Abstract

Chromoblastomycosis (CBM) is a chronic disease caused by several species of dematiaceous fungi. In this study, a regional collection of 45 CBM cases was conducted in Guangdong, China, a hyper-endemic area of CBM. Epidemiology findings indicated that the mean age of cases was 61.38 ± 11.20 years, long duration ranged from 3 months to 30 years, and the gender ratio of male to female was 4.6:1. Thirteen cases (29%) declared underlying diseases. Verrucous form was the most common clinical manifestation (n = 19, 42%). Forty-five corresponding clinical strains were isolated, and 28 of them (62%) were identified as F. monophora; the remaining 17 (38%) were identified as F. nubica through ITS rDNA sequence analysis. Antifungal susceptibility tests in vitro showed low MICs in azoles (PCZ 0.015–0.25 μg/ml, VCZ 0.015–0.5 μg/ml, and ITZ 0.03–0.5 μg/ml) and TRB (0.015–1 μg/ml). Itraconazole combined with terbinafine was the main therapeutic strategy used for 31 of 45 cases, and 68% (n = 21) of them improved or were cured. Cytokine profile assays indicated upregulation of IL-4, IL-7, IL-15, IL-11, and IL-17, while downregulation of IL-1RA, MIP-1β, IL-8, and IL-16 compared to healthy donors (p < 0.05). The abnormal cytokine profiles indicated impaired immune response to eliminate fungus in CBM cases, which probably contributed to the chronic duration of this disease. In conclusion, we investigated the molecular epidemiological, clinical, and laboratory characteristics of CBM in Guangdong, China, which may assist further clinical therapy, as well as fundamental pathogenesis studies of CBM.

Highlights

  • Chromoblastomycosis (CBM) is a chronic cutaneous and subcutaneous fungal infection disease caused by several species of dematiaceous fungi, and mainly distributed in tropical and subtropical areas worldwide

  • Incidence of CBM usually follows a trauma with a contaminated organic material such as plant thorns, wood, plant debris, grass, and tree cortex, leading to the implantation of the fungus in the subcutaneous tissues, where the fungus changes from mycelial form to its parasitic form composed of muriform cells

  • F. pedrosoi and F. nubica appear to be exclusively associated with CBM under skin (De Hoog et al, 2004), whereas F. monophora and F. pugnacius were found to gain a much wider tissue tropism, e.g., brain, gallbladder and lymph node (Saberi et al, 2003; Surash et al, 2005; de Azevedo et al, 2015)

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Summary

Introduction

Chromoblastomycosis (CBM) is a chronic cutaneous and subcutaneous fungal infection disease caused by several species of dematiaceous fungi, and mainly distributed in tropical and subtropical areas worldwide. Incidence of CBM usually follows a trauma with a contaminated organic material such as plant thorns, wood, plant debris, grass, and tree cortex, leading to the implantation of the fungus in the subcutaneous tissues, where the fungus changes from mycelial form to its parasitic form composed of muriform cells. The muriform cells are the key to CBM development, which are extremely resistant to the harsh conditions imposed by the host immune system (Queiroz-Telles et al, 2017). Fonsecaea are the most common pathogens of CBM (Najafzadeh et al, 2011), including four clinical related species, F. pedrosoi, F. nubica, F. monophora, and F. pugnacius. Itraconazole (ITC) and terbinafine (TRB) are the most commonly used antifungal drugs in the treatment of CBM (Lopez and Mendez, 2007; Daboit et al, 2013; Daboit et al, 2014)

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