Andreas Kronbichler1, David R W Jayne, Gert Mayer. 1. Department of Internal Medicine IV (Nephrology and Hypertension), Medical University of Innsbruck, Innsbruck, Austria; Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge, UK.
Abstract
BACKGROUND: Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are potentially life-threatening disorders. MATERIALS AND METHODS: Even though immunosuppressive therapy improves the prognosis, adverse events, either attributable to persistent disease activity or side effects of treatment remain a challenge. Infectious complications are the leading cause of death in the first year after diagnosis and a major cause of morbidity and mortality thereafter. RESULTS: Their incidence in clinical trials varies considerably but opportunistic and life-threatening infections, such as Pneumocystis jirovecii pneumonia or systemic cytomegalovirus infections, are frequent and thus predisposing/risk factors need to be defined. Pneumocystis jirovecii pneumonia has been associated with a lymphocyte count below 300/mm(3) . Additionally, besides the aggressiveness of the immunosuppressive regimen administered (especially the cumulative dose of steroids and cyclophosphamide), an elevated serum creatinine or dialysis dependency, older age and pulmonary involvement increase the rate of infectious complications. CONCLUSIONS: We suggest to routinely prescribe trimethoprim-sulfamethoxazole or antimicrobial agents such as pentamidine in case of intolerance or contraindication in the early phase of induction therapy irrespective of the immunosuppressive strategy used and to continue therapy, together with other targeted measures (antiviral, antimycotic or antibiotic) in the presence of risk factors for a prolonged period of time. Finally, there is an urgent need to standardize the reporting of infectious complications in clinical trials to enable comparing the adverse event spectrum of distinct treatment approaches more appropriately.
BACKGROUND: Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are potentially life-threatening disorders. MATERIALS AND METHODS: Even though immunosuppressive therapy improves the prognosis, adverse events, either attributable to persistent disease activity or side effects of treatment remain a challenge. Infectious complications are the leading cause of death in the first year after diagnosis and a major cause of morbidity and mortality thereafter. RESULTS: Their incidence in clinical trials varies considerably but opportunistic and life-threatening infections, such as Pneumocystis jirovecii pneumonia or systemic cytomegalovirus infections, are frequent and thus predisposing/risk factors need to be defined. Pneumocystis jirovecii pneumonia has been associated with a lymphocyte count below 300/mm(3) . Additionally, besides the aggressiveness of the immunosuppressive regimen administered (especially the cumulative dose of steroids and cyclophosphamide), an elevated serum creatinine or dialysis dependency, older age and pulmonary involvement increase the rate of infectious complications. CONCLUSIONS: We suggest to routinely prescribe trimethoprim-sulfamethoxazole or antimicrobial agents such as pentamidine in case of intolerance or contraindication in the early phase of induction therapy irrespective of the immunosuppressive strategy used and to continue therapy, together with other targeted measures (antiviral, antimycotic or antibiotic) in the presence of risk factors for a prolonged period of time. Finally, there is an urgent need to standardize the reporting of infectious complications in clinical trials to enable comparing the adverse event spectrum of distinct treatment approaches more appropriately.
Authors: El Hakem Matraiah; Nkiruka Olisaka; Mariana Philipos; David Walbaum; Paula Dospinescu; Nicholas Fluck; Neil Basu; Dana Kidder Journal: Clin Rheumatol Date: 2018-05-28 Impact factor: 2.980