eMedicine Specialties > Infectious Diseases > Mycobacterial Infections

Mycobacterium Avium-Intracellulare: Differential Diagnoses & Workup

Author: Janak Koirala, MD, MPH, FACP, Associate Professor, Department of Internal Medicine, Division of Infectious Diseases, Southern Illinois University School of Medicine
Contributor Information and Disclosures

Updated: Sep 30, 2008

Differential Diagnoses

Aspergillosis
Lung Cancer, Oat Cell (Small Cell)
Bartonellosis
Lymphoma, B-Cell
Benign Lung Tumors
Lymphoma, Mediastinal
Blastomycosis
Lymphoma, Non-Hodgkin
Catscratch Disease
Mycobacterium Kansasii
Cryptococcosis
Pneumonia, Aspiration
Cytomegalovirus
Pneumonia, Bacterial
Fever of Unknown Origin
Pneumonia, Fungal
Histoplasmosis
Toxoplasmosis
Infectious Mononucleosis
Tuberculosis
Lung Cancer, Non-Small Cell

Other Problems to Be Considered

Mumps
Parotid tumor
HIV wasting
Mycobacterium scrofulaceum infection

Workup

Laboratory Studies

  • At least 3 sputum specimens, preferably early-morning samples taken on different days, should be collected for acid-fast bacillus (AFB) staining and culture. Sputum AFB stains are positive for M avium complex (MAC) in most patients with pulmonary MAC infection. Mycobacterial cultures grow MAC in about 1-2 weeks, depending on the culture technique and bacterial burden. However, interpretation of sputum AFB stain and culture may be difficult, as MAC can colonize the respiratory tract without causing clinical infection.
  • The American Thoracic Society (ATS) and Infectious Disease Society of America (IDSA) guidelines recommend the following criteria to establish a diagnosis of NTM lung disease:10
    • Clinical
      • Pulmonary signs and symptoms such as cough, fatigue, weight loss; less commonly, fever and weight loss; dyspnea
      • Appropriate exclusion of other diseases (eg, carcinoma, tuberculosis)
    • Radiographic
      • Chest radiograph with nodular or cavitary opacities
      • High-resolution computerized tomography (HRCT) scan showing multifocal bronchiectasis and multiple small nodules
    • Bacteriologic (meeting one of the below criteria within one year)
      • At least 2 culture-positive sputum samples
      • At least one culture-positive bronchial washing or lavage
      • Biopsy with histopathologic features consistent with mycobacterial infections (eg, granulomatous inflammation or positive AFB stain) and positive culture result (sputum, endobronchial, or biopsy specimen)
  • In a study that evaluated the significance of positive sputum culture results using ATS guidelines for the diagnosis of NTM infection, only 7 of 46 (15%) patients infected with HIV and 1 of 34 (3%) patients without HIV infection but with MAC-positive sputum met the clinical, bacteriologic, and radiographic criteria for MAC pulmonary disease.
  • Blood cultures in appropriate mycobacterial culture media should be performed for suspected disseminated MAC (DMAC) infection. This should be performed routinely in patients with advanced AIDS and persistent undiagnosed febrile illness. Cultures generally take 1-2 weeks to turn positive. Early in the course of infection, bacteremia may be low-level or intermittent, possibly causing false-negative blood culture results. Later in the course of infection, blood cultures results are invariably positive.
  • Diagnosis of MAC lymphadenitis is based on a high level of clinical suspicion and biopsy of the nodes with histological and microbiological confirmation. Fine-needle aspiration of lymph nodes has been used to obtain tissue for diagnosis when complete excision is not feasible. Results of acid-fast staining of tissue or pus are usually negative because of the small number of bacilli present. The culture result may take a few weeks to become positive. Nucleic acid amplification methods can provide a more rapid diagnosis. Skin testing (MAC tuberculin test) contributes very little in establishing diagnosis.
  • ATS and IDSA guidelines recommend to base the diagnosis of hot-tub lung (hypersensitivity pneumonitislike lung disease) on a compatible clinical picture, including hot-tub exposure, microbiological data, radiographic findings, and histopathology. In the absence of histopathology, evidence for hot-tub lung needs to include (1) subacute onset of respiratory symptoms, (2) hot-tub exposure, (3) characteristic radiological changes, and (4) isolation of MAC from sputum, bronchoalveolar lavage (BAL), lung tissue, and hot-tub water. The radiographic changes include ground-glass opacities, centrilobular nodules, and air trapping on expiratory CT scan images.
  • The species-specific molecular probes are used for rapid identification of mycobacterial species grown in culture (eg, Mycobacterium tuberculosis, M kansasii, MAC). Various nucleic acid amplification techniques (eg, polymerase chain reaction [PCR], ligase chain reaction, transcription-mediated amplification) are also used for this purpose, as well as for direct detection of mycobacteria in the sputum. However, these assays need further refinement to improve their sensitivity to detect mycobacteria directly in patient's specimens.
  • Mycobacterial susceptibility testing for various antimycobacterial agents is available in specialized laboratories. Because studies have shown poor correlations between in vitro susceptibility results and clinical outcome, the ATS and IDSA guidelines recommend routine antibiotic susceptibility for clarithromycin only. Based on the experience at the author's institution, susceptibility tests are reliable if performed selectively at highly experienced laboratories specializing in mycobacteriology.

Imaging Studies

  • Chest radiography generally reveals MAC pulmonary lesions. However, in cases with limited lung infection, CT scanning of the chest and even HRCT scanning are needed to reveal the lung lesions. HRCT scanning has been shown to be more sensitive than chest radiography for revealing pulmonary abnormalities associated with MAC infection.
    • Patients with pulmonary MAC infection with underlying lung disease often have cavities revealed by imaging studies. Typically, these patients have fibrocavitary changes and nodules that involve the upper lung zones.
    • Elderly women without underlying lung disease but with MAC pulmonary infection develop a fibronodular bronchiectasis that often involves the lingula and right middle lobe. A strong association between MAC infection and bronchiectasis with circumscribed nodules has been shown in these patients. Surveys of patients with fibronodular bronchiectasis have documented MAC infection in 25-50% of patients.
    • Other radiological changes include atelectasis, consolidation, tree-in-bud appearance, and ground-glass opacities.
  • In patients with AIDS and DMAC infection, CT scan of the abdomen reveals retroperitoneal or periaortic lymphadenopathy and hepatosplenomegaly.
  • Hypersensitivity pneumonitislike changes characterized by ground-glass attenuation, centrilobular nodules, and air trapping on expiratory images are seen on CT scans in patients with hot-tub lung, which is a type of hypersensitivity pneumonitislike syndrome described in patients exposed to aerosolized MAC. 

Other Tests

  • Patients with DMAC usually have elevated transaminase and alkaline phosphatase levels.
  • They are also usually anemic and occasionally pancytopenic due to bone marrow suppression secondary to the infection.
  • An enzyme immunoassay (EIA) kit used in Japan has been used to detect serum IgA antibody to MAC-specific glycopeptidolipid core antigen. This could be useful for serodiagnosis of MAC pulmonary infection. Sensitivity and specificity of this EIA kit were reported as 84% and 100%, respectively.11

Procedures

  • Bronchoscopy and transbronchial biopsy may be needed to diagnose pulmonary MAC infection. Alternatively, a CT-guided needle biopsy, video-assisted thoracoscopic (VAT) biopsy, or open lung biopsy may be performed, depending on the size and location of the lesion.
  • Procedures that may be helpful to establish diagnosis of DMAC infection in patients with AIDS include lymph node biopsy, bone marrow biopsy, and liver biopsy. These procedures are indicated if the blood cultures fail to grow the mycobacteria. They are also helpful to exclude other causes of lymphadenopathy, anemia, or pancytopenia. Liver biopsy is rarely necessary to establish a diagnosis of MAC infection.
  • The procedure for lymphadenitis in children generally involves lymph node biopsy or complete excision of lymph nodes. A needle aspiration is performed for inaccessible nodes, such as those that overlie the facial nerve.

Histologic Findings

Histologic findings of MAC infection include necrotizing and nonnecrotizing granulomas and positive AFB smear results. Numbers of AFB are usually higher in MAC infection than in M tuberculosis infection. Patients with HIV/AIDS have evidence of DMAC infection in multiple organs, but granuloma formation is less common. DMAC infection in patients with AIDS typically demonstrates the presence of sheets of macrophages laden with AFB.

Histologic findings of lymph node biopsies in children infected with MAC in a reported series generally showed bright eosinophilic serpiginous necrosis with nuclear debris scattered throughout the necrotic foci. Most of these cases also had Langhans-type giant cells, but infiltration by plasma cells and neutrophils was not consistently observed.

Patients with hypersensitivity pneumonitis secondary to MAC infection show multiple well-formed nonnecrotizing granulomas positive for AFB.

More on Mycobacterium Avium-Intracellulare

Overview: Mycobacterium Avium-Intracellulare
Differential Diagnoses & Workup: Mycobacterium Avium-Intracellulare
Treatment & Medication: Mycobacterium Avium-Intracellulare
Follow-up: Mycobacterium Avium-Intracellulare
Multimedia: Mycobacterium Avium-Intracellulare
References
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Further Reading

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Keywords

Mycobacterium avium complex, MAC, M avium complex , Mycobacterium avium-intracellulare, M avium-intracellulare, Mycobacterium avium, M avium, Mycobacterium intracellulare, M intracellulare, MAI, Lady Windermere syndrome, MAC lung disease, disseminated MAC, DMAC, disseminated M avium complex, MAC bacteremia, MAC infection, MAC lymphadenitis, hot-tub lung, MAC mastitis, MAC pyomyositis, Mycobacterium avium avium, M avium avium, Mycobacterium avium paratuberculosis, M avium paratuberculosis

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Contributor Information and Disclosures

Author

Janak Koirala, MD, MPH, FACP, Associate Professor, Department of Internal Medicine, Division of Infectious Diseases, Southern Illinois University School of Medicine
Janak Koirala, MD, MPH, FACP is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians-American Society of Internal Medicine, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, International Society for Infectious Diseases, and International Society of Travel Medicine
Disclosure: Nothing to disclose.

Medical Editor

Klaus-Dieter Lessnau, MD, FCCP, Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital
Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Artificial Internal Organs, American Thoracic Society, Physicians for Social Responsibility, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Aaron Glatt, MD, Professor of Clinical Medicine, New York Medical College; President and CEO, Former Chief Medical Officer, Departments of Medicine and Infectious Diseases, New Island Hospital
Aaron Glatt, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Infectious Diseases Society of America, International AIDS Society, and Society for Healthcare Epidemiology of America
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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