Aggressive cutaneous infection with Mycobacterium marinum in two patients receiving anti–tumor necrosis factor-alfa agents

Abstract

To the Editor: Cutaneous infections with Mycobacterium marinum usually affect people in contact with water or fish, especially from tropical areas. We report two additional cases of unusually aggressive cutaneous infection with M marinum in fish tank owners receiving anti–tumor necrosis factor-alfa (TNFα) antibodies, underscoring the pitfalls of histologic diagnosis. Case 1, a 41-year-old woman who had received methotrexate and infliximab for psoriatic arthritis over the previous 2 years, developed a rapidly progressive nodular lesion on her right index finger followed by the onset of inflammatory nodules on the right hand and forearm with a sporotrichoid pattern (Fig 1). Because she regularly cleaned a fish tank, infection with M marinum was first considered and confirmed by skin culture and molecular identification using polymerase chain reaction amplification of the 16S-23S ribosomal DNA spacer followed by hybridization with specific probes (GenoType Mycobacterium; Hain Diagnostika, Nehren, Germany). A biopsy specimen taken from a forearm nodule revealed a nonspecific neutrophil-rich inflammation with no significant granuloma formation and Ziehl–Nielsen staining was negative (Fig 2). Infliximab was discontinued, and a treatment with minocycline and clarithromycin was introduced, but the sporotrichoid nodules continued to increase in size. Rifabutin and ethambutol were then added to the patient's regimen and a complete clinical clearance was seen by 4 months posttreatment.Fig 2Biopsy specimen from the forearm lesion (patient 1) revealed a neutrophil-rich inflammatory infiltrate without significant granuloma formation. (Hematoxylin-eosin stain; original magnification: ×10.)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Case 2 was a 50-year-old woman who had been treated with adalimumab for rheumatoid arthritis over the previous 18 months. She was referred for an inflammatory lesion on her right index finger that was rapidly followed by the development of several nodules on her right forearm. The regular care of a fish tank containing tropical fish led to the suspicion of M marinum infection, which was confirmed by the presence of acid-fast bacilli upon direct examination by auramine and Ziehl–Nielsen staining of smears obtained from cutaneous biopsy, skin culture, and identification procedures. The histologic examination revealed nonspecific inflammation with no significant granulomas, and Ziehl–Nielsen staining was also negative. Adalimumab was discontinued, and treatment with minocycline and clarithromycin resulted in complete clinical clearance after 3 months. Humans usually become infected by M marinum after a small traumatic wound in an aquatic environment. Rather surprisingly, M marinum infection during anti-TNFα treatment has been reported in only three patients,1Chopra N. Kirschenbaum A.E. Widman D. Mycobacterium marinum tenosynovitis in a patient on etanercept therapy for rheumatoid arthritis.J Clin Rheumatol. 2002; 8: 265-268Crossref Scopus (38) Google Scholar, 2Rallis E. Koumantaki-Mathioudaki E. Frangoulis E. Chatziolou E. Katsambas A. Severe sporotrichoid fish tank granuloma following infliximab therapy.Am J Clin Dermatol. 2007; 8: 385-388Crossref Scopus (38) Google Scholar, 3Fallon J.C. Patchett S. Gulmann C. Murphy G.M. Mycobacterium marinum infection complicating Crohn's disease, treated with infliximab.Clin Exp Dermatol. 2008; 33: 43-45Google Scholar including two receiving infliximab, with cutaneous lesions displaying unusually rapid sporotrichoid extension as in our patients.2Rallis E. Koumantaki-Mathioudaki E. Frangoulis E. Chatziolou E. Katsambas A. Severe sporotrichoid fish tank granuloma following infliximab therapy.Am J Clin Dermatol. 2007; 8: 385-388Crossref Scopus (38) Google Scholar, 3Fallon J.C. Patchett S. Gulmann C. Murphy G.M. Mycobacterium marinum infection complicating Crohn's disease, treated with infliximab.Clin Exp Dermatol. 2008; 33: 43-45Google Scholar This aggressive outcome is reminiscent of the accelerated progression of other mycobacterial infections in patients receiving anti-TNFα agents and is probably partly related to the inhibition of granuloma formation. As a consequence, histologic examination is unlikely to show granulomas but may instead display a misleading nonspecific inflammation with a prominent infiltrate of macrophages and neutrophils, as in our two patients. The inhibition of granuloma formation and subsequent more aggressive disease with rapid sporotrichoid extension, or disseminated lesions caused by M marinum, are not specific features of anti-TNFα agents because they also have been reported in immunocompromised patients on different medications.4Bartralot R. Pujol R.M. García-Patos V. Sitjas D. Martín-Casabona N. Coll P. et al.Cutaneous infections due to nontuberculous mycobacteria: histopathological review of 28 cases. Comparative study between lesions observed in immunosuppressed patients and normal hosts.J Cutan Pathol. 2000; 27: 124-129Crossref Scopus (154) Google Scholar, 5Streit M. Böhlen L.M. Hunziker T. Zimmerli S. Tscharner G.G. Nievergelt H. et al.Disseminated Mycobacterium marinum infection with extensive cutaneous eruption and bacteremia in an immunocompromised patient.Eur J Dermatol. 2006; 16: 79-83Google Scholar No specific therapeutic guidelines have been issued in this specific setting. As illustrated by our first patient, first-line antibiotics may fail to control the disease, and other antimycobacterial agents may have to be added. Discontinuation of anti-TNFα treatment must be considered but is not always mandatory.2Rallis E. Koumantaki-Mathioudaki E. Frangoulis E. Chatziolou E. Katsambas A. Severe sporotrichoid fish tank granuloma following infliximab therapy.Am J Clin Dermatol. 2007; 8: 385-388Crossref Scopus (38) Google Scholar