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Dermatologic Manifestations of Mycobacterium Avium-Intracellulare Infection

  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Feb 18, 2016
 

Overview

This article reviews the dermatologic manifestations of Mycobacterium avium-intracellulare (MAI, or MAC) infection.

Although the prevalence of MAI infection has increased following the epidemic of acquired immunodeficiency syndrome (AIDS), MAI infection remains a rare cause of skin disease. However, MAI has been found to cause cutaneous disease in individuals with immunocompetence and immunosuppression.

Primary cutaneous MAI infection generally occurs in hosts who are immunocompetent after traumatic introduction into the soft tissue. Local disease ensues, manifested primarily as nodules that may progress to ulcers. One case report described primary MAI infection resulting in a clinical picture resembling lupus vulgaris.[1]

Disseminated disease (DMAI) most commonly occurs in individuals who are immunosuppressed, and hematogenous seeding of the skin may result in a wide variety of skin lesions, including nodules and abscesses, panniculitis,[2] folliculitis, and acute disease with hemorrhagic pustules. See the image below.

CT thorax scan of a 77-year-old woman who presente CT thorax scan of a 77-year-old woman who presented with chronic cough and sputum production, without a history of underlying preexisting lung disease. Sputum culture grew Mycobacterium avium complex. The diagnosis was Lady Windermere syndrome.

An interesting case reported in 2012 involved in a child with complete interferon (IFN)–γ receptor-1 deficiency interrupting the interleukin (IL)–12/IFN-γ pathway and resulting in granulomatous skin papules and plaques and lower extremity edema. In this child, recurrent infection with MAI, Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium fortuitum all occurred.[3]

MAI is the most common cause of pediatric cervical adenitis. Skin involvement in this setting is not uncommon and includes sinus track and abscess formation. Cervical adenitis rarely involves deeper structures, but it may result in extensive superficial destruction with cosmetic deformity.

See also Mycobacterium Avium-Intracellulare.

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Epidemiology

In the United States, Mycobacterium avium-intracellulare (MAI, or MAC) infection is considered a nonreportable infectious disease. The US Centers for Disease Control and Prevention (CDC) surveillance data from Houston and Atlanta suggest an incidence of 1 case per 100,000 persons per year. The highest incidence of disseminated MAI (DMAI) in 1994, 37,000 cases, was measured, a peak that was coincident with the peak in the epidemic of acquired immunodeficiency syndrome (AIDS). Because DMAI infection often occurs in association with HIV, this was not surprising. One case series revealed cutaneous involvement in 6 of 30 cases of DMAI infection. CDC data also suggest that the incidence of MAI infection may be decreasing as a result of highly active antiretroviral therapy and antimicrobial prophylaxis.[4]

Primary cutaneous MAI infection is rare, with 12 cases reported in the literature prior to 1997. This condition has been reported in all age groups; although most case reports of primary cutaneous MAI infection have been in individuals aged 2-10 years, adult cases have also been described. A review of 8 cases of cutaneous MAI infection occurring secondary to disseminated disease found a median patient age of 22.2 years, with a range of 2-28 years.

The degree to which skin involvement occurs as a sequela of cervical adenitis has not been well studied; however, the literature suggests that the risk of skin involvement increases with advanced disease. Cervical adenitis most commonly affects children. One chart review series of 47 children with cervical adenitis revealed a median age of 3 years when MAI infection was diagnosed by doctors.

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Clinical Evaluation

It is important to consider cutaneous infection with Mycobacterium avium-intracellulare (MAI, or MAC) in patients with antibiotic-resistant cellulitis, in those with nonhealing nodules and ulcers, and in patients who are immunosuppressed with evidence of disseminated MAI (DMAI) infection.

Data on skin and soft-tissue infection caused by nontuberculous mycobacteria in Taiwan (1997-2008) suggest that MAI is an important pathogen.[5]

Any history of the introduction of a foreign object (eg, needle, splinter) should be sought if (MAI) infection is suspected. Fever and other constitutional symptoms are generally absent. Skin abscess and sinus tracks may be present. Sporotrichoid spread of cutaneous MAI complex infection can occur.[6]

Patients with MAI cervical adenitis may present with an indolent course of a unilaterally expanding mass in the neck, such as enlarged submandibular or submaxillary nodes.

Cutaneous disease

Cutaneous MAI infection should be suspected when an individual who is immunocompromised presents with obscure skin lesions. Additional symptoms, including fatigue, fever, diarrhea, weight loss, back or bone pain, shortness of breath, and/or cough may suggest disseminated disease.

Nutritional status impacts susceptibility to MAI infection; a patient with anorexia nervosa who also developed MAI and leukocytoclastic vasculitis is notable but not altogether surprising.[7]

Cutaneous MAI infection in an human immunodeficiency virus (HIV)-positive patient mimicking histoid leprosy has been reported.[8] In another report, Perrin noted a patient with acquired immunodeficiency syndrome (AIDS) and a cutaneous MAI infection mimicking histoid leprosy.[9] Subcutaneous and muscular abscesses due to MAI can occur as a manifestation of immune restoration in patients with AIDS.[10] A case mimicking sarcoid has been reported.[11] Cutaneous pseudotumor related to MAI has been reported.[12]

Primary cutaneous MAI infection is most often the result of traumatic inoculation, although a specific history of trauma is generally absent. Patients may describe the development of a single nodule or multiple nodules progressing over time into ulcerative lesions with or without serosanguineous exudates. Painful subcutaneous nodules and ulcers that occur on the extremities and the trunk may be noted. Lesions may be present in multiple stages of development, and nodules have been described as both flesh colored and purple-red.

Teraki et al have noted that MAI can be associated with Sweet syndrome.[13]

Henoch-Schönlein purpura associated with pulmonary MAI complex infection has been noted.[14]

MAI can be associated with osteomyelitis. Primary nontraumatic MAI complex osteomyelitis of the distal phalanx has occurred.[15] Multifocal osteomyelitis caused by nontuberculous mycobacteria in patients with a genetic defect of the interferon-gamma receptor has also been noted.

Murdoch and McDonald reported MAI cellulitis occurring with septic arthritis after joint injection.[16]

After initiating treatment for MAI complex involving osteomyelitis, DRESS syndrome has been reported to occur.[17]

MAI olecranon bursitis resolving without surgical or antimicrobial intervention has been noted to occur.[18]

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Workup Considerations

Primary cutaneous Mycobacterium avium-intracellulare (MAI, or MAC) infection is rare, but it does not necessarily mandate a workup for immunosuppression.

Biopsy should be performed for suspected dermatologic manifestations of MAI infection. Tissue samples of cutaneous lesions may be obtained for histopathologic evidence of mycobacterial infection, and staining with Ziehl-Neelsen stain may reveal acid-fast bacilli (AFB).

Faruqi et al noted that a positive antineutrophil cytoplasmic antibody (ANCA) test result can coexist with MAI, complicating diagnosis.[19]

Cultures of cutaneous lesions should be performed, and polymerase chain reaction (PCR) studies of tissue may yield organism identification in 24 hours.

A 2012 report notes a 66-year-old women who developed sudden redness and swelling of her left thumb. Histology showed well-formed granulomas along with a mixed inflammation. The infiltrate was characterized by a predominance of neutrophils, and stains showed acid-fast bacilli. Culture results were negative. Doctors sent tissue for a broad-range polymerase chain reaction amplification followed by suspension array identification, and this lead to identification of the pathogenic Mycobacterium as MAI.[20]

18 F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning can be used to distinguish disseminated MAI from paraneoplastic syndromes or malignant metastasis.[21]

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Histologic Features

A spectrum of histologic findings is present in skin infection with Mycobacterium avium-intracellulare (MAI, or MAC). This is not surprising, because tissue pathology varies with the stage of the disease and the host's immune status.

Granulomas are often present in tissue infected with MAI. Tuberculid, palisading, and sarcoidlike granulomas can be found in the context of a diffuse infiltrate of foamy histiocytic cells. Other nonspecific findings include panniculitis, chronic inflammation, cutaneous abscesses, necrotizing folliculitis, and suppurative granulomas.

Spindle cell pseudotumors and MAI

Liou et al noted that spindle cell pseudotumors due to mycobacterial infection may occur in immunocompromised hosts.[22] The investigators reported a case of spindle cell pseudotumor in a 37-year-old man with acquired immunodeficiency syndrome (AIDS), in which the tumor manifested as a firm nodule on the right arm. Histologically, the tumor was composed of spindle cells mixed with histiocytes and inflammatory cells. Ziehl-Neelsen stain revealed many acid-fast bacilli, which were identified as MAI. Culture and sequencing of the polymerase chain reaction (PCR) product of the mycobacterial 65-kd heat-shock protein gene helped to establish the diagnosis. Immunohistochemically, the spindle cells stained with CD68, a marker found on active tissue macrophages.[22]

Similarly, Shiomi et al reported the case of a 58-year-old Japanese woman with systemic lupus erythematosus (SLE) and interstitial pneumonia for 17 years who was diagnosed with mycobacterial spindle cell pseudotumor.[23] The patient had a nodule in the deep dermis with extension into the subcutaneous fat tissue. Under histologic examination, the nodule was composed of spindle cells focally showing a vaguely storiform pattern, with focal foam cells, epithelioid histiocytes, and multinucleated giant cells. Ziehl-Neelsen staining showed numerous acid-fast bacilli within the spindle cells and epithelioid histiocytes, which were determined to be MAI after culture and PCR testing.[23]

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Treatment and Monitoring Considerations

Patients hospitalized with Mycobacterium avium-intracellulare (MAI, or MAC) disease require inpatient care. However, primary cutaneous MAI infection and cervical adenitis may be treated in an outpatient setting if patients are medically compliant.

A standard chemotherapy regimen has not been established for MAI infection because of significant resistance to antimycobacterial drugs. MAI is usually resistant to single-drug therapy and must be treated with multiple antitubercular medications. Sparfloxacin has good antimicrobial activity against several acid-fast bacteria (AFB) and is expected to be an effective drug for treating mycobacteriosis.

MAI infection can be related to infliximab use.[24]

In cases of cervical adenitis and primary cutaneous MAI infection, follow-up care is required to assess for toxicity due to therapeutic agents and to monitor patients for possible disease recurrence or surgical complications.

Also see Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics.[4]

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Management of Cervical Adenitis

All cases of cervical adenitis must be referred to a surgeon.

The mainstay of treatment for cervical adenitis due to Mycobacterium avium-intracellulare (MAI, or MAC) infection is surgical excision, with chemotherapy as primary treatment mainly reserved for cases with surgical contraindications.[25] Vuppalapati et al reported treating MAI infection involving the skin and soft tissues of the hand with radical debridement and reconstruction in addition to multidrug chemotherapy.[26]

The relative infrequency of this condition has precluded clinical trials; therefore, treatment schedules are derived from anecdotal evidence.

Macrolides should be used in combination with rifamycin or ethambutol. Combination therapy with clarithromycin, ethambutol, and rifamycin has also been used.

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Management of Primary Cutaneous MAI Infection

Treatment of a 9-year-old patient with Mycobacterium avium-intracellulare (MAI, or MAC) infection with a combination of surgery and cycloserine (500 mg/d), isoniazid (200 mg/d), and clarithromycin (150 mg/d) following susceptibility testing resulted in complete clearance after 2 months of medical therapy, followed by surgical excision.[27]

For adult patients, streptomycin (1 g intramuscularly [IM] daily for 3 mo), isoniazid (300 mg/d), and rifampicin (600 mg/d for 9 mo) have been used as treatment.

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Outcomes

Primary cutaneous involvement of Mycobacterium avium-intracellulare (MAI) does not usually result in systemic disease and most often occurs in otherwise healthy individuals; therefore, the prognosis is favorable, because treatment is generally curative.

The relationship between cutaneous lesions and mortality in disseminated MAI (DMAI) infection is unknown, and controversy remains regarding the impact of disseminated MAI (DMAI) infection on life expectancy in patients with acquired immunodeficiency syndrome (AIDS). Nonetheless, untreated DMAI infection in this population (patients with AIDS) is clearly associated with an increased mortality rate.

Primary cutaneous MAI infection and atypical Mycobacterium -induced cervical adenitis are responsive to combined surgical and medical treatment. However, cervical adenitis may cause local destruction of superficial structures and may result in significant cosmetic and functional impairment without treatment. Dissemination beyond the primary site is rare. Nonetheless, the proximity to the trachea and the oropharynx may result in airway compromise and should be considered when evaluating patients with cervical adenitis.

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Contributor Information and Disclosures
Author

Noah S Scheinfeld, JD, MD, FAAD Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Abbvie<br/>Received income in an amount equal to or greater than $250 from: Optigenex<br/>Received salary from Optigenex for employment.

Coauthor(s)

Douglas W Kress, MD Program Director, Medical Director of Clinical Services, Department of Dermatology, University of Pittsburgh Medical Center

Douglas W Kress, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Supriya Tomar, MD Consulting Staff, Mohs College

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American College of Rheumatology

Disclosure: Received income in an amount equal to or greater than $250 from: XOMA; Biogen/IDEC; Novartis; Janssen Biotech, Abbvie, CSL pharma<br/>Received honoraria from UpToDate for author/editor; Received honoraria from JAMA Dermatology for associate editor and intermittent author; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for i inherited these trust accounts; for: Celgene; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Jessica M Allan, MD, and Nicole Restauri, MD, to the development and writing of the source article.

References
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CT thorax scan of a 77-year-old woman who presented with chronic cough and sputum production, without a history of underlying preexisting lung disease. Sputum culture grew Mycobacterium avium complex. The diagnosis was Lady Windermere syndrome.
 
 
 
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