Systemic and localized infection by Candida species in patients with rheumatic diseases receiving anti-TNF therapy / Infecção sistêmica e localizada por Candida spp. em pacientes reumatológicos em terapia anti-TNF

ABSTRACT Objective: To evaluate the prevalence of systemic and localized infection by Candida species and its possible association with demographic, clinical and laboratory manifestations and therapy in patients with rheumatic diseases taking TNF blockers. Methods: Consecutive patients with rheumatic diseases receiving anti-TNF agents were included. The following risk factors up to four weeks prior to the study were analyzed: use of antibiotics, immunosuppressant drugs, hospitalization and invasive procedures. All subjects were evaluated for clinical complaints; specific blood cultures were obtained for fungi and blood samples were collected for Candida spp. detection by polymerase chain reaction. Results: 194 patients [67 with rheumatoid arthritis (RA), 47 with ankylosing spondylitis (AS), 36 with juvenile idiopathic arthritis (JIA), 28 with psoriatic arthritis and 16 with other conditions] were included. The average age of patients was 42 ± 16 years, with 68 (35%) male and mean disease duration of 15 ± 10 years. Sixty-four (33%) patients were receiving adalimumab, 59 (30%) etanercept and 71 (36%) infliximab. Eighty-one percent of patients were concomitantly taking immunosuppressant drugs. At the time of the study, only one (0.5%) patient had localized fungal infection (vaginal candidiasis). None of the patients included had systemic candidiasis with positive blood cultures for fungi or PCR positive for Candida spp. in peripheral blood sample. Conclusions: This was the first study to assess the prevalence of invasive and localized fungal disease by Candida in a significant number of patients with rheumatic diseases on anti-TNF therapy, and demonstrated low risk of candidiasis, despite the high prevalence of immunosuppressive drug use.

RESUMO Objetivo: Avaliar a prevalência de infecção sistêmica e localizada por Candida spp. e sua possível associação com dados demográficos, manifestações clínicas e laboratoriais e terapêutica em pacientes com doenças reumatológicas em uso de anti-TNF. Métodos: Foram incluídos pacientes consecutivos com doenças reumatológicas em uso de agentes anti-TNF. Foram analisados os seguintes fatores de risco até quatro semanas antes do estudo: uso de antibioticoterapia, imunossupressores, hospitalização e procedimentos invasivos. Todos foram avaliados para queixas clinicas, coletaram hemocultura específica para fungos e amostras de sangue para pesquisa de Candida spp. por reação em cadeia de polimerase. Resultados: Foram incluídos 194 pacientes [67 com artrite reumatoide (AR), 47 espondilite anquilosante (EA), 36 artrite idiopática juvenil (AIJ), 28 artrite psoriásica e 16 outros]. A média de idade era de 42 ± 16 anos, com 68 (35%) do sexo masculino e média de duração de doença de 15 ± 10 anos; 64 (33%) pacientes usavam adalimumabe, 59 (36%) etanercepte e 71 (36%) infliximabe; 81% faziam uso concomitante de imunossupressores. No momento do estudo, apenas um (0,5%) paciente apresentou infecção fúngica localizada (candidíase vaginal). Nenhum dos pacientes incluídos apresentou candidíase sistêmica com hemocultura positiva para fungos ou PCR positiva para Candida spp. em amostra de sangue periférico. Conclusões: Este foi o primeiro estudo que avaliou prevalência de doença fúngica invasiva e localizada por Candida em um expressivo número de pacientes reumatológicos em terapia anti-TNF e demonstrou baixo risco de candidíase, apesar da alta prevalência de uso de imunossupressores.

Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy

OBJECTIVE: To assess the potential acute effects regarding the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with mixed connective tissue disease and healthy controls. METHODS: Sixty-nine mixed connective tissue disease patients that were confirmed by Kasukawa's classification criteria and 69 age- and gender-matched controls participated in the study; the participants were vaccinated with the non-adjuvanted influenza A/California/7/2009 (H1N1) virus-like strain. The percentages of seroprotec-tion, seroconversion, geometric mean titer and factor increase in the geometric mean titer were calculated. The patients were clinically evaluated, and blood samples were collected pre- and 21 days post-vaccination to evaluate C-reactive protein, muscle enzymes and autoantibodies. Anti-H1N1 titers were determined using an influenza hemagglutination inhibition assay. ClinicalTrials.gov: NCT01151644. RESULTS: Before vaccination, no difference was observed regarding the seroprotection rates (p = 1.0) and geometric mean titer (p = 0.83) between the patients and controls. After vaccination, seroprotection (75.4% vs. 71%, (p = 0.7), seroconversion (68.1% vs. 65.2%, (p = 1.00) and factor increase in the geometric mean titer (10.0 vs. 8.0, p = 0.40) were similar in the two groups. Further evaluation of seroconversion in patients with and without current or previous history of muscle disease (p = 0.20), skin ulcers (p = 0.48), lupus-like cutaneous disease (p = 0.74), secondary Sjogren syndrome (p = 0.78), scleroderma-pattern in the nailfold capillaroscopy (p = 1.0), lymphopenia #1000/mm³ on two or more occasions (p = 1.0), hypergammaglobulinemia $1.6 g/d (p = 0.60), pulmonary hypertension (p = 1.0) and pulmonary fibrosis (p = 0.80) revealed comparable rates. Seroconversion rates were also similar in patients with and without immunosuppressants. Disease parameters, such as C-reactive protein (p = 0.94), aldolase (p = 0.73), creatine phosphokinase (p = 0.40) and ribonucleoprotein antibody levels (p = 0.98), remained largely unchanged pre and post-vaccination. No severe side effects were reported. CONCLUSIONS: The non-adjuvanted influenza A/H1N1 vaccination immune response in mixed connective tissue disease patients is adequate and does not depend on the disease manifestations and therapy.