Chromoblastomycosis Caused by <i>Fonsecaea monophora</i> : Using <scp>SEM</scp> and <scp>TEM</scp> to Decipher the “Blackish‐Red Dot Sign” Observed in Dermoscopy

Fonsecaea monophora, a melanized fungus, causes chromoblastomycosis (CBM) with subcutaneous infections. Timely diagnosis and effective treatment are critical. The “blackish-red dot sign” is a characteristic dermoscopic finding in chronic subcutaneous fungal infections [1-5]. We report a CBM case presenting this sign, observed via scanning and transmission electron microscopes (SEM/TEM) to evaluate its diagnostic and therapeutic monitoring potential as a dermoscopic marker. A 60-year-old woman developed erythematous plaques on her right hand for 3 years, following post-traumatic soil exposure. Previous itraconazole 200 mg/day for 2 years failed, and subsequent terbinafine 250 mg/day achieved only modest improvement. Physical examination revealed two well-defined erythematous plaques with hyperkeratotic crusts (1.5 × 3 cm and 4 × 2 cm), on the dorsum and wrist of her right hand, respectively, with “black dots” under the crusts (Figure 1a). Dermoscopy revealed yellow adherent scales and scattered blackish-red dots on a white-pink background (Figure 1b). CFW staining showed yeast cells (Figure 1c). Dermoscopy-directed biopsy of the blackish-red dots exhibited dermal abundant neutrophilic and lymphocytic infiltration, and multinucleated giant cells (HE stain, Figure 1d), and several round, thick-walled, brownish sclerotic cells in the dermis (PAS stain, Figure 1e). Biopsy tissues cultured on Sabouraud dextrose agar (SDA) yielded black velvety colonies (Figure 1f). Slide culture (Figure 1g) and SEM (Figure 1h) showed numerous septated hyphae with characteristic sympodial conidiophores and conidia. API ZYM analysis showed high esterase (C4), esterase-lipase (C8), and leucine arylamidase activities; stratum corneum lipid/protein digestion likely supplies carbon and nitrogen for invasion. Vacuolization observed around yeast cells by TEM may indicate enzyme-mediated tissue damage. Sampling of blackish-red dots revealed yeast cells via SEM (Figure 1i–k) and TEM (Figure 1l–n) at low and high continuous magnifications. The strain was initially identified as Fonsecaea spp. by morphology, then further confirmed as F. monophora via tissue metagenomic next-generation sequencing (mNGS), PCR amplification with ITS 1/4 primers, and sequencing (GenBank: PV242203). Given prior monotherapy failure, combination therapy was administered: terbinafine (500 mg/day for 112 days, then 250 mg/day for 147 days) plus itraconazole (200 mg/day for 112 days, then 100 mg/day for 147 days), adjoined with topical naftifine-ketoconazole cream and 42°C thermotherapy (60 min, twice daily). Lesions resolved completely with acceptable scarring and no recurrence. Dermoscopic “blackish-red dots” gradually resolved. A follow-up biopsy was planned but declined by the patient. Fungal fluorescence microscopic examinations on multiple sites of the dorsum and wrist of the right hand were negative results. We report a F. monophora-induced CBM case. The dermoscopic “blackish-red dot sign” was correlated with numerous yeast cells, as confirmed by SEM/TEM, suggesting it may serve as a diagnostic clue. Supported by TEM-observed pathogens migration from the basal layer to stratum corneum, this sign likely corresponds to “transepithelial elimination”-a host antifungal defense mechanism [1-5]. The resolution of blackish-red dots paralleled clinical improvement in this case, which may indicate a potential association with treatment response. More cases are required to establish the relationship with fungal species and to determine whether the sign's disappearance predicts mycological cure and can guide therapy. We thank Senior Experimentalists Guo Yang and Jie He (Chengdu Lilai Biotechnology Co. Ltd) for technical support of SEM and TEM observations. This work was supported by 135 project for disciplines of excellence—Clinical Research Incubation Project, West China Hospital, Sichuan University (21HXFH010), and the National Key Research and Development Program of China (2022YFC2504800). The patient in this manuscript has given written informed consent to publish his case details. The authors declare no conflicts of interest. The authors have nothing to report.