Dermatologic Manifestations of Mycobacterium Avium-Intracellulare Infection 

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.

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.

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.^[3]

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.

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.^[4]

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.^[5]

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.

Cutaneous MAI infection in an human immunodeficiency virus (HIV)-positive patient mimicking histoid leprosy has been reported.^[6] In another report, Perrin noted a patient with acquired immunodeficiency syndrome (AIDS) and a cutaneous MAI infection mimicking histoid leprosy.^[7] Subcutaneous and muscular abscesses due to MAI can occur as a manifestation of immune restoration in patients with AIDS.^[8]

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.^[9]

Henoch-Schönlein purpura associated with pulmonary MAI complex infection has been noted.^[10]

MAI can be associated with osteomyelitis. Primary nontraumatic MAI complex osteomyelitis of the distal phalanx has occurred.^[11] 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.^[12]

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.^[13]

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

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.^[14] 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.^[14]

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.^[15] 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.^[15]

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.^[16]

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 prevention and treatment of opportunistic infections in HIV-infected adults and adolescents.^[3]

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.^[17] 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.^[18]

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.

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.^[19]

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.

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.