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MOTT were identified as human pathogens in 1938 (Mycobacterium fortuitum), in 1948 (Mycobacterium ulcerans), and in 1954 (Mycobacterium marinum). However, overshadowed by the infectious disease burden due to M. leprae and M. tuberculosis, the pathogenic potential of slow-growing MOTT species has been recognized only in recent decades. Because MOTT infections usually closely mimic infections with M. tuberculosis, and the bacteria have strict and often unusual requirements for culture, they are still probably underdiagnosed.
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Identification of Mycobacteria Other Than M. Tuberculosis
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As with other infectious diseases, the diagnosis of mycobacterial infection depends on the identification of the microorganism isolated from the host. Specimens for culture should be sent to a special laboratory familiar with the special growth requirements of these organisms.
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Antigens for intradermal skin testing (PPDs) for many of the clinically relevant mycobacterial species have been prepared in analogy to PPD from M. tuberculosis, but their accessibility is very limited and they are therefore little used.
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Histopathologic analysis is supportive but cannot distinguish among mycobacterial species, because all share similar histopathologic features.33
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Treatment is summarized in Table 184-4. Importantly, some MOTT organisms are resistant to standard tuberculosis therapy. PCR testing for mycobacterial DNA is not yet reliable enough to play a role in the diagnosis of disease but can sometimes be useful in distinguishing among species.
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Etiology and Pathogenesis
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MOTT are widely distributed in nature and are usually commensals or saprophytes, rather than pathogens. Atypical Mycobacteria are usually acquired from environmental sources such as water or soil, and their role in disease reflects their natural distribution and, possibly, local lifestyles. These organisms are thought to cause mycobacterial skin disease more often than does M. tuberculosis. Cases tend to be sporadic, but certain types of exposures may lead to small community outbreaks.3,34 Any organ or organ system may be affected (Table 184-5), but MOTT seem much less likely to disseminate than M. tuberculosis, and infections usually run a more benign and limited course. As a rule, MOTT are much less responsive to antituberculosis drugs but may be sensitive to other chemotherapeutic agents.
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Only two organisms, M. ulcerans and M. marinum, produce a characteristic clinical picture. An immunosuppressed state of the host or damage to a particular organ (e.g., in M. kansasii infection of the lung) facilitates these infections.
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New mycobacterial pathogens are described from time to time, which suggests that their full pathogenic potential is not yet appreciated. Recently, an outbreak of skin disease caused by a nontuberculous Mycobacteria in Pacific Islanders from Satowan was reported in the literature.35 These patients presented with long-standing verrucous and keloidal plaques (locally known as “spam” disease) (Fig. 184-10). Histopathological and PCR data demonstrated a nontuberculous mycobacterial infection as the cause.
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Skin Infections with Mycobacteria Other Than M. Tuberculosis
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Mycobacterium Ulcerans (Buruli Ulcer Disease)
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The natural habitat of M. ulcerans is still not known, and it has never been found outside the human body, but M. ulcerans infection occurs in wet, marshy, or swampy areas and seems to have to do with contaminated water. M. ulcerans is the third most frequent mycobacterial pathogen, after M. tuberculosis and M. leprae.
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The disease is found most often in children and young adults, and affects females more often than males. A subcutaneous nodule gradually enlarges and eventually ulcerates. A blister may develop before ulceration. The ulcer is deeply undermined, and necrotic fat is exposed (Fig. 184-11). The preceding nodule as well as the ulcer is painless, and the patient continues to feel well. The painless nature of the ulcer has been attributed to nerve damage and tissue destruction caused by the toxin mycolactone. The lesions may occur anywhere on the body but tend to be limited to the extremities in adults. They may be large, involving a whole limb. The ulceration may persist for months and years, and healing and progression of the ulceration may occur in the same patient. This process may lead to appreciable and sometimes disabling scarring and lymphedema. Neither lymphadenopathy nor any constitutional signs appear at any time unless the disease process is complicated by bacterial superinfection.
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Differential Diagnosis
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Mycobacterium Marinum (Mycobacterium Balnei, Fishtank/Swimming Pool Granuloma)
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M. marinum occurs in freshwater and saltwater, including swimming pools and fish tanks.
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Risk factors for M. marinum infection are a history of trauma and water- or fish/seafood-related hobbies and occupations. The disease begins as a violaceous papule at the site of a trauma 2–3 weeks after inoculation. Patients may have a nodule or a psoriasiform or verrucous plaque at the site of inoculation, usually the hands, feet, elbows, or knees (Fig. 184-12). The lesions may ulcerate. Usually, the lesions are solitary, but occasionally lymphocutaneous spread occurs. They may heal spontaneously within 1–2 years, with residual scarring. Occasionally, the lesions are suppurative, rather than granulomatous, and may be multiple in both normal or immunosuppressed hosts.
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Differential Diagnosis
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Mycobacterium Kansasii
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M. kansasii is the atypical Mycobacterium most closely related to M. tuberculosis. It is usually acquired from the environment. Endemic areas include Texas, Louisiana, the Chicago area, California, and Japan. Skin disease caused by M. kansasii usually occurs in adults, and is more common in individuals with underlying immunosuppression caused by Hodgkin disease, treatment for organ transplantation, or AIDS. Inoculation is usually attributable to minor trauma such as a puncture wound.
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M. kansasii infection may present in several forms. Most frequently, there are papules in a sporotrichoid distribution. Sometimes, subcutaneous nodules extend to deeper structures and may result in a carpal tunnel syndrome or joint disease. An ulcerated plaque may also develop as a metastatic lesion. Disseminated disease caused by M. kansasii infection occurs in immunosuppressed patients, and such patients have cellulitis and abscesses rather than granulomatous lesions. The most commonly affected organ is the lung, usually in patients with other pulmonary conditions (silicosis, emphysema). Infection may also cause cervical lymphadenopathy. As with M. tuberculosis, M. kansasii present in nasopharyngeal secretions can lead to periorificial cutaneous infection. These infections usually progress slowly, although a chronic stable lesion or even spontaneous regression may occur. Drug therapy should be initiated as soon as the diagnosis is made.
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Differential Diagnosis
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Mycobacterium Scrofulaceum
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Mycobacterium scrofulaceum is widely distributed in the environment.
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The usual manifestation of M. scrofulaceum infection is cervical lymphadenitis, frequently unilateral, in children, mainly between the ages of 1 and 3 years. Submandibular and submaxillary nodes are typically involved, rather than the tonsillar and anterior cervical nodes, as is characteristic for M. tuberculosis infection. There are no constitutional symptoms. Involved lymph nodes enlarge slowly over several weeks, and eventually ulcerate and develop fistulae. There is rarely an evidence of lung or other organ involvement. In most cases, the disease is benign and self-limited.
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Differential Diagnosis
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The differential diagnosis includes other forms of bacterial lymphadenitis; viral infections, including mumps and mononucleosis; and malignancy, including solid tumors, lymphoma, and leukemia.
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Mycobacterium Avium-Intracellulare
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M. avium-intracellulare encompasses organisms with a wide variety of microbiologic and pathogenic properties. Well over 20 subtypes can be separated by immunologic techniques, although this is not necessary for clinical purposes.
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These organisms are usually grouped together with M. scrofulaceum in the so-called M. avium-intracellulare-scrofulaceum complex, but are separated here for clinical reasons. Whereas M. scrofulaceum produces only a benign, self-limited lymphadenopathy with no organ involvement, M. avium-intracellulare infection usually causes lung disease or, less frequently, osteomyelitis. It may also produce a cervical lymphadenitis with sinus formation that is clinically indistinguishable from tuberculous scrofuloderma.
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Primary skin disease caused by M. avium-intracellulare has been reported in rare instances, presenting as single or multiple painless, scaly yellowish plaques, sometimes resembling LV, or as subcutaneous nodules with a tendency to ulceration and a slowly progressive, chronic course. Sometimes, skin involvement occurs secondary to disseminated infection with M. avium-intracellulare. Skin lesions have included generalized cutaneous ulcerations, granulomas, infiltrated erythematous lesions on the extremities, pustules, and soft-tissue swelling. M. avium-intracellulare infections are an important cause of morbidity in patients with AIDS (see Chapter 198).
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Mycobacterium Szulgai, Mycobacterium Haemophilum, Mycobacterium Genavense
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Mycobacterium szulgai, Mycobacterium haemophilum, and M. genavense are rarely found to cause human disease in cases of otherwise unexplained cervical lymphadenitis, cellulitis, draining nodules and plaques, bursitis, pneumonia, and subcutaneous granulomatous eruptions.
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Mycobacterium Fortuitum, Mycobacterium Chelonae, Mycobacterium Abscessus
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M. fortuitum, Mycobacterium chelonae, and Mycobacterium abscessus—three species of fast-growing, facultative pathogenic Mycobacteria—were previously grouped in the M. fortuitum complex but are now recognized as distinct species. These organisms seem to be widely distributed and can commonly be found in soil and water. Contamination of various materials, including surgical supplies, occurs but does not always result in clinical disease.
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M. fortuitum, M. chelonae, and M. abscessus cause similar clinical diseases. Infection usually follows a puncture wound or a surgical procedure. The disease manifests itself as a painful red infiltrate at the site of inoculation; there are no signs of dissemination and no constitutional symptoms. Cold postinjection abscesses, especially in the tropics, may also be caused by fast-growing Mycobacteria. Recent cases in the United States have followed after pedicures and water immersion in salons.
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The lesion is a dark red nodule, often with abscess formation and clear fluid drainage. Healthy children and adults may become infected, but disseminated disease usually occurs in hemodialysis patients or other immunologically compromised individuals. The disease course consists of multiple recurrent episodes of abscesses on the extremities or a generalized macular and papular eruption. Internal organs may be involved.
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There is simultaneous occurrence of polymorphonuclear leukocyte microabscesses and granuloma formation with foreign body-type giant cells, the so-called dimorphic inflammatory response. There is usually necrosis but no caseation. Acid-fast bacilli may occasionally be found within microabscesses.
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Organisms of the M. fortuitum complex may be identified by special laboratories to permit a rational treatment.