Cromoblastomicosis: abordaje con terapia combinada / Chromoblastomycosis: a combination therapy approach

La cromoblastomicosis es una micosis de implantación crónica y progresiva causada por diversos hongos de la familia Dematiaceae. En Latinoamérica, las especies en-contradas con más frecuencia son Fonsecaea pedrosoi y Cladophialophora carrionii. El tratamiento de esta micosis puede ser un desafío por la falta de respuesta y la recidiva, en especial en individuos con lesiones crónicas y extensas.Se presenta un individuo con recaída de cromoblastomico-sis (causada por Fonsecaea pedrosoi) en miembro inferior derecho que había realizado tratamiento incompleto con terbinafina e itraconazol. El paciente respondió de mane-ra favorable al retratamiento con itraconazol y terbinafina combinado con resección quirúrgica parcial de la lesión e injerto de piel en sitio quirúrgico

Chromoblastomycosis is a chronic and subcutaneous mycosis caused by various dematiaceous fungi, In Latin America, the most frequently found species are Fonsecaea pedrosoi and Cladophialophora carrionii.Treatment is a challenge because of the lack of response and recurrence in in some cases, especially in patients with extensive and chronic lesions.We report an individual with relapse of chromoblastomycosis (by Fonsecaea pedrosoi) in the right lower limb, who had undergone incomplete treatment with terbinafine and itraconazole. The patient responded favorably to retreatment with itraconazole and terbinafine combined with partial surgical resection of the lesion and skin grafting at the surgical site.

An impressive case of chromoblastomycosis due to Fonsecaea pedrosoi in a patient with a long history of fungal infection.

Chromoblastomycosis is defined as a chronic cutaneous and subcutaneous fungal infection caused by melanized or brown-pigmented fungi. A 63-year-old man farmer showed on external and internal part of the right arm, a well-delimited verrucous and hyperkeratotic plaque, with atrophic and cicatricial areas. Direct examination of skin scrapings samples showed the presence of muriform cells, a classic feature of chromoblastomycosis. Fungal isolation was performed in Sabouraud dextrose agar, and dark olivaceous colonies were isolated. Skin biopsy samples were obtained for histopathological and molecular diagnosis. DNA extracted from both, paraffin-embedded skin biopsy samples and fungal colonies, was used for molecular identification by 18S-ITS1-5.8S-ITS2-28S rRNA amplification and sequencing. Fonsecaea pedrosoi was identified from paraffin-embedded skin samples and fungal colonies. A combined therapy with terbinafine and itraconazole, plus cryotherapy was applied with an important improvement. Herein, we report an impressive case of chromoblastomycosis due to Fonsecaea pedrosoi with a successful outcome.

Chromoblastomycosis: an etiological, epidemiological, clinical, diagnostic, and treatment update.

Chromoblastomycosis is a chronic, granulomatous, suppurative mycosis of the skin and subcutaneous tissue caused by traumatic inoculation of dematiaceous fungi of the family Herpotrichiellaceae. The species Fonsecaea pedrosoi and Cladophialophora carrionii are prevalent in regions where the disease is endemic. Chromoblastomycosis lesions are polymorphous: verrucous, nodular, tumoral, plaque-like, and atrophic. It is an occupational disease that predominates in tropical and subtropical regions, but there have been several reports of cases in temperate regions. The disease mainly affects current or former farm workers, mostly males, and often leaving disabling sequelae. This mycosis is still a therapeutic challenge due to frequent recurrence of lesions. Patients with extensive lesions require a combination of pharmacological and physical therapies. The article provides an update of epidemiological, clinical, diagnostic, and therapeutic features.

Chromoblastomycosis: an etiological, epidemiological, clinical, diagnostic, and treatment update

Abstract: Chromoblastomycosis is a chronic, granulomatous, suppurative mycosis of the skin and subcutaneous tissue caused by traumatic inoculation of dematiaceous fungi of the family Herpotrichiellaceae. The species Fonsecaea pedrosoi and Cladophialophora carrionii are prevalent in regions where the disease is endemic. Chromoblastomycosis lesions are polymorphous: verrucous, nodular, tumoral, plaque-like, and atrophic. It is an occupational disease that predominates in tropical and subtropical regions, but there have been several reports of cases in temperate regions. The disease mainly affects current or former farm workers, mostly males, and often leaving disabling sequelae. This mycosis is still a therapeutic challenge due to frequent recurrence of lesions. Patients with extensive lesions require a combination of pharmacological and physical therapies. The article provides an update of epidemiological, clinical, diagnostic, and therapeutic features.

Wide Morphologic Variability of Chromoblastomycosis in the Western Hemisphere.

Chromomycosis is an uncommon fungal disease seen in tropical and subtropical regions of the world. The disorder is most likely the result of traumatic percutaneous inoculation of one of several etiologic dematiaceous fungi. Causative organisms have been associated with dead wood, soil, and plants. Chromomycosis may present clinically in a wide variety of manners. We illustrate the characteristic morphologic appearances of mycosis as it was encountered in both Panama and Texas, including verrucous papules and nodules, scaly plaques, exophytic or ulcerative tumor-like masses, and cicatricial plaques of both small and large dimension. As is typical of this disease, all lesions in this series were located on the extremities, and all patients had frequent and intimate exposure to vegetation in hot, humid environments. Chromomycosis characteristically runs an indolent course and is rarely fatal. The patients described herein had experienced cutaneous lesions for many months to several decades prior to diagnosis. This mycosis is often difficult to treat. Successful therapy may involve one or more oral antifungal drugs (such as itraconazole and terbinafine) and/or use of physically ablative modalities (such as laser, photodynamic therapy, and cryosurgery).

Fonsecaea pedrosoi as a rare cause of acute conjunctival ulceration.

Conjunctival ulceration accompanied with secretion and pain was observed in a 30-year-old male, 3 days after a perforating corneal trauma. Cultures of conjunctival ulcer samples grew Fonsecaea pedrosoi, a major causative agent of chromoblastomycosis that is typically transmitted during trauma. The conjunctival ulcer was successfully treated with amphotericin B, itraconazole, and fluconazole. This case report summarizes the diagnosis and treatment of a conjunctival ulcer due to F. pedrosoi, which is a rare complication of contaminated ocular trauma. To the best of our knowledge, this is the first reported case of F. pedrosoi causing acute conjunctival ulceration in the literature.

Fonsecaea pedrosoi as a rare cause of acute conjunctival ulceration / Fonsecaea pedrosoi como agente raramente associado à úlcera conjuntival aguda

ABSTRACT Conjunctival ulceration accompanied with secretion and pain was observed in a 30-year-old male, 3 days after a perforating corneal trauma. Cultures of conjunctival ulcer samples grew Fonsecaea pedrosoi, a major causative agent of chromoblastomycosis that is typically transmitted during trauma. The conjunctival ulcer was successfully treated with amphotericin B, itraconazole, and fluconazole. This case report summarizes the diagnosis and treatment of a conjunctival ulcer due to F. pedrosoi, which is a rare complication of contaminated ocular trauma. To the best of our knowledge, this is the first reported case of F. pedrosoi causing acute conjunctival ulceration in the literature.

RESUMO O quadro clínico de uma úlcera conjuntival acompanhada de secreção e dor foi observado em homem de 30 anos de idade, 3 dias após um trauma perfurante da córnea. As culturas de uma amostra retirada da úlcera conjuntival foi positiva para Fonsecaea pedrosoi, uma cromoblastomicose, geralmente transmitido após traumatismos. O caso foi tratado com sucesso com a anfotericina B, itraconazol e fluconazol. Este relato de caso reporta o diagnóstico e tratamento de uma úlcera conjuntival causada por F. pedrosoi, que raramente é visto nos olhos expostos a traumatismos contaminados. Até onde sabemos, este é o primeiro caso relatado na literatura de F. pedrosoi causando úlcera conjuntival aguda.

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.

Cromomicose: relato de caso e revisão da literatura / Chromomycosis: case report and literature review

A cromomicose é uma micose profunda, crônica, com acometimento da pele e do subcutâneo. O fungo é encontrado na natureza nas plantas e no solo, sendo introduzido no organismo através de traumas ou ferimentos. A localização das lesões é, principalmente, nos membros inferiores, podendo também comprometer outras regiões. Os trabalhadores rurais são mais frequentemente acometidos por falta de proteção e exposição contínua. O objetivo deste relato foi apresentar um caso de cromomicose de evolução crônica, fazendo diagnóstico diferencial com outras doenças que causam a síndrome verrucosa (leishmaniose, esporotricose e tuberculose) e realizando breve revisão da literatura. Paciente do gênero masculino, 83 anos, branco, trabalhador rural, procurou Ambulatório de Dermatologia apresentando lesão vegetante, verrucosa, de base eritematosa, com distribuição linear, localizada no membro superior direito com evolução de 9 anos. As características da lesão sugeririam como hipóteses diagnósticas doenças que causam a síndrome verrucosa LECT (iniciais de leishmaniose, esporotricose, cromomicose e tuberculose). Para confirmação diagnóstica, foi realizada biópsia da lesão e exame histopatológico, que revelou presença de células arredondadas de cor castanho escuro em processo de reprodução binária, confirmando o diagnóstico de cromomicose. O paciente foi submetido ao tratamento com itraconazol e crioterapia combinados. A cromomicose possui diagnósticos diferencias em decorrência das características clínicas da lesão,sendo fundamentais, para sua confirmação diagnóstica, exames específicos.

Chromomycosis is a deep and chronic mycosis that affects the skin and the subcutaneous tissues. The fungus is found in nature, in plants and soil, being introduced into the body through trauma or injury. Lesions occur mainly on the lower limbs, but can also involve other regions. Rural workers are more frequently affected due to lack of protection and continuous exposure. The objective of this report was to present a case of chronic chromomycosis evolution, making differential diagnosis with other diseases that cause warty syndrome (leishmaniasis, sporotrichosis and tuberculosis) and performing a brief literature review. Male patient, 83 years old, white, farm laborer, sought the Dermatology Department presenting vegetative, verrucous lesion, with erythematous base, linear distribution, located on the right upper limb, with a 9-year progression. Lesion characteristics would suggest as diagnostic hypotheses diseases that cause warty syndrome LECT (acronym in Portuguese from leishmaniasis, sporotrichosis, chromomycosis and tuberculosis). For diagnostic confirmation, a biopsy and an histopathological examination were performed and revealed the presence of round, dark brown cells in binary reproduction process, confirming the diagnosis of chromomycosis. The patient was treated with itraconazole and cryotherapy combination. Chromomycosis has differential diagnosis due to the clinical characteristics of the lesion; therefore specific tests are fundamental to confirm the diagnosis.

DNA-hsp65 vaccine as therapeutic strategy to treat experimental chromoblastomycosis caused by Fonsecaea pedrosoi.

Chromoblastomycosis (CBM) is a chronic subcutaneous mycosis, caused by several dimorphic, pigmented dematiaceous fungi. Patients with the disease are still considered a therapeutic challenge, mainly due to its recalcitrant nature. There is no "gold standard" treatment for this neglected mycosis, but rather there are several treatment options. Chemotherapy alternatives include 5-flucytosine, itraconazole, terbinafine, fluconazole, thiabendazole, ketoconazole and amphotericin B, although the healing of severe cases is still uncommon. However, several studies have reported the DNA vaccine to be promising in the treatment for fungal infections; this vaccine allows the host to restore depressed cellular immunity, minimizing the toxic effects from conventional antifungal therapies. This work was therefore carried out aiming to establish a suitable model for experimental CBM, suggesting also new therapies, including DNA-hsp65 vaccine. By analyzing the morphometrical and histopathological aspects and by quantifying the fungal burden, the results showed the establishment of a chronic, although transitory, experimental CBM model with lesions similar to those presented in humans. A treatment regimen using intralesional itraconazole or amphotericin B was effective in treating experimental CBM, as was a therapy using naked DNA-hsp65 vaccine. It has also been shown that chemotherapy associated with DNA-hsp65 vaccine is promising in the treatment for CBM.

[Chromomycosis: report of a disabling case]. / Cromomicosis: reporte de un caso incapacitante.

Chromomycosis is a deep subcutaneous mycosis caused by different dymorphic fungi species that normally live in vegetal debris. We report the case of a 51 year-old patient that six years previous to the evaluation worked making roof tiles in Madre de Dios, Peru; where he presented an initial papular lesion in a leg, which continued expanding until the 4 limbs were affected with disabling verrucous lesions. Fumagoid cells were found in the skin biopsy. The patient was hospitalized and received topical cleaning, antibiotics and terbinafine. He was discharged two months later with clinical improvement.

Cromomicosis: reporte de un caso incapacitante / Chromomycosis: report of a disabling case

La cromomicosis es una micosis profunda subcutánea producida por hongos dimórficos que de forma habitual habitan en restos vegetales. Se presenta el caso de un paciente de 51 años que seis años antes del ingreso se dedicaba a la fabricación de tejas en Madre de Dios, Perú; donde sufrió una lesión inicial papular en una pierna la cual se extendió hasta comprometer los cuatro miembros, con lesiones verrucosas que lo llevaron a la discapacidad. Se observaron cuerpos fumagoides en la biopsia de piel. El paciente fue hospitalizado y recibió curaciones tópicas, antibioticoterapia y terbinafina. Fue dado de alta al cabo de dos meses con mejoría clínica.

Chromomycosis is a deep subcutaneous mycosis caused by different dymorphic fungi species that normally live in vegetal debris. We report the case of a 51 year-old patient that six years previous to the evaluation worked making roof tiles in Madre de Dios, Peru; where he presented an initial papular lesion in a leg, which continued expanding until the 4 limbs were affected with disabling verrucous lesions. Fumagoid cells were found in the skin biopsy. The patient was hospitalized and received topical cleaning, antibiotics and terbinafine. He was discharged two months later with clinical improvement.

Auricular chromoblastomycosis: a case report and review of published literature.

Subcutaneous chromoblastomycosis is an infection commonly seen in tropical and subtropical climates, usually caused by trauma with vegetables and often affects the host's lower limbs. We report a case of auricular chromoblastomycosis in a 67-year-old man and discuss the rarity of this clinical manifestation of chromoblastomycosis in the medical literature. In the present case, the etiologic agent was Fonsecaea pedrosoi, the most common agent found in Brazil.

Chromoblastomycosis: an overview of clinical manifestations, diagnosis and treatment.

Chromoblastomycosis is one of the most frequent infections caused by melanized fungi. It is a subcutaneous fungal infection, usually an occupational related disease, mainly affecting individuals in tropical and temperate regions. Although several species are etiologic agents, Fonsecaea pedrosoi and Cladophialophora carrionii are prevalent in the endemic areas. Chromoblastomycosis lesions are polymorphic and must be differentiated from those associated with many clinical conditions. Diagnosis is confirmed by the observation of muriform cells in tissue and the isolation and the identification of the causal agent in culture. Chromoblastomycosis still is a therapeutic challenge for clinicians due to the recalcitrant nature of the disease, especially in the severe clinical forms. There are three treatment modalities, i.e., physical treatment, chemotherapy and combination therapy but their success is related to the causative agent, the clinical form and severity of the chromoblastomycosis lesions. There is no treatment of choice for this neglected mycosis, but rather several treatment options. Most of the patients can be treated with itraconazole, terbinafine or a combination of both. It is also important to evaluate the patient's individual tolerance of the drugs and whether the antifungal will be provided for free or purchased, since antifungal therapy must be maintained in long-term regimens. In general, treatment should be guided according to clinical, mycological and histopathological criteria.

Cromoblastomicose. Estudo de uma série de 14 casos atendidos no Instituto de Pesquisa Clínica Evandro Chagas - Fundação Oswaldo Cruz, Rio de Janeiro, de 1994 a 2005 / Chromoblastomycosis. Study of series of 14 cases attended in Instituto de Pesquisa Clínica Evandro Chagas - Fundação Oswaldo Cruz, Rio de Janeiro, de 1994 a 2005

Este estudo de série de casos englobou 14 casos de Cromoblastomicose (CBM), micose crônica de longa evolução, atendidos no Serviço de Dermatologia no Instituto de Pesquisa Clínica Evandro Chagas (IPEC) - Fiocruz, no período de 1994 a 2005, e teve o objetivo de avaliar os aspectos epidemiológico, clínico, diagnóstico e terapêutico da micose. A presença de células muriformes no exame histopatológico ou micológico foi o critério de inclusão dos pacientes no estudo. Os resultados foram apresentados sob forma de dois artigos. O sexo masculino foi predominante em 71,4 por cento dos casos (10/14), a idade variou de 39 a 77 anos (média 61). Contato com o solo foi relatado por 11 pacientes, sendo 8 deles por motivos profissionais e 3 por atividades de lazer. Destes 11, apenas 3 referiam trauma com planta e madeira. Hipertensão arterial sistêmica (HAS) em seis pacientes (42,9 por cento), Diabetes mellitus (DM) em quatro pacientes (28,6 por cento), neurocisticercose em um paciente (7,1 por cento) e imunossupressão induzida por drogas (tacrolimus, micofenolato mofetil e prednisoma) em um paciente (7,1 por cento) foram as comorbidades apresentadas. O tempo da doença variou de 8 meses a 32 anos, sendo em metade dos pacientes maior que 10 anos. O tipo clínico verrucoso (seis casos) e a forma grave (sete casos) (lesões disseminadas segundo a classificação proposta por Queiroz-Telles e cols., 1992a) foram os mais encontrados, assim como a localização em membros inferiores em metade dos pacientes. As formas graves estiveram ao longo tempo de evolução. O exame micológico isolou Fonsecaea pedrosoi em 71,4 por cento (10 casos) e Cladophialophora carrionii em um caso (7,1 por cento), não havendo o isolamento em dois casos e um dos isolados não pôde ser classificado. Confirmação das espécies pela técnica de reação em cadeia de polimerase (PCR) foi realizada em dez isolados de cultura. Tratamento no IPEC foi realizado em 11 pacientes, 2 foram transferidos para outros estados e...paciente.

Tropical dermatology: fungal tropical diseases.

UNLABELLED: Fungal infections are common in tropical countries and can have an important impact on public health. Lobomycosis is a common fungal infection in the tropical rain forest of South America, and paracoccidioidomycosis (South American blastomycosis) is a widespread and sometimes severe illness. Penicilliosis marneffei is an opportunistic infection of AIDS patients in southeast Asia. Chromoblastomycosis and mycetomas are causes of morbidity around the world. Sporotrichosis is a worldwide subcutaneous mycosis with a high incidence in tropical countries and is an important illness in immunocompromised patients. Rhinosporidiosis was classed as a fungal infection but is now considered a protistan parasite that belongs to the class Mesomycetozoea. It is included in this review because of its historical classification. In the past, most of these mycoses were restricted to specific geographic areas and natural reservoirs. There are, however, situations in which people from other regions come in contact with the pathogen. A common situation involves an accidental contamination of a traveler or worker who has contact with a tropical mycosis. Even minor trauma to the skin surface or inhalation of the fungal conidia can infect the patient. Thus recognition of the clinical symptoms and the dermatologic findings of the diseases, as well as the geographic distribution of the pathogens, can be critical in diagnosis of the tropical mycoses. This review discusses some of the more common tropical subcutaneous and systemic mycoses, as well as their signs, symptoms, methods of diagnosis, and therapies. LEARNING OBJECTIVE: At the completion of this learning activity, participants should be able to recognize the clinical and histologic presentations of tropical fungal diseases with cutaneous manifestations and be familiar with the appropriate therapies.

[An ELISA test for the study of the therapeutic evolution of chromoblastomycosis by Cladophialophora carrionii in the endemic area of Falcon State, Venezuela]. / Inmunoanálisis enzimático (ELISA) en la evolución terapéutica de la cromoblastomicosis por Cladophialophora carrionii en el área endémica del Estado Falcón, Venezuela.

The purpose of this research was to evaluate an ELISA indirect method in patients with chromoblastomycosis caused by Cladophialophora carrionii. Samples collected before, during and postreatment with ajoene or itraconazole, and those from apparently healthy people from the endemic area were evaluated with the ELISA test. 94 individuals were studied, 10 with chromoblastomycosis, and 84 apparently healthy subjects. All of them were evaluated by clinical-dermatological examinations. On those with lesions suggestive of chromoblastomycosis, mycological studies were carried out to confirm the disease. This approach was repeated during and at the end of therapy. Five patients with lesions < or = 5 cms were treated with ajoene and five with lesions > 5 cms, received itraconazole. Mycological cure (60%) was similar in both groups of patients and persisted three months after therapy. One hundred and fourteen sera were analyzed by ELISA, 30 from 10 patients with chromoblastomycosis, before, during and postreatment and 84 from apparently healthy people, using a somatic antigen of C. carrionii (AgSPP). All patients with chromoblastomycosis were positive before-treatment, two became negative on day 45 of treatment and a total of six patients were negative three months post-treatment. All sera from apparently healthy individuals were negative. The sensitivity and specificity was 100% and 98.9%, respectively. The relationship between clinical-mycological studies and the ELISA assay was 100% before and after treatment. In summary, ELISA could be a valuable tool for the diagnosis and evolution of the therapeutic efficacy in patients with chromomycosis (C. carrionii). The use of an ELISA test is therefore highly recommended to establish remission criteria in chromoblastomycosis caused by C. carrionii.