Cutaneous Manifestations of Mycobacterium kansasii Infection

Abstract

Purpose of Review

Mycobacterium kansasii is a slow-growing member of the nontuberculous mycobacterial species that manifests clinically with pulmonary, cutaneous, or disseminated forms. Most cases of M. kansasii infection occur in immunocompromised hosts including HIV/AIDS, solid-organ transplantation, anti-interferon-γ antibody disorder, or among those with pulmonary disorders such as chronic obstructive pulmonary disease or cystic fibrosis. In this review, we aim to discuss relevant literature regarding the clinical manifestations of this infection with a particular emphasis on the clinical spectrum and treatment of the cutaneous manifestations of this mycobacterial infection.

Recent Findings

Infection caused by M. kansasii is associated with exposure to contaminated municipal water systems since this organism thrives in human-engineered environments. Chronic or subacute skin lesions may represent the primary source of entry of the organism due to open sores or traumatic injuries. Alternatively, cutaneous lesions may occur secondary to dissemination of the organism to the skin from pulmonary infection. The diagnosis of M. kansasii of the skin and soft tissues should be entertained among immunocompetent or immunocompromised individuals presenting with subacute or chronic lesions. The differential diagnosis of M. kansasii infection includes infections of skin and soft tissues caused by rapidly growing mycobacteria, subcutaneous mycosis, pyogenic bacterial infections, nocardiosis, free-living amoebas, and protothecosis.

Summary

Cutaneous lesions caused by M. kansasii most commonly manifest in the setting of concomitant pulmonary disease or in the setting of disseminated infection among immunocompromised hosts. When clinicians suspect a cutaneous mycobacterial infection either due to slow-growing mycobacteria such as M. kansasii or due to rapidly growing mycobacteria, obtaining a skin biopsy of chronic nonhealing lesions for histopathologic evaluation and for microbiological assessment is crucial. Mycobacteriology assessment of clinical specimen includes acid-fast bacilli staining, culture in solid/liquid media, and molecular assays for confirmation. Treatment of M. kansasii infection of the skin and subcutaneous tissues follows the same management recommendations as those for the treatment of isolated pulmonary forms or disseminated disease.

Introduction

In the USA and Japan, infection due to the slowly growing species of Mycobacterium kansasii is the second most common cause of chronic mycobacterial infections within the nontuberculous mycobacteria (NTM) group, after Mycobacterium avium-intracellulare complex (MAC) [1••, 2, 3]. Increased detection of M. kansasii has also been reported in South Korea [3]. In contrast to most other mycobacterial pathogens, M. kansasii resides in municipal tap water. This mycobacterial pathogen has never been isolated in natural water supplies or in soil [4–5]. Risk factors for M. kansasii infection include cigarette smoking, chronic obstructive pulmonary disease, cystic fibrosis, alcoholism, pneumoconiosis, malignancy, renal transplantation, and HIV infection [6, 7, 8•]. M. kansasii infection may also occur among those with anti-interferon-γ antibody disorder [6, 7, 8•]. After MAC, M. kansasii is the second most common NTM infection causing disseminated disease in patients with HIV/AIDS [6, 7, 8•].

Microbiology of M. kansasii

This human pathogen can be seen on direct smear and tissue or recovered in cultures by techniques used to isolate M. tuberculosis including Lowenstein-Jensen Agar, BACTEC broth, and Middlebrook 7H10 Agar [1••, 9–10]. Morphologically, M. kansasii appears as a long bacillus with unusual beading when stained with acid-fast stains. High-performance liquid chromatography (HPLC) and biochemical testing can also assist in identifying M. kansasii. Molecular techniques used for identifying M. kansasii from clinical specimens include sequence based techniques and direct probe hybridization [1••, 12••, 13]. There are commercially available molecular direct hybridization probes for identifying rRNA of M. kansasii (AccuProbe; Hologic, San Diego, CA) [14••]. Initial susceptibility testing is only recommended for rifampin as susceptibility to rifampin correlates with improved clinical outcomes [11]. Histopathological evaluations of cutaneous lesions demonstrate the presence of necrotizing granulomatous inflammation and large numbers of acid-fast bacilli without peripheral nerve involvement. There are, however, no specific histopathologic findings that differentiate M. kansasii infection from other mycobacterial diseases (Fig. 1) [12••, 13].

Fig. 1.

Skin biopsy showing granulomas and skin infiltration with acid-fast bacilli (red arrow) caused by Mycobacterium kansasii (10x magnification)

Overview of Clinical Manifestations of M. kansasii Infection

M. kansasii was first identified as an infectious disease in 1953, primarily in patients presenting with cavitary lung lesions resembling those of pulmonary tuberculosis [6–8]. This infection presents among both immunocompetent and immunocompromised hosts including persons with HIV/AIDS, those on anti-interferon-γ antibody therapy, and renal transplant recipients [12••]. M. kansasii infections of the lungs, which correspond to more than 80% of all cases of M. kansasii infection, often occur in patients with preexisting lung disease, especially chronic obstructive pulmonary disease or cystic fibrosis [8•, 9, 10]. It is also the second most common NTM isolated in patients with HIV infection, following MAC [6]. Patients coinfected with M. kansasii and HIV present with lower CD4₊ lymphocyte counts, and at the time of their diagnosis, they tend to have various concomitant opportunistic infections [6, 7, 8•]. The likelihood of surviving pulmonary M. kansasii is higher among patients who are using highly active antiretroviral therapy, have high CD4⁺ counts, and have negative smears upon microscopy [1••, 6, 7, 8•]. As M. kansasii expresses ESAT-6 and CFP-10 analogs, interferon-γ release assays (IGRAs) are usually positive and cannot be used to distinguish this infection from M. tuberculosis [12••]. Clinical symptoms of M. kansasii infection can be identical to those of pulmonary tuberculosis or MAC (i.e., fever, cough, weight loss, and hemoptysis). The radiographic presentation usually includes fibronodular or fibrocavitary lesions with a predilection for the upper lobes, often resembling pulmonary tuberculosis except that the cavities may be thin-walled and bulla-like [6, 7, 8•]. In patients with HIV infection who have CD4⁺ T cell counts greater than 200/mm³, M. kansasii pulmonary disease can be cavitary as well [6, 8•]. However, patients with lower CD4₊ T cell counts are more likely to have noncavitary pulmonary disease, sometimes in association with disseminated forms of this disease [1••, 6, 7, 8•].

Cutaneous Manifestations of M. kansasii Infection

The most common nontuberculous mycobacterial species involving the skin and soft tissues are the rapidly growing mycobacterium including M. fortuitum, M. abscessus, M. chelonae, M. marinum and M. ulcerans [1••]. Cutaneous disease is the most common extrapulmonary presentation of M. kansasii, following pulmonary disease [12••, 13, 14••, 15, 16••]. It may also less commonly manifest as osteomyelitis, septic arthritis, and disseminated disease. Cutaneous manifestations of M. kansasii infection may also occur in the setting of disseminated disease in those with severe forms of immunosuppression [12••, 13, 14••, 15, 16••]. Skin and soft tissue lesions caused by M. kansasii usually present in immunocompromised hosts and sometimes in those with concomitant pulmonary disease [12••, 15]. Cutaneous lesions caused by M. kansasii may present with a wide range of lesions including nodules (often sporotrichoid-like), pustules, verrucous lesions, nodular lymphangitic lesions, erythematous plaques, seromas, cellulitis, ulcers, and abscesses (Fig. 2) [1••, 12••, 13, 14••, 15, 16••]. When cutaneous infections with M. kansasii occur, they are usually due to local inoculation at a site of minor trauma rather than from hematological dissemination [13]. As such, lesions are usually confined to one anatomic region and occur most frequently on the upper or lower extremities [12••]. Skin lesions caused by M. kansasii need to be distinguished from other mycobacterial diseases including cutaneous tuberculosis, leprosy, M. ulcerans, M. marinum, and rapidly growing mycobacterial infections. Other infectious diseases that need to be considered in the differential diagnosis include cutaneous/subcutaneous mycosis (i.e., sporotricosis or chromoblastomycosis), treponemal infections, staphylococcal and streptococcal infections, and infections caused by free-living amoebas and protothecosis.

Fig. 2.

Facial ulcerative nodular skin lesion with crusting and hypopigmentation (blue arrow) caused by Mycobacterium kansasii. Clinically, these cutaneous lesions may mimic those caused by M. marinum or cutaneous tuberculosis (tuberculosis verrucosa cutis or lupus vulgaris)

Treatment of M. kansasii

The management of the cutaneous manifestations of M. kansasii infection follows the treatment recommendations as for pulmonary or disseminated forms. From an antimicrobial susceptibility perspective, M. kansasii is considered to be resistant to pyrazinamide but susceptible to isoniazid, rifampin, ethambutol, clarithromycin, fluoroquinolones, aminoglycosides, sulfamethoxazole and linezolid [1••, 16••, 17]. Primary treatment for patients with pulmonary, cutaneous, or disseminated M. kansasii typically involves an 18-month course of daily isoniazid, rifampin, and ethambutol, although total duration is dependent on the ability to clear cultures. Newer data suggest that a regimen of clarithromycin, ethambutol, and rifampin, administered three times a week for 12 months after the last positive sputum culture might also be effective [17].

Since the introduction of rifampin-based treatment regimens in the late 1970s, outcomes have greatly improved with cure rates approaching 98%. Further, surgical removal is now uncommon and not recommended for routine cases. However, treatment failures may result from rifampin resistance, and rifampin susceptibility is recommended to be tested prior to starting treatment, particularly in patients who have previously received this drug. For patients with rifampin-resistant isolates, full susceptibility testing is recommended, though breakpoints for susceptibility and resistance have not been established for INH and streptomycin [12••, 13, 14••, 15, 18]. A daily regimen consisting of isoniazid, pyridoxine, ethambutol, and sulfamethoxazole is an effective alternative [12••]. Multidrug regimens containing a macrolide (i.e., clarithromycin or azithromycin), moxifloxacin, and at least one other agent based on in vitro susceptibilities, such as ethambutol or sulfamethoxazole, are likely to be effective for treatment of a patient with rifampin-resistant M. kansasii disease [1••, 11]. Though no clinical trials have been performed, newer fluoroquinolones and linezolid have also proven to have excellent in vitro activity against M. kansasii [11, 12••, 13]. The recommendation for duration of therapy for cutaneous or disseminated M. kansasii disease in patients with AIDS or other immunocompromised patients does not differ from the recommendations for immunocompetent individuals with disseminated disease [1••]. There is no recommended prophylaxis or suppressive regimen for disseminated M. kansasii disease [1••].

Summary

Mycobacterium kansasii is a slow growing and photochromogenic species of nontuberculous mycobacteria that it is often found in many settings and linked to exposure to municipal water systems including tap water. The spectrum of clinical disease produced by Mycobacterium kansasii infection ranges from pulmonary involvement in individuals with chronic pulmonary diseases including chronic obstructive pulmonary disease or cystic fibrosis to cutaneous manifestations and disseminated disease. Additionally, isolated pulmonary or disseminated disease may occur in the setting of severe immunosuppression including HIV/AIDS, solid-organ transplantation, hematologic malignancies, or anti-interferon-γ antibody disorder. Infection of the skin and soft tissues is usually the result of direct inoculation via trauma or a manifestation of disseminated disease but it may also represent dissemination from pulmonary foci of infection. Treatment of M. kansasii of the skin and soft tissues follows the same treatment recommendations as those for isolated pulmonary disease or disseminated disease.