Cutaneous non-tuberculous mycobacterial infections: An update

M. abscessus

Among the RGM species, M. abscessus is the major cause of skin infections. It was first described by Moore and Frerichs in 1953 in a woman with chronic osteoarthritis of knee, who developed a gluteal abscess.^[12] M. abscessus is the most pathogenic and clinically challenging of RGM species. It frequently demonstrates a higher degree of antimicrobial resistance. The single most important factor that determines the course and prognosis of M. abscessus infection is the underlying immune status of the host.^[13] Disseminated cutaneous infections have been reported in patients on immunosuppressive therapy.^[14]

Multiple outbreaks following medical, surgical, and cosmetic procedures and acupuncture have been reported.^[1] Forty-five surgical site infections due to M. abscessus among pediatric patients were reported in 1998 from New Delhi, India, in a single hospital.^[15] M. abscessus was isolated from the tap water in the operating rooms, which was used for rinsing instruments. In 2004, the Centers for Disease Control and Prevention reported an outbreak of 24 cases of M. abscessus infection among patients who had undergone a variety of cosmetic procedures in The Dominican Republic.^[16]

Cutaneous manifestations are non-specific. Initial presentation may be an abscess at the site of inoculation. Nodules, abscesses, and non-healing ulcers may be seen [Figure 1]. Sporotrichoid distribution of lesions has also been reported.^[17] Disseminated disease presents with systemic symptoms and may be associated with red to violaceous, subcutaneous nodules, and lymphadenopathy.^[18,19]

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Figure 1:

Mycobacterium abscessus infection on the scalp of a patient following hair transplantation presenting as multiple nodular lesions and abscesses – picture courtesy Dr. Anisha K Janardhanan, Consultant Dermatologist, Baby Memorial Hospital, Kozhikode.

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M. chelonae

M. chelonae can infect surgical and traumatic wounds, and cause injection site abscess, especially in diabetic patients on insulin. Reported infections with M. chelonae are on the rise.^[20] Surgical site infections as well as wound infections are associated with tap water contamination – such an outbreak was reported from India in association with laparoscopic surgery [Figure 2].^[21] Infection is also reported following acupuncture, tattooing, mesotherapy, and cosmetic procedures.

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Figure 2:

Mycobacterium chelonae infection presenting as nodules with discharging sinuses at the laproscopic port site on the abdomen – picture courtesy Dr Soumya Jagadeesan, Associate Professor, Dept of Dermatology, Amrita Institute of Medical sciences, Kochi.

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There are reports of non-healing leg ulcer after penetrating injury.^[22] Fatal and disseminated chelonae infections have been rarely reported in immunosuppressed patients and following administration of biologicals such as adalimumab.^[2,23]

Cutaneous manifestations include localized cellulitis, nodules, sinuses, abscesses, and ulcers.^[1]

They are resistant to conventional anti-tuberculosis treatment (ATT), with varied susceptibility to other antimicrobials.

M. fortuitum

M. fortuitum was first isolated by Da Costa Cruz in 1938, from a patient with an injection site abscess.^[24,25] In contrast to M. chelonae and M. abscessus infections, which commonly occur in immunocompromised hosts, infection due to M. fortuitum tends to occur mostly in otherwise healthy individuals of younger age group, and typically present with single lesion at the site of trauma.^[1,26] In 2002, Winthrop et al. reported a community outbreak of M. fortuitum furunculosis following footbath at a nail salon in California. Shaving the legs before the procedure was identified as a possible risk factor.^[27] Thus, mycobacterial infections should be considered and enquiry should be made regarding recent pedicures underwent by the patient when lower extremity, treatment-resistant furunculosis is encountered.^[26]

Lesions can vary from painful nodules, abscesses, ulcers, draining sinuses, and tracts to cellulitis. M. fortuitum is a rare cause of dialysis catheter line infection.^[28]

M. fortuitum is more susceptible to antibiotics, adjuvant surgical intervention is recommended as and when necessary.

M. marinum (M. balnei)

M. marinum was first isolated by Aronso in 1926; later in 1951, Norden and Linel identified it as the pathogen in a patient, who developed a granulomatous lesion after visiting a contaminated swimming pool.^[29,30] It is an aerobic organism which grows best at a temperature of 30–32°C, and poorly at 37°C.

M. marinum infection may be an occupational hazard, as in pet shop workers, or in fish fanciers with home aquariums as it is found both in fresh and salt water. It causes a characteristic skin infection termed fish-tank or swimming pool granuloma, which presents as solitary or multiple violaceous papulonodular lesions at the site of inoculation after 2–3 weeks, usually in the extremities. This may spread proximally in a sporotrichoid fashion due to lymphocutaneous spread or evolve to nodular, psoriasiform, or verrucous plaques which may later ulcerate [Figure 3]. Lymphadenopathy is rarely seen. Specific membrane lipids, called phenolic glycolipids, have been demonstrated to recruit macrophages to the site of infection, which facilitates further spread.^[7]

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Figure 3:

Mycobacterium marinum infection presenting as nodules on the hand – picture courtesy Dr Soumya Jagadeesan, Associate Professor, Department of Dermatology, Amrita Institute of Medical sciences, Kochi.

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Spontaneous resolution can occur after many months, while deeper infections can lead to tenosynovitis (“fish tank finger”), bursitis, arthritis, and osteitis.^[31,32]

There are reports of outbreak of infection due to NTM, probably M. marinum in Pacific islanders (locally known as spam disease), which manifest as verrucous and keloid plaques.^[33,34]

M. marinum infection associated with TNF-α inhibitors was first reported in 1994, in a patient, who developed septic arthritis following etanercept therapy. Similar infections have been reported following infliximab and adalimumab.^[35-39]

M. ulcerans

Infection with this species was first described in 1948 by MacCallum et al. from Australia in patients presenting with solitary ulcerative lesions in extremities, and the Mycobacterium was named “Bairnsdale bacillus,” after the region, where most of the patients lived.^[40] Later, it was renamed as M. ulcerans. Skin ulcers caused by M. ulcerans were reported from Buruli in Uganda in 1961, a region near the Nile River, and following several reports from the region, the disease was subsequently named Buruli ulcer (BU).^[40]

M. ulcerans is the third most common cause of mycobacterial infection after tuberculosis and leprosy worldwide and BU is one of the skin-related neglected tropical diseases according to the WHO.^[1]

Children and young adults are most commonly affected. Onset is typically as a subcutaneous nodule, which subsequently enlarges and ulcerates. It may later bore through the soft tissue, right up to the bone. Extremities are commonly affected, although head, neck, trunk, and genital region can be involved. Mycolactone, a highly diffusible and cytotoxic lipid has been identified as the pathogenic factor, and explains the distinct clinical presentation. Three major biological properties of mycolactone are cytotoxicity, immunosuppression, and analgesia, which correspond well to the characteristic features of the disease: extensive deep ulceration with thick yellowish necrotic tissue, undermining with limited inflammatory response and minimal or absent pain.^[40-42]

Antibiotic therapy is usually effective; however, patients with severe illness or delayed initiation of treatment may have permanent deformities. Without treatment, the disease resolves in some patients, while in others it ends in contractures that cause disfigurement, long-term disability, and social stigmatization, known as “bankruptcy wound”.^[41] Early detection and treatment is the only measure to prevent deleterious outcomes.^[7,42]

MAC

This includes M. avium, M. intracellulare, M. chimaera, and other species. Primary cutaneous infections are rare. Skin lesions in disseminated disease have been described in immunocompromised patients, especially advanced AIDS. With the onset of the AIDS epidemic, MAC became more recognized as an opportunistic pathogen. Clinical manifestations include scaly papules, granulomatous plaques, subcutaneous nodules, pustules, verrucous ulcers, abscesses, and discharging sinuses.^[3,43-45] A case of papulonecrotic tuberculid like presentation secondary to disseminated MAC infection in AIDS has been reported.^[46]

Emerging pathogen: M. chimaera

M. chimaera was described by Tortoli et al. in 2004 as a colonizer of respiratory tract, in specimens from patients with chronic obstructive pulmonary disease and other lung diseases.^[47] It is grouped under MAC. Since it shares features with M. avium, M. intracellulare and M. scrofulaceum, it was named M. chimaera – after chimera, a Greek mythological character composed of the parts of more than one animal.^[47]

Clinical infections have a long and variable incubation period of up to 6 years. Outbreaks have been reported after open heart surgery. Cutaneous infection with M. chimaera is extremely rare. A case of cutaneous infection with M. chimaera was reported by Moutsoglou et al. in a patient with a non-healing leg ulcer.^[48] George et al. reported a case of primary cutaneous infection with M. chimaera in a patient with diabetes mellitus that manifested with ulcerating nodules on the face [Figure 4].^[49]

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Figure 4:

Mycobacterium chimaera infection presenting as ulcerating nodules on the face.

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M. haemophilum

M. haemophilum is an aerobic fastidious organism, similar to M. marinum and M. ulcerans, and shows a predilection for the extremities, particularly over the joints. The name originates from the requirement of iron or hemin supplementation for growth.^[50]

Infection generally occurs in immunocompromised hosts and may include erythematous to violaceous papules, plaques, or nodules which may progress to abscesses or deep-seated ulcers. It has certain similarities with M. leprae, including the presence of large quantities of docosanoic acid and analogous phenolic glycolipid. Immune reconstitution events similar to lepra reactions are described after initiation of anti-mycobacterial therapy.^[44]

M. kansasii

M. kansasii is closely related antigenically to M. tuberculosis. Cutaneous infections may present as nodules, pustules, verrucous plaques, ulcers, and abscesses. The lesions may be arranged in a sporotrichoid pattern.^[44] Similar to M tuberculosis, M.kansasii is present in nasopharyngeal secretions and can lead to periorificial cutaneous infection.