Nontuberculous Mycobacterial Skin and Soft-Tissue Infections

Epidemiology

In adults, NTM infections are usually manifested as pulmonary disease. In children, lymphadenitis comprises 75% to 85% of total infections. Extrapulmonary presentations in adults include SSTIs, tenosynovitis, septic arthritis, osteomyelitis, and keratitis. Disseminated NTM disease, occasionally involving the central nervous system, can occur, especially with Mycobacterium avium or Mycobacterium abscessus infections in immunocompromised hosts.

NTM SSTIs are usually caused by exposure to environmental water and soil sources of contamination. Such infections have been reported with traumatic skin lesions, exposure to contaminated gentian violet, nail salon pedicures, and tattoos. Few surveillance data are available on the public health burden of NTM SSTIs, because they are not reportable in most states.

NTM SSTIs are more commonly caused by rapidly growing mycobacteria (RGM) species, including Mycobacterium fortuitum , M. abscessus , and Mycobacterium chelonae and the slowly growing mycobacteria (SGM), Mycobacterium marinum , Mycobacterium ulcerans , Mycobacterium chimaera , and Mycobacterium haemophilum . M. haemophilum and Mycobacterium genavense SSTIs are usually diagnosed in immunocompromised patients. However, virtually all NTM species can cause SSTIs.

Immunocompromised hosts, including patients with advanced HIV infection, organ or stem cell transplantation and rare individuals with mendelian susceptibility to mycobacterial disease (MSMD) or anti–interferon-γ antibody are at greatest risk of disseminated NTM disease to multiple sites, including skin and soft tissues.

Pathogenesis

Direct NTM inoculation —either traumatic or iatrogenic—can breach the skin barrier and cause SSTIs. Skin punctures by foreign bodies such as wood splinters, metal fragments, fish spines, or associated with intravascular catheters or devices can introduce environmental NTM into wounds. Infections can arise through inadvertent contamination of surgical wounds, usually from water sources. Skin and soft-tissue involvement can also result from hematogenous dissemination of NTM (e.g., from primary pulmonary infection), resulting in multifocal lesions, mostly in immunosuppressed hosts.

Biofilm formation is another factor in NTM pathogenesis. Myco‑bacterial biofilms form both in environmental sites of colonization, such as water distribution systems, aquariums, hot tubs, swimming pools, and water-containing medical devices, and after insertion of various biomaterials, such as catheters and implantable prosthetic devices. Biofilms are a factor in antimicrobial resistance of bacterial populations, protecting the NTM against antibiotics that might otherwise be effective against bacteria growing in the absence of biofilms. RGM are the most common NTM associated with foreign body biofilms, but virtually any NTM species can be involved in such infections. Formation of NTM biofilms on foreign bodies and implanted biomaterials underscores the importance of foreign body removal and debridement in managing NTM SSTIs, as an adjunct to antibiotic therapy.

Impaired cell-mediated immunity can increase susceptibility to and alter the pathogenic response to NTM SSTIs, for example as associated with AIDS, malignancy, solid organ or hematopoietic stem cell transplantation, or treatment with biologic response modifiers or other immunosuppressive therapy. The NTM species and the quality of the host inflammatory response to NTM SSTIs can affect the clinical presentation and suspicion of mycobacterial infection and therefore the timeliness of diagnosis. For example, RGM NTM species can elicit more of an acute inflammatory response than the typical granulomatous response seen with slowly growing NTM species during chronic infection, and both types of inflammatory responses can be rendered less intense and characteristic by immunosuppressive conditions or therapies. Therefore it is important to use a combination of tissue histopathology, acid-fast bacilli (AFB) stain and mycobacterial culture to define the cause of SSTI lesions, especially in immunocompromised hosts.