Primary cutaneous trichosporonosis caused by Trichosporon dermatis in an immunocompetent man
2011; Elsevier BV; Volume: 65; Issue: 2 Linguagem: Inglês
10.1016/j.jaad.2010.01.020
ISSN1097-6787
AutoresYi‐Ming Fan, Wenming Huang, Yanping Yang, Wen Li, LI Shun-fan,
Tópico(s)Mycobacterium research and diagnosis
ResumoTo the Editor: Trichosporon species are soil inhabitants, but may also be normal flora in the gastrointestinal tract and transiently colonize the skin and respiratory tract in humans.1Ruan S.Y. Chien J.Y. Hsueh P.R. Invasive trichosporonosis caused by Trichosporon asahii and other unusual Trichosporon species at a medical center in Taiwan.Clin Infect Dis. 2009; 49: e11-e17Crossref PubMed Scopus (119) Google Scholar, 2Chagas-Neto T.C. Chaves G.M. Colombo A.L. Update on the genus Trichosporon.Mycopathologia. 2008; 166: 121-132Crossref PubMed Scopus (119) Google Scholar They have increasingly become important opportunistic pathogens in immunocompromised subjects over the past 2 decades. Thirteen of 38 species in the genus Trichosporon may be potential human pathogens, with Trichosporon asahii being the most common.1Ruan S.Y. Chien J.Y. Hsueh P.R. Invasive trichosporonosis caused by Trichosporon asahii and other unusual Trichosporon species at a medical center in Taiwan.Clin Infect Dis. 2009; 49: e11-e17Crossref PubMed Scopus (119) Google Scholar, 2Chagas-Neto T.C. Chaves G.M. Colombo A.L. Update on the genus Trichosporon.Mycopathologia. 2008; 166: 121-132Crossref PubMed Scopus (119) Google Scholar, 3Chagas-Neto T.C. Chaves G.M. Melo A.S. Colombo A.L. Bloodstream infections due to Trichosporon spp.: species distribution, Trichosporon asahii genotypes determined on the basis of ribosomal DNA intergenic spacer 1 sequencing, and antifungal susceptibility testing.J Clin Microbiol. 2009; 47: 1074-1081Crossref PubMed Scopus (118) Google Scholar There have been some reports of T dermatis infections in the literature, with infection sites including the skin, nails, and blood.1Ruan S.Y. Chien J.Y. Hsueh P.R. Invasive trichosporonosis caused by Trichosporon asahii and other unusual Trichosporon species at a medical center in Taiwan.Clin Infect Dis. 2009; 49: e11-e17Crossref PubMed Scopus (119) Google Scholar, 3Chagas-Neto T.C. Chaves G.M. Melo A.S. Colombo A.L. Bloodstream infections due to Trichosporon spp.: species distribution, Trichosporon asahii genotypes determined on the basis of ribosomal DNA intergenic spacer 1 sequencing, and antifungal susceptibility testing.J Clin Microbiol. 2009; 47: 1074-1081Crossref PubMed Scopus (118) Google Scholar, 4Rodriguez-Tudela J.L. Diaz-Guerra T.M. Mellado E. Cano V. Tapia C. Perkins A. et al.Susceptibility patterns and molecular identification of Trichosporon species.Antimicrob Agents Chemother. 2005; 49: 4026-4034Crossref PubMed Scopus (148) Google Scholar However, none of these cases included definite clinicopathologic evidence except for the patient with fungemia reported by Gunn et al,5Gunn S.R. Reveles X.T. Hamlington J.D. Sadkowski L.C. Johnson-Pais T.L. Jorgensen J.H. Use of DNA sequencing analysis to confirm fungemia due to Trichosporon dermatis in a pediatric patient.J Clin Microbiol. 2006; 44: 1175-1177Crossref PubMed Scopus (20) Google Scholar and it is unknown whether the clinical isolate is pathogenic to humans. We report the first case to our knowledge of skin infection caused by T dermatis in humans.A 70-year-old man presented with a 9-month history of a painless subcutaneous nodule on the right medial malleolus. The lesion progressively enlarged and ulcerated. He recalled a puncture with an unknown plant at the site of the lesion 3 months earlier. The patient had been treated intermittently with various systemic antibiotics, including ceftazidime, azithromycin, ofloxacin, and metronidazole for more than 1 month before he came to our hospital, but there was no clinical response. Cutaneous examination revealed a poorly demarcated area of swelling (6- × 5-cm) with yellow crusts and a few fistulous tracts on the right medial malleolus (Fig 1, A), which yielded scanty seropurulent discharge on pressure. The physical examination was otherwise normal. The biochemical and immunologic parameters including liver and renal function, serum glucose and lipids, immunoglobulins (IgG, IgA, IgM, IgD, and IgE), and complements (C3, C5, and CH50) were normal. A radiographic scan of the foot showed no bone erosion. Repeated smears of the pus and crushed tissue at 1-week intervals were negative for fungal elements when assessed by 10% potassium hydroxide preparation and Gram stain. Periodic acid–Schiff (PAS)-stained sections revealed purple-red hyphae and pink spores in the dermis (Fig 2). Clinical specimens were cultured on Sabouraud dextrose agar (SDA) without antimicrobial agents and yielded yellowish white, finely wrinkled, and butyrous colonies at 27°C after 2 weeks. Microscopic examination of slide culture revealed pseudohyphae, branched septate hyphae, arthroconidia, and blastoconidia. The isolate was identified as T dermatis based on the morphologic features and internal transcribed spacer (ITS) sequence analysis (GenBank accession number: GQ499277), and has been deposited in the China General Microbiological Culture Collection Center (Beijing) under catalog number CGMCC-2.4166. In vitro antifungal susceptibility testing was performed using NeoSensitabs (Rosco; Taastrup, Denmark) according to the instructions of the manufacturers. After 48 to 72 hours of incubation at 27°C, the diameter of inhibition zone was recorded. The strain was very sensitive to amphotericin B, itraconazole, voriconazole, and nystatin, moderately sensitive to ketoconazole and clotrimazole, and resistant to flucytosine, miconazole, econazole, and terbinafine. The patient was initially treated with oral itraconazole 200 mg once daily and topical application of 0.1% ethacridine solution for 1 month, and then with itraconazole 200 mg twice daily for another month. The patient discontinued the therapy for 1 month because the lesion improved remarkably. He was asked to pursue the same regimen for another 2 months, and the lesion healed with scarring (Fig 1, B). There was no relapse for 2-month follow-up.Fig 2Biopsy specimen showing purple-red hyphae in the dermis. (Periodic acid–Schiff stain; original magnification: ×1000.)View Large Image Figure ViewerDownload Hi-res image Download (PPT)T dermatis has been confirmed to be a potential human pathogen after it was transferred to the genus Trichosporon from the Cryptococcus humicola complex in 2001.6Sugita T. Takashima M. Nakase T. Ichikawa T. Ikeda R. Shinoda T. Two new yeasts, Trichosporon debeurmannianum sp. nov. and Trichosporon dermatis sp. nov., transferred from the Cryptococcus humicola complex.Int J Syst Evol Microbiol. 2001; 51: 1221-1228Crossref PubMed Scopus (28) Google Scholar Eight strains of T dermatis were isolated from skin, nails, and blood of 49 Spanish and Argentinean patients with Trichosporon infection.4Rodriguez-Tudela J.L. Diaz-Guerra T.M. Mellado E. Cano V. Tapia C. Perkins A. et al.Susceptibility patterns and molecular identification of Trichosporon species.Antimicrob Agents Chemother. 2005; 49: 4026-4034Crossref PubMed Scopus (148) Google Scholar One case of T dermatis was found in 22 Trichosporon isolates recovered from blood cultures in Brazil.3Chagas-Neto T.C. Chaves G.M. Melo A.S. Colombo A.L. Bloodstream infections due to Trichosporon spp.: species distribution, Trichosporon asahii genotypes determined on the basis of ribosomal DNA intergenic spacer 1 sequencing, and antifungal susceptibility testing.J Clin Microbiol. 2009; 47: 1074-1081Crossref PubMed Scopus (118) Google Scholar Five patients were positive for T dermatis in 43 Trichosporon cases from Taiwan, but only one had invasive infection.1Ruan S.Y. Chien J.Y. Hsueh P.R. Invasive trichosporonosis caused by Trichosporon asahii and other unusual Trichosporon species at a medical center in Taiwan.Clin Infect Dis. 2009; 49: e11-e17Crossref PubMed Scopus (119) Google Scholar The first case of fungemia caused by T dermatis was observed in a male infant in 2006.5Gunn S.R. Reveles X.T. Hamlington J.D. Sadkowski L.C. Johnson-Pais T.L. Jorgensen J.H. Use of DNA sequencing analysis to confirm fungemia due to Trichosporon dermatis in a pediatric patient.J Clin Microbiol. 2006; 44: 1175-1177Crossref PubMed Scopus (20) Google Scholar Our immunocompetent patient suffered from a skin infection after a plant puncture. It is difficult to identify the Trichosporon species only by phenotypic methods; however, two different reproductive modes (eg, pseudohyphae and true hyphae) may be distinctive features of T dermatis. Molecular typing can provide a definitive identification. Although some authors believe that T dermatis is phylogenetically closely related to T mucoides and cannot be distinguished by ITS sequencing,3Chagas-Neto T.C. Chaves G.M. Melo A.S. Colombo A.L. Bloodstream infections due to Trichosporon spp.: species distribution, Trichosporon asahii genotypes determined on the basis of ribosomal DNA intergenic spacer 1 sequencing, and antifungal susceptibility testing.J Clin Microbiol. 2009; 47: 1074-1081Crossref PubMed Scopus (118) Google Scholar, 5Gunn S.R. Reveles X.T. Hamlington J.D. Sadkowski L.C. Johnson-Pais T.L. Jorgensen J.H. Use of DNA sequencing analysis to confirm fungemia due to Trichosporon dermatis in a pediatric patient.J Clin Microbiol. 2006; 44: 1175-1177Crossref PubMed Scopus (20) Google Scholar our sequence analysis showed that the ITS sequence of the isolate was identical with that of the type strain of T dermatis (CBS2043, AY143557), but differed from that of the type strain of T mucoides (CBS7625, AB018030) by two nucleotides. Our patient was initially treated with low-dose itraconazole because he was elderly, but the therapeutic efficacy was unsatisfactory. The treatment regimen was interrupted by the patient’s noncompliance. Therefore, we recommend continued regimen with high-dose itraconazole (400 mg/day), which is effective in the treatment of cutaneous trichosporonosis caused by T dermatis. To the Editor: Trichosporon species are soil inhabitants, but may also be normal flora in the gastrointestinal tract and transiently colonize the skin and respiratory tract in humans.1Ruan S.Y. Chien J.Y. Hsueh P.R. Invasive trichosporonosis caused by Trichosporon asahii and other unusual Trichosporon species at a medical center in Taiwan.Clin Infect Dis. 2009; 49: e11-e17Crossref PubMed Scopus (119) Google Scholar, 2Chagas-Neto T.C. Chaves G.M. Colombo A.L. Update on the genus Trichosporon.Mycopathologia. 2008; 166: 121-132Crossref PubMed Scopus (119) Google Scholar They have increasingly become important opportunistic pathogens in immunocompromised subjects over the past 2 decades. Thirteen of 38 species in the genus Trichosporon may be potential human pathogens, with Trichosporon asahii being the most common.1Ruan S.Y. Chien J.Y. Hsueh P.R. Invasive trichosporonosis caused by Trichosporon asahii and other unusual Trichosporon species at a medical center in Taiwan.Clin Infect Dis. 2009; 49: e11-e17Crossref PubMed Scopus (119) Google Scholar, 2Chagas-Neto T.C. Chaves G.M. Colombo A.L. Update on the genus Trichosporon.Mycopathologia. 2008; 166: 121-132Crossref PubMed Scopus (119) Google Scholar, 3Chagas-Neto T.C. Chaves G.M. Melo A.S. Colombo A.L. Bloodstream infections due to Trichosporon spp.: species distribution, Trichosporon asahii genotypes determined on the basis of ribosomal DNA intergenic spacer 1 sequencing, and antifungal susceptibility testing.J Clin Microbiol. 2009; 47: 1074-1081Crossref PubMed Scopus (118) Google Scholar There have been some reports of T dermatis infections in the literature, with infection sites including the skin, nails, and blood.1Ruan S.Y. Chien J.Y. Hsueh P.R. Invasive trichosporonosis caused by Trichosporon asahii and other unusual Trichosporon species at a medical center in Taiwan.Clin Infect Dis. 2009; 49: e11-e17Crossref PubMed Scopus (119) Google Scholar, 3Chagas-Neto T.C. Chaves G.M. Melo A.S. Colombo A.L. Bloodstream infections due to Trichosporon spp.: species distribution, Trichosporon asahii genotypes determined on the basis of ribosomal DNA intergenic spacer 1 sequencing, and antifungal susceptibility testing.J Clin Microbiol. 2009; 47: 1074-1081Crossref PubMed Scopus (118) Google Scholar, 4Rodriguez-Tudela J.L. Diaz-Guerra T.M. Mellado E. Cano V. Tapia C. Perkins A. et al.Susceptibility patterns and molecular identification of Trichosporon species.Antimicrob Agents Chemother. 2005; 49: 4026-4034Crossref PubMed Scopus (148) Google Scholar However, none of these cases included definite clinicopathologic evidence except for the patient with fungemia reported by Gunn et al,5Gunn S.R. Reveles X.T. Hamlington J.D. Sadkowski L.C. Johnson-Pais T.L. Jorgensen J.H. Use of DNA sequencing analysis to confirm fungemia due to Trichosporon dermatis in a pediatric patient.J Clin Microbiol. 2006; 44: 1175-1177Crossref PubMed Scopus (20) Google Scholar and it is unknown whether the clinical isolate is pathogenic to humans. We report the first case to our knowledge of skin infection caused by T dermatis in humans. A 70-year-old man presented with a 9-month history of a painless subcutaneous nodule on the right medial malleolus. The lesion progressively enlarged and ulcerated. He recalled a puncture with an unknown plant at the site of the lesion 3 months earlier. The patient had been treated intermittently with various systemic antibiotics, including ceftazidime, azithromycin, ofloxacin, and metronidazole for more than 1 month before he came to our hospital, but there was no clinical response. Cutaneous examination revealed a poorly demarcated area of swelling (6- × 5-cm) with yellow crusts and a few fistulous tracts on the right medial malleolus (Fig 1, A), which yielded scanty seropurulent discharge on pressure. The physical examination was otherwise normal. The biochemical and immunologic parameters including liver and renal function, serum glucose and lipids, immunoglobulins (IgG, IgA, IgM, IgD, and IgE), and complements (C3, C5, and CH50) were normal. A radiographic scan of the foot showed no bone erosion. Repeated smears of the pus and crushed tissue at 1-week intervals were negative for fungal elements when assessed by 10% potassium hydroxide preparation and Gram stain. Periodic acid–Schiff (PAS)-stained sections revealed purple-red hyphae and pink spores in the dermis (Fig 2). Clinical specimens were cultured on Sabouraud dextrose agar (SDA) without antimicrobial agents and yielded yellowish white, finely wrinkled, and butyrous colonies at 27°C after 2 weeks. Microscopic examination of slide culture revealed pseudohyphae, branched septate hyphae, arthroconidia, and blastoconidia. The isolate was identified as T dermatis based on the morphologic features and internal transcribed spacer (ITS) sequence analysis (GenBank accession number: GQ499277), and has been deposited in the China General Microbiological Culture Collection Center (Beijing) under catalog number CGMCC-2.4166. In vitro antifungal susceptibility testing was performed using NeoSensitabs (Rosco; Taastrup, Denmark) according to the instructions of the manufacturers. After 48 to 72 hours of incubation at 27°C, the diameter of inhibition zone was recorded. The strain was very sensitive to amphotericin B, itraconazole, voriconazole, and nystatin, moderately sensitive to ketoconazole and clotrimazole, and resistant to flucytosine, miconazole, econazole, and terbinafine. The patient was initially treated with oral itraconazole 200 mg once daily and topical application of 0.1% ethacridine solution for 1 month, and then with itraconazole 200 mg twice daily for another month. The patient discontinued the therapy for 1 month because the lesion improved remarkably. He was asked to pursue the same regimen for another 2 months, and the lesion healed with scarring (Fig 1, B). There was no relapse for 2-month follow-up. T dermatis has been confirmed to be a potential human pathogen after it was transferred to the genus Trichosporon from the Cryptococcus humicola complex in 2001.6Sugita T. Takashima M. Nakase T. Ichikawa T. Ikeda R. Shinoda T. Two new yeasts, Trichosporon debeurmannianum sp. nov. and Trichosporon dermatis sp. nov., transferred from the Cryptococcus humicola complex.Int J Syst Evol Microbiol. 2001; 51: 1221-1228Crossref PubMed Scopus (28) Google Scholar Eight strains of T dermatis were isolated from skin, nails, and blood of 49 Spanish and Argentinean patients with Trichosporon infection.4Rodriguez-Tudela J.L. Diaz-Guerra T.M. Mellado E. Cano V. Tapia C. Perkins A. et al.Susceptibility patterns and molecular identification of Trichosporon species.Antimicrob Agents Chemother. 2005; 49: 4026-4034Crossref PubMed Scopus (148) Google Scholar One case of T dermatis was found in 22 Trichosporon isolates recovered from blood cultures in Brazil.3Chagas-Neto T.C. Chaves G.M. Melo A.S. Colombo A.L. Bloodstream infections due to Trichosporon spp.: species distribution, Trichosporon asahii genotypes determined on the basis of ribosomal DNA intergenic spacer 1 sequencing, and antifungal susceptibility testing.J Clin Microbiol. 2009; 47: 1074-1081Crossref PubMed Scopus (118) Google Scholar Five patients were positive for T dermatis in 43 Trichosporon cases from Taiwan, but only one had invasive infection.1Ruan S.Y. Chien J.Y. Hsueh P.R. Invasive trichosporonosis caused by Trichosporon asahii and other unusual Trichosporon species at a medical center in Taiwan.Clin Infect Dis. 2009; 49: e11-e17Crossref PubMed Scopus (119) Google Scholar The first case of fungemia caused by T dermatis was observed in a male infant in 2006.5Gunn S.R. Reveles X.T. Hamlington J.D. Sadkowski L.C. Johnson-Pais T.L. Jorgensen J.H. Use of DNA sequencing analysis to confirm fungemia due to Trichosporon dermatis in a pediatric patient.J Clin Microbiol. 2006; 44: 1175-1177Crossref PubMed Scopus (20) Google Scholar Our immunocompetent patient suffered from a skin infection after a plant puncture. It is difficult to identify the Trichosporon species only by phenotypic methods; however, two different reproductive modes (eg, pseudohyphae and true hyphae) may be distinctive features of T dermatis. Molecular typing can provide a definitive identification. Although some authors believe that T dermatis is phylogenetically closely related to T mucoides and cannot be distinguished by ITS sequencing,3Chagas-Neto T.C. Chaves G.M. Melo A.S. Colombo A.L. Bloodstream infections due to Trichosporon spp.: species distribution, Trichosporon asahii genotypes determined on the basis of ribosomal DNA intergenic spacer 1 sequencing, and antifungal susceptibility testing.J Clin Microbiol. 2009; 47: 1074-1081Crossref PubMed Scopus (118) Google Scholar, 5Gunn S.R. Reveles X.T. Hamlington J.D. Sadkowski L.C. Johnson-Pais T.L. Jorgensen J.H. Use of DNA sequencing analysis to confirm fungemia due to Trichosporon dermatis in a pediatric patient.J Clin Microbiol. 2006; 44: 1175-1177Crossref PubMed Scopus (20) Google Scholar our sequence analysis showed that the ITS sequence of the isolate was identical with that of the type strain of T dermatis (CBS2043, AY143557), but differed from that of the type strain of T mucoides (CBS7625, AB018030) by two nucleotides. Our patient was initially treated with low-dose itraconazole because he was elderly, but the therapeutic efficacy was unsatisfactory. The treatment regimen was interrupted by the patient’s noncompliance. Therefore, we recommend continued regimen with high-dose itraconazole (400 mg/day), which is effective in the treatment of cutaneous trichosporonosis caused by T dermatis. We thank Dr Feng-Yan Bai for assistance with DNA analysis.
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