Primary immunodeficiencies underlying fungal infections

Curr Opin Pediatr. 2013 Dec;25(6):736-47. doi: 10.1097/MOP.0000000000000031.

Abstract

Purpose of review: We review the primary immunodeficiencies (PIDs) underlying an increasing variety of superficial and invasive fungal infections. We also stress that the occurrence of such fungal infections should lead physicians to search for the corresponding single-gene inborn errors of immunity. Finally, we suggest that other fungal infections may also result from hitherto unknown inborn errors of immunity, at least in some patients with no known risk factors.

Recent findings: An increasing number of PIDs are being shown to underlie fungal infectious diseases in children and young adults. Inborn errors of the phagocyte NADPH oxidase complex (chronic granulomatous disease), severe congenital neutropenia (SCN) and leukocyte adhesion deficiency type I confer a predisposition to invasive aspergillosis and candidiasis. More rarely, inborn errors of interferon-γ immunity underlie endemic mycoses. Inborn errors of interleukin-17 immunity have recently been shown to underlie chronic mucocutaneous candidiasis (CMC), while inborn errors of caspase recruitment domain-containing protein 9 (CARD9) immunity underlie deep dermatophytosis and invasive candidiasis.

Summary: CMC, invasive candidiasis, invasive aspergillosis, deep dermatophytosis, pneumocystosis, and endemic mycoses can all be caused by PIDs. Each type of infection is highly suggestive of a specific type of PID. In the absence of overt risk factors, single-gene inborn errors of immunity should be sought in children and young adults with these and other fungal diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Aspergillosis / genetics
  • Aspergillosis / immunology
  • Autoantibodies
  • Candidiasis, Chronic Mucocutaneous / genetics
  • Candidiasis, Chronic Mucocutaneous / immunology
  • Child
  • Child, Preschool
  • Disease Susceptibility
  • Female
  • Genetic Diseases, Inborn / genetics
  • Genetic Diseases, Inborn / immunology*
  • Humans
  • Immunity, Cellular / genetics
  • Immunologic Deficiency Syndromes / complications
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / immunology*
  • Infant
  • Infant, Newborn
  • Interleukin-17 / immunology
  • Male
  • Mycoses / genetics*
  • Mycoses / immunology*
  • Pneumonia, Pneumocystis / genetics
  • Pneumonia, Pneumocystis / immunology
  • Risk Factors
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Autoantibodies
  • Interleukin-17