Retinoid combined with photodynamic therapy against hyperkeratotic chromoblastomycosis: A case report and literature review.

Chromoblastomycosis (CBM) is a chronic granulomatous fungal infection caused by melanised or brown-pigmented fungi. It can lead to chronic persistent infections and may cause incapacity for labour in some severe clinical forms. The optimal therapy for CBM is still uncertain. Here, we reported the case of a 66-year-old male who has had red plaque and recurrent keratinised protrusions on his right forearm for 20 years. He was treated orally with terbinafine, itraconazole and isotretinoin. He also received carbon dioxide(CO2 ) laser to eradicate the keratinised protrusions and promote the penetration of photosensitiser. After the CO2 laser, 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) was adopted immediately to inhibiting the growth of fungi in subcutaneous tissue. The patient received an important improvement with a plaque and crust reduction after 4 months. For such recalcitrant case of chromoblastomycosis, the use of retinoid, CO2 laser combined with ALA-PDT may be a new adjuvant therapy. We further reviewed the cases of chromoblastomycosis treated with laser, photodynamic therapy or retinoic acid.

Photodynamic therapy combined with antifungal drugs against chromoblastomycosis and the effect of ALA-PDT on Fonsecaea in vitro.

BACKGROUND: Chromoblastomycosis is a chronic skin and subcutaneous fungal infection caused by dematiaceous fungi and is associated with low cure and high relapse rates. In southern China, Fonsecaea monophora and Fonsecaea pedrosoi are the main causative agents. PRINCIPAL FINDINGS: We treated 5 refractory and complex cases of chromoblastomycosis with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with oral antifungal drugs. The lesions improved after 4 to 9 sessions of ALA-PDT treatment at an interval of one or two weeks, and in some cases, mycological testing results became negative. The isolates were assayed for susceptibility to antifungal drugs and ALA-PDT in vitro, revealing sensitivity to terbinafine, itraconazole and voriconazole, with ALA-PDT altering the cell wall and increasing reactive oxygen species production. CONCLUSIONS: These results provide the basis for the development of a new therapeutic approach, and ALA-PDT combined with oral antifungal drugs constitutes a promising alternative method for the treatment of refractory and complex cases of chromoblastomycosis.

Successful treatment of chromoblastomycosis of 10-year duration due to Fonsecaea nubica.

We report a case of chromoblastomycosis due to the presence of large plaque and verrucous hyperplasia lesions on the left upper limb, with elbow abnormal activities, in a 56-year-old male. The diagnosis of chromoblastomycosis was based on gross and microscopic morphologies, histopathological examination and clinical manifestation. Molecular tools were applied to identifying the causative agent Fonsecaea nubica, which is rarely reported to be associated with chromoblastomycosis. The patient was initially treated orally with terbinafine (250 mg/day) and itraconazole (200 mg/day), subsequently patient received thermotherapy (45-50°C, 3 h/day) for 1 month. The patient was successfully cured. A literature review was performed to assess general features, treatment and outcome of chromoblastomycosis due to F.  nubica. All the 5 reviewed patients were male, over 30 years old and their lesions occurred after traumatic inoculation.

Non-healing verrucous plaque over upper limb for 1 year in a tea garden worker.

A 55-year-old tea garden worker presented with a slowly growing verrucous plaque on the right arm. The diagnosis of chromomycosis was confirmed by the identification of brown sclerotic bodies in a skin biopsy.

A refractory case of chromoblastomycosis due to Fonsecaea monophora with improvement by photodynamic therapy.

Chromoblastomycosis is one of the most frequently encountered mycoses in tropical and temperate regions caused by the implantation of the infectious structures and one which is associated with low cure and high relapse rates. The etiologic agents play a critical role affecting clinical outcome and in southern China, Fonsecaea pedrosoi and F. monophora are the main causative agents of chromoblastomycosis. We treated, for two years, a 55-year-old male patient with chromoblastomycosis caused by F. monophora with itraconazole and terbinafine, two antifungals recommend in earlier papers in the literature but without any positive response. As a result we introduced the photodynamic therapy (PDT) employing 5-aminolevulinic acid (ALA) irradiation. The lesions were improved after two periods of ALA-PDT treatment, each consisting of exposures at weekly intervals for 5 weeks but new lesions developed with the cessation of ALA-PDT treatment. Thereafter, positive clinical improvement was obtained when voriconazole at 200 mg was combined with terbinafine at 250 mg in treating the patient. The in vitro susceptibility of the F. monophora isolate to terbinafine, itraconazole, and voriconazole was assessed and the fungus was found to be sensitive to all three, with the minimal inhibitory concentrations of 0.125, 1, 0.0625 µg/ml, respectively. However, the determination of in vitro susceptibility profiles may not predict clinical response.

[Chromoblastomycosis caused by Fonsecaea monophora].

Fonsecaea species are major etiologic agents of Chromoblastomycosis (CBM). By genetic analysis, the genus Fonsecaea has recently been revised and classified into F. pedorosoi, F. monophora and F. nubica. Here we report a severe chronic case of CBM caused by F. monophora. A 55-year-old Filipino male developed progressive skin lesions on the left lateral ankle in 1973, when he worked at a coconut plantation in the Philippines. In 1999, he received medical treatments for enlarged, multiple lesions on the left lower limb. When he moved to Japan in 2005, the lesions were remarkably improved and he discontinued taking the medicine. On our first examination in October 2008, a large, reddish, cicatricial plaque was observed on the left lower aspect of his leg. Several tumorous lesions surrounded the plaque, indicating that the therapies performed before had been insufficient. In addition, there were many patchy scars scattered on the thigh and the upper part of the lower leg. The diagnosis of CBM was made by the presence of muriform cells. Black, pulverulent colonies were yielded in culture of skin scrapings and tissues. Although the fungus could not be identified by microscopic morphology, r-RNA ITS sequence analysis enabled identification of Fonsecaea monophora. The patient responded well to oral voriconazole combined with local thermotherapy using pocket warmers. The tumoral masses subsided in 6 months, leaving pink scars with negative fungal culture. Voriconazole treatment was continued for 18 months. It seems that drugs are insufficiently delivered in the cicatricial lesions because of the paucity of blood flow, suggesting that a long-term follow-up is necessary for such a case.

[A case of chromomycosis caused by Fonsecaea pedrosoi presenting as a small plaque on the left upper arm: a review of reported cases of dematiaceous fungal infection in Japan].

We report a case of a 67-year-old woman with chromomycosis on the left upper arm. The plaque was a very small, erythematous and scaly lesion with a diameter of 1.5 cm. Fonsecaea pedrosoi was isolated as the causal fungus, and a number of Phialophora type conidia, the formation of which is considered rare, were observed. Treatment involved surgical excision of the lesion with a 5 mm margin. Follow up three years later revealed no recurrence. In Japan, 536 patients with chromomycosis were reported from 1955 to 2004. This consisted of 296 cases from 1955 to 1981 as reported by Fukushiro, and 240 cases from 1982 to 2004 as reviewed by us. Our examination of data showed that the most common causal fungi was F. pedrosoi with 137 cases (57.15%), followed by Exophiala jeanselmei with a total of 41 cases (17.15%), other fungal species comprised of 16 cases (6.7%), Phialophora verrucosa in 9 cases ( 3.8%) and E. dermatitidis in 4 cases (1.7%). Compared to the previous report by Fukushiro, the incidence of infection with E. jeanselmei had increased. Of the 235 cases we reported, the site of infection involved: upper extremities in 91 (38.7%), face and neck in 42 (17.9%), buttocks in 41 (17.4%), lower extremities in 33 (14%) and body in 23 (9.8%). Compared to Fukushiro's report, cases affecting the lower extremities had decreased, whilst cases involving the buttocks had increased. Overall, the treatment for chromomycosis was either oral administration of antifungal agents, excision, thermotherapy, or a combination of these methods.

Successful treatment of chromomycosis using carbon dioxide laser associated with topical heat applications.

A 59-year-old Japanese man presented with a slightly elevated, pruritic, erythematous plaque on his left buttock measuring 5 x 5 cm in diameter. The man had a history of chromomycosis, dating 6 years prior to the current consultation, for which he had been treated with oral terbinafine. Diagnosis of a recurrence of chromomycosis of the skin due to infection by Foncecaea pedrosoi was made after careful analysis of the clinical features, skin biopsy, KOH mounts, and fungal culture results. We administered topical heat therapy followed by treatment with CO2 laser to eradicate the unresponsive remnants of the lesion. The operative site re-epithelized within 10 weeks, and 1 year after the treatment there was no evidence of recurrence. For a recalcitrant case of chromomycosis, as in this case, the use of CO2 laser combined with topical heat therapy may be a new therapeutic modality.

Auricular chromoblastomycosis caused by Rhinocladiella aquaspersa.

An unusual case of chromoblastomycosis localized in the ear and caused by R. aquaspersa is presented. The patient was a 60-year-old male urban resident, who had had the disease for 5 years. The lesion was darkly pigmented, infiltrative and crusty. Sclerotic cells were seen on direct examinations and the fungus was recovered in culture and identified on the basis of the characteristic sporulation. Itraconazole therapy at a dose of 200 mg day-1 for 7 months produced complete healing.

A case of chromomycosis with tumor-like growth.

A 66-year-old woman who lived on Tokunoshima Island, a small and remote southern island of the Japanese archipelago, had suffered from chromomycosis for more than 30 years and presented with a tumor-like growth on the posterior crural region of his right leg. Fonsecaea pedrosoi was identified as the pathogen from its growth pattern and micromorphological characteristics. The patient was successfully treated with 5-fluorocytosine, itoraconazole, and topical thermotherapy.

Concurrent chromoblastomycosis caused by Fonsecaea pedrosoi and actinomycetoma caused by Nocardia brasiliensis.

Chromoblastomycosis and mycetoma are chronic infections caused by the repeated traumatic inoculation of organisms into the skin and subcutaneous tissue. Chromoblastomycosis is caused by several dematiaceous (pigmented) fungi, occurs in tropical regions, and usually affects the lower extremities. The lesions may be nodules, plaques, or tumorous masses. Mycetomas are caused by either true fungi (eumycetes) or filamentous bacteria (actinomycetes); they also occur predominantly in tropical areas and most frequently affect the foot or leg. Typically there is a firm swelling with multiple sinus tracts that drain small granules. The treatment of these infections is difficult. Surgery, cryotherapy, heat therapy, and antimicrobial agents are used to treat chromoblastomycosis. Surgery and antimicrobial agents are used for treatment of mycetomas. This is the first report of concurrent infections caused by these agents.

Hyperthermic treatment of chromomycosis with disposable chemical pocket warmers. Report of a successfully treated case, with a review of the literature.

A case of chromomycosis in which hyperthermia proved effective is reported. The patient was a 56-year-old male bean curd maker who, without any previous history of minor trauma, developed on the extensor side of the left upper arm an eczematous lesion that underwent gradual radial expansion. The lesion showed a well-defined, 7 x 10 cm infiltrated erythematous plaque with the central area healed and, at the upper and lower borders, adherent scales and crusts on the surface. Histological examination revealed granulomatous changes in the dermis, as well as sclerotic cells within giant cells and microabscesses. On culturing, Fonsecaea pedrosoi was isolated. The patient was treated with disposable chemical pocket warmers, which were secured over the lesion with a rather tight elastic bandage, so that they kept the affected area warm for 24 hours a day. After a month of such hyperthermic treatment, the erythema and infiltration had decreased considerably, and microscopic examination and culture of the crusts both yielded negative results. Examination of biopsy specimens of the lesion after the third month showed that it had cicatrized. The treatment was stopped after 4 months, and no relapse occurred. We also summarize the published results of local hyperthermic treatment of chromomycosis in Japan.

Topical heat therapy for cutaneous chromomycosis.

An aged man with a large scaly plaque over the left buttock was successfully treated by local heat therapy using an electric bed-warmer with a surface temperature of 46 degrees C. Clinically, the lesion involuted completely after two months of treatment. This was concomitantly confirmed by histopathological and mycological studies of biopsy specimens obtained from the lesion at an interval of several weeks. The isolated fungus strain of Fonsecaea pedrosol could grow at 37 degrees C on Sabouraud's dextrose agar, but was totally eradicated 24 hours after the culture was incubated at 46 degrees C. We consider that local heat therapy carried out under strict supervision is a quite effective treatment for chromomycosis. Moreover, it can be performed safely and without much discomfort to patients, and can yield satisfactory results in a relatively short time.

In vitro sensitivity to 5-fluorocytosine of strains isolated from patients under treatment for chromomycosis.

In vitro 5-fluorocytosine sensitivity tests of strains were isolated from chromomycosis patients undergoing therapy. Tests were rountinely performed for 0.1, 1.0, 5.0 and 10.0 mug/ml 5-fluorocytosine concentrations. In two cases resistance could be demonstrated up to 60.0 and 100.0 mug/ml. Fungistatic activity of 5-fluorocytosine against the agents of chromomycosis was confirmed. Sensitivity tests are useful to detect resistance which may occur during treatment. They are also helpful for guiding the clinician in the establishment of new therapeutic schedules.