RESUMO
INTRODUCTION: Infections are the leading cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Invasive fungal infections (IFI) comprise a group of diseases caused by Cryptococcus, Histoplasma, Aspergillus and Candida. Few studies of IFI have been published in patients with SLE and associated factors have not been completely defined. OBJECTIVES: The objectives of this paper are to estimate the frequency of IFI in admitted patients with SLE in our hospital, to determine the risk factors associated with IFI in our patients with SLE, and to compare IFI group with a control group (SLE without IFI). METHODS: The medical charts of patients with IFI (EORTC/MSG, 2008) and SLE (ACR, 1997) admitted to our hospital from June 2001 until June 2012 were reviewed. To identify factors associated with IFI, we developed a case-control study (SLE + IFI vs SLE alone) in a one to three ratio adjusted for sex and age and hospitalization for other reasons. Comparison was made of demographic characteristics, duration of disease and disease activity previous to IFI diagnosis, especially three months before fungal infection. We defined severe activity as SLEDAI ≥ 8. Infection by fungi of the genus Candida was considered only in its disseminated form. RESULTS: Ten cases of IFI were identified in 208 patients with SLE admitted between June 2001 and June 2012. We included 40 patients with SLE (10 with IFI and 30 controls). Of the SLE-IFI patients, eight were women and the average age was 27.5 years (range, 19-42 years). Fungal isolation: eight Cryptococcus neoformans, one Histoplasma capsulatum and one Candida albicans. Sites affected: five in peripheral blood, five in central nervous system (CNS), four in skin/soft tissue and one in pleura. Mortality was 40% (p = 0.002), with Cryptococcus neoformans being the most common fungus. The SLE disease activity was severe in 70% of infected patients and no significant difference with the control group was found (p = 0.195). We also found no association with leukopenia, lymphopenia, hypocomplementemia, hypogammaglobulinemia or anti-DNA positivity; neither with meprednisone doses >20 mg/day or intravenous methylprednisolone pulse therapy before fungal infection. The use of immunosuppressive therapy with azathioprine showed a significant association (p = 0.017). Cyclophosphamide (p = 0.100) or mycophenolate mofetil (p = 0.256) did not show similar results. CONCLUSION: The frequency of IFI in hospitalized SLE patients in our hospital was 4.8%. Cryptococcus neoformans was the most common etiologic agent and was primarily responsible for the deaths in this cohort. These data are consistent with publications in East Asia rather than North America where Candida spp. is more common. Unlike other publications, previous immunosuppression with azathioprine was the only risk factor associated with the development of the infection. Invasive fungal infection should be suspected in hospitalized patients with SLE and immunosuppression with CNS or atypical cutaneous manifestation of SLE in order to start appropriate treatment early and obtain better outcome.
Assuntos
Azatioprina/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Micoses/epidemiologia , Adulto , Argentina/epidemiologia , Azatioprina/efeitos adversos , Estudos de Casos e Controles , Feminino , Hospitalização , Humanos , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Micoses/etiologia , Micoses/microbiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
Objetivo: Actualizar los resultados del registro BIOBADASAR sobre seguridad, duración y causas de interrupción del tratamiento luego de 8 años de seguimiento. Métodos: BIOBADASAR es un registro de seguridad de terapias biológicas establecido por la Sociedad Argentina de Reumatología. Se presenta la descripción de BIOBADASAR 3.0, una cohorte compuesta por 53 centros de Argentina seguidos prospectivamente desde agosto de 2010 hasta enero de 2018. Resultados: Se registraron 4656 pacientes, 6234 tratamientos [3765 casos (terapia con biológicos) y 2469 controles (terapia no biológicos)]. Se interrumpió el tratamiento en el 44,6% en los casos vs. 27,9% en los controles. Causa principal de discontinuación fue por ineficacia (40% casos vs. 32% controles). Se presentaron 3154 eventos adversos (2230 en casos vs. 924 en controles), de los cuales el 13,6% fueron graves (9,8% en casos y 3,7% en controles). El evento adverso (EA) más frecuente en ambos grupos fueron las infecciones (43,56% en casos vs. 34,31% en los controles, RR: 3,42; IC 95%: 3,02-3,88), y de ellas las de vías aéreas superiores (14,5%). Las neoplasias se presentaron en 78 casos vs. 45 en controles (RR: 1,98; IC 95%: 1,37-2,86). Conclusiones: En este sexto reporte no se observan tendencias diferentes sobre seguridad, duración y causas de interrupción del tratamiento respecto a informes previos. Las infecciones fueron el principal EA y la ineficacia, seguido por EA y la pérdida de pacientes las principales causas de suspensión del tratamiento. El advenimiento de nuevos agentes biológicos y la necesidad de control en seguridad a largo plazo, fortalece el uso de este tipo de registro.
Objective: Update the results of the BIOBADASAR registry on safety, duration and causes of treatment interruption after 8 years of follow-up. Methods: BIOBADASAR is a safety record of biological therapies established by the Argentine Society of Rheumatology. The description of BIOBADASAR 3.0 is presented, a cohort of 53 centers in Argentina followed prospectively from August 2010 to January 2018. Results: 4656 patients were registered, 6234 treatments [3765 cases (therapy with biologicals) and 2469 controls (non-biological therapy)]. Treatment was interrupted in 44.6% in cases vs. 27.9% in controls. Main cause of discontinuation was due to inefficiency (40% cases vs. 32% controls). There were 3154 adverse events (2230 in cases vs. 924 in controls), of which 13.6% were tombs (9.8% in cases and 3.7% in controls). The most frequent adverse event (AE) in both groups were infections (43.56% in cases vs. 34.31% in controls, RR: 3.42, 95% CI: 3.02-3.88), and the upper airway pathways (14.5%). Neoplasms were published in 78 cases versus 45 controls (RR: 1.98, 95% CI: 1.37-2.86). Conclusions: In this article, there are no different trends regarding safety, duration and causes of interruption of treatment compared to previous reports. Infections were the main causes of treatment discontinuation. The advent of new biological agents and the need for control over long-term security, strengthens the use of this type of registration.