Recalcitrant cutaneous phaeohyphomycosis caused by Medicopsis romeroi successfully treated by oral terbinafine: A case report

Dear Editor, Phaeohyphomycosis is a group of dematiaceous fungal infections mainly caused by Exophiala, Phialophora, and Cladophialophora species.[1]Medicopsis romeroi, formerly known as Pyrenochaeta romeroi, is present in soil and plants of subtropical and tropical regions.[2] Phaeohyphomycosis caused by M. romeroi is rare, up to 32 cases involving the skin [Supplementary Table 1 of M. romeroi infection] have been reported to date,[1] with 21 cases being immunocompromised due to solid organ transplants, rheumatoid arthritis (RA) or asthma on long-term corticosteroids,[1] diabetes mellitus, leukemia, and patients with local trauma.[3] Herein, we describe a new case of cutaneous Medicopsis that was itraconazole resistant but successfully treated by oral terbinafine.Supplementary Table 1: Summary of reported cases of Medicopsis romeroi infection involving the skinA man in his late 60s presented in January 2021, with an 11-month history of a progressively worsening, slightly pruritic papulonodular rash on his left forearm. The patient had hypertension and gout for several years and had been treated with colchicine and feburic at another hospital. However, he took the drugs irregularly, resulting in multiple acute gouty attacks each year, and requiring frequent intermittent prednisolone treatment. Moreover, sulfasalazine was prescribed due to suspected RA couple months earlier. He denied gardening or local trauma before the rash onset. A skin biopsy with fungal culture was performed at the same hospital and revealed phaeohyphomycosis caused by M. romeroi. Despite 9 months of itraconazole 200 mg daily, new lesions continued to appear on his left forearm. Meanwhile, he had intermittent painful swelling of multiple joints in the past 2 months. Examination in our clinics revealed many papules and nodules forming annular plaques with some black dots and scattered pustules on the left forearm [Figure 1a]. No lymphadenopathy was noted. There was marked erythematous swelling of the right wrist, metacarpophalangeal and proximal interphalangeal joints, bilateral knee, and the right tarsal joints. A biopsy specimen from a papule revealed a suppurative granulomatous infiltrate in the dermis with scattered fungal structures, highlighted by periodic acid–Schiff stain [Figure 2]. Fungal culture yielded M. romeroi. As the infection was resistant after 9 months of itraconazole therapy, we asked one of the coauthors (Wu CJ) to perform a minimal inhibitory concentration (MIC) test. Using internal transcribed spacer region (ITS) sequencing with polymerase chain reaction primers (ITS1 and ITS4), the isolate was identified as M. romeroi. The MIC (μg/mL) to achieve 100% inhibition was as follows: amphotericin B (0.5), itraconazole (16), voriconazole (2), posaconazole (1), isavuconazole (0.12), anidulafungin (>8), flucytosine (8), and terbinafine (0.25).Figure 1: Cutaneous Medicopsis romeroi infection in an elderly man presenting with progressively worsening of skin lesions on the left forearm despite 9 months of itraconazole therapy. Sequential photos of the skin lesions from left to right. (a) Many erythematous papulonodular and pustular lesions present on the extensor left forearm at the first visit, (b) at the time of initiation of terbinafine therapy, (c) marked clinical improvement 4 months later, (d) residual pigmentary change after 6 months of terbinafine therapy.Figure 2: Histopathology of a papule obtained from the left forearm at presentation reveals (a) a suppurative granulomatous infiltrate in the dermis (H and E, ×100), (b) scattered fungal spores and short hyphae (Black arrow) in the suppurative infiltrate, highlighted by periodic acid–Schiff stain, ×200.Other significant laboratory data included leukocytosis 13,700/mL with 79.4% neutrophils, creatinine (1.56 mg/dL), C-reactive protein (CRP) (67.1 mg/L), and uric acid (10.2 mg/dL). Rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) Ab levels were within normal limits. X-ray of joints showed no obvious erosion. A rheumatology consultation was obtained, and the diagnoses of RA and gouty arthritis were made based on the American College of Rheumatology/European League Against Rheumatism 2010 RA classification and 2015 gout classification criteria (with a total score of 7 and 8, respectively). Celebrex, Ultracet, methotrexate (7.5 mg/week), folic acid 5 mg qw, sulfasalazine (500 mg twice daily), and prednisolone (5 mg daily) were prescribed. The arthritis symptoms improved in 1 month with CRP levels (mg/L) decreased gradually from 67.1 (1/19, initiation of terbinafine) to 23.9 (1/23), 34.2 (2/2, due to a gouty attack), and 3.6 (2/22). Based on the MIC results, terbinafine 250 mg/day was initiated on February 9 [Figure 1b] with significant clinical improvement noted in 2 months. A follow-up skin biopsy on April 6 still showed fungus in the tissue with positive fungal isolation. A second follow-up biopsy on June 8 [Figure 1c] showed negative for fungus in the tissue and fungal culture, indicating pathologic and mycological cure. Because of the immunosuppressive therapy for RA and the patient's concern about focal new erythema and pruritic papules, terbinafine was continued. After further clinical improvement, another biopsy was undertaken on July 27 to ensure that the infection was cured. With negative finding in the tissue and fungal culture, the infection was considered cured after 6 months of terbinafine therapy [Figure 1d]. Mycological identification of Medicopsis is usually arduous due to the difficulty in growing the fungus in culture, so other techniques, such as nucleic acid sequencing, are often required.[4] Antifungal susceptibility testing is not routinely performed, and this is particularly true for Medicopsis because of its poor spore production. Therefore, the MIC data for Medicopsis remain scarce.[1,4] The treatment in the previous cases included itraconazole, amphotericin B, topical terbinafine, and voriconazole for 4 weeks to 3 years or by surgical excision[3,5,6] [Supplementary Table 1]. Treatment outcomes were documented in 23 of the 32 previously reported cases of M. romeroi infection involving the skin, including 12 cured by antifungal agents with or without excision or drainage and 4 cured by only surgical excision. In the present case, the M. romeroi infection was refractory to itraconazole, probably mainly due to the high MIC against itraconazole. In sum, we report a case of itraconazole-resistant cutaneous M. romeori infection occurring in a patient with RA and gouty arthritis. Our patient would represent the 33rd reported case of M. romeori infection of the skin, and the first case successfully treated by oral terbinafine. Our case highlights the importance of MIC testing in treating recalcitrant M. romeroi infection and illustrates terbinafine as a potentially effective therapy for M. romeroi infections. 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 his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Data availability statement Data sharing is 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. Julia Yu-Yun Lee, an editorial board member at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.