Mediastinal and Disseminated Mycobacterium kansasii Disease in GATA2 Deficiency

Abstract

Rationale: Mycobacterium kansasii usually causes chronic pulmonary infections in immunocompetent patients. In contrast, disseminated M. kansasii disease is commonly associated with advanced human immunodeficiency virus infection, but is reported infrequently in other immunocompromised patients.Objectives: To identify common clinical manifestations and potential risk factors for M. kansasii infection in patients with GATA2 deficiency.Methods: We reviewed M. kansasii disease associated with GATA2 deficiency at one institution and disease associated with primary and other immunodeficiencies reported in the literature. Measurements and Main Results:Nine patients with GATA2 deficiency developed M. kansasii infections. Six patients developed disseminated disease. All patients presented with significant mediastinal lymphadenopathy or abscesses. Seven patients had pulmonary risk factors, including six smokers. The majority of patients had low numbers of neutrophils, monocytes, B cells, CD4 1 T cells, and natural killer cells. Other conditions associated with disseminated M. kansasii disease were thymic disorders and IFN-g/IL-12 defects.Conclusions: Disseminated M. kansasii disease involving mediastinal lymph nodes is surprisingly common in GATA2 deficiency, but also occurs in defects of IFN-g synthesis and response. Disseminated M. kansasii should be considered a marker indicating a need to evaluate for immunodeficiency syndromes.

Germline GATA2 Mutation and Bone Marrow Failure

“…NTM infections were found in up to in 53% of patients in one study 29 , often disseminated and difficult to control, due to slow ( Mycobacterium avium complex (MAC), M kansasii , and M szulgai ) and rapid growing ( M fortuitum, M abscessus, and M chelonae ) organisms 29,53,54 . M kansasii can cause a characteristic necrotizing mediastinal lymphadenitis 55 . Disseminated NTM disease correlates with cytopenias in adolescents or young adults; it is uncommon in childhood when the cell numbers are intact.…”

Case Report: Disseminated Mycobacterium kansasii Disease in a Patient with Anti–Interferon-Gamma Antibody

“…Unlike M. tuberculosis infections, lymphadenitis is infrequent in M. kansasii infections; lymphadenitis suggests immunodeficiencies, including the presence of anti-IFN-γ Abs. 15 In addition to lymphadenitis, other extrapulmonary manifestations, including involvement of the musculoskeletal and genitourinary systems, are suggestive of disseminated infections. These infections are very rare and usually occur in immunosuppressed individuals, in contrast to infections with other NTM.…”

Hematopoietic Stem Cell Transplantation in Primary Immunodeficiencies Beyond Severe Combined Immunodeficiency

“…Infections include viral infections such as warts, disseminated mycobacteria, and, less frequently, fungal infections such as disseminated histoplasmosis. Although Mycobacterium avium complex infections have been most common in this disease cohort (52% of the NTM infections), Mycobacterium kansasii is also fairly common (31% of the NTM infections), and the M kansasii frequently causes mediastinal infections [8] (Figure 2). Laboratories often show low monocytes, although as the disease progresses there may be increased monocytes with progression towards leukemia.…”