Atypical Clinical Presentation of Sporotrichosis Caused by Sporothrix globosa Resistant to Itraconazole

Abstract

Sporotrichosis is a polymorphic disease of humans and animals, which is acquired via traumatic inoculation of Sporothrix propagules into cutaneous or subcutaneous tissue. The etiological agents are in a clinical complex, which includes Sporothrix brasiliensis, Sporothrix schenckii, Sporothrix globosa, and Sporothrix luriei, each of which has specific epidemiological and virulence characteristics. Classical manifestation in humans includes a fixed localized lesion at the site of trauma plus lymphocutaneous sporotrichosis with fungal spreading along the lymphatic channels. Atypical sporotrichosis is a challenge to diagnosis because it can mimic many other dermatological diseases. We report an unusual, itraconazole-resistant cutaneous lesion of sporotrichosis in a 66-year-old Brazilian man. Histopathological examination of the skin revealed vascular and fibroblastic proliferation with chronic granulomatous infiltrate composed of multinucleated giant cells. Sporothrix were isolated from the skin lesion, and phylogenetic analyses confirmed it to be sporotrichosis due to S. globosa, a widespread pathogen. Immunoblotting analysis showed several IgG-reactive molecules in autochthonous preparations of the whole cellular proteins (160, 80, 60, 55, 46, 38, 35, and 30 kDa) and exoantigen (35 and 33 kDa). The patient was first unsuccessfully treated with daily itraconazole, and then successfully treated with potassium iodide.

Figure 1.

Atypical sporotrichosis due to Sporothrix globosa. (A) Plaque sporotrichosis lesion with a well-demarcated lesion. The patient was unsuccessfully treated with itraconazole (200 mg/day) for 6 months. (B) The cured atrophic sporotrichosis lesion after 6 months of treatment with oral potassium iodide.

Figure 2.

Microscopic morphology of Sporothrix globosa after 21 days of culture at 30°C in potato dextrose agar (CBS 132925 = Ss236). Hyaline, thin, septated hyphae and numerous globose, dark-brown sessile conidia are visible. (A) 20× and (B) 40× magnifications.

Figure 3.

Neighbor-joining phylogenetic tree using the Kimura-2 parameter distance matrix. The tree was based on partial calmodulin-encoding gene sequences from Sporothrix species. GenBank accession numbers and geographic origin of strains are shown. The percentage of replicate trees in which the associated taxa clustered together in the bootstrap test (1,000 replicates) is shown next to the branches (neighbor-joining/maximum likelihood). All positions containing gaps and missing data were eliminated.

Figure 4.

Immunoblot assay using Sporothrix globosa (CBS 132925 = Ss236) whole cellular yeast proteins and the mycelium exoantigen. Fungal proteins were resolved on 10% SDS-PAGE, electrotransferred to polyvinylidene difluoride (PVDF) membranes, and incubated with the patient's serum (dilution 1:500). Several IgG-reactive molecules in the whole cellular proteins (160, 80, 60, 55, 46, 38, 35, and 30 kDa) and exoantigen (35 kDa and 33 kDa) were detected using patient's serum due to antibodies against S. globosa. Lanes labeled SDS-PAGE show all proteins as visualized using silver staining, and lanes labeled WB are membranes probed using patient serum.