Severe combined immunodeficiency: new advances in diagnosis and treatment
ABSTRACT Severe combined immunodeficiency (SCID) is a condition characterized by lack of cellular and humoral immunity. Uniformly fatal before 1968, SCID was first cured by allogeneic bone marrow transplantation (BMT). Despite improvements in BMT, particularly for cases in which there is no matched related donor, difficulties in SCID treatment persist. Because of incomplete reconstitution and transplant-related complications, gene therapy has been pioneered in SCID with success, but also adverse events in the form of leukemic proliferations related to retroviral insertional mutagenesis. Infectious complications are a major limitation to effective treatment. Early diagnosis of SCID in the pre-symptomatic period could be achieved by population-based newborn screening.
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ABSTRACT: To determine the incidence and temporal trends of primary immunodeficiency diseases (PIDs) and examine whether an association exists between delayed diagnosis and increased morbidity. We performed a historical cohort study to describe the epidemiology of PIDs in Olmsted County, Minnesota, during a 31-year period from January 1, 1976, through December 31, 2006, using the Rochester Epidemiology Project. Incidence and trends over time, presence of comorbid conditions, and trends in management were determined. During the 31-year study period, 158 new cases of PIDs were diagnosed, with an overall incidence rate of 4.6 per 100,000 person-years. The rate of PIDs from 2001 through 2006 (10.3 per 100,000 person-years) was nearly 5 times higher than that from 1976 through 1980 (2.4 per 100,000 person-years). The associations between continuous variable(s) and categorical outcome(s) were assessed by using the Wilcoxon rank sum test. Longer delay in diagnosis was significantly associated with recurrent sinusitis (P<.001), recurrent pneumonia (P=.03), and subsequent treatment with immunoglobulins (P<.001). On the basis of Kaplan-Meier survival estimates, the proportion of patients surviving at 10 years after diagnosis was 93.5% (95% confidence interval, 85.9%-97.1%). However, older age at diagnosis was significantly associated with mortality (P=.01). This is one of the first population-based studies to examine the temporal trends of PIDs. The incidence of PIDs increased markedly between 1976 and 2006. In this cohort, a delay in diagnosis was common and was associated with increased morbidity. Despite substantial morbidity, most patients with PIDs can expect a normal life span.Mayo Clinic Proceedings 01/2009; 84(1):16-22. DOI:10.1016/S0025-6196(11)60802-1 · 5.81 Impact Factor
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ABSTRACT: Antibiotic prophylaxis is one of the mainstays of therapy of primary immunodeficiencies. We aim to summarize what is known about antibiotic prophylaxis for select primary immunodeficiencies. In recent years, there has been a push towards more evidence-based practices for antimicrobial prophylaxis for many conditions such as antifungal prophylaxis for extremely premature neonates and antibiotic prophylaxis for neutropenia associated with chemotherapy. However, there are remarkably few data regarding antibiotic prophylaxis in primary immunodeficiencies and regimens vary greatly between practices. Currently, antibiotic prophylaxis is guided by the common microbial pathogens seen in specific immunodeficiencies, and experience with other chronic illnesses such as cystic fibrosis, HIV, and immunosuppression from transplantation. Controlled studies are necessary to address the preferred antimicrobial and immunomodulator regimens for most of the primary immunodeficiencies.Current Opinion in Allergy and Clinical Immunology 10/2009; 9(6):525-30. DOI:10.1097/ACI.0b013e328332be33 · 3.66 Impact Factor