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.

Cromoblastomicosis: primer caso alóctono tratado en Chile / Chromoblastomycosis: first allochthonous case treated in Chile

Resumen La cromoblastomicosis es una infección fúngica de la piel y del tejido subcutáneo, de evolución crónica, causada por hongos dematiáceos que se caracterizan por presentar melanina en su pared celular. La enfermedad se presenta en todo el mundo, principalmente en regiones tropicales y subtropicales. En Chile, solo hay un reporte de caso humano hace más de 30 años. Se presenta el caso de un varón de 46 años, haitiano, residente en Chile, con placas verrucosas en la zona tibial anterior de un año de evolución. El diagnóstico de cromoblastomicosis se confirmó al observar células muriformes en la histopatología y colonias dematiáceas en el cultivo micológico; además, en la miscroscopía directa se observaron conidias compatibles con Fonsecaea spp. Luego de seis meses de tratamiento con antimicóticos sistémicos y crioterapia, se logró la remisión completa de las lesiones.

Abstract Chromoblastomycosis is a fungal infection of the skin and subcutaneous tissue, of chronic evolution, caused by dematiaceous fungi. The disease occurs worldwide, mainly in tropical and subtropical regions, but in regions like Chile there is only one report of a human case more than 30 years ago. We present the case of a 46-year-old Haitian man, resident in Chile, with verrucous plaques in the right anterior tibial area of one year of evolution. The diagnosis of chromoblastomycosis was confirmed when muriform cells and dematiaceous colonies were observed in the histopathological analysis and the direct microscopy, respectively. After six months of treatment with systemic antimycotics and cryotherapy, complete remission of the lesions was achieved.

Melanin particles isolated from the fungus Fonsecaea pedrosoi activates the human complement system

BACKGROUND Melanin production has been associated with virulence in various pathogenic fungi, including Fonsecaea pedrosoi, the major etiological agent for chromoblastomycosis, a subcutaneous fungal disease that occurs in South America. OBJECTIVE The aim of this study was to evaluate the effects of acid-basic extracted F. pedrosoi melanin particles and fungal cell ghosts obtained by Novozym 234 treatment on their ability to activate the human complement system. METHODS The ability of melanin particles and fungal cell ghosts to activate the human complement system was evaluated by complement consumption, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). FINDINGS Unsensitised melanin particles and melanin ghosts presented complement consumption of 82.67 ± 2.08% and 96.04 ± 1.13%, respectively. Immunofluorescence assays revealed intense deposition of the C3 and C4 fragments on the surface of melanin particles and ghosts extracted from F. pedrosoi. Deposition of the C3, C4, and C5 fragments onto melanin samples and zymosan was confirmed by ELISA. Deposition of small amounts of C1q and C9 onto melanin samples and zymosan was detected by ELISA. CONCLUSION Fonsecaea pedrosoi melanin particles and fungal cell ghosts activated the complement system mainly through an alternative pathway.

Presentación de un paciente con cromomicosis / Presentation of a Patient with Chromomycosis

La cromomicosis es una micosis subcutánea o profunda, de curso crónico, causada por un grupo de hongos, se caracteriza por la formación de nódulos cutáneos verrucosos, localizados comúnmente en miembros inferiores, de evolución crónica y difícil curación total. Se presentó un paciente de 34 años de edad, que hace cinco años le salieron placas (de tres a cuatro) dispuestas de forma lineal, aspecto papuloverrucoso en dorso del brazo izquierdo. Se indicó examen micológico, donde se informó la presencia Fonsecaea pedrosoi, para lo cual recibió tratamiento con fluconazol; por elevación de las transaminasas se interrumpió el tratamiento, luego se aplicó crioterapia y por último recibió tratamiento quirúrgico.

Chromomycosis is a subcutaneous or deep mycosis of chronic course, caused by a group of fungi; it is characterized by the formation of coetaneous verrucous nodules, commonly located in lower limbs, of chronic evolution and total difficult cure. A 34- year-old patient that 5 years ago presented plaques (three-four) of lineal form, papulo verrucous in dorsum of the left arm, mycosis exam was indicated, and the diagnosis of Fonsecaea pedrosoiwas confirmed, treatment with fluconazol was given that was interrupted due to transaminase increase, thus cryotherapy was given and later surgical treatment.

Chromoblastomycosis in Kerala, India.

Background: We are reporting 35 new cases of Chromoblastomycosis from Central Kerala. A majority of the cases from India are reported from the Sub Himalayan belt and South India. The disease scenario in India and abroad is briefly reviewed. Aims: To study chromoblastomycosis in Central Kerala including the demographic and clinico- investigative profile. Methods: This report is a retrospective record analysis of 35 cases of chromoblastomycosis who presented to the Dermatology Outpatient department of our tertiary center from January 2003 to July 2010 after obtaining Institutional Review Board approval. Results: The disease was found to be more common among male agriculturists. The majority of cases were from the central districts of Kerala in and around the Western Ghats. The lower extremity (60%) was more affected with 40% of the subjects remembering a prior history of trauma. Sclerotic bodies were demonstrable in scrapings from black dots in 42.8%. The characteristic mixed mycotic granuloma was demonstrable in 77.1% of cases. The most common species isolated was Fonsecaea pedrosoi. Conclusions: Chromoblastomycosis is very common in Central Kerala. The disease mainly affects male agriculturists especially those employed in rubber plantations. The most common organism is F. pedrosoi.

Casuística de cromomicosis en el estado Bolívar (1987-2010) y evaluación de la sensibilidad in vitro de dos aislados de Fonsecaea pedrosoi / Chromomycosis cases in Bolivar State (1987-2010) and evaluation of the in vitro sensitivity of two Fonseca pedrosoi isolates

El objetivo de este estudio fue determinar la prevalencia de cromomicosis en un período de 23 años en dos hospitales de referencia del estado Bolívar. Se realizó un estudio retrospectivo, mediante la revisión de historias clínicas de pacientes con diagnóstico de cromomicosis, registrándose catorce casos de la enfermedad. El 78,6% correspondieron al sexo masculino, en su mayoría agricultores provenientes de zonas rurales; el 28,6% presentaron lesiones verrugosas. El tiempo de evolución de las lesiones osciló entre 5 meses y 35 años. Fonsecaea pedrosoi fue el agente etiológico aislado en tres (21,4%) de los cuatro pacientes en que las muestras fueron cultivadas. Sólo a dos aislados conservados de F. pedrosoi se les evaluó la sensibilidad in vitro mediante E-test®, demostrándose resistencia a los antifúngicos sistémicos: anfotericina B, 5-fluorocitosina, ketoconazol, fluconazol e itraconazol. Dos pacientes fueron tratados con itraconazol: uno de ellos mejoró; el otro presentó comorbilidad con micetoma eumicótico y falleció. La prevalencia de cromomicosis durante el período estudiado fue baja (0,6 casos/año), sin embargo esta infección representa un problema de salud en el personal de riesgo, principalmente agricultores y mineros del estado Bolívar, que presentan lesiones verrugosas de evolución crónica.

The purpose of this study was to determine chromomycosis prevalence during a 23-year period at two reference hospitals of Bolivar State. A retrospective study was carried out through the revision of clinical case histories of patients with a chromomycosis diagnosis, registering fourteen cases of this disease. Of these cases, 78.6% corresponded to males, most of them agricultural workers from rural areas; 28.6% presented verrucous lesions. The period of evaluation of the lesions varied between 5 months and 35 years. Fonsecae pedrosoi was the etiologic agent isolated in three (21.4%) of the four patients whose samples were cultured. Sensitivity was evaluated in vitro in only two cases through E-test®, showing resistance to systemic antifungals agents: amphotericine-B, 5-fluorocytosine, ketoconazole, fluconazole and itraconazole. Two patients were treated with itraconazol, one of them improved and the other presented co-morbility with eumycotic mycetoma and died. Chromomycosis prevalence during the period studied was low (0.6 cases/year); nevertheless, this infection constitutes a health problem for risk populations, mainly agricultural and mining workers at Bolivar State who present verrucous lesions with a chronic evolution.

Concurrent mycetoma and chromomycosis.

Chromoblastomycosis and Madura foot are chronic localised mycotic infection of the skin and subcutaneous tissue that follows the implantation of the fungi through minor trauma, mainly found in persons working outdoors on bare foot. In cases where both Madura and chromoblastomycosis are present, the treatment becomes difficult with low cure rates and frequent relapses. Here, we present such a very rare case of a 38-year-old cattle farmer who presented with verrucose nodules, tumefaction and multiple discharging nodules on the left lower 1/3 rd leg and foot since last 9 years. Direct KOH mount of the verrucose tissue showed Fonsecaea pedrosoi sclerotic muriform bodies and a biopsy of one granule discharging nodule demonstrated fungal mycetoma. He was put on tab. Itraconazole 200 mg o.d. and cotrimoxazole bid for 6 months with very little improvement. The rarity of this combination is most probably due to different geographical distribution.

Chromoblastomycosis Caused by Fonsecaea pedrosoi

We report herein a case of chromoblastomycosis caused by Fonsecaea (F.) pedrosoi in a 39-year-old male, who showed multiple, asymptomatic, scaly erythematous plaques on the left shin for 12 months. Histopathologically, chronic granulomatous inflammation and either sclerotic or muriform cells were observed. The fungal culture produced typical black colonies of F. pedrosoi. The DNA sequence of the internal transcribed spacer (ITS) region of the clinical sample was 100% match to that of F. pedrosoi IFM 47061 (GenBank accession number AB240943). The patient was treated with 200 mg of itraconazole daily, for 3 months. Skin lesions were improved. In Korea, only 9 cases of chromoblastomycosis, including this case, have been reported until now. The etiologic agent was F. pedrosoi in the majority of cases (6/9;67%). The incidence of chromoblastomycosis was slightly higher in female, and the upper limbs were more affected than the lower limbs in patients.

Bacillus subtilis induces morphological changes in Fonsecaea pedrosoi in vitro resulting in more resistant fungal forms in vivo

Interactions among microorganisms may be the cause of morphological modifications, particularly in fungal cells. The aim of this work was to examine the changes that occur in cells of the fungus Fonsecaea pedrosoi after in vitro co-culturing with Bacillus subtilis and to explore the results of this interaction in vivo in an experimental murine infection. B. subtilis strain was inoculated into a 15-day pure culture of F. pedrosoi. In vitro, after 48 hours of co-culturing, the fungal cells were roundish. The secretion of fungal dark pigments and production of terminal chlamydoconidia were observed in hyphae after one week. In the in vivo study, two animal groups of 30 BALB/c mice each were employed. One group was inoculated intraperitoneally with hyphal fragments from the co-culture of bacteria and fungi; the other group was infected only with F. pedrosoi hyphae. After seven days of infection, both animal groups developed neutrophilic abscesses. Phagocytosis of bacilli by macrophages occurred at three days. At later periods, generally after 25 days, only roundish cells similar to sclerotic bodies remained in the tissues while hyphae were eliminated by 15 to 20 days. These fungal forms originated mainly from terminal chlamydoconidia. The co-culturing between bacteria and fungi may constitute a mechanism to rapidly obtain resistant fungal forms for host defenses, especially for chromoblastomycosis (CBM) experimental infections.

Cromomicosis: una endemia rural en la región noroccidental en Venezuela / Chromomycosis: rural endemic in the north-western region of Venezuela

INTRODUCCIÓN: la cromomicosis, descrita por Max Rudolph en 1914, es una micosis subcutánea de desarrollo crónico, que se adquiere generalmente a partir de un traumatismo cutáneo y es causada por hongos dematíaceos. En Venezuela se ha reportado en todo el país aunque hay franco predominio en los estados de Lara, Zulia y Falcón. OBJETIVO: establecer algunos factores que pudieran explicar la endemia en la zona rural del estado de Falcón, Venezuela. MÉTODOS: se procedió a la detección in vitro de Cladophialophora carrionii a partir de la vegetación típica de esta región, semiárida, descrita como "bosque xerófilo de espinar". Se realizó además, búsqueda activa de casos clínicos entre los habitantes de la zona, mediante examen directo y cultivo de las escamas obtenidas a partir de lesiones y se trató de establecer, la existencia un factor de susceptibilidad hereditario mediante el cálculo del factor de heredabilidad de Falconer y la metodología de problemas genéticos heredables de Arias. RESULTADOS: se pudo aislar C. carrionii a partir de especies xerófilas abundantes en la zona: Prosopis juliflora; y varias cactáceas. La casuística acumulada, en nuestro estado representa 54,4 % (490/900) de todos los casos reportados en Venezuela, desde 1983 hasta 2005. La mayoría de los pacientes fueron infectados por C. carrionii y refirieron traumas frecuentes con espinas de cactáceas. Mediante estudios genealógicos se demostró la concentración de los casos en grupos familiares (hasta 11 % superior a la comunidad) así como un factor de heredabilidad de 65 % y alta frecuencia de matrimonios consanguíneos (25 %) asociados con 7 % de personas con cromomicosis. CONCLUSIONES: se consideró que se trata de una endemia rural, laboral y familiar, posiblemente relacionada con un factor de susceptibilidad heredable.

INTRODUCTION: chromomycosis, described by Max Rudolph in 1914, is a chronic subcutaneous mycosis that are generally caught from a cutaneous trauma and caused by dematiaceous fungi. This disease has been reported throughout Venezuela, but it is predominant in the states of Lara, Zulia and Falcón. OBJECTIVE: to ascertain some factors that might explain the endemic at Falcon State rural zone. METHODS: in vitro detection of Cladophialophora carrionii from the typical vegetation of this semiarid area known as "xerophilous woods of prickles" and also, active search of clinical cases among inhabitants of this area through direct testing and culture of flakes from skin lesions. It was intended to determine a hereditary susceptibility factor through the estimation of Falconer´s heritability factor and Arias´ methodology of heritable genetic disorders. RESULTS: it was possible to isolate C. carrionii from abundant xerophilous species in the area such as Prosopis juliflora and several Cactaceae. The accumulated casuistry in our state accounts for 54,4% (490/900) of all cases reported in Venezuela from 1983 to 2995. Most of the patients were infected by C. carrionii and they mentioned frequent injures by cactaceae prickles. On the basis of genealogical studies, it was proved that cases were concentrated in family groups (up to 11% higher than in the community) as well as 65% heritability factor and high frequency of blood-related marriages (25%) associated with 7% of people affected by chromomycosis. CONCLUSIONS: it was concluded that this is a rural, work and family endemic that is likely associated with a hereditary susceptibility factor.

Experimental murine chromoblastomycosis obtained from Fonsecaea pedrosoi isolate cultured for a long periodt

The present study aimed to describe F. pedrosoi propagules capable of causing chronic murine disease. Several changes in F. pedrosoi hyphae were identified in fungal cells cultured for a long period. Optical microscopy found many rounded cells with double-rigid melanin-rich walls. Terminal and intercalary chlamydoconidia were also frequently observed. Analyses of images from transmission electron microscopy (TEM) revealed several cells with walls composed of at least three layers and an outer layer enriched with melanin. Two groups of twenty BALB/c mice were subcutaneously infected in their footpads with F. pedrosoi cells at an inoculum concentration of approximately 1 x 10(4) cells/mL. In one group, long-term cultured F. pedrosoi cells were inoculated in one footpad, whereas in the other group, both footpads were infected. Active lesions were observed up to seven months post-infection, particularly in mice inoculated at two sites. After this period, animals were killed. Histological sections revealed characteristics bearing a strong resemblance to the human form of the disease such as tissue hyperplasia, granulomas with microabscesses and sclerotic cells. Based on this study, we identified fungal cells from old cultures capable of provoking chronic chromoblastomycosis under experimental conditions, especially when more than one site is infected.

Secretion of five extracellular enzymes by strains of chromoblastomycosis agents / Secreção de cinco enzimas extracelulares por amostras de agentes da cromoblastomicose

The gelatinase, urease, lipase, phospholipase and DNase activities of 11 chromoblastomycosis agents constituted by strains of Fonsecaea pedrosoi, F. compacta, Phialophora verrucosa, Cladosporium carrionii, Cladophialophora bantiana and Exophiala jeanselmei were analyzed and compared. All strains presented urease, gelatinase and lipase activity. Phospholipase activity was detected only on five of six strains of F. pedrosoi. DNase activity was not detected on the strains studied. Our results indicate that only phospholipase production, induced by egg yolk substrate, was useful for the differentiation of the taxonomically related species studied, based on their enzymatic profile.

As atividades gelatinase, urease, lipase, fosfolipase e DNase de 11 agentes da cromoblastomicose constituídos por amostras de Fonsecaea pedrosoi, F. compacta, Phialophora verrucosa, Cladosporium carrionii, Cladophialophora bantiana e Exophiala jeanselmei foram analisadas e comparadas. Todas as amostras apresentaram atividade urease, gelatinase e lipase. A atividade fosfolipase foi detectada apenas em cinco das seis amostras de F. pedrosoi. A atividade DNase não foi detectada nas amostras estudadas. Os resultados indicam que para a diferenciação entre espécies taxonomicamente relacionadas estudadas, baseado no seu perfil enzimático, apenas a produção de fosfolipase, induzida pelo substrato com gema de ovo, foi útil.

Fungal Keratitis Caused by Chromomycetes

PURPOSE: Chromomycetes is a plant parasite and one of the pigmented filamentous fungi, which rarely causes human infection. The authors report the first case of fungal keratitis caused by chromomycetes in korea. METHODS: A 65-year-old woman developed pain, redness, and an yellowish-brown infiltrate in her right eye. She had a history of corneal scratch by a pumpkin stalk and transferred by a local clinic after management for about 1 months. The clinical features suggested fungal keratitis, and the patient was undertaken surgical debridement with amniotic membrane graft and treated with oral terbinafine with natamycin and amphotericin B eyedrops. Surgically taken biopsy specimen was cultured. Amniotic membrane was removed after 1 week. After slight improvement of symptom, necrotizing ulceration was enlarged in spite of continuous antifungal therapy. Lamellar keratoplasty with amniotic membrane graft was done with antifungal therapy. Systemic agent was changed to fluconazole. Clinical improvement was achieved after about 2 months. The fungus was identified as Fonsecaea pedrosoi. RESULTS: Fungal keratitis was successfully treated with antifungal medication combined with amniotic membrane graft. CONCLUSIONS: This is a rare case of infectious keratitis caused by chromomycetes. But its clinical course was severe, so exact culture and identification following aggressive surgical and medical treatment was needed.

Chromoblastomycosis Treated with Occlusive Dressing of Amphotericin B Cream / 대한의진균학회지

We report a case of chromoblastomycosis in a 65 year-old woman. She had a 3x4 cm sized, annular, erythematous, plaque with crusts and ulcers on the right lower arm. The lesion had grown slowly for 2 years. In fungal and histopathologic examinations, several muriform cells were found in dermis as well as in scales and crusts on the lesional skin surface. Isolated fungus was identified as Fonsecaea pedrosoi. We treated the patient occlusive dressing of amphotericin B (3%) ointment for 8 weeks and achieved a good response without any evidence of recurrence. We propose that the occlusive dressing therapy of amphotericin B cream is a good modality among the various treatments of small localized chromoblastomycosis.

Cromoblastomicose no Rio Grande do Sul: relato de 12 casos / Chromoblastomycosis in Rio Grande do Sul: a report of 12 cases

São relatados 12 casos de cromoblastomicose diagnosticados no interior do Rio Grande do Sul, no período 1988-1995. Os aspectos clínicos e evolutivos são analisados e comparados com a literatura. O único agente isolado foi Fonsecaea pedrosoi.

Twelve cases of chromoblastomycosis diagnosed in Rio Grande do sul during 1988-1995 are reported. The clinical aspects are analyzed and compared with the literature. Fonsecaea pedrosoi was the only microorganism isolated.

A Case of Chromoblastomycosis Caused by Fonsecaea pedrosoi / 대한피부과학회지

We report a case of chromoblastomycosis caused by Fonsecaea(F.) pedrosoi in a 58-year-old female, who showed a 2 x1.5cm sized, scply erythematous plaque on the left wrist for 7 months. Histopathologically, chronic granulomatous inflammation and sclerotic cells were observed. Fungal culture grew out th typical black colonies of F. pedrosoi. The patient had been treated with weekly intralesional injections of amphotericin B for 3 months. We observed a good response without evidence of recurrence.