A 70-year-old man presented with a 10-month history of deep erythemas, subcutaneous nodules, and skin ulcers on the right upper limb and a 2-month history of ache and tumidness. These lesions had initially appeared 1 month prior as an isolated indolent nodule on the right wrist after a minor laceration to the second digit of his right hand, which was his dominant hand. As the disease progressed, the primary nodule enlarged and multiple nodules developed in an ascending fashion along the path of lymphatic drainage. A skin biopsy of a nodule performed at a local hospital showed infectious granuloma formation with acid-fast bacilli (AFB) identified within the tissue. Routine histopathology examination was repeated 1 month later, and this also produced an infectious granuloma reaction. Tissue cultures indicated that Sporotrichum schenckii could be growing in diseased tissues. The patient was diagnosed with sporotrichosis and prescribed orally administered potassium iodide and itraconazole. After 3 months of treatment, the lesions improved but had not completely healed. At this point, the patient topically applied a nonprescription Chinese herbal preparation, which exacerbated the skin lesions; these became swollen, red, and intensely painful on the whole right upper limb with ulceration of even the partial lesions. The patient was advised to continue antifungal treatment with terbinafine, itraconazole, and potassium iodide for several months. Fresh nodules and erosive papules developed on the dorsum of the right hand during the treatment, followed by diffuse tumidness with deep ulceration. In April 2011 after 8 months of no significant therapeutic effects with antifungal treatment, the patient was transferred to our hospital. Another two biopsies were re-examined before admission, and consistent results were obtained that exhibited granulomatous changes. All special stains, including AFB stains, and tissue cultures were negative for infectious organisms. Since the onset of the disease, the patient did not complain of systemic discomfort. He was in good general condition and did not have a history of hepatitis or tuberculosis. He had not travelled abroad but reported having a fish tank at home.
Dermatological examination revealed a large area of deep erythema and edema with nodules, ulcerations, and crusts on the right upper limb that was abnormally sensitive to the touch. He had a nummular deep ulcer with severe tenderness on the dorsum of the second digit, which limited movement (Figure 1A and B). No axillary lymph node was palpable.
Routine laboratory analysis demonstrated mild anemia and hypoproteinemia. Human immunodeficiency virus antibody test indicated negative results, and no active pulmonary disease was detected by chest radiography. A skin biopsy of a nodule on the patient's right forearm displayed a neutrophilic and histiocytic granuloma, with no caseous necrosis. Multinucleated giant cells were also observed (Figure 2). All special stains, including AFB and periodic acid-Schiff (PAS) stains, were negative for infectious organisms. Tissue cultures showed that the colonies grew on Lowenstein-Jensen (LJ) medium at 32 C for 10 days (Figure 3). Fungal and other standard bacterial cultures were negative.
After identifying a nontuberculous mycobacteria (NTM) infection based upon the positive tissue cultures, certain species of NTM were suspected. M. marinum, a relatively common cause of mycobacterial skin infection that can spread in a sporotrichoid manner, was the first to be considered. The patient was then treated with orally administered rifampicin (450 mg, once daily), clarithromycin (500 mg, twice daily), and moxifloxacin (400 mg, once daily) for 4 weeks. However, the right upper limb became swollen again, with purulent secretions draining from the ulcer, and new lesions appeared during the treatment.
Because the aggressive infection progressed so rapidly that multiple ulcers resistant to the combined therapy presented one after another, M. ulcerans infection was also suspected. The therapeutic regimen was then altered with the addition of intravenous amikacin (400 mg, once daily) to the antimicrobial regimen and suspension of moxifloxacin. Surprisingly, the skin nodules rapidly decreased in size, and ulcer cavities had fresh tissue within several weeks (Figure 1C and D). The organism was subsequently identified as M. marinum, sensitive to clarithromycin, rifampin, moxifloxacin, and amikacin, and all the four drugs were consistent with the prescribed regimen. With close surveillance of liver and kidney function and other side effects of amikacin, the combined antibiotics were used consistently for 6 months. After this period, the lesions had significantly subsided, leaving hyperplastic and atrophic scars, and new nodules did not recur (Figure 1E and F). A skin biopsy and culture taken at this stage were negative for AFB.