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.

The present paper describes 22 cases of chromoblastomycosis (CBM) caused by Cladophialophora carrionii in children and adolescents (2-19 years old). The patients were seen between 1992 and 2004 and all resided in a CBM endemic area in the semi-arid zone of the Falcón state, Venezuela. Twelve of the 22 patients (54.55%) had close relatives who also had CBM and 19 (86.36%) were male. Lesions consisted of erythematous papules with desquamation or squamous plaques (0.12-14.19 cm in diameter), located primarily on the upper limbs (77.27% of patients). Thirteen of the patients were treated with topical 5-fluorouracil (5-FU; 1% cream), seven with topical ajoene (0.5% gel) and two had electrodesiccation and/or fulguration. Two patients who did not respond to 5-FU were treated with oral itraconazole (100 mg/day for 1 month). Complete clinical and mycological remission was achieved in 17/20 (85%) of the patients treated with 5-FC, ajoene and electrodesiccation and/or fulguration. In addition, similar results were obtained with the two patients who received itraconazole therapy. These cases emphasize the importance of early diagnosis in difficult-to-treat mycotic diseases such as CBM. By early intervention we were able to employ topical treatment with a minimum of adverse effects to achieve a high percentage of favorable therapeutic responses. The patients were thus able to avoid the evolution of the chronic, deforming and incapacitation clinical manifestations associated with CBM.

The antifungal activity of six drugs was evaluated against 41 clinical and environmental isolates of Cladophialophora carrionii and its sister species C. yegresii. Drugs tested, including their ranges, were: 16-0.016 microg/ml for amphotericin B (AMB), itraconazole (ITZ) and voriconazole (VCZ), 8-0.008 microg/ml for terbinafine (TBF), and 64-0.063 microg/ml for flucytosin (5-FC) and fluconazole (FCZ). Strains were tested according to the CLSI guidelines (M38A). The MIC Gmeans for clinical strains in microg/ml were; 0.02 for TBF and ITZ, 0.07 microg/ml for VCZ, 0.49 for 5FC, 6.14 for FCZ and 9.42 for AMB. The MFC Gmeans in microg/ml were; 0.04 for TBF, 0.13 for ITZ, 0.72 for VCZ, 18.83 for 5FC, 36.16 for FCZ and 31.35 for AMB. The most active drugs against the fungi were TBF, ITZ, VCZ and 5FC. However, for all drugs more than two dilution steps were noted between the MIC and the MFC, indicating fungistatic activity. Despite in vitro susceptibility of C. carrionii to antifungal agents, the efficacy of therapy was shown to be not optimal.

Ajoene and 5-fluorouracil (5-FU) are compounds that have shown in-vitro activity against Cladophialophora carrionii, an important etiologic agent of chromoblastomycosis. An open comparative trial was conducted to assess safety and effectiveness of topical ajoene and 5-FU in the treatment of localized chromoblastomycosis. Thirty-seven patients with a clinically and mycologically confirmed diagnosis were randomly distributed into two groups allocated to ajoene (0.5% gel; n = 19) or 5-FU (1% cream; n = 18). Topical treatment was applied to localized lesions (< or = 2.5-cm diameter) once a day, with occlusion, for 12-16 weeks. Complete clinical and mycological remission was achieved in 14/19 patients (74%) treated with ajoene and 14/18 patients (78%) treated with 5-FU. All 5-FU-treated patients developed a post-treatment scar at the site of the lesion, while ajoene-treated patients showed only a slight depigmentation of the skin. The differences observed in cure rate between ajoene and 5-FU are not statistically significant. Follow-up of all patients for 4 years revealed no relapses in the ajoene-treated group, while one patient in the 5-FU-treated group had a relapse 6 months after the end of therapy. This trial represents the first clinical use of ajoene in the control of a deep mycosis.

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