Overview of nontuberculous mycobacterial disease in children

Abstract

Nontuberculous mycobacteria (NTM) are ubiquitous organisms in our surrounding environment. Four distinct clinical syndromes associated with NTM infection have been described: skin and soft tissue disease, lymphadenitis, disseminated disease and pulmonary disease. In children, lymphadenitis is the most common NTM clinical entity, particularly affecting those aged 1-5 years who have no known risk factors for disease. Optimal management of NTM lymphadenitis is not entirely clear, although surgical intervention is likely a definitive therapy. Disseminated NTM disease is uncommon and only seen in the setting of immunocompromise. In previously well children, this presentation should always lead to consideration of an underlying immune defect, such as Mendelian susceptibility to mycobacterial disease. Identification of the underlying cause enables more targeted therapy and better prognostic understanding. Pulmonary NTM disease is fundamentally different to the other clinical syndromes, presenting in different hosts, who have different comorbidities, and follow a different clinical course.

Case Report: Disseminated Mycobacterium intracellulare Infection With More Than 1-Year Follow-Up in a Young Boy With IFNGR1 Deficiency

“…Human IFN-γ levels and genetic patterns are traits that define the outcome of mycobacterial infection (21). For treatment of disseminated NTM disease associated with MSMD, aggressive, long-term antimycobacterial therapy to treat the acute infection and to prevent later recrudescence is required (1). In addition to antimycobacterial drugs, IFN-γ therapy is considered efficacious for improving the prognosis of partial IFNGR1 deficiency, and successful cases have been reported (19,22).…”

“…In recent years, the incidence of non-tuberculous mycobacterium (NTM) infections in children and adolescents has been increasing. NTM infections have four distinct clinical syndromes: skin and soft-tissue disease, lymphadenitis, disseminated disease, and pulmonary disease (1). In children, lymphadenitis is its most common form (1); disseminated disease is uncommon and indicates primary immunodeficiency diseases (PIDs).…”

“…One such mutation is IFN-γ receptor 1 (IFNGR1) deficiency (2). Overall, disseminated NTM diseases underlying MSMD are a challenge in previously healthy children because of their non-specific symptoms, and optimal management requires a more accurate definition (1).…”

When a Nontuberculous Mycobacterial Infection Reveals an Error of Immunity

“…and the Mendelian Susceptibility to Mycobacterial Diseases (MSMD-IEI), a group of continuously emerging and allelic heterogenous genetic defects that impair interferon (IFN)-γ immunity. [4][5][6][7][8][9][10][11][12] However, pediatric physicians may frequently observe NTM infections in otherwise healthy children. An important question is if it should be suitable to test every child who experiences a NTM infection for a primary immunodeficiency.…”

“…Notably, inherited immunodeficiencies predisposing to NTM infection may include inborn errors of immunity (IEI), that is, severe combined immunodeficiencies, combined immunodeficiencies, hyper-IgE syndromes, chronic granulomatous disease, nuclear factor-kappa B essential modulator deficiency, hyper-IgM syndromes and the Mendelian Susceptibility to Mycobacterial Diseases (MSMD-IEI), a group of continuously emerging and allelic heterogenous genetic defects that impair interferon (IFN)-γ immunity. 4–12…”