REVIEW crossm Chromoblastomycosis Flavio Queiroz-Telles,a Sybren de Hoog,b Daniel Wagner C. L. Santos,c Claudio Guedes Salgado,d Vania Aparecida Vicente,e Alexandro Bonifaz,f Emmanuel Roilides,g Liyan Xi,h Conceição de Maria Pedrozo e Silva Azevedo,i Moises Batista da Silva,j Zoe Dorothea Pana,g Arnaldo Lopes Colombo,k l Thomas J. Walsh Downloaded from Department of Public Health, Hospital de Clínicas, Federal University of Paraná, Curitiba, Paraná, Brazila; CBS- KNAW Fungal Biodiversity Centre, Utrecht, The Netherlandsb; Special Mycology Laboratory, Department of Medicine, Federal University of São Paulo, São Paulo, Brazilc; Dermato-Immunology Laboratory, Institute of Biological Sciences, Federal University of Pará, Marituba, Pará, Brazild; Microbiology, Parasitology and Pathology Graduation Program, Department of Basic Pathology, Federal University of Paraná, Curitiba, Paraná, Brazile; Dermatology Service and Mycology Department, Hospital General de México, Mexico City, Mexicof; Infectious Diseases Unit, 3rd Department of Pediatrics, Aristotle University School of Health Sciences and Hippokration General Hospital, Thessaloniki, Greeceg; Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat- h sen University, Guangzhou, China ; Department of Medicine, Federal University of Maranhão, Vila Bacanga, http://cmr.asm.org/ Maranhão, Brazili; Dermato-Immunology Laboratory, Institute of Biological Sciences, Pará Federal University, Marituba, Pará, Brazilj; Division of Infectious Diseases, Paulista Medical School, Federal University of São Paulo, São Paulo, Brazilk; Departments of Medicine, Pediatrics, and Microbiology and Immunology, Weill Cornell Medicine of Cornell University, New York, New York, USAl SUMMARY......................................................................................234 Published 16 November 2016 INTRODUCTION................................................................................234 Citation Queiroz-Telles F, de Hoog S, Santos A BRIEF HISTORY OF CHROMOBLASTOMYCOSIS .........................................235 DWCL, Salgado CG, Vicente VA, Bonifaz A, on November 16, 2016 by guest TAXONOMY ....................................................................................236 Roilides E, Xi L, Azevedo CDMPES, da Silva MB, Etiology.......................................................................................236 Pana ZD, Colombo AL, Walsh TJ. 2017. Molecular Phylogeny ........................................................................237 Chromoblastomycosis. Clin Microbiol Rev 30: Biodiversity ...................................................................................239 233–276. https://doi.org/10.1128/CMR.00032-16. EPIDEMIOLOGY ................................................................................240 Copyright © 2016 American Society for Potential Environmental Sources of Infection .............................................240 Microbiology. All Rights Reserved. Geographic Distribution.....................................................................241 Chromoblastomycosis in the Americas ....................................................242 Address correspondence to Flavio Queiroz- Chromoblastomycosis in Asia and Oceania................................................243 Telles, [email protected]. Chromoblastomycosis in Africa.............................................................243 Chromoblastomycosis in Europe ...........................................................243 Demographics and Risk Factors ............................................................243 PATHOGENESIS AND HOST DEFENSE ......................................................244 Cell Morphology and Architecture .........................................................245 Virulence Factors ............................................................................246 Melanin .......................................................................................247 Extracellular Enzymes and Metabolites ....................................................248 Innate Immune Response ...................................................................249 Adaptive Immune Response ................................................................250 CLINICAL MANIFESTATIONS .................................................................253 Initial Cutaneous Lesions....................................................................253 Clinical Classification and Severity .........................................................254 Complications and Sequelae................................................................255 Differential Diagnosis........................................................................256 LABORATORY DIAGNOSIS....................................................................256 Mycology.....................................................................................256 Immunodiagnosis............................................................................259 TREATMENT AND OUTCOME ................................................................259 Treatment with Physical Methods..........................................................260 Conventional Surgery .......................................................................260 Cryotherapy ..................................................................................260 Heat Therapy.................................................................................260 Laser Therapy ................................................................................261 Photodynamic Therapy......................................................................261 (continued) January 2017 Volume 30 Issue 1 Clinical Microbiology Reviews cmr.asm.org 233 Queiroz-Telles et al. Clinical Microbiology Reviews In Vitro Antifungal Susceptibility ...........................................................261 First-Line Therapy............................................................................262 Combined Systemic Antifungal Treatment ................................................263 Role of Other Triazoles ......................................................................263 Abandoned Antifungal Agents .............................................................263 Adjuvant Therapy............................................................................264 CRITERIA OF CURE ............................................................................264 PREVENTION ...................................................................................265 CONCLUSIONS .................................................................................265 ACKNOWLEDGMENTS.........................................................................266 REFERENCES ...................................................................................266 AUTHOR BIOS..................................................................................274 Downloaded from SUMMARY Chromoblastomycosis (CBM), also known as chromomycosis, is one of the most prevalent implantation fungal infections, being the most common of the gamut of mycoses caused by melanized or brown-pigmented fungi. CBM is mainly a tropical or subtropical disease that may affect individuals with certain risk factors around the world. The following characteristics are associated with this disease: (i) traumatic inoculation by implantation from an environmental source, leading to an initial cutaneous lesion at the inoculation site; (ii) chronic and progressive cutaneous and subcutaneous tissular involvement associated with fibrotic and granulomatous http://cmr.asm.org/ reactions associated with microabscesses and often with tissue proliferation; (iii) a nonprotective T helper type 2 (Th2) immune response with ineffective humoral in- volvement; and (iv) the presence of muriform (sclerotic) cells embedded in the af- fected tissue. CBM lesions are clinically polymorphic and are commonly misdiag- nosed as various other infectious and noninfectious diseases. In its more severe clinical forms, CBM may cause an incapacity for labor due to fibrotic sequelae and also due to a series of clinical complications, and if not recognized at an early stage, on November 16, 2016 by guest this disease can be refractory to antifungal therapy. KEYWORDS black fungi, chromoblastomycosis, chromomycosis, melanized fungi, muriform (sclerotic) cells, neglected disease INTRODUCTION eglected tropical diseases (NTDs) include a diverse series of endemic tropical and Nsubtropical diseases that prevail in tropical or subtropical zones worldwide. They usually affect individuals living in low-income regions of Asia, Africa, and Latin America. NTDs normally affect populations who do not travel aboard, with little political voice and low visibility. According to the World Health Organization (WHO), the prevalence of NTDs is linked to poverty and disadvantage. Those who suffer most from NTDs are mainly the poorest populations, often living in remote rural areas, urban slums, and conflict zones. With little health care attention and political support, NTDs are not under the radar of public health systems, and they are not a part of their priority lists (1). Several endemic diseases, including helminthic, protozoal, bacterial, and viral infections but not fungal diseases other than mycetoma (implantation mycosis), are defined as “neglected diseases” by the WHO (1, 2). Implantation mycoses are also classified as “subcutaneous mycoses” and refer to a diverse group of heterogeneous