Use of intravenous immunoglobulin and adjunctive therapies in the treatment of primary immunodeficiencies

Abstract

There are an expanding number of primary immunodeficiency diseases (PIDDs), each associated with unique diagnostic and therapeutic complexities. Limited data, however, exist supporting specific therapeutic interventions. Thus, a survey of PIDD management was administered to allergists/immunologists in the United States to identify current perspectives and practices. Among 405 respondents, the majority of key management practices identified were consistent with existing data and guidelines, including the provision of immunoglobulin therapy, immunoglobulin dosing and selective avoidance of live viral vaccines. Practices for which there are little specific data or evidence-based guidance were also examined, including evaluation of IgG trough levels for patients receiving immunoglobulin, use of prophylactic antibiotics and recommendations for complementary/alternative medicine. Here, variability applied to PIDD patients was identified. Differences between practitioners clinically focused upon PIDD and general allergists/immunologists were also identified. Thus, a need for expanded clinical research in PIDD to optimize management and potentially improve outcomes was defined.

Introduction

Primary immunodeficiency diseases (PIDDs) represent more than 150 rare disorders, which impair immunological defenses resulting in increased susceptibility to infections. While many PIDDs result from mutations in genes required for specific elements of immunity [1], the diagnoses can be classified according to the impaired immunologic host defense mechanisms. This can be useful as particular groups of defects are associated with susceptibility to specific types of infections [2]. Such categorization of defects has been central to diagnosis and guides patient management.

Expanded understanding of the defective immunological mechanisms in, and genes responsible for PIDDs has led to improved diagnostic precision [3] as well as greater insight into human immunity [4]. Despite these advances, there has been a relative paucity of research in the practical management of PIDD. Furthermore, as the number of diagnoses increase, the potential for expanded and more specialized management strategies is likely to increase proportionally. This has led to a complex clinical discipline with numerous patient management options, some of which are only supported by expert opinion [5].

To better define management practices applied to PIDD patients in the United States, a survey of allergist/immunologists who were members of the American Academy of Allergy Asthma and Immunology (AAAAI) was performed. The objectives were: (1) to identify consistencies in the management of PIDD patients in order to suggest standards of care and (2) to identify areas in which there is more variability or inconsistency with published data in order to define important questions for future research. The results demonstrated areas of agreement in the care of PIDD patients provided by sub-specialists, but also identified some management practices that were more divergent. Thus, in order to optimize the quality and uniformity of PIDD clinical care, specific areas for clinical research studies should be promoted, prioritized, and merit enhanced funding support.