Mycetoma, chromoblastomycosis and other deep fungal infections: diagnostic and treatment approach.

PURPOSE OF REVIEW: to review recent advances in the epidemiology, diagnosis, and treatment of deep fungal infections. RECENT FINDINGS: Mycetoma and chromoblastomycosis are the only deep fungal infections incorporated in the list of neglected tropical diseases. These infections start in the skin but progress to deep tissues if not recognized early. A wide array of fungal pathogens are the causative agents. Molecular methods allow for early and accurate identification of the pathogens, but are unfortunately not available in endemic areas. Treatment options are mostly based upon clinical experience rather than on well-designed clinical trials. SUMMARY: Deep fungal infections of the skin and soft tissues are rare conditions of wide world distribution but mostly reported from tropical countries. Urgent need for affordable and easily accessible molecular methods and well-conducted studies to allow for accurate diagnosis and to provide evidence to guide proper therapy are urgently needed.

Molecular epidemiology and clinical-laboratory aspects of chromoblastomycosis in Mato Grosso, Brazil.

INTRODUCTION: Chromoblastomycosis is a disease caused by melanized fungi, primarily belonging to the genera Fonsecaea and Cladophialophora, mainly affecting individuals who are occupationally exposed to soil and plant products. This research aimed to determine the clinical, epidemiological and laboratory characteristics of chromoblastomycosis in the state of Mato Grosso, Brazil. MATERIALS AND METHODS: Patients diagnosed with chromoblastomycosis treated at the Júlio Müller University Hospital, Cuiabá, Brazil, from January 2015 to December 2020, whose isolates were preserved in the Research Laboratory of the Faculty of Medicine of the Federal University of Mato Grosso. Isolates were identified by partly sequencing the Internal Transcribed Spacer (ITS) and ß-tubulin (BT2) loci. AFLP fingerprinting was used to explore the genetic diversity. Susceptibility to itraconazole, voriconazole, 5-fluorocytosine, terbinafine and amphotericin B was determined by the broth microdilution technique. RESULTS: Ten patients were included, nine were male (mean age = 64.1 years). Mean disease duration was 8.6 years. Lesions were mainly observed in the lower limbs. Predominant clinical forms were verrucous and scarring. Systemic arterial hypertension and type II diabetes mellitus were the predominant comorbidities. Leprosy was the main concomitant infectious disease. Fonsecaea pedrosoi was the unique aetiological agent identified with moderate genetic diversity (H = 0.3934-0.4527; PIC = 0.3160-0.3502). Antifungal agents with the highest activity were terbinafine, voriconazole and itraconazole. CONCLUSION: Chromoblastomycosis is affecting the poor population in rural and urban areas, mainly related to agricultural activities, with F. pedrosoi being the dominant aetiologic agent. All isolates had low MICs for itraconazole, voriconazole and terbinafine, confirming their importance as therapeutic alternatives for chromoblastomycosis.

Chromoblastomycosis-Leprosy Co-Infection in Central West Brazil. Presentation of Three Cases and Literature Review.

Chromoblastomycosis and leprosy are chronic diseases with high prevalence in tropical and subtropical regions. Brazil is one of the countries with the highest incidence and prevalence for both diseases, however, reports of co-infections are scarce. The aim of this study was to describe three cases of chromoblastomycosis-leprosy co-infection in patients from Mato Grosso state, Brazil. A review of chromoblastomycosis-leprosy co-infection was performed of English, Portuguese and Spanish publications in LILACS, SciELO, PubMed and Web of Science databases using the descriptors (chromoblastomycosis OR cromoblastomicose OR cromoblastomicosis) AND (leprosy OR hanseníase OR lepra), without time period delimitation. Nineteen cases were included, 16 cases were published in 11 articles, plus the three cases reported in the current study. Most reported coninfection cases came from Brazil. Majority of the patients were male with a mean age of 52.2 years. Farmer was the main occupational activity reported. In 12 patients, the clinical signs and symptoms of leprosy started first. No contacts with patients affected by leprosy, armadillos or history of injuries at the anatomical site of chromoblastomycosis lesions were reported. Five leprosy patients who received steroid treatment for leprosy reactions or neuropathies, were diagnosed with chromoblastomycosis during immunosuppressive therapy. Four cases (21.1%) were reported among the elderly patients. Co-infections in patients with chromoblastomycosis or leprosy are uncommon, but the possibility should always be considered, especially if the patient is undergoing immunosuppressive treatment or is elder.

Molecular Characteristics of Regional Chromoblastomycosis in Guangdong, China: Epidemiological, Clinical, Antifungal Susceptibility, and Serum Cytokine Profiles of 45 Cases.

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-1ß, 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.

Chromoblastomycosis in Latin America and the Caribbean: Epidemiology over the past 50 years.

Chromoblastomycosis is a chronic disease caused by melanized fungi that mainly affect individuals performing soil-related labor. The objective of this study was to analyze the epidemiological and clinical characteristics of chromoblastomycosis in Latin America and the Caribbean by an extensive literature review. An integrative review was performed of English, French, Portuguese, and Spanish publications in LILACS, SciELO, PubMed, SCOPUS and Web of Science databases covering the period 1969-2019. A total of 1211 articles were identified, of which 132 were included in the review, covering 2081 patients, 80.3% were males, the mean age was 56.1 years. The mean duration of the disease was 10.8 years. The lesions were mainly described in the lower limbs (60%). The most frequent clinical forms were verrucous (46.4%) and tumorous (21.7%). Major disease symptoms and signs consisted of itching and pain. Bacterial infection and functional limitation were important complications. Immunosuppression post-kidney transplantation was the most frequent comorbidity while leprosy was the main concomitant infectious disease. Fonsecaea pedrosoi and Cladophialophora carrionii were the predominant etiological agents. Majority of the cured cases were treated with itraconazole as monotherapy or in combination with other antifungals, surgery or cryosurgery. Chromoblastomycosis affects hundreds of rural workers in Latin America and the Caribbean, causing disability and personal, family and economic losses. It is important to prioritize epidemiological surveillance and early diagnosis of this disease in order to reveal its real prevalence and direct resources to preventive actions, diagnosis and early treatment. LAY SUMMARY: Chromoblastomycosis is a slowly progressing chronic disease caused by melanized fungi. We collected data from South America and the Caribbean covering 1969-2019, the 132 articles included 2081 patients, mean disease duration was 10.8 years. Fonsecaea pedrosoi and Cladophialophora carrionii predominated.

The global burden of chromoblastomycosis.

BACKGROUND: Chromoblastomycosis (CBM), represents one of the primary implantation mycoses caused by melanized fungi widely found in nature. It is characterized as a Neglected Tropical Disease (NTD) and mainly affects populations living in poverty with significant morbidity, including stigma and discrimination. METHODS AND FINDINGS: In order to estimate the global burden of CBM, we retrospectively reviewed the published literature from 1914 to 2020. Over the 106-year period, a total of 7,740 patients with CBM were identified on all continents except Antarctica. Most of the cases were reported from South America (2,619 cases), followed by Africa (1,875 cases), Central America and Mexico (1,628 cases), Asia (1,390 cases), Oceania (168 cases), Europe (35 cases), and USA and Canada (25 cases). We described 4,022 (81.7%) male and 896 (18.3%) female patients, with the median age of 52.5 years. The average time between the onset of the first lesion and CBM diagnosis was 9.2 years (range between 1 month to 50 years). The main sites involved were the lower limbs (56.7%), followed by the upper limbs (19.9%), head and neck (2.9%), and trunk (2.4%). Itching and pain were reported by 21.5% and 11%, respectively. Malignant transformation was described in 22 cases. A total of 3,817 fungal isolates were cultured, being 3,089 (80.9%) Fonsecaea spp., 552 (14.5%) Cladophialophora spp., and 56 Phialophora spp. (1.5%). CONCLUSIONS AND SIGNIFICANCE: This review represents our current knowledge on the burden of CBM world-wide. The global incidence remains unclear and local epidemiological studies are required to improve these data, especially in Africa, Asia, and Latin America. The recognition of CBM as NTD emphasizes the need for public health efforts to promote support for all local governments interested in developing specific policies and actions for preventing, diagnosing and assisting patients.

Endemic Chromoblastomycosis Caused Predominantly by Fonsecaea nubica, Madagascar1.

Chromoblastomycosis is an implantation fungal infection. Twenty years ago, Madagascar was recognized as the leading focus of this disease. We recruited patients in Madagascar who had chronic subcutaneous lesions suggestive of dermatomycosis during March 2013-June 2017. Chromoblastomycosis was diagnosed in 50 (33.8%) of 148 patients. The highest prevalence was in northeastern (1.47 cases/100,000 persons) and southern (0.8 cases/100,000 persons) Madagascar. Patients with chromoblastomycosis were older (47.9 years) than those without (37.5 years) (p = 0.0005). Chromoblastomycosis was 3 times more likely to consist of leg lesions (p = 0.003). Molecular analysis identified Fonsecaea nubica in 23 cases and Cladophialophora carrionii in 7 cases. Of 27 patients who underwent follow-up testing, none were completely cured. We highlight the persistence of a high level of chromoblastomycosis endemicity, which was even greater at some locations than 20 years ago. We used molecular tools to identify the Fonsecaea sp. strains isolated from patients as F. nubica.

Chromoblastomycosis in the Amazon region, Brazil, caused by Fonsecaea pedrosoi, Fonsecaea nubica, and Rhinocladiella similis: Clinicopathology, susceptibility, and molecular identification.

Chromoblastomycosis is a chronic subcutaneous disease caused by human contact with melanized fungi occurring mainly in tropical and subtropical zones worldwide. This study assessed 12 patients with chromoblastomycosis from Rondônia, Brazil, Amazon region. In sum, 83.3% were men, 41.6% were from Monte Negro city, median age was 52.9 years, and median time to disease progression was 12.2 years. Lesions were located on the lower limbs (75%), and verruciform was prevalent form (66.6%). After 3 years of treatment with itraconazole, two patients were considered cured. The etiological agents were identified by the molecular sequence of the ribosomal internal transcribed spacer ITS1, 5.8S, and ITS2 region and ß-tubulin genes. Eight strains were identified as Fonsecaea pedrosoi, two were F. nubica, and two were Rhinocladiella similis. The antifungal activity of five drugs was evaluated, and the most active drug was terbinafine (range minimal inhibitory concentration [MIC] 0.015-0.12 µg/ml), itraconazole (range MIC 0.03-0.5 µg/ml) and voriconazole (range MIC 0.06-0.5 µg/ml). The highest MIC was 5-fluorocytosine (range MIC 2-32 µg/ml), and amphotericin B (range MIC 0.25-2 µg/ml). In conclusion, the present study expanded the epidemiological disease database and described for the first time F. nubica and R. similis as chromoblastomycosis agents in the Brazilian Amazon region. Our results confirmed the importance of using molecular methods to identify the melanized fungi and stimulate the recognition of the disease in other places where no cases have been reported.

Mixed secondary bacterial infection is associated with severe lesions of chromoblastomycosis in a neglected population from Brazil.

Chromoblastomycosis (CBM) is a chronic subcutaneous infection caused by melanotic fungi, affecting mainly rural workers in tropical and subtropical regions. Secondary bacterial infections (SBIs) in CBM lesions bring complications to the disease, but little is known about the agents involved. Fungal and bacterial identification and epidemiological profile of 50 patients with CBM were analyzed in this study. Bacteria were tested for susceptibility to antibacterial drugs. Fonseacea pedrosoi and Rhinocladiella aquaspersa were the fungal agents isolated. 88% of the patients presented SBI. Gram-positive bacteria coinfected mainly upper limbs, and Gram-negative bacteria were more isolated from lower limbs. Streptococcus pyogenes and mixed bacterial microbiota were associated with severe lesions. Staphylococcus aureus was associated with mixed infections and consequently with the severity of the infection. Resistance to ß-lactams and methicillin was detected. Our results emphasize the necessity of bacterial culture and susceptibility testing as part of routine monitoring CBM cases.

Chromoblastomycosis Caused by Fonsecaea nubica: First Report in Northern China and Literature Review.

Chromoblastomycosis is found worldwide with higher incidence in tropical and subtropical regions. Fonsecaea spp. is one of the major causative agents of this disease. First case of chromoblastomycosis due to Fonsecaea nubica in Northern China is reported in a 75-year-old Chinese male. We firstly summarized molecular identification methods of Fonsecaea spp. and all the strains of F. nubica reported in the literature. Sequencing of internal transcribed spacer alone and/or combined with actin (ACT1), partial cell division cycle (CDC42) and partial beta-tubulin (BT2) were most commonly used to identify species, while lactase (Lac), homogentisate (HmgA) and polyketide synthase (PKS1) were also used in some cases. Most strains were isolated from South America and Eastern China. Five clinical cases of chromoblastomycosis due to F. nubica from Asia and Europe were also reviewed. All the five patients were male, over 30 years old, and their lesions occurred after trauma.

Cromomicosis: presentación de un caso / Chromomycosis: a case report

Fundamento: la cromomicosis es una micosis subcutánea, crónica, ocasionada por hongos dematiáceos o feoides de los géneros Fonsecaea, Cladophialophora, Phialophora, Rhinocladiella y Exophiala, entre otros. Afecta piel y tejido celular subcutáneo en extremidades inferiores, sobre todo en pies, se caracteriza por lesiones verrugosas, nodulares o atróficas y es de difícil tratamiento. Los hongos que causan la cromomicosis pueden aislarse en el ambiente a partir de madera, los restos de plantas o el suelo.Objetivo: presentar el caso clínico de un paciente con el diagnóstico de cromomicosis.Caso clínico: paciente masculino de 56 años de edad, trabajador agrícola, que hace alrededor de 15 años presentó lesión de antebrazo izquierdo, que creció de forma lenta hasta alcanzar un gran tamaño, por lo que acudió a consulta médica en su municipio, fue remitido a la consulta de Dermatología. Al examen dermatológico se constata un cuadro cutáneo localizado constituido por una lesión en placa eritematoescamosa, con costras aisladas de bordes bien definidos, arciformes de veinte centímetros, imbricados con zonas hipocrómicas, que asienta en región medial posterior de brazo y antebrazo izquierdo. Resto del examen físico sin alteraciones.Conclusión: la cromomicosis es una enfermedad rara, que conlleva complicaciones, por lo que es importante tener en cuenta la enfermedad para su diagnóstico precoz(AU)

Background: chromomycosis is a chronic subcutaneous mycosis caused by dematiaceous or feoid fungi from the genera Fonsecaea, Cladophialophora, Phialophora, Rhinocladiella and Exophiala, among others. It affects skin and subcutaneous cellular tissue, preferably in the lower extremities, especially in feet, characterized by warty, nodular or atrophic lesions and it is difficult to treat. Fungi that cause Chromomycosis can be isolated in the environment from wood, plant remains or soil.Objective: to present the clinical case of a patient diagnosed with chromomycosis.Case report: a 56-year-old male, agricultural worker, who presented a left forearm lesion approximately 15 years ago, which grew slowly until reaching a large size, so he went to medical consultation in his municipality, being referred to the dermatology consultation. Dermatological examination showed a localized cutaneous lesion consisting of an erythematous-scaly lesion, with isolated scabs with well-defined edges, approximately 20 centimeters long, imbricated with hypochromic zones, which sit in the posterior medial region of the left arm and forearm. The rest of the physical examination did not present alterations.Conclusion: chromomycosis is a rare disease, leading to complications. Therefore it is important to consider the disease for its early diagnosis(AU)

Chromoblastomycosis in India: Review of 169 cases.

Chromoblastomycosis (CBM) is a chronic, progressive, cutaneous and subcutaneous fungal infection following the traumatic implantation of certain dematiaceous fungi. The disease has worldwide prevalence with predominant cases reported from humid tropical and subtropical regions of America, Asia, and Africa. Diagnosis is often delayed or misdirected either due to poor degree of clinical suspicions or clinical simulation of dermatological conditions. The infection is not uncommon in India and several case reports from the sub-Himalayan belt and western and eastern coasts of India have been published; however, very few have reviewed the cases. We reviewed 169 cases published in English literature from India during 1957 through May 2016, including 2 recent cases from our institute. A tremendous increase in the number of reported cases was noticed since 2012, since which, more than 50% of the cases had been published. A majority of the patients (74.1%) were involved in various agricultural activities directly or indirectly. The mean age at presentation was 43.3 years ± 16.0, with male to female ratio of 4.2:1. The duration of disease at the time of presentation varied from 20 days to 35 years. Any history of trauma was recalled only in 33.8% of the studied cases. The lower extremity was the most common site afflicted, followed by the upper extremity. The culture was positive in 80.3% of the cases with Fonsecaea pedrosoi, isolated as the most common fungal pathogen, followed by Cladophialophora carrionii. Although all the commercially available antifungals were prescribed in these cases, itraconazole and terbinafine were the most commonly used, either alone or in combination with other drugs/physical methods, with variable degrees of outcome. Combinations of different treatment modalities (chemotherapy and physical methods) yielded a cure rate of 86.3%. CBM is refractory to treatment and no single antifungal agent or regimen has demonstrated satisfactory results. Increased awareness with early clinical suspicion of the disease and adequate therapy are necessary to improve the outcome. However, depending upon the causative agent, disease severity, and the choice of antifungals, variable outcomes can be observed.

Chromoblastomycosis and sporotrichosis, two endemic but neglected fungal infections in Madagascar.

Chromoblastomycosis and sporotrichosis are endemic fungal infections of tropical and subtropical regions, including Madagascar. The causal fungi develop in the soil or on plants and infect humans through wounds, either directly (wounding by the plant, through thorns, for example), or through the contact of an existing wound with contaminated soil. For this reason, the lesions predominantly occur on the limbs, and these fungi principally infect people working outside with bare hands and/or feet. The subcutaneous lesions of chromoblastomycosis are initially nodular, subsequently becoming warty, tumoral, cauliflower-like and pruriginous, which promotes dissemination. The chronic nature of the infection and its progression over long periods lead to highly disabling lesions in essentially rural and agricultural populations. The lesions of sporotrichosis are also nodular, but more ulcerous, and they form an extended chain following the route of the lymph vessels. Pus, squamous or skin biopsy specimens are used for the mycological examination of these mycoses. Treatment depends on the severity and form of the lesions and is based on antifungal drugs sometimes combined with physical methods. There has been no study of these infections for more than two decades in Madagascar, despite the large numbers of cases seen by doctors in all parts of the island. The nature, diversity and distribution of the plants responsible for contamination have not been described in Madagascar. In this review, we described these two endemic mycoses in terms of their epidemiological, mycological, clinical and therapeutic characteristics, focusing particularly on Madagascar, which is one of the leading foci of these two infections worldwide.

Subcutaneous mycoses in Peru: a systematic review and meta-analysis for the burden of disease.

BACKGROUND: There is a worrying lack of epidemiological data on the geographical distribution and burden of subcutaneous mycoses in Peru, hindering the implementation of surveillance and control programs. OBJECTIVES: This study aimed to estimate the disease burden of subcutaneous mycoses in Peru and identify which fungal species were commonly associated with these mycoses. METHODS: We performed a meta-analysis after a systematic review of the published literature in PubMed, LILACS, and SciELO to estimate the burden of subcutaneous mycoses in 25 regions in Peru. The disease burden was determined in terms of prevalence (number of cases per 100,000 inhabitants) and the number of reported cases per year per region. RESULTS: A total of 26 studies were eligible for inclusion. Results showed that sporotrichosis was the most common subcutaneous mycosis (99.7%), whereas lobomycosis, chromoblastomycosis, and subcutaneous phaeohyphomycosis were rare. Cases of eumycetoma and subcutaneous zygomycosis were not found. Of the 25 regions, the burden of sporotrichosis was estimated for four regions classified as endemic; in nine regions, only isolated cases were reported. The highest burden of sporotrichosis was in Apurimac (15 cases/100,000 inhabitants; 57 cases/year), followed by Cajamarca (3/100,000 inhabitants; 30/year), Cusco (0.5/100,000 inhabitants; 4/year), and La Libertad (0.2/100,000 inhabitants; 2/year). In two regions, the mycoses predominantly affected children. CONCLUSIONS: Sporotrichosis is the most common subcutaneous mycosis in Peru, with a high disease burden in Apurimac. Chromoblastomycosis, lobomycosis, and subcutaneous phaeohyphomycosis are rare mycoses in Peru.

Chromoblastomycosis.

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 reactions associated with microabscesses and often with tissue proliferation; (iii) a nonprotective T helper type 2 (Th2) immune response with ineffective humoral involvement; and (iv) the presence of muriform (sclerotic) cells embedded in the affected tissue. CBM lesions are clinically polymorphic and are commonly misdiagnosed 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, this disease can be refractory to antifungal therapy.

Molecular Epidemiology of Agents of Human Chromoblastomycosis in Brazil with the Description of Two Novel Species.

The human mutilating disease chromoblastomycosis is caused by melanized members of the order Chaetothyriales. To assess population diversity among 123 clinical strains of agents of the disease in Brazil we applied sequencing of the rDNA internal transcribed spacer region, and partial cell division cycle and ß-tubulin genes. Strains studied were limited to three clusters divided over the single family Herpotrichiellaceae known to comprise agents of the disease. A Fonsecaea cluster contained the most important agents, among which F. pedrosoi was prevalent with 80% of the total set of strains, followed by 13% for F. monophora, 3% for F. nubica, and a single isolate of F. pugnacius. Additional agents, among which two novel species, were located among members of the genus Rhinocladiella and Cyphellophora, with frequencies of 3% and 1%, respectively.

Subcutaneous mycoses in coastal Karnataka in south India.

BACKGROUND: Subcutaneous mycoses are chronic, localized infections of the skin and subcutaneous tissue which occur following traumatic implantation of the etiological agent. The causative organisms are soil saprophytes of regional epidemiology with varying ability to adapt to the tissue environment and elicit disease. OBJECTIVES: This study was conducted to evaluate the various types of subcutaneous mycoses, including actinomycotic mycetomas, in south coastal Karnataka, India. METHODS: Between January 2005 and January 2013, a total of 25 patients were diagnosed with subcutaneous mycoses based on a detailed clinical history and presentation, histopathology, and culture of organisms. RESULTS: Chromoblastomycosis was the infection most commonly seen (n = 16 patients, 64%), followed by mycetoma (n = 4, 16%), sporotrichosis (n = 4, 16%), and rhinoentomophthoromycosis (n = 1, 4%). The extremities were the most common site of involvement, with the lower limb being most affected (64%). Males were more commonly afflicted (64%) than females (36%). Most patients were agricultural workers, although preceding trauma was noted in only three patients. The majority of patients responded well to therapy and were disease-free on follow-up. CONCLUSIONS: Subcutaneous mycoses are a rare group of disorders. Chromoblastomycosis is the most frequent subcutaneous fungal infection in south India. Morphologically, chromomoblastomycoses present as verrucous, ulcerative, nodular, or eczematous lesions. Clinical diagnosis is important as culture is often negative. The incidence of infection is higher among rubber tappers. It is important to clinically differentiate chromoblastomycosis from tuberculosis verrucosa cutis. Most of the subcutaneous mycoses respond well to treatment, with the exception of rhinoentomophthoromycosis, which is a rare form of deep mycosis with associated mutilation. Eumycetomas are not observed in this part of India.

Global Spread of Human Chromoblastomycosis Is Driven by Recombinant Cladophialophora carrionii and Predominantly Clonal Fonsecaea Species.

Global distribution patterns of Cladophialophora carrionii, agent of human chromoblastomycosis in arid climates of Africa, Asia, Australia, Central-and South-America, were compared with similar data of the vicarious Fonsecaea spp., agents of the disease in tropical rain forests. Population diversities among 73 C. carrionii strains and 60 strains of three Fonsecaea species were analyzed for rDNA ITS, partial ß-tubulin, and amplified fragment-length polymorphism (AFLP) fingerprints. Populations differed significantly between continents. Lowest haplotype diversity was found in South American populations, while African strains were the most diverse. Gene flow was noted between the African population and all other continents. The general pattern of Fonsecaea agents of chromoblastomycosis differed significantly from that of C. carrionii and revealed deeper divergence among three differentiated species with smaller numbers of haplotypes, indicating a longer evolutionary history.

CHROMOBLASTOMYCOSIS: A NEGLECTED TROPICAL DISEASE.

Chromoblastomycosis (CMB) is a chronic fungal infection of the skin and the subcutaneous tissue caused by a transcutaneous traumatic inoculation of a specific group of dematiaceous fungi occurring mainly in tropical and subtropical zones worldwide. If not diagnosed at early stages, patients with CBM require long term therapy with systemic antifungals, sometimes associated with physical methods. Unlike other neglected endemic mycoses, comparative clinical trials have not been performed for this disease. Nowadays, therapy is based on a few open trials and on expert opinion. Itraconazole either as monotherapy or associated with other drugs, or with physical methods, is widely used. Recently, photodynamic therapy has been successfully employed in combination with antifungals in patients presenting with CBM. In the present revision the most used therapeutic options against CBM are reviewed as well as the several factors that may have impact on the patient's outcome.

Chromoblastomycssis: a neglected tropical disease / Cromoblastomicose: doença tropical negligenciada

SUMMARYChromoblastomycosis (CMB) is a chronic fungal infection of the skin and the subcutaneous tissue caused by a transcutaneous traumatic inoculation of a specific group of dematiaceous fungi occurring mainly in tropical and subtropical zones worldwide. If not diagnosed at early stages, patients with CBM require long term therapy with systemic antifungals, sometimes associated with physical methods. Unlike other neglected endemic mycoses, comparative clinical trials have not been performed for this disease. Nowadays, therapy is based on a few open trials and on expert opinion. Itraconazole either as monotherapy or associated with other drugs, or with physical methods, is widely used. Recently, photodynamic therapy has been successfully employed in combination with antifungals in patients presenting with CBM. In the present revision the most used therapeutic options against CBM are reviewed as well as the several factors that may have impact on the patient's outcome.

RESUMOCromoblastomicose (CMB) é uma infecção fúngica crônica da pele e tecido subcutâneo causada pela inoculação transcutânea traumática de um grupo específico de fungos dermatiáceos que ocorrem principalmente em zonas tropicais e subtropicais do mundo. Quando não são diagnosticados nas fases iniciais, pacientes com CBM necessitam de tratamentos prolongados com antifúngicos sistêmicos, por vezes associados a métodos físicos. Diferentemente de outras micoses endêmicas negligenciadas, não foram realizados ensaios clínicos comparativos para esta doença. Atualmente a terapia é baseada em alguns poucos ensaios abertos e em opiniões de especialistas. Itraconazol é amplamente utilizado como monoterapia ou em associação com outras drogas, ou com métodos físicos. Recentemente, a terapia fotodinâmica foi empregada com sucesso combinada a antifúngicos em pacientes com CBM. Neste manuscrito as opções terapêuticas mais utilizadas contra CBM foram revistas, assim como os diversos fatores que podem influenciar a evolução dos pacientes.