Use of local thermal therapy as an adjunct to topical ketoconazole therapy for cutaneous protothecosis
Year: 2024
Type: article
Abstract: Dear Editor, Protothecosis is a rare infection caused by achlorophyllic algae of the genus Prototheca, belonging to the family Chlorellaceae.[1] Despite its rarity, there is a growing global incidence of protothecosis.[1]Prototheca infection manifests in three clinical forms: cutaneous, articular, and systemic, with Prototheca wickerhamii identified as the primary causative agent, followed by Prototheca zopfii.[1,2] The common treatments include systemic antifungals such as amphotericin B, fluconazole, voriconazole, and itraconazole.[2] Despite the reports of Prototheca growth inhibition at 40°C in vitro, the utilization of local thermal therapy has been limited. To date, only two documented cases used this therapy in conjunction with systemic antifungal medications.[3,4] In this report, we present a case of cutaneous protothecosis managed with topical thermal therapy as an adjunct to topical ketoconazole, aiming to avoid the potential toxicity associated with systemic antifungal drugs. A 71-year-old woman presented with an enlarging erythematous plaque on her right forearm for 2 years following an injury. She had a medical history of hypertension, heart failure, type 2 diabetes mellitus, asthma, and hypercholesterolemia. Cutaneous examination revealed a well-defined erythematous papuloplaque studded with yellowish pustules on the right forearm, measuring 6 cm × 8 cm [Figure 1a]. Histopathological examination obtained from the lesional skin demonstrated suppurative granulomatous inflammation with multinucleated giant cells, lymphocytes, plasma cells, neutrophils, and multiple thick-walled spherical structures containing internal septation and tightly packed endospores [Figure 2a]. Periodic acid–Schiff (PAS) staining highlighted PAS-positive endospores forming morula-like bodies in the dermis and granulomatous areas [Figure 2b]. The morphology of these endospores is the characteristic of Prototheca genus. The culture of skin biopsy tissue grew white mucoid colonies. Sporangia with internal sporangiospores was seen by microscopy which was identified as Prototheca species [Figure 2c]. The isolate was further identified as Prototheca wickerhamii by the sequence of its cytochrome b gene;[5] the sequence of the isolate was deposited in GenBank under the accession number PP780440. Systemic evaluation revealed signs of neither systemic involvement nor immunodeficiency, apart from long-term prednisolone 10 mg daily for asthma. The dosage could not be tapered due to her relatively unstable comorbidity. While common treatments for protothecosis include systemic antifungal agents such as amphotericin B, fluconazole, voriconazole, and itraconazole, these options pose significant drug–drug interactions with the multiple medications prescribed for her underlying diseases. Consequently, treatment was initiated with topical 2% ketoconazole cream twice daily. Although the lesion exhibited reduced erythema during the 1-month follow-up period, the continued growth of papules and pustules was still noted [Figure 1b]. This is likely attributed to the limited ability of drug penetration, resulting from the deep involvement of organisms in the subcutaneous layer. Local thermal therapy with a disposable hot pack was suggested as an additional therapy. However, the patient decided to use a hair dryer instead of local thermal therapy due to its accessibility and ease of use. Subsequently, a hairdryer was used for 10 minutes twice daily, resulting in a significant improvement. Complete resolution of the lesions was observed at the 6-month follow-up [Figure 1c], and no signs of recurrence were noted at the 10-month follow-up.Figure 1: Clinical findings of cutaneous protothecosis before and after topical thermal therapy in combination with topical ketoconazole. (a) A well-defined erythematous papuloplaque studded with yellowish pustules on the right forearm measuring 6 cm × 8 cm; (b) Partial regression of the lesion on the right forearm 1 month after topical ketoconazole therapy; (c) Resolution of the lesion on the right forearm 6 months after topical thermal therapy in combination with topical ketoconazole.Figure 2: Histopathological and laboratory findings of cutaneous protothecosis. (a) Granulomatous dermal infiltrate consisting of lymphocytes, multinucleated giant cells, plasma cells, and neutrophils. Multiple thick-walled spherical microorganisms are depicted, exhibiting septations in their cytoplasm (arrow) (H and E, ×20); (b) Periodic acid–Schiff (PAS)-positive endospores form morula-like bodies with cartwheel-like appearance scattered in the dermis and granulomatous areas (arrow) (PAS, ×40); (c) Light microscopy examination of lactophenol cotton blue slide preparations, derived from culture colonies of the patient, revealed round sporangia with internal sporangiospores, exhibiting a mulberry-like appearance of Prototheca wickerhamii (scale bar = 20 μm).Treatment for protothecosis is challenging due to the organism’s general low susceptibility to antimicrobials and inconsistent clinical responses.[6] Most reported cases are initially treated with oral antifungals, typically starting with itraconazole or fluconazole. In cases of severe infections or those unresponsive to azole treatments, intravenous amphotericin B is administered.[1] Surgical debridement and topical or local injection of antifungals are the other reported treatments for superficial cutaneous infections.[3] The application of thermal therapy was based on the temperature effects on organism growth. Culturing at 30°C for 72 hours is suitable for most Prototheca species, with poor growth typically observed at temperatures exceeding 38°C.[1,7] Furthermore, the growth of P. wickerhamii is inhibited in vitro at 46°C. This inhibition was evidenced by the degeneration of Prototheca cells observed following exposure to 46°C for 12 hours, as detailed in transmission electron microscopy studies conducted by Yamada et al.[4] Although thermal therapy has been previously explored, its utilization was limited to conjunction with systemic antifungal therapy. Given the biological plausibility, we present this case to emphasize the potential of thermal therapy as a viable treatment for protothecosis. Although the application of thermotherapy is operator-dependent and may pose challenges in standardizing a protocol due to variations in thermal devices and pathogen types, this approach remains particularly beneficial for cutaneous infections that have proven refractory to conventional treatments, as well as for patients burdened with multiple comorbidities necessitating the avoidance of potential toxicity associated with systemic fungal treatments. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent form. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Data availability statement Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. Financial support and sponsorship Nil. Conflicts of interest Prof. Ching-Chi Chi (the Editor-in-Chief of Dermatologica Sinica) and Dr. Pei-Lun Sun (an editorial board member of Dermatologica Sinica) had no roles in the peer review process or decision to publish this article. Dr. Shih declared none.
Source: Dermatologica Sinica
Authors: Hsin-Yu Shih, Ching-Chi Chi, Pei-Lun Sun
Language: English
Subfield: Small Animals
Field: Veterinary
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $70
OpenAlex ID: W4402491062