Célio Roberto Gonçalves

Circulating follicular helper-like T cells in systemic lupus erythematosus: Association with disease activity

To assess circulating follicular helper T (Tfh)–like CD4+ T cells in patients with systemic lupus erythematosus (SLE) and determine their relationship to disease activity.

Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases

Background Despite the WHO recommendation that the 2010–2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus there is no consistent data regarding its immunogenicity and safety in a large autoimmune rheumatic disease (ARD) population. Methods 1668 ARD patients (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, psoriatic arthritis (PsA), Behçets disease (BD), mixed connective tissue disease, primary antiphospholipid syndrome (PAPS), dermatomyositis (DM), primary Sjögrens syndrome, Takayasus arteritis, polymyositis and Granulomatosis with polyangiitis (Wegeners) (GPA)) and 234 healthy controls were vaccinated with a non-adjuvanted influenza A/California/7/2009(H1N1) virus-like strain flu. Subjects were evaluated before vaccination and 21 days post-vaccination. The percentage of seroprotection, seroconversion and the factor increase in geometric mean titre (GMT) were calculated. Results After immunisation, seroprotection rates (68.5% vs 82.9% p<0.0001), seroconversion rates (63.4% vs 76.9%, p<0.001) and the factor increase in GMT (8.9 vs 13.2 p<0.0001) were significantly lower in ARD than controls. Analysis of specific diseases revealed that seroprotection significantly reduced in SLE (p<0.0001), RA (p<0.0001), PsA (p=0.0006), AS (p=0.04), BD (p=0.04) and DM (p=0.04) patients than controls. The seroconversion rates in SLE (p<0.0001), RA (p<0.0001) and PsA (p=0.0006) patients and the increase in GMTs in SLE (p<0.0001), RA (p<0.0001) and PsA (p<0.0001) patients were also reduced compared with controls. Moderate and severe side effects were not reported. Conclusions The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. (ClinicalTrials.gov #NCT01151644)

Reduced seroprotection after pandemic H1N1 influenza adjuvant-free vaccination in patients with rheumatoid arthritis: implications for clinical practice

Background Reduced response to pandemic (2009) H1N1 (pH1N1) vaccine in patients with rheumatoid arthritis (RA) was recently reported. Objectives To evaluate the contribution of age, disease activity, medication and previous antibody levels to this reduced response. Methods 340 adult RA patients and 234 healthy controls were assessed before and 21 days after adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. Disease activity (DAS28), current treatment and pH1N1 antibody titres were collected. Seroprotection, seroconversion and factor increase in geometric mean titre (GMT) were calculated and adverse events registered. Results RA and controls showed similar (p>0.05) prevaccination GMT (8.0 vs 9.3) and seroprotection (10.8% vs 11.5%). After vaccination a significant reduction (p<0.001) was observed in all endpoints: GMT and factor increase in GMT, seroprotection and seroconversion rates. Disease activity did not preclude seroconversion or seroprotection and remained unchanged in 97.4% of patients. Methotrexate was the only disease-modifying antirheumatic drug associated with reduced responses (p=0.001). Vaccination was well tolerated. Conclusions The data confirmed both short-term anti-pH1N1 vaccine safety and, different from most studies with seasonal influenza, reduced seroprotection in RA patients, unrelated to disease activity and to most medications (except methotrexate). Extrapolation of immune responses from one vaccine to another may therefore not be possible and specific immunisation strategies (possibly booster) may be needed. Clinicaltrials.gov no NCT01151644.

Cross-cultural adaptation of the Behçet’s Disease Current Activity Form (BDCAF) to Brazilian Portuguese language

The Behçet’s Disease Current Activity Form (BDCAF) is a clinical instrument used to assess the activity of Behçet’s disease (BD), which was originally developed in English. The aim of the present study was to perform a cross-cultural adaptation of the BDCAF to Brazilian Portuguese language and to evaluate its reliability in a population of Brazilian patients with BD. Brazilian Portuguese version of the BDCAF, named BR-BDCAF, was obtained according to established guidelines. Forty Brazilian patients with BD diagnosed according to the International Study Group for Behçet’s Disease criteria were assessed by two rheumatologists in independent sessions and submitted to the BR-BDCAF. Inter- and intraobserver agreement were then evaluated by kappa scores (values higher than 0.6 indicated good agreement). Good inter- and intraobserver agreements were achieved for the most common manifestations of BD: kappa scores higher than 0.6 were obtained for oral and genital ulcerations, skin lesions, and articular and general complaints. Moderate interobserver agreement was obtained for ocular activity (kappa 0.483) and fair interobserver agreement was obtained for gastrointestinal (kappa 0.322), major vessel (kappa 0.281), and central nervous system activity (kappa 0.304). BR-BDCAF was found to be a reliable instrument for the classic mucocutaneous and articular manifestations of BD and for general complaints, but complementary assessment is needed to evaluate specific visceral involvement for disease activity.

Consenso Brasileiro de Espondiloartropatias: espondilite anquilosante e artrite psoriásica diagnóstico e tratamento - primeira revisão

1. Assistente-doutor da Disciplina de Reumatologia do Departamento de Clinica Medica da Faculdade de Ciencias Medicas da Universidade Estadual de Campinas (FCM-UNICAMP). Presidente da Comissao de Espondiloartropatias da Sociedade Brasileira de Reumatologia (SBR). 2. Professor Assistente da Disciplina de Reumatologia da Universidade Federal do Parana (UFPR). Mestre em Medicina Interna. 3. Professor Assistente da Disciplina de Reumatologia da Pontificia Universidade Catolica de Campinas (PUCCAMP). 4. Professor Adjunto, Doutor em Oftalmologia da Universidade Federal de Minas Gerais (UFMG). 5. Professora Adjunta da Faculdade de Ciencias Medicas da Universidade Estadual do Rio de Janeiro (UERJ) e Professora do Programa de Pos-Graduacao em Medicina da Universidade Federal do Rio de Janeiro (UFRJ). 6. Professor Adjunto, Doutor de Reumatologia do Departamento do Aparelho Locomotor da Universidade Federal de Minas Gerais (UFMG). 7. Professor Doutor-Assistente e Coordenador da Unidade de Espondiloartropatias da Disciplina de Reumatologia da Faculdade de Medicina da Universidade de Sao Paulo (FMUSP). 8. Professora Associada e Responsavel pelo Setor de Reumatologia Pediatrica da Universidade Federal de Sao Paulo (UNIFESP). 9. Professor Regente da Disciplina de Reumatologia da Faculdade de Medicina da Pontificia Universidade Catolica do Rio Grande do Sul (PUC-RS). 10. Professor Titular de Reumatologia da Faculdade de Medicina Souza Marques, Rio de Janeiro – RJ. 11. Professora da Disciplina de Coloproctologia da Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre (FFFCMPA). 12. Assistente-Doutor e Chefe do Grupo de Reumatologia do Instituto de Ortopedia e Traumatologia da FMUSP. 13. Chefe do Servico de Reumatologia e Coordenador da Residencia Medica do Hospital Geral de Fortaleza. 14. Chefe do Departamento de Medicina Interna do Hospital Geral de Goiânia. Doutor em Reumatologia pela FMUSPUniversidade Estadual de Campinas Faculdade de Ciencias Medicas Departamento de Clinica Medica

Gender characterization in a large series of Brazilian patients with spondyloarthritis

An increasing number of women have been diagnosed with spondyloarthritis (SpA) in recent decades. While a few studies have analyzed gender as a prognostic factor of the disease, no studies have addressed this matter with a large number of patients in South America, which is a peculiar region due to its genetic heterogeneity. The aim of the present study was to analyze the influence of gender on disease patterns in a large cohort of Brazilian patients with SpA. A prospective study was carried out involving 1,505 patients [1,090 males (72.4%) and 415 females (27.6%)] classified as SpA according to the European Spondyloarthropaties Study Group criteria who attended at 29 reference centers for rheumatology in Brazil. Clinical and demographic variables were recorded and the following disease indices were administered: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Radiologic Index (BASRI), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), and Ankylosing Spondylitis Quality of Life (ASQoL). Ankylosing spondylitis (AS) was the most frequent disease in the group (65.4%), followed by psoriatic arthritis (18.4%), undifferentiated SpA (6.7%), reactive arthritis (3.3%), arthritis associated to inflammatory bowel disease (3.2%), and juvenile SpA (2.9%). The male-to-female ratio was 2.6:1 for the whole group and 3.6:1 for AS. The females were older (p < 0.001) and reported shorter disease duration (p = 0.002) than the male patients. The female gender was positively associated to peripheral SpA (p < 0.001), upper limb arthritis (p < 0.001), dactylitis (p = 0.011), psoriasis (p < 0.001), nail involvement (p < 0.001), and family history of SpA (p = 0.045) and negatively associated to pure axial involvement (p < 0.001), lumbar inflammatory pain (p = 0.042), radiographic sacroiliitis (p < 0.001), and positive HLA-B27 (p = 0.001). The number of painful (p < 0.001) and swollen (p = 0.006) joints was significantly higher in the female gender, who also achieved higher BASDAI (p < 0.001), BASFI (p = 0.073, trend), MASES (p = 0.019), ASQoL (p = 0.014), and patient’s global assessment (p = 0.003) scores, whereas the use of nonsteroidal anti-inflammatory drugs (p < 0.001) and biological agents (p = 0.003) was less frequent in the female gender. Moreover, BASRI values were significantly lower in females (p < 0.001). The female gender comprised one third of SpA patients in this large cohort and exhibited more significant peripheral involvement and less functional disability, despite higher values in disease indices.

Anticardiolipin antibodies in Behçet's syndrome: A predictor of a more severe disease

SummaryA high incidence of anticardiolipin antibodies were detected in 7 of 20 patients (35%) with Behçets Syndrome. Three patients had IgGab, three had IgMab and one had both IgG and IgM antibodies. IgGACA was detected mainly in patients with ocular disease (30%) and one of them also has cerebral vascular disease. A lower incidence of ACA was found in the patients taking steroids compared with the ones taking other drugs. This work draws attention to the more severe disease present in patients with ACA and also the possibility of such tests become negative in patients taking immunosupressive drugs.

Espondiloartrites: análise de uma série Brasileira comparada a uma grande casuística Ibero-Americana (estudo RESPONDIA)

Recent studies have outlined the clinical and epidemiological profile of the spondyloarthritides in Ibero-American countries. The objective of this study was to compare the data collected in a Brazilian epidemiological study with the data obtained from other Ibero-American countries that used the same protocol of investigation. The Brazilian series presented a higher frequency of patients with ankylosing spondylitis (72.3% Brazilian vs. 57.7% Ibero-American), being associated with the male gender (73.6% vs. 66.0%) and histocompatibility antigen positive HLA-B27 (65.9% vs. 51.8%). Regarding the treatment, hormonal anti-inflammatory drugs - NSAIDS were more frequently prescribed to Brazilian patients (77.0% vs. 71.2%) and less often, corticosteroids (7.5% vs. 18.5%).

Brazilian-Portuguese version of the Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) in patients with ankylosing spondylitis: a translation, cross-cultural adaptation, and validation

To translate and cross-culturally adapt to the Brazilian-Portuguese language (BP), five items were added to Health Assessment Questionnaire (HAQ) to validate the resulting HAQ-S BP version for ankylosing spondylitis (AS). The items were translated into BP following translation and back-translation. To assess validity, 25 patients were evaluated using the HAQ, Bath AS Functional Index (BASFI), Bath AS Disease Activity Index (BASDAI), Bath AS Metrology Index (BASMI), and laboratory variables (erythrocyte sedimentation rate, C-reactive protein). One question required modification to adapt culturally to Brazilian conditions. The test–retest and interobserver correlation coefficients were 0.990 (p < 0.05) and 0.993 (p < 0.05), respectively. HAQ-S BP correlated to BASFI (r = 0.574; p < 0.05) and to HAQ (r = 0.963; p < 0.05), but not to BASDAI (r = 0.282), BASMI (r = 0.194), and laboratory variable. Individually, the fifth item referring to driving correlated highly to neck rotation (r = 0.900; p < 0.05), while the HAQ-S BP correlated to the neck rotation component (r = 0.303), but did not reach statistical significance. The HAQ-S BP version demonstrated adequate reproducibility, internal consistency and validity, confirming its utility in the research of AS in Brazil.

Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy?

OBJECTIVE To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. METHODS A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) ≥20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. RESULTS The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED ≥20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED ≥20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED ≥20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED ≥20 mg + IS + CQ (57.4%; P = 0.09). CONCLUSION Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity. Trial registration. www.clinicaltrials.gov, NCT01151644.