May 2008

Fig.2 A,B

Diagnosis: Mycobacterium marinum infection complicating Adalimumab therapy for rheumatoid arthritis.

Histopathology: Necrotizing granulomatous dermatitis (Figure 2 A). There were admixed plasma cells and neutrophils and a prominent granulation tissue-like proliferation of blood vessels. The intact epidermis showed pseudoepitheliomatous hyperplasia. Rare intracellular, slender acid-fast organisms were seen on the acid-fast bacilli (AFB) and the Fite-stained specimens (Figure 2 B). Tissue culture revealed infection with Mycobacterium marinum.

Clinical course: The patient was referred to infectious diseases where treatment with rifampin 300 mg BID and clarithromycin 1000 mg BID was initiated. Adalimumab therapy was discontinued and she underwent one year of antibiotic therapy with rifampin, clarithromycin, and ethambutol. Her lesions resolved with minor residual scarring.

Discussion: This case demonstrates an unusual clinical manifestation of Mycobacterium marinum infection with an ulcer on the nasal tip. Human infection with Mycobacterium marinum most often occurs following contact with contaminated water or fish, earning the name "fish-tank granuloma." It is primarily a superficial skin infection, usually limited to the extremities, but may spread to deeper structures leading to tenosynovitis, arthritis, and osteomyelitis (1). Nodules are the most common clinical manifestation of infection and are often accompanied by a sporotrichoid clinical appearance; ulcers, abscesses, and pustules have also been reported (2).
Histopathologic features include poorly formed noncaseating granulomas with epidermal ulceration, acanthosis or pseudoepitheliomatous hyperplasia. Rare intracellular acid-fast bacilli may be identified (3).
The clinical course of M. marinum infection is variable with some lesions resolving spontaneously in 1-3 years. However, patients may require antibiotic therapy and/or surgical debridement. The most common antibiotics prescribed are clarithromycin, rifampin, and minocycline, alone or in combination, and patients may require treatment up to one year (3).
In the immunocompetent patient, history of trauma often precedes infection with non-tuberculous mycobacteria (NTM), while immunosuppressed patients tend to present with no such history and with multiple cutaneous and subcutaneous nodules (3). M. marinum has been reported more often as a causative organism in immunocompetent patients, while M. chelonae and M. abscessus have been associated with infection in immunosuppressed patients (2).
Patients with rheumatoid arthritis are at increased risk for developing skin and soft tissue infections (4). While abnormalities in circulating T cells have been implicated in the observed increased infection risk (4), the increasing use of immunosuppressive agents such as corticosteroids, methotrexate, and newer biologic agents remain a confounding issue. TNF-a-blocking agents have been associated with an increased incidence of tuberculosis as well as serious fungal, mycobacterial, and intracellular bacterial infections (5). In patients receiving TNF-a-blocking therapy, dermatological events have been reported at a rate significantly higher than that seen in control patients (6).
Although an increased rate of skin infection has been seen in patients with rheumatoid arthritis as well as in patients taking immunosuppressive drugs, atypical mycobacterial infections have not been previously reported in these patients. The lack of prior trauma or exposure to contaminated water preceding M. marinum infection is not unheard of in immunosuppressed patients, but remains a rare occurrence.

References:
1. Aubry A, Chosidow O, Caumes E, Robert J, Cambau E. Sixty-three Cases of Mycobacterium marinum Infection. Arch Intern Med 2002;162:1746-1752.
2. Bartralot R, Garcia-Patos V, Sitjas D, Rodriguez-Cano L, Mollet J, Martin-Casabona N, Coll P, Castells A, Pujol RM. Clinical patterns of cutaneous nontuberculous mycobacterial infections. Br J Derm 2005;152:727-734.
3. Palenque E. Skin disease and nontuberculous atypical mycobacteria. Int J Derm 2000;39:659-666.
4. Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE. Frequency of Infection in Patients with Rheumatoid Arthritis Compared with Controls. Arthritis Rheum 2002;46:2287-2293.
5. Flendrie M, Vissers WHPM, Creemers MCW, de Jong EMGJ, van de Kerkhof PCM, van Riel PLCM. Dermatological conditions during TNF-a-blocking therapy in patients with rheumatoid arthritis: a prospective study. Arthritis Res Ther 2005;7:R666-R676.
6. Ellerin T, Rubin RH, Weinblatt ME. Infections and Anti-Tumor Necrosis Factor a Therapy. Arthritis Rheum 2003;48:3013-3022.

This case is presented by Drs. Ilana Rosman, Grace Bandow and Jeffrey Petersen.