An update on X-Linked agammaglobulinaemia: clinical manifestations and management.

PURPOSE OF REVIEW: X-linked agammaglobulinaemia (XLA) is a congenital defect of development of B lymphocytes leading to agammaglobulinaemia. It was one of the first primary immunodeficiencies described, but treatment has remained relatively unchanged over the last 60 years. This summary aims to outline the current outcomes, treatments and future research areas for XLA. RECENT FINDINGS: Immunoglobulin therapy lacks IgA and IgM, placing patients at theoretical risk of experiencing recurrent respiratory tract infections and developing bronchiectasis despite best current therapy. Recent cohort studies from Italy and the USA conform that bronchiectasis remains a major burden for this group despite best current efforts. However, gene therapy offers a potential cure for these patients with proven proof of concept murine models. SUMMARY: The potential limitations of current immunoglobulin therapy appear to be confirmed by recent cohort studies, and therefore further work in the development of gene therapy is warranted. Until this is available, clinicians should strive to reduce the diagnostic delay, regularly monitor for lung disease and individualize target immunoglobulin doses to reduce infection rates for their patients.

Congenital pleural effusions: 15 years single-centre experience from North-East England.

AIM: The aim of this study is to add to the scant literature on congenital pleural effusions to aid counselling and clinical management decisions. METHODS: Retrospective case series of 15 years of congenital pleural effusions resulting in live birth in a single tertiary foetal medicine/neonatal centre in North East England. RESULTS: Data were available for 21 infants. Mortality rates were 43% overall. All spontaneous resolution occurred within 9 d, and active management was used where effusions persisted beyond this. CONCLUSION: Prematurity was associated with a poor prognosis. Resolution without active management occurred before day 10 and active strategies should be considered by this time.

Respiratory Health and Related Quality of Life in Patients with Congenital Agammaglobulinemia in the Northern Region of the UK.

INTRODUCTION: Patients with congenital agammaglobulinemia, characterized by a defect in B lymphocyte differentiation causing B alymphocytosis, require life-long IgG replacement. There is scant literature regarding the effectiveness of IgG treatment at preventing mucosal (particularly sinopulmonary tract) infection and whether current management adequately restores "normal" health and quality of life (QoL). We aimed to document infective episodes pre- and post-commencing IgG replacement, determine any change in lung function and structure and assess respiratory status and QoL in a cohort of patients treated in Newcastle. METHODS: Clinical data were extracted from medical records of 15 patients identified from the immunology database, focusing on infective episodes, serial chest CT and spirometry results. Thirteen patients completed a selection of standardized and validated questionnaires assessing physical health, respiratory health and QoL. RESULTS: Pediatric patients on IgG therapy suffered fewer infections per patient year (0.74) than adults (2.13). 6/14 patients showed deteriorating respiratory status despite adequate therapy. Health questionnaires revealed a significant burden of respiratory disease on a patient's life. CONCLUSION: Clinical data showed patients with congenital agammaglobulinemia receiving immunoglobulin therapy retained a higher than average infection rate, most of which affected mucosal barriers. Most patients self-reported worse respiratory symptoms, a lower respiratory-related QoL and a lower general health QoL relative to a healthy population. Most participants had progressive structural lung damage and decreased lung function. These results suggest that current management is not entirely effective at preventing deterioration of respiratory health or restoring QoL.