A Difficult Treatment Case of Chromoblastomycosis Responding to Combination Therapy

Background: Chromoblastomycosis is a chronic fungal infection that affects the skin and subcutaneous tissue, primarily characterized by verrucous or nodular lesions. It often arises particularly in tropical and subtropical regions, where agricultural workers are most commonly affected. The most commonly isolated species are Fonsecaea pedrosoi and Cladophialophora carrionii. The disease progresses slowly, can be poorly responsive to antifungal therapy, and carries a high risk of recurrence. This report describes a challenging case of chromoblastomycosis of the right knee that proved unresponsive to several single-agent therapies but demonstrated improvement with combination antifungal treatment. Case Description: A 53-year-old male mushroom farmer presented in 2020 with nodular and plaque-like lesions on his right knee. A skin biopsy pathology confirmed chromoblastomycosis (with round, pigmented, thick-walled copper penny spores in the microscopic description). Despite undergoing first-line antifungal treatments, including itraconazole, terbinafine, and fluconazole, the patient saw limited improvement. He subsequently underwent two debridement surgeries in 2022 and 2023, with both histopathology confirming the presence of chromoblastomycosis. A fungal culture obtained during surgery in 2023 yielded Fonsecaea species. Following the surgeries, the patient received combination therapy of itraconazole 400 mg per day and terbinafine 250 mg per day, resulting in clinical improvement and a reduction in pigmentation and lesions. A follow-up skin biopsy in September 2023 showed hyperkeratosis and spindle cell proliferation without fungal elements, and no fungal growth on culture for 4 weeks. Discussion: Chromoblastomycosis is difficult to treat, with treatment options including pharmaceutical, surgical, and chemotherapeutic approaches. Systemic antifungal therapy with itraconazole (200–400 mg daily) or terbinafine (500–1000 mg daily) for 6–12 months is often the first-line treatment choice. This case underscores the challenges of treating chromoblastomycosis that is poorly responsive to single-agent antifungal therapy. The combination therapy of itraconazole and terbinafine offered significant improvement, suggesting it could be an effective option for refractory cases. New-generation triazoles such as voriconazole, posaconazole, and isavuconazole have shown in vitro antifungal activity against chromoblastomycosis. However, there is currently a lack of clinical experience with these drugs, and for many countries, the cost of treatment remains too high. Conclusion: The successful response to combination therapy of itraconazole and terbinafine indicates its potential as an effective treatment strategy for chromoblastomycosis.