Residency · Residency · Dermatology

Mycobacterial Skin Infections: Tuberculosis and Atypical Mycobacteria

Overview

Cutaneous mycobacterial infections encompass disease caused by Mycobacterium tuberculosis complex and nontuberculous (atypical) mycobacteria (NTM). Skin involvement may result from direct inoculation, hematogenous spread, contiguous extension, or immune-mediated (tuberculid) reactions. These infections are increasingly relevant with rising immunosuppression and the popularity of cosmetic procedures.

Cutaneous Tuberculosis

Classification

True Cutaneous TB (M. tuberculosis in tissue)

Exogenous Inoculation

Tuberculous chancre (primary inoculation TB) results from direct inoculation in a non-immune host, presenting as a painless papule or nodule at the inoculation site that progresses to an ulcer with regional lymphadenopathy. It is rare, occurring through occupational exposure in pathologists and lab workers or through ritual circumcision.

Endogenous Spread

Lupus vulgaris is the most common form of cutaneous TB in developed nations. It presents as a slowly progressive, red-brown plaque with "apple jelly" nodules visible on diascopy, predominantly on the head and neck (nose, cheeks, earlobes). It can cause significant tissue destruction involving cartilage and bone. Histology reveals well-formed tuberculoid granulomas with Langhans giant cells and variable caseation. The condition is paucibacillary, meaning AFB stain is often negative and cultures may also be negative. SCC can develop within chronic lupus vulgaris lesions. Treatment is standard anti-TB therapy (RIPE: rifampin, isoniazid, pyrazinamide, ethambutol).

Scrofuloderma results from direct extension from underlying TB lymphadenitis or bone/joint TB. It presents as a firm subcutaneous nodule that softens, ulcerates, and forms draining sinuses, most commonly on the neck overlying cervical lymph nodes. Histology shows caseating granulomas with AFB often identifiable. Treatment is standard anti-TB therapy, with surgical debridement sometimes needed.

Miliary TB of the skin occurs through hematogenous dissemination in severely immunosuppressed patients, presenting as widespread papules, vesicles, or purpuric lesions. It carries a high bacillary load with positive AFB stains and a poor prognosis without treatment.

TB verrucosa cutis (warty TB) results from exogenous reinoculation in a previously sensitized (immune) host, presenting as a verrucous plaque on the dorsal hands, fingers, or feet. The term "prosector's wart" describes this condition in pathologists and autopsy workers. Histology shows pseudoepitheliomatous hyperplasia with granulomas, and the condition is paucibacillary.

Orificial TB (TB cutis orificialis) results from autoinoculation of mucous membranes or perioral/perianal skin from advanced internal TB, presenting as painful ulcers of the mouth, nose, anus, or genitalia. It indicates advanced pulmonary, GI, or genitourinary TB, carries a high bacillary load, and has a poor prognosis.

Tuberculids (Immune-Mediated; No Viable Organisms in Skin)

Tuberculids are hypersensitivity reactions to M. tuberculosis antigens in a sensitized host, characterized by a positive tuberculin skin test, evidence of TB elsewhere, negative AFB cultures from skin lesions, and response to anti-TB therapy.

Erythema induratum of Bazin presents as recurrent tender, erythematous-violaceous nodules on the posterior calves that may ulcerate, predominantly affecting women. Histology shows lobular panniculitis with granulomatous vasculitis. PCR for M. tuberculosis may be positive in tissue. Treatment is anti-TB therapy if TB is confirmed, or potassium iodide for idiopathic nodular vasculitis.

Papulonecrotic tuberculid presents as symmetrically distributed, recurrent papulonecrotic lesions on the extensor extremities and buttocks that heal with varioliform scars. Histology shows wedge-shaped caseous necrosis with vasculitis.

Lichen scrofulosorum presents as follicular and perifollicular papules on the trunk of children and young adults, associated with underlying lymph node or bone TB, and is self-limited with anti-TB therapy.

Diagnosis of Cutaneous TB

Diagnostic tools include TST (Mantoux) or IGRA (QuantiFERON, T-SPOT), skin biopsy with evaluation for granulomatous inflammation and AFB staining (Ziehl-Neelsen or Fite), tissue culture on Lowenstein-Jensen media (gold standard but requiring 4 to 8 weeks), PCR for M. tuberculosis (rapid and helpful in paucibacillary forms), chest X-ray to assess for pulmonary TB, and NAAT (nucleic acid amplification test) on tissue.

Treatment

The standard anti-TB regimen consists of 2 months of RIPE (rifampin, isoniazid, pyrazinamide, ethambutol) followed by 4 months of RI (rifampin, isoniazid) for a total of 6 months. Lupus vulgaris may require prolonged therapy of 9 to 12 months. Drug susceptibility testing is essential given rising MDR-TB.

Nontuberculous (Atypical) Mycobacteria

Mycobacterium marinum ("Fish Tank Granuloma")

M. marinum is the most common NTM skin infection in immunocompetent patients, acquired from freshwater aquariums, swimming pools, or saltwater exposure, with an incubation period of 2 to 4 weeks. It presents as a solitary papule or nodule at the inoculation site (hand, finger) that may ulcerate. Sporotrichoid spread (ascending nodular lymphangitis following lymphatic drainage) mimics sporotrichosis. The organism grows optimally at 30 to 32 degrees Celsius, cooler than body temperature, which explains its predilection for the skin. Histology shows tuberculoid or suppurative granulomas, and AFB may be seen. Culture must be performed on Lowenstein-Jensen media at 30 to 32 degrees Celsius, not the standard 37 degrees, and this temperature must be specified on the culture request. Treatment is clarithromycin plus ethambutol (or rifampin) for 3 to 4 months, with minocycline or TMP-SMX as alternatives and surgical debridement for deep or refractory infections.

Rapidly Growing Mycobacteria (RGM)

The rapidly growing mycobacteria include M. abscessus, M. chelonae, and M. fortuitum, all of which grow in culture within 7 days (compared to weeks for slow-growing species). Common settings include post-procedural infections from cosmetic procedures (mesotherapy, liposuction, fillers), surgery, and injections; contaminated medical devices, water supplies, and tattoo inks; and hot tub/spa exposure. Clinical presentation includes subcutaneous nodules, abscesses, and draining sinuses, often at injection sites, with possible disseminated disease in immunocompromised patients. Treatment varies by species: M. abscessus is the most difficult, often macrolide-resistant, requiring combination IV amikacin plus imipenem plus oral macrolide for a prolonged course of months; M. chelonae is clarithromycin-based and often susceptible; and M. fortuitum is the most treatment-responsive, with options including TMP-SMX, doxycycline, and fluoroquinolones. Susceptibility testing is essential.

Mycobacterium ulcerans (Buruli Ulcer)

M. ulcerans causes Buruli ulcer in tropical regions (West Africa, Australia). It produces mycolactone toxin, which causes tissue necrosis and immunosuppression. It presents as a painless nodule progressing to a large undermined ulcer. According to the WHO, it is the most common mycobacterial skin disease worldwide after TB and leprosy. Treatment is rifampin plus clarithromycin for 8 weeks, with surgery for advanced lesions.

Mycobacterium leprae (Leprosy/Hansen Disease)

Leprosy is a chronic granulomatous infection of the skin and peripheral nerves. The Ridley-Jopling classification defines a spectrum: tuberculoid (TT) leprosy shows few, well-defined, hypopigmented or erythematous, anesthetic plaques with strong cell-mediated immunity and paucibacillary disease; lepromatous (LL) leprosy shows numerous, symmetric, poorly defined papules and nodules with madarosis and leonine facies, weak CMI, and multibacillary disease; and borderline (BT, BB, BL) forms show intermediate features.

Nerve involvement produces enlarged peripheral nerves (great auricular, ulnar, peroneal) with sensory loss. Diagnosis relies on slit-skin smear for AFB, skin biopsy with Fite stain, and PCR. Treatment follows WHO multidrug therapy: paucibacillary disease is treated with dapsone plus rifampin for 6 months, and multibacillary disease with dapsone plus rifampin plus clofazimine for 12 months. Type 1 reactions (reversal) involve upgrading of CMI with inflammation of existing lesions and nerve damage, treated with corticosteroids. Type 2 reactions (erythema nodosum leprosum, ENL) are immune complex-mediated, presenting as tender nodules with fever, treated with thalidomide or corticosteroids.

<image>Clinical photograph panel of mycobacterial skin infections: (A) lupus vulgaris showing red-brown plaque on the nose with apple jelly nodules visible on diascopy, (B) scrofuloderma with draining sinus tracts overlying cervical lymphadenopathy, (C) M. marinum infection showing sporotrichoid spread of nodules along the forearm from a primary inoculation site on the hand, (D) post-procedural rapidly growing mycobacterial infection with subcutaneous nodules and abscesses at injection sites. Show on diverse skin tones.</image>

<image>Classification diagram of cutaneous tuberculosis organized by pathogenesis: exogenous inoculation (tuberculous chancre, TB verrucosa cutis), endogenous spread (lupus vulgaris, scrofuloderma, miliary TB, orificial TB), and tuberculids (erythema induratum of Bazin, papulonecrotic tuberculid, lichen scrofulosorum). For each entity, include the immune status (naive vs. sensitized), bacillary load (pauci vs. multibacillary), and typical clinical appearance.</image>

Key Clinical Pearls

"Apple jelly" nodules on diascopy (pressing a glass slide against the lesion) is the classic clinical finding of lupus vulgaris and reflects underlying granulomatous inflammation. M. marinum requires culture at 30 to 32 degrees Celsius; if the standard 37 degrees is requested, the organism will not grow, so always specify "incubate at 30C" on the culture request. Sporotrichoid spread (ascending nodular lymphangitis) has a limited differential: M. marinum, Sporothrix schenckii, Nocardia, Leishmania, and rarely other mycobacteria or fungi. Post-procedural infections presenting weeks to months after cosmetic procedures (fillers, mesotherapy) should raise suspicion for rapidly growing mycobacteria, and biopsy with AFB stain and culture is essential. Tuberculids are immune-mediated reactions to distant TB foci in which the skin lesions are AFB-negative but respond to anti-TB treatment directed at the primary infection. Leprosy should be considered in any patient from an endemic area presenting with hypopigmented anesthetic patches and enlarged peripheral nerves.

References

• Barbagallo J, Tager P, Ingleton R, Hirsch RJ, Weinberg JM. Cutaneous tuberculosis: diagnosis and treatment. Am J Clin Dermatol. 2002;3(5):319-328.
• Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007;175(4):367-416.
• Aubry A, Chosidow O, Caumes E, Robert J, Cambau E. Sixty-three cases of Mycobacterium marinum infection. Arch Intern Med. 2002;162(15):1746-1752.
• van Zyl L, du Plessis J, Viljoen J. Cutaneous tuberculosis overview and current treatment regimens. Tuberculosis. 2015;95(6):629-638.

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