, atypical presentations appear. We report the case of a 66-year-old hypertensive male smoker who presented progressive proximal muscular weakness and, in two months, evolved to dysphagia, dysphonia, and V-shaped skin lesions on the chest. A chest X-ray showed a spiculated pulmonary nodule in the right upper lobe. The biochemical analysis revealed elevated creatine kinase levels. After complementary tests and biopsies, the patient underwent right upper lobectomy. Histopathology showed a moderately differentiated adenocarcinoma. The overall analysis of the case and a review of the literature allow us to suggest that the clinical profile of the patient was a result of an overlap of two paraneoplastic syndromes (dermatomyositis and Lambert-Eaton myasthenic syndrome) secondary to lung adenocarcinoma.Keywords: Lung neoplasms; Paraneoplastic syndromes; Dermatomyositis; Lambert-Eaton myasthenic syndrome; Adenocarcinoma. ResumoA incidência das neoplasias pulmonares vem aumentando no Brasil e no mundo, provavelmente como resultado do aumento do tabagismo. Com o maior número de casos, surgem as apresentações atípicas. Relatamos o caso de um paciente do sexo masculino, 66 anos, tabagista e hipertenso, que apresentava quadro de fraqueza muscular proximal progressiva e, em dois meses, evoluiu com disfagia para alimentos sólidos, disfonia e lesões cutâneas em forma de "V" no tórax. O radiograma de tórax mostrou um nódulo pulmonar espiculado no lobo superior direito. A análise bioquímica revelou aumento da creatinoquinase. Após exames complementares e biópsias, o paciente foi submetido à lobectomia superior direita. A histopatologia evidenciou um adenocarcinoma moderadamente diferenciado. A análise global do caso e a revisão de literatura permitem sugerir que o quadro clínico do paciente era resultante da sobreposição de duas síndromes paraneoplásicas, a saber, a dermatomiosite e a síndrome miastênica de Lambert-Eaton, secundárias a um adenocarcinoma pulmonar.

55rev bras reumatol, v. 48, n.1, p. 55-58, jan/fev, 2008 relato de caso case rePort INtRODUÇÃOO hipertireoidismo é uma doença endócrina auto-imune bastante prevalente, e as medicações de escolha para o tratamento são, com muita freqüência, o propiltiouracil (PTU) e o metimazol. O tratamento com PTU geralmente tem duração prolongada e diversos efeitos colaterais são descritos, entre os quais agranulocitose, anemia aplástica e pneumonia intersticial (1,2) . O uso do PTU tem sido relacionado ainda à formação de auto-anticorpos, como anticorpos anticitoplasma de neutrófilos (ANCA), e às manifestações de doenças autoimunes, que incluem vasculite cutânea e lúpus induzido por drogas (LID AbStRActThe use of propylthiouracil (PTU) is associated with the development of different auto-antibodies, amongst them are antineutrophil cytoplasmic antibodies (ANCA) that are involved in the pathogenesis of ANCA associated systemic vasculitis. The case of a 46-years old woman who presented cutaneous vasculitis when taking PTU for Graves' disease is reported. Perinuclear ANCA (p-ANCA) was positive with titer ≥ 1/320, but anti-myeloperoxidase antibodies were not detected. Skin biopsy showed leucocytoclastic vasculitis. The patient improved within ten days after withdrawing PTU and the resolution of hyperthyroidism was achieved with radioiodine ( 131 I). The p-ANCA test remained positive ≥ 1/320 eight months and four years after PTU withdrawal.Keywords: antineutrophil cytoplasmic antibodies, vasculitis, propylthiouracil, hyperthyroidism. RESUMOO uso do propiltiouracil (PTU) está associado ao desenvolvimento de diferentes auto-anticorpos, entre eles anticorpos anticitoplasma de neutrófilos (ANCA), que estão envolvidos na patogênese das vasculites sistêmicas ANCA-associadas (VSAA). Será relatado o caso de um paciente do sexo feminino, de 46 anos, que apresentou vasculite cutânea durante o uso de PTU como terapêutica para doença de Graves. O ANCA com padrão perinuclear (p-ANCA) foi positivo em títulos ≥ 1/320, porém anticorpos antimieloperoxidase (MPO) não foram detectados. A biópsia de pele revelou uma vasculite leucocitoclástica. Houve melhora clínica em dez dias após a retirada do PTU e optou-se pelo iodo radioativo (I 131 ) para o tratamento do hipertireoidismo. O p-ANCA mantevese positivo em títulos ≥ 1/320 em duas medidas, realizadas oito meses e quatro anos após a suspensão do PTU.Palavras-chave: anticorpos anticitoplasma de neutrófilos, vasculite, propiltiouracil, hipertireoidismo. cursa com a presença de p-ANCA e com manifestações musculoesqueléticas e vasculite cutânea, que freqüentemente regridem após a suspensão do medicamento (1)(2)(3) . Outras medicações como hidralazina, penicilamina, procainamida e alopurinol também podem estar relacionadas a quadros de vasculites ANCA-associadas, porém com freqüência bem menor da relatada com o uso das medicações antitireoidianas, em especial o PTU (1) . A associação entre a positividade dos ANCAs e as vasculites é conhecida, porém sua fisiopatologia ainda não é totalmente compre...

BackgroundHip involvement is considered an important prognostic factor associated with radiographic progression in ankylosing spondylitis (AS) patients. However, there are no studies regarding hip involvement impact on clinical response and radiographic progression in AS patients under anti-TNF therapy.ObjectivesCompare clinical and radiographic progression in AS patients receiving anti-TNF therapy with and without moderate-severe hip involvement.MethodsForty-seven AS patients referred to receive anti-TNF treatment were included and classified according to baseline hip involvement based on Bath Ankylosing Spondylitis Radiology Hip Index (BASRI-Hip): none-minimal hip disease (hip grade <3) or moderate-severe disease (hip grade ≥3). Demographic data, presence of HLA-B27, extra-articular involvement, DMARD and NSAID use, clinical and laboratorial disease parameters (BASDAI, BASMI, BASFI, ASQol, mSASSS and inflammatory markers) were assessed at baseline and two years after anti-TNF treatment.ResultsThirty-four (72.3%) patients were classified as none-minimal hip disease and 13 (27.7%) as moderate-severe hip involvement. Both groups were similar at baseline considering age, HLA-B27, extra-articular involvement and comedication use. Laboratorial markers (ESR, CRP) and disease parameters (BASDAI, BASFI and mSASSS) showed no difference at baseline. Moderate-severe group had longer disease (10.0±7.6 vs. 14.9±8.6, P=0.002, years), higher BASMI (3.8±2.4 vs. 6.5±2.5, P=0.002) and lower ASQoL (13.7±4.4 vs. 9.9±4.9, P=0.007). After two-years of anti-TNF therapy, both groups presented similar BASDAI response (delta BASDAI, p=0.134; final BASDAI, p=0.324) and an increase in mSASSS [no-minimal involvement: 13.6±18.3 vs. 16.1±19.4, P<0.001); moderate-severe involvement: 21.7±19.9 vs. 28.6±18.5, P=0.003]. At final evaluation patients with moderate-severe hip involvement presented higher mSASSS (28.6±18.5 vs. 16.1±19.4, P=0.02), despite similar delta BASDAI and final BASDAI.ConclusionsOur study provides evidence that hip involvement did not impact on clinical response in AS patients under anti-TNF therapy but may have an effect on radiographic progression of these patients.Disclosure of InterestNone declared

BackgroundIn spite of recent evidences regarding the relevance of IL-23/IL-17 axis in Ankylosing Spondylitis (AS) pathogenesis, there are no data on the long-term effect of anti-TNF therapy in this pathway and their possible correlation with treatment, clinical, laboratory and radiographic parameters.ObjectivesInvestigate the influence of TNF-blockage in IL-23/IL-17 axis of AS patients.MethodsEighty-six AS patients, 47 with refractory active disease (BASDAI≥4) referred to anti-TNF therapy and 39 AS patients with BASDAI<4 (AS control group) were included. The AS active group was evaluated at baseline, 12 months and 24 months after TNF blockage and compared at baseline to the AS control group and to 47 healthy age- and gender-matched controls. Plasma levels of IL-17A, IL-22, TNFα, IL-23, PGE2 were measured. Radiographic severity and progression was assessed by mSASSS.ResultsAt baseline, active AS patients presented higher IL-23 and PGE2 plasma levels compared to AS control group (p<0.001 and p=0.008) and to healthy controls (p<0.001 and p=0.02). After 24 months of TNF blockage, IL-23 and PGE2 remained elevated with higher levels compared to healthy group (p<0.001 and p=0.03) in spite of significant improvement in all clinical (ASDAS-CRP, BASFI, BASMI and ASQol, p<0.001) and inflammatory parameters (C-reactive protein and ESR, p<0.001). Further analysis of 27 anti-TNF treated patients that achieved good-response (ASDAS-CRP<2.1 with Δ≥1.1) at 24 months revealed that their IL-23 plasma levels were higher than healthy controls (p<0.001) and higher than 21 AS control group with similar disease activity (ASDAS-CRP<2.1),(p=0.01). No predictor for anti-TNF response or to radiographic progression was identified. In AS active group (n=47), there was a strong correlation between IL-23 and IL-17A at baseline (r=0.64, p<0.001), 12 months (r=0.47, p=0.001) and 24 months (r=0.61, p<0.001). IL-23 was also correlated with PGE2 at 12 months (r=0.45, p=0.001) and 24 months (r=0.33, p<0.05). No correlation was observed between NSAID, cytokines levels and radiographic progression (p>0.05).ConclusionsThis study provides novel data demonstrating that IL-23/IL-17 axis is not influenced by TNF blockage in AS patients despite clinical and inflammation improvement and NSAID intake. In this context, IL-23/IL-17 blockage emerges as potential additional target in AS patients.ReferencesHreggvidsdottir HS, Noordenbos T, Baeten DL. Inflammatory pathways in spondyloarthritis. Mol Immunol 2014;57:28-37.Yeremenko N, Paramarta JE, Baeten D. The interleukin-23/interleukin-17 immune axis as a promising new target in the treatment of spondyloarthritis. Curr Opin Rheumatol 2014;26:361-370.Disclosure of InterestNone declared