Author
Lars Grimm, MD, MHS
House Staff
Department of Internal Medicine
Duke University Medical Center
Durham, North Carolina
Disclosure: Lars Grimm, MD, MHS, has disclosed no relevant financial relationships.
Editor
Robert A. Schwartz, MD
Professor and Head, Dermatology
Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health
UMDNJ-New Jersey Medical School
Newark, New Jersey
Disclosure: Robert A. Schwartz, MD, has disclosed no relevant financial relationships.
Tuberculosis and leprosy are the most well known of the mycobacterial diseases of the approximately 30 identified. Atypical or nontuberculous mycobacteria can be found in a wide variety of different environmental conditions and are responsible for a host of disease processes that can easily be misdiagnosed. Atypical mycobacteria have been increasing in frequency because of better detection methods and a steadily growing population of immunosuppressed individuals. In general, mortality from infection is low, but the morbidity may be high depending on the specific disease process. The chest x-ray shown is from a patient infected with Mycobacterium kansasii, a nontuberculous mycobacteria; it demonstrates cavitating consolidation with volume loss in the right upper lobe.
Mycobacterium avium complex (MAC), consisting of M avium and M intracellulare, is the most common atypical mycobacteria responsible for disease in humans. MAC has been found in an extremely wide variety of locations, including freshwater, saltwater, birds, soil, farm animals, tobacco, and house dust. MAC may manifest in several different forms depending on the host age, immune status, and exposure history.
MAC lymphadenitis occurs in children age 1-4 years. It involves the unilateral cervical lymph nodes, which enlarge slowly and take on a rubbery to firm texture. The overlying skin may appear shiny, thin, and erythematous. The nodes usually resolve spontaneously, but they may caseate and rupture, producing a sinus tract with chronic drainage. Diagnosis is based on clinical suspicion and lymph node biopsy with histologic and microbiological confirmation. Bright, eosinophilic, serpiginous necrosis with scattered nuclear debris is characteristic for MAC lymphadenitis. Surgical excision of the affected lymph nodes results in a cure rate of > 90% without antibiotics. The image shown is a Ziehl-Neelsen stained micrograph of M avium courtesy of the US Centers for Disease Control and Prevention.
Disseminated MAC occurs in patients with AIDS or lymphoma when their CD4 count falls below 50 cells/μL. Patients present with fever of unknown origin, diaphoresis, weight loss, fatigue, diarrhea, shortness of breath, and right-upper-quadrant pain. Patients may also develop mastitis, soft tissue or brain abscesses, or pyomyositis. On examination, patients usually have generalized wasting, skin pallor, tender hepatosplenomegaly, and lymphadenopathy. Diagnosis is made by blood cultures with mycobacterial culture media; cultures generally take 1-2 weeks to turn positive, and false-negative results are common. Biopsied lesions usually are nongranulomatous and show extensive acid-fast bacilli with plump histiocytes, as shown. Treatment of disseminated MAC in patients with AIDS is usually with a macrolide antibiotic, ethambutol, and rifabutin until resolution of symptoms and sustained CD4 counts of > 100 cells/μL. Image courtesy of the US Centers for Disease Control and Prevention.
Pulmonary MAC may develop in immunocompetent patients if there is underlying pulmonary disease. Patients typically present with cough, productive sputum, weight loss, fever, lethargy, and night sweats. On examination, patients may have crackles, rhonchi, tachypnea, dullness to percussion, and bronchial breath sounds. Diagnosis is made by acid-fast bacillus staining and culture of sputum specimens, but cultures may take 1-2 weeks to grow. Chest x-rays may show nodular or cavitary opacities. On computed tomography (CT), diagnostic features include centrilobular parenchymal nodules, multifocal bronchiectasis, and progressive fibrosis. The CT scan shown demonstrates nodules and multifocal bronchiectasis in the middle lobe and lingula. In some cases, lesion biopsy via one of several techniques, such as CT-guided bronchoscopy, may be needed for confirmation. Treatment for pulmonary MAC is with antimicrobials, usually a macrolide, ethambutol, and rifabutin, for at least 1 year.
Two other variants of MAC have been described. Lady Windermere syndrome is MAC infection with bronchiectasis in elderly women without any underlying lung disease. Lady Windermere refers to a character in Oscar Wilde’s Victorian play Lady Windermere’s Fan. It is thought to be associated with voluntary cough suppression leading to stagnation of secretions. The image shown demonstrates bronchiectasis of an elderly woman with Lady Windermere syndrome. Treatment is the same for pulmonary MAC. MAC may also produce hypersensitivity pneumonitis associated with bathing in a hot tub. Patients may experience dyspnea, cough, and hypoxemia. Hot-tub lung MAC should resolve once the exposure is removed, but in some cases steroids may be needed to reduce inflammation.
Mycobacterium kansasii is the second most common nontuberculous mycobacterial infection associated with AIDS (MAC is the most frequent). The primary manifestation of M kansasii is a chronic pulmonary infection. Unlike MAC, this organism is not readily isolated from environmental sources, but it has been identified in water supplies in areas of high endemicity, such as the American Midwest and Southwest. In most cases, M kansasii infection is indistinguishable from tuberculosis with cough, sputum production, weight loss, breathlessness, chest pain, hemoptysis, and diaphoresis; however, symptoms may be more chronic and less severe than in tuberculosis. Immunocompromised patients may also develop disseminated disease, pericarditis with tamponade, oral ulcers, chronic sinusitis, osteomyelitis, and cellulitis. On examination, patients may have hepatosplenomegaly, lymphadenopathy, fevers, and crackles. Diagnosis is usually made by sputum sample staining and culture, or by blood culture for disseminated disease. Approximately 90% of patients with pulmonary disease will have cavitary infiltrates on chest radiography, as demonstrated by the left-lower-lobe infiltrate in the chest x-ray shown.
High-resolution CT may be helpful to differentiate among other potential abnormalities because the culture results take several weeks to return. Classically, M kansasii pulmonary infection is a right-sided, apical, thin-walled cavitary infiltrate, as shown on the CT scan. Histologic findings are similar to those seen with tuberculosis: acute suppuration, nonnecrotic tubercles, or caseation. Primary treatment for M kansasii is a 3-drug regimen, with rifampin as the most important component. Treatment continues for 12 months after sputum cultures become negative. Cures rates are excellent with antimicrobial adherence. Image courtesy of Raj Sreedhar, MD, Southern Illinois University School of Medicine, Springfield, Illinois.
Mycobacterium marinum is an atypical mycobacteria found in water with a wide range of temperatures and salinities. It has been identified as a natural infection in over 150 species of fish, amphibians, reptiles, and marine mammals. Infection in humans occurs when skin or soft tissue injuries are exposed to water or marine products. Fishermen, oyster harvesters, aquarium workers, and swimmers are at greatest risk for infection. Patients typically report tender papules or nodules that develop 2-3 weeks after exposure. The lesions slowly enlarge and then suppurate or ulcerate, as shown. In 25%-50% of cases, an ascending lymphangitis develops, and new lesions arise along the lymphatics. In one third of cases, the infection will spread to deeper structures.
Patients with M marinum will usually have a tuberculin skin test result between 5 and 9 mm of induration. Growth in culture media takes 2-3 weeks. Laboratories must be notified in advance because cultures grow at higher than normal temperatures. M marinum infection takes a long time to be treated effectively. Treatment for skin and soft-tissue infections lasts 1-2 months after clearance of lesions and symptomatic relief; this typically results in 3-4 months of therapy, but it is not uncommon for treatment durations of greater than a year. M marinum is resistant to many antituberculosis medications. Combination therapy with clarithromycin and ethambutol is the recommended first-line regimen, with rifampin added for osteomyelitis or deep structure involvement. The overall prognosis with treatment is good.
Mycobacterium chelonae is a fast-growing, nontuberculous mycobacterium` responsible for a wide range of clinical syndromes. M chelonae may infect the lungs, skin, bones, joints, eyes, lymphatics, heart, surgical sites, and implanted devices and may be disseminated in immunosuppressed individuals. History and physical examination findings vary widely depending on the type of infection. For skin infections, patients will typically develop nonhealing, nonspreading skin ulcerations, as shown. Pulmonary infections usually present with chronic cough; rales or rhonchi are heard on examination. Patients with disseminated disease may experience fever, night sweats, and weight loss. Valvular murmurs may be auscultated in M chelonae endocarditis, while ulcers or keratitis may be present in ocular infections. Diagnosis is based on biopsy and culture testing but may be difficult given the protean manifestations. Prolonged antibiotic therapy for at least 4 months with clarithromycin plus another agent is needed. Surgical therapy is often necessary for cutaneous, ocular, lymphatic, and bone lesions, and infected implanted devices need to be removed. Image courtesy of K. Galil, US Centers for Disease Control and Prevention.
Mycobacterium fortuitum is a rapidly growing nontuberculous mycobacterium found in natural and processed water sources. Infection can produce a wide variety of clinical syndromes, including lung disease, local cutaneous disease, osteomyelitis, joint infection, ocular disease, and disseminated disease in patients with immunosuppression. Surgical site infections are well-documented and are usually the result of contamination with colonized tap water. M fortuitum causes nonhealing but nonspreading ulcerative skin lesions with subcutaneous nodules. Patients with lung disease may have chronic cough with rales or rhonchi. Disseminated disease will typically present with fever, night sweats, and weigh loss. Diagnosis is based on culture results. Localized skin lesions may heal without any therapy, but chronic infection is common in other sites and usually requires surgical debridement. Long-term therapy with amikacin and another antibiotic is usually required for several months, but no standard duration of therapy has been established. A colored scanning electron micrograph showing the rod-shaped structure of M fortuitum is shown, courtesy of Margaret M. Williams and Janice Haney Carr, US Centers for Disease Control and Prevention.
Mycobacterium xenopi is a slow-growing, nontuberculous mycobacterium often considered an environmental contaminant. It was named after isolation from skin lesions of the African clawed frog Xenopus laevis, as shown. M xenopi has low pathogenicity; host impairment is required for infection. Colonization of hospital water systems is associated with nosocomial infection. Most infections are pulmonary and occur in patients with lung disease or other predisposing conditions, such as malignancy, HIV, alcoholism, or diabetes mellitus. Patients may present with productive cough, dyspnea, weakness, malaise, weight loss, hemoptysis, night sweats, and fevers. There are no specific physical examination findings -- they are usually related to the underlying disease process. Diagnosis is based on culture results. Treatment standards have not been established but usually consist of 2-4 drugs prescribed for several months. Image courtesy of Wikimedia Commons.
Mycobacterium haemophilum is a nontuberculous mycobacterium that causes skin, joint, bone, and pulmonary infections in immunocompromised patients and lymphadenitis in children. Lymphadenitis in children presents as slowly enlarging, painful lymphadenopathy in the neck, usually submandibular and cervical. Skin lesions are the most common presentation in immunosuppressed patients. They typically develop over the joints, beginning as papules, nodules, or cysts that may become tender and pruritic and then ulcerate. Overlying cutaneous lesions may lead to a septic joint or osteomyelitis. Pulmonary infection presents with fever, cough, pleuritic chest pain, and dyspnea. Diagnosis is made with culture results, but M haemophilum requires species-specific growth media and low temperatures, leading to underdiagnosis. Biopsy specimens may show localized necrosis, granulomas, and bacilli, as shown. Treatment for lymphadenitis is with surgical excision, but immunosuppressed patients require multidrug antimicrobial therapy of long duration. Reversal of the underlying immunosuppression is the most successful means of treatment, if possible. Image courtesy of Michael A. Saubolle, US Centers for Disease Control and Prevention.
Author
Lars Grimm, MD, MHS
House Staff
Department of Internal Medicine
Duke University Medical Center
Durham, North Carolina
Disclosure: Lars Grimm, MD, MHS, has disclosed no relevant financial relationships.
Editor
Robert A. Schwartz, MD
Professor and Head, Dermatology
Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health
UMDNJ-New Jersey Medical School
Newark, New Jersey
Disclosure: Robert A. Schwartz, MD, has disclosed no relevant financial relationships.
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