Certain slow-growing species of mycobacteria, namely Mycobacterium marinum, M. ulcerans, M. chimaera,andM. He completed his residency in internal medicine and fellowship in infectious diseases at Emory University in Atlanta, GA. Thank you for sharing this Clinical Microbiology Reviews article. from Universidad Peruana Cayetano Heredia in Lima, Peru, in 2003. The histopathology of BU demonstrates large numbers of extracellular bacilli during the acute phase of infection (24, 47, 109). Cutaneous infection may present as nodules, pustules, verrucous lesions, erythematous plaques, ulcers, and abscesses (Fig. Molecular assays are useful in some cases. There are many different kinds. Cutaneous forms of tuberculosis are a rare clinical manifestation of M. tuberculosis or M. bovis infection, comprising approximately only 1 to 2% of all TB cases (47, 64–67). “Nontuberculous mycobacterial infections of the skin”. This strategy has helped to reduce the prevalence of this infection (93–97). Rapid diagnostic tests to detect mycolactone are currently under evaluation for use as point-of-care tests in areas of high endemicity (109). Andrés F. Henao-Martínez, M.D., graduated from Universidad del Valle, School of Medicine, in Colombia in 2003. Susceptibilities to antimicrobials depend on the species. Treatment of this mycobacterial infection requires a combination of at least two drugs, including a macrolide, ethambutol, trimethoprim-sulfamethoxazole, or rifamycin, with a duration of therapy ranging from two to six months depending on the degree of cutaneous involvement (24, 42, 120). He also obtained a Masters in Public Health in Global Health from the Rollins School of Public Health of Emory University. massiliense among patients with cystic fibrosis (43, 44). His main research interests are vector-borne diseases and emerging infectious diseases in the United States and overseas. Cold abscess caused by Mycobacterium avium-intracellulare complex infection in a 60-year-old male. Chau, C. L. F., et al. The management of extensive scrofuloderma sometimes requires surgical intervention. The most common clinical presentations of mycobacterial infections include pulmonary, cutaneous and disseminated forms in immunocompromised hosts. Among patients with advanced immunosuppression, Mycobacterium kansasii, the Mycobacterium avium-intracellulare complex, and Mycobacterium haemophilum may cause cutaneous or disseminated disease. Antimicrobial regimens of 8 weeks or longer are recommended, irrespective of the clinical staging, and include a combination of rifampin and streptomycin (31, 109). Mycobacterium marinumM. An initial nodular or papular lesion frequently identified in the extremities or in the face evolves into a shallow ulcer with associated regional lymphadenopathy (67, 69, 71). 9) (120). The identification of Buruli ulcer often relies on the presence of characteristic nodules or ulcers, ecological risk factors, and at-risk age groups residing in settings of endemicity. All of these species have been isolated from humans, frogs, and fish. He received his M.P.H. Scrofuloderma may be associated with concomitant pulmonary tuberculosis, particularly when it is associated with right supraclavicular and cervical lymphadenitis (47, 66, 67, 69). Mycobacterium kansasii leading to a sporotrichoid nodular lymphangitis of the right arm. Visceral tuberculosis (pulmonary or extrapulmonary) is rarely associated with concomitant cutaneous involvement (68). These organisms (called nontuberculous mycobacteria) are commonly present in soil and water and are much less virulent in humans than is Mycobacterium tuberculosis.Infections with these organisms have been called atypical, environmental, and nontuberculous mycobacterial infections. Patients with M. haemophilum may also experience immune reconstitution events analogous to leprosy reactions or to paradoxical immune reactions seen after initiating antimycobacterial therapy in patients with M. tuberculosis infection (35, 36, 119). His H index is currently 24. From a large mycobacterial pool, some species have evolved into potential major human pathogens (20, 23–25) (Fig. The most important conditions that should be considered in the differential diagnosis of BU include tropical phagedenic ulcers, cutaneous tuberculosis, vascular (venous or arterial) ulcerations, diabetic foot ulcerations, pyoderma gangrenosum, infections due to Haemophilus ducreyi, cutaneous leishmaniasis, ulcerative yaws, fungal infections (e.g., chromoblastomycosis), and pyogenic ulcerations (e.g., caused by Staphylococcus aureus) (24, 109, 112). See this image and copyright information in PMC. Cutaneous TB cases associated with increased CMI and few noted bacilli are classified as high-immune forms (i.e., tuberculosis verrucose cutis, lupus vulgaris, and tuberculids) (47, 69) (Table 2). Many of these patients presented with surgical wound infections (41, 116, 125). Detection of in vivo resistance to macrolides requires incubation of NTM isolates with clarithromycin prior to determining an MIC (117, 118). In many individuals, pathogenic mycobacterial species may breach our first-line barrier defenses of the innate immune system and modulate the activation of phagocytes to cause disease of the respiratory tract or the skin and soft tissues, sometimes resulting in disseminated infection. Molecular assays are useful in some cases. Free-living amoebas, including Acanthamoeba or Vermamoeba, may act as reservoirs of M. leprae and NTM (38–41). Primary-inoculation TB occurs after exogenous inoculation in individuals not previously sensitized to M. tuberculosis, and it represents a phenomenon analogous to the Ghon complex in the lung (47, 69). Keywords: Epidemiology of disease caused by nontuberculous mycobacteria. Clinical spectrum of leprosy and leprosy reactions (reversal reactions and erythema nodosum leprosum). Classification of major pathogenic mycobacteria. The precise mode of transmission of leprosy remains uncertain but probably involves human-to-human contact through respiratory droplets (29, 30, 45–47) or through blood transfusion (48). M. ulcerans and all mycolactone-producing mycobacterial species evolved from M. marinum and have become specialized variants living in restricted environments (2, 3). Mycobacterium marinum, a close relative of M. ulcerans, is an important cause of cutaneous sporotrichoid nodular lymphangitic lesions. The infection may then be carried to other sites by immature cells (83, 84). Clinically, cutaneous mycobacterial infections present with widely different clinical presentations, including cellulitis, nonhealing ulcers, subacute or chronic nodular lesions, abscesses, superficial lymphadenitis, verrucous lesions, and other types of findings. The clinical spectrum of cutaneous manifestations of M. haemophilum includes multiple skin lesions presenting as erythematous or violaceous papules, plaques, or nodules. eCollection 2020 Dec. Microorganisms. Of these, rapidly growing mycobacteria, M. haemophilum, and M. marinum are important agents involving cutaneous structures. Cosmetic procedures such as mesotherapy (multiple injections of pharmaceutical products, plant extracts, homeopathic substances, vitamins, or other compounds into subcutaneous fat) have been involved in the transmission of rapidly growing mycobacteria (1, 24, 42, 117). Treatment involves a combination of clarithromycin, ciprofloxacin, and rifampin or rifabutin for 12 to 24 months (34–36, 42). The correct identification of the specific RGM infecting the skin will enhance … The spectrum of clinical manifestations includes papular, nodular lesions with a sporotrichoid pattern, verrucous ulcers, inflammatory pseudotumors, draining sinuses, and cold abscesses (Fig. 2) (47, 69). Preclinical Models of Nontuberculous Mycobacteria Infection for Early Drug Discovery and Vaccine Research. 2010 Oct;23(5):445-55. doi: 10.1097/QCO.0b013e32833c2209. Modern molecular genomic analysis of ancient human remains and records of ancient texts demonstrate that the spread of some mycobacterial diseases, including TB and leprosy, track historical milestones of human societies (7–10). Early diagnosis and treatment are crucial to minimize morbidity and prevent long-term disability (2, 3, 109). Mycobacterium ulcerans produces a mycolactone toxin that leads to subcutaneous tissue destruction and immunosuppression, resulting in deep ulcerations that often produce substantial disfigurement and disability. Mycobacterium marinum (M. marinum) is a slow-growing atypical mycobacterium that is commonly found in bodies of fresh or saltwater in many parts of the world.Skin infections with Mycobacterium marinum in humans are relatively uncommon and are usually acquired from contact with contents of aquariums or fish. Category II is defined by the presence of nonulcerative or ulcerative plaques and edematous forms (Fig. Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback, Print ISSN: 0893-8512; Online ISSN: 1098-6618, Sign In to Email Alerts with your Email Address. The clinical spectrum of cutaneous disease caused by M. marinum includes a solitary papule or nodule that may ulcerate and then spreads in a sporotrichoid pattern (lymphangitic spread) (Fig. NLM Tissue biopsies of lesions may demonstrate, using Fite-Faraco staining, the presence of acid-fast bacilli residing inside nerves and perineural or intraneural granulomas (47). Comparative genomic analyses have demonstrated that M. lepromatosis and M. leprae are related mycobacterial species that are distinguishable at the genomic level but cause similar clinical manifestations (104–107). He is the former director of the Tropical Medicine Institute “Alexander von Humboldt” and Professor of Medicine and Infectious Diseases at Universidad Peruana Cayetano Heredia in Lima, Peru. Cutaneous tuberculosis exhibits different clinical phenotypes acquired through different routes, including via extrinsic inoculation of the tuberculous bacilli and dissemination to the skin from other sites, or represents hypersensitivity reactions to M. tuberculosis infection. Atypical mycobacterial infections are infections caused by a species of mycobacterium other than Mycobacterium tuberculosis, the causative bacteria of pulmonary TB and extrapulmonary TB including cutaneous TB; and Mycobacterium leprae, the cause of leprosy.. Atypical mycobacteria may cause many different types of infections… An infection … The clinical manifestations of cutaneous involvement include cellulitis, papular lesions, nodules with purple discoloration, abscesses, draining sinuses, subcutaneous nodules (pseudoerythema nodosum), and ulcerations (117). He is President of the Travel Medicine Committee of the Pan American Infectious Diseases Association (API), as well Secretary of the Colombian Infectious Diseases Association (ACIN). It occurs predominantly in the extremities and manifests as violaceous or brownish warty plaque-like lesions that present in a previously sensitized host because of direct inoculation of the TB bacillus (47). They share phenotypic and genotypic features, including the large virulence plasmid (pMUM) required for mycolactone production. Since the early 1980s, multidrug therapy (MDT) has been universally instituted through active case finding in highly affected communities. He has 172 publications in peer-reviewed journals. Tuberculosis verrucosa cutis of the hand, manifesting as verrucous plaques caused by direct inoculation of the tuberculous bacilli into the skin of an individual previously sensitized to this pathogen. 1999 Jul;26(6):271-8. doi: 10.1111/j.1600-0560.1999.tb01844.x. The treatment for cutaneous mycobacterial infections depends on the specific pathogen and therefore requires a careful consideration of antimicrobial choices based on official treatment guidelines. Untreated cases of lupus vulgaris may evolve into verrucous squamous cell carcinoma (67, 69). He is a member of multiple national and international associations in dermatology, medical mycology, and tropical medicine (especially in mycetoma, chromoblastomycosis, sporotrichosis, mucormycosis, superficial cutaneous mycoses, mycobacterial infections, leprosy, and cutaneous parasitoses). Still others cause infections that are called atypical mycobacterial infections… Mycobacterium lepromatosis, a mycobacterial species related to M. leprae, is linked to diffuse lepromatous leprosy of Lucio and Latapí. Lesions of lupus vulgaris may have the appearance of “apple jelly” on diascopy (47, 69, 71). Treatment of cutaneous TB follows the same recommendations as for other forms of TB, with multidrug therapy (MDT) and ideally adjusted by culture and susceptibility data (47, 67, 69). 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Henao-Martínez, DIAGNOSIS OF CUTANEOUS MYCOBACTERIAL INFECTIONS. Infection caused by Mycobacterium fortuitum associated with mesotherapy. Their geographic distribution has not been completely described; RGM-borne cutaneous disease has been reported throughout the world. This clinical form affects women predominantly and manifests as smoldering nodules and annular plaques, or it may present with hypertrophic or vegetative lesions. Cutaneous involvement of M. kansasii is usually present in immunocompromised hosts and sometimes with concomitant pulmonary disease or disseminated disease (24, 37). We do not retain these email addresses. The American Thoracic Society (ATS), Infectious Diseases Society of America (IDSA), and several case reports imply that like M. marinum, RGM may be ubiquitous, perhaps particularly in water, and may be transmitted to the host through breaks in colonized or contaminated skin. Tuberculosis verrucosa cutis represents primary M. tuberculosis infection. {MC} atypical mycobacterium to cause infection Reddish bumps may appear, enlarge, and turn purple. Lupus vulgaris occurs predominantly in Asia and southern Africa. Clinically, BU affects predominantly the lower extremities (>55%) and less often the upper extremities or other body parts (31, 109, 111, 112) The toxin (polyketide), mycolactone secreted by M. ulcerans causes tissue destruction (111, 113), local immunosuppression through the inhibition of protein translocation into the endoplasmic reticulum of cytokines of the innate immune system, membrane receptors, adhesion molecules, and T-cell-dependent cytokines (114). Disruption of skin and soft tissues frequently constitutes the portal of entry of NTM from environmental niches (soil, natural water systems, engineered water networks, etc.) This infection may occur among immunocompetent and immunocompromised hosts, including those with HIV infection/AIDS or with renal transplantation. Wilmer E. Villamil-Gómez, M.D., Ph.D.(c), is a medical doctor (graduated from the University of Cartagena), family medicine specialist (University of Cartagena), specialist in epidemiology (School of Medicine, Juan N Corpas University), candidate for Ph.D. in tropical medicine and infectious diseases (University of Cartagena and University of the Atlantic), and fellow in infectology (University of Buenos Aires). Susceptibility testing for M. leprae involves assessments of specific genetic markers of antimycobacterial resistance (99). However, in most countries, at least 70% of all cases are diagnosed in the stage with deep ulceration. Their gene loss or acquisition reflects fluctuating environmental challenges and host-specific pathoadaptations (2, 3, 5) (Table 1). 2020 Jul 27;9(8):450. doi: 10.3390/antibiotics9080450. Mycobacteria are a type of germ. The most common one causes tuberculosis. Tuberculosis verrucosa cutis of the hand, manifesting as verrucous plaques caused by direct…, Scrofuloderma presenting in the neck, resulting from direct extension of an infected left…, Clinical manifestations of leprosy: borderline…, Clinical manifestations of leprosy: borderline tuberculoid (BT) (A), borderline borderline (BB) (B), and…, An 11-year-old male demonstrating a destructive panniculitis causing ulceration with undermined borders, characteristic…, An adult with Mycobacterium abscessus infection presenting as scrofuloderma with extensive tissue destruction…, Infection caused by Mycobacterium fortuitum…. He is also the Associate Director for Research for the Global Health Institute at Stony Brook University. This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Infections due to NTM can produce pulmonary or extrapulmonary disease in immunocompromised hosts (1, 24, 42). Tuberculosis is a mycobacterial infection that most frequently occurs due to infection with Mycobacterium tuberculosis, an acid-fast bacillus. ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology. An adult with Mycobacterium abscessus infection presenting as scrofuloderma with extensive tissue destruction in the right cervical and supraclavicular areas. Untreated cases or those with extensive and deep ulcerations develop scarring contractures, deformity, osteonecrosis, and limb loss (31, 109). Lupus vulgaris may occur concomitantly with scrofuloderma, or it rarely may be associated with primary-inoculation TB. The pathogenesis of cutaneous mycobacterial infections is the result of hematogenous dissemination, local or regional spread from a deep-seated infection, or direct inoculation into the skin and soft tissues (24). Azithromycin is the preferred agent in M. abscessus infections, whereas clarithromycin or azithromycin is effective in cases of M. massiliense (117, 118). The diagnosis of Buruli ulcer is mostly a clinical one and is based on the age of presentation, geographic area, and location (31, 109, 112). This form is also known as tuberculosis colliquative cutis. Nontuberculous mycobacteria (NTM), i.e., those mycobacterial species that do not cause tuberculosis or leprosy, are frequently present in municipal water systems, residing mostly in the pipeline biofilms (21, 22, 38, 39). Recent advances in leprosy and Buruli ulcer (Mycobacterium ulcerans infection). In many settings, leprosy remains an important cause of neurological impairment, deformity, limb loss, and stigma. These lesions eventually lead to significant scarring (47, 69). Identifying M. tuberculosis in tissue specimens through culture or molecular detection is of paramount significance when suspecting most clinical forms of cutaneous tuberculosis. Severe hand swelling and nodular lymphangitic lesions caused by Mycobacterium marinum infection. Mycobacterium ulcerans produces a mycolactone toxin that leads to subcutaneous tissue destruction and immunosuppression, resulting in deep ulcerations that often produce substantial disfigurement and disability. Surgical debridement and skin grafting are used to speed wound healing in those with large lesions. USA.gov. In contrast, the pathogenicity of M. ulcerans derives from the acquisition of a plasmid encoding the polyketide toxin mycolactone (2, 5). He is an Associate Researcher, Colciencias and winner of the Wiliam Jarvis 2014 Award, Best International Research, awarded by SHEA. The most common cutaneous forms of acquisition of NTM involve direct inoculation via trauma (33), postsurgical infections (42), or iatrogenic acquisition with indwelling medical devices, plastic surgery, cosmetic procedures, or prosthetic implants (24, 42). The use of point-of-care diagnosis of Buruli ulcer is under evaluation in field studies in settings of endemicity (1, 42). In England, Ireland, and Scotland, red squirrels may be infected and develop leprosy-like lesions due to M. lepromatosis (53). Enter multiple addresses on separate lines or separate them with commas. Genomic events such as genome reduction, critical gene acquisition, gene transfer, mutations, and recombination permitted environmental mycobacteria to evolve into host-associated pathogens (2, 5, 9, 11, 14–16, 19). M. fortuitum is susceptible to macrolides, amikacin, doxycycline, fluoroquinolones, and trimethoprim-sulfamethoxazole. Early identification of new cases likely prevents further transmission, but, importantly, it may also reduce the risk of neurological dysfunction and disability associated with leprosy (96–98). [Cutaneous and soft skin infections due to non-tuberculous mycobacteria]. An 11-year-old male demonstrating a destructive panniculitis causing ulceration with undermined borders, characteristic of Buruli ulcer. Another one causes leprosy. Some mycobacterial species have specific growth requirements in solid or liquid culture media. The diagnosis of BU maybe confirmed by direct microscopy of suspicious lesions, histopathology of skin biopsy specimens, culture, and IS2404 PCR (PCR) (24, 31, 109). Skin biopsies of cutaneous lesions to identify acid-fast staining bacilli and cultures represent the cornerstone of diagnosis. These topics have been dealt with elsewhere in the CDS. In addition, histopathological evaluation of tissue samples contributes to defining the immunopathological spectrum of polar and borderline forms of leprosy (47). In addition, Dr. Henao-Martínez directs the Outpatient Infectious Diseases Rotation for the internal medicine and preventive medicine residency programs. Carlos Franco-Paredes, M.D., M.P.H., is an infectious diseases clinician with expertise in tropical medicine and neglected tropical diseases. 2000. pp. The responsible acid-fast bacilli are slow-growing opportunistic pathogens but may invade the skin of immunocompetent individuals causing indolent granulomatous disease. Rampacci E, Stefanetti V, Passamonti F, Henao-Tamayo M. Pathogens. Based on these similarities, researchers have proposed recognizing all these bacteria as M. ulcerans (31, 32, 111, 113). Mycobacterial infections generally cause one of three different types of disease: Tuberculosis: the term used to describe disease where there is the formation of granulomas (inflammatory nodules) in the body; Leprosy: the term used to describe disease where infection results in the formation of granulomas in the skin (seen as skin … Alternatively, a combination of rifampin and clarithromycin or rifampin and moxifloxacin could be used (109, 112). Enferm Infecc Microbiol Clin. We have no conflicts of interest to disclose. Please enable it to take advantage of the complete set of features! (Lon), F.F.T.M R.C.P.S.  |  NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. Mycobacterium peregrinum is a rapidly growing mycobacterium (RGM) that rarely causes skin infections. He has been the director of the travel clinic at University of Colorado Hospital since 2016. 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