Treatment of chromoblastomycosis with a combination of debulking surgery, intralesional amphotericin B, and oral terbinafine

Abstract

Treatment of chromoblastomycosis with a combination of debulking surgery, intralesional amphotericin B, and oral terbinafine Dear Editor, Chromoblastomycosis is a chronic occupational disease caused by dematiaceous fungi from Fonsecaea and Cladophialophora species. Its recalcitrant and polymorphic nature makes its diagnosis and management difficult. Studies about its treatment are limited. This is a case of severe chromoblastomycosis in an elderly farmer treated with excision followed by weekly intralesional amphotericin B (AMB) and 500 mg of terbinafine daily. The initial management included surgical debulking of the lesion. Intralesional AMB was administered the following day and was given weekly for 19 weeks. Intralesional AMB was prepared by dissolving 25 mg of AMB in 20 ml of sterilized water. Five milliliters of 2% lidocaine solution was added, making 1 mg/ml of AMB. Since the lesion was large, intralesional AMB was injected at the edge of the wound using 0.25–0.5 ml of AMB solution per cm of the lesion. Simultaneous treatment with 500 mg oral terbinafine was given daily. Terbinafine was extended for 2 weeks more until the raised active edges subsided. There were no reported adverse drug events during the course of treatment and no recurrence after 6 months. Shorter treatment duration may have been warranted with early initiation. This is a case of a 75-year-old farmer with a 12-year history of a verrucous and hyperkeratotic plaque on the right foot with foul-smelling discharge and associated lymphedema of the leg. Biopsy showed muriform cells or Medlar bodies which are characteristic of chromoblastomycosis. Tissue culture showed Fonsecaea pedrosoi. He had initially been treated with cryotherapy, itraconazole 200 mg per day for more than 8 months, and even complete surgical excision, but recurrence of the lesions prompted consult at our institution. Upon consult, he had a large foul-smelling warty plaque and lymphedema of the right leg which he insisted on amputating (Fig. 1). The initial management included surgical debulking of the lesion. Intralesional amphotericin B (AMB, Gufic Stridden Biopharma Pvt Ltd, India) was administered the following day and was given weekly for 19 weeks. Intralesional AMB solution was prepared by dissolving 25 mg of AMB in 20 ml of sterilized water. Five milliliters of 2% lidocaine solution was added making 1 mg/ml of AMB. Since the lesion was large, intralesional AMB was injected at the edge of the wound using 0.25–0.5 ml of AMB solution per cm2 of the lesion. Simultaneous treatment with 500 mg oral terbinafine was given daily. After 19 weeks, treatment with AMB and terbinafine was discontinued, and wounds were treated conservatively (Fig. 2). Persistence of the raised wound edges prompted an extended duration of terbinafine monotherapy for 2 weeks until the active wound edges subsided. There were no reported adverse drug events during the course of treatment. On follow-up after 6 months, there was still no recurrence of chromoblastomycosis lesions observed. However, lymphedema, hypopigmentation, and atrophic scarring were already irreversible. Chromoblastomycosis is a chronic fungal infection involving the skin and subcutaneous tissues with associated granulomatous, purulent, and fibrotic tissue formation. It is caused by dematiaceous fungi from the Fonsecaea and Cladophialophora species, with Fonsecaea pedrosoi being one of the most common. It is an occupational disease, frequently found among farmers and manual laborers in tropics such as India, Sri Lanka, Central and South America, Cuba, and Jamaica. Lack of protective garments and poor nutrition and hygiene are the main risk factors. The recalcitrant and polymorphic nature of the disease coupled with low cure rate and high relapse rates make its diagnosis and management difficult. Existing clinical trials about its treatment are limited. Oral antifungal agents, such as itraconazole and terbinafine, are the primary therapeutic options with varying treatment response. Physical interventions like surgical excision and cryotherapy are used as adjuncts to reduce the duration of systemic therapy and to improve treatment