Recognition, Clinical Diagnosis and Management of Patients With Primary Antibody Deficiencies: A Systematic Review

Abstract

Wood P, Stanworth S, Burton J, et al. Clin Exp Immunol. 2007;149(3):410–423 PURPOSE OF THE STUDY. To create an evidence-based literature review of clinical diagnosis and management of primary antibody deficiency. METHODS. Computer literature searches were conducted for randomized clinical trials in medical literature databases including the US National Library of Medicine (Medline), the Excerpta Medica database (EMBASE), the Cochrane Library, the Database of Abstracts of Reviews of Effects (DARE) of the Centre for Reviews and Dissemination (University of York), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) up to June 2006. Reports were rated on the basis of relevance and quality or type of evidence. Disease entities included were X-linked agammaglobulinemia, common variable immunodeficiency, hyper–immunoglobulin M (IgM) syndromes, IgG subclass deficiency with and without IgA deficiency, and specific antibody deficiency. Reports that involved only a limited number of patients were not included. RESULTS. Individuals who present with recurrent respiratory infections of all types, especially with excessive frequency and severity, should be screened for antibody deficiency. In children, common associations included growth delay and failure to thrive, recurrent fevers without a source, and poor school attendance or performance. Chronic diarrhea was found in 40% to 60% of the patients at all ages. The median delay in diagnosis was 1 year but ranged to >10 years. Delayed diagnosis led to increased risk of bronchiectasis, pulmonary hypertension, and cor pulmonale. Randomized trials of the efficacy of γ-globulin replacement versus placebo do not currently exist. Many observational studies have confirmed the benefit of IgG therapy for reducing infectious morbidity. Higher IgG doses are associated with reduced incidence and severity of infections. CONCLUSIONS. Delayed diagnosis was common as a result of lack of recognition of presenting symptoms and signs. Delay was less frequent when patients were referred to specialists. Delayed diagnosis led to delayed therapy (IgG) and a higher rate of infections and morbidity. Several areas for additional research were identified, including studies of efficacy and dose of IgG and adjunct therapies (antibiotics), microbiologic study of pathogens, identification of prognostic markers, and effective monitoring of disease (eg, lung function, other organs, cancer). Collaboration and pooling of data among centers nationally and internationally would likely lead to better data. REVIEWER COMMENTS. This study again points out the human cost of delayed or undiagnosed immunodeficiency and the difficulties in accumulating high-quality data on therapy and outcomes. Several initiatives are taking shape in the United States and abroad to collaborate to answer many of the remaining questions pointed out in this study.