Azole-resistant Candida tropicalis-induced ulcer

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A 68-year-old immunocompetent woman presented with an 18-month tender ulcer on the extensor aspect of the left knee following a fall two years earlier. The wound failed to heal over six months [Figure 1a]. The previous year, she received antibiotics, dexamethasone, and debridement. The ulcer continued to enlarge. Examination revealed a well-demarcated ulcerated plaque with overlying eschars, erythema, and oedema [Figure 1b]. Two prior skin-biopsies showed no organisms on periodic acid-Schiff (PAS) stains. Although tissue culture from the second biopsy grew azole-susceptible Candida glabrata, oral fluconazole failed to improve the lesion.

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Figure 1: (a) Oval and well-demarcated shallow ulcer with mild purulent exudates on the extensor aspect of the left knee 6 months after a fall. (b) Ulcerative plaque developed to an 8×9 cm area with eschars and surrounding erythema and edema on the day of the third skin biopsy. (c) Erythematous plaque with overlying granulation tissue 2 weeks after initiating systemic caspofungin therapy. (d) Skin healed with a scar at the 3-month follow-up.

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A third skin-biopsy demonstrated abundant spores and pseudohyphae on PAS sections [Figures 2a-c]. Tissue culture from the biopsy and five separate abscess cultures yielded Candida tropicalis. Blood culture was unremarkable. A diagnosis of cutaneous candidal infection was made. Treatment with oral itraconazole for 2 weeks resulted in minimal improvement. Subsequent antifungal susceptibility testing (AFST), as per the Clinical and Laboratory Standards Institute M27 guideline, revealed minimum inhibitory concentrations (mg/L) of: micafungin (0.06), caspofungin (0.25), 5-fluorocytosine (0.12) (susceptible); voriconazole (4), itraconazole (1), fluconazole (256), posaconazole (1) (resistant); amphotericin B (0.25) (susceptible). These results confirmed azole resistance, prompting discontinuation of itraconazole and initiation of systemic caspofungin (70 mg on the first day, followed by 50 mg daily for 14 days). The ulcer improved within 2 weeks [Figure 1c]. Residual scarring was noted at the 3-month follow-up [Figure 1d].

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Figure 2: (a) Periodic acid-Schiff staining showing abundant spores and pseudohyphae in the dermis, 4x. (b) Spores (black arrow), 20x. (c) Pseudohyphae (black arrow), 40x.

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Candida tropicalis is a commensal yeast of the human microbiota usually associated with vulvovaginal or catheter-related infections, rarely pathogenic in immunocompetent hosts.¹ Nonetheless, its global incidence has risen sharply, establishing it as an emerging pathogenic yeast.² Through biofilm formation, C. tropicalis adheres to epithelial surfaces to proliferate, colonize, and invade host tissue, leading to cutaneous ulceration.³

An extensive search of all major databases from inception until July 6, 2025 [summarised in Table 1], revealed only five reports comprising seven patients (aged 24 to 60 years, mean 44.5; both immunocompetent (71.4%) and immunocompromised) with confirmed C. tropicalis- induced skin ulcers.^1,4-7 Most reports emerged from the USA (n=3), while there was one report each from Slovakia, and China.^1,4-7 Ulcers involved the legs; interdigital webs of hands; lower abdomen, flanks, and lower extremities and the peri-sacral area.^1,4-7 They often exhibited necrosis, bulla formation, underlying erythema and peripheral scattered lesions. One case mimicked ecthyma gangrenosum.⁶ Two patients reported systemic symptoms: one experienced fever one week before developing a rash, which progressed to ulcers, and another developed sepsis related to a peripherally inserted central catheter with a positive tip culture.^6,7

While no specific triggers were identified, the patient with interdigital ulcers reported frequent water exposure,⁵ and two patients developed lesions following chemotherapy.^6,7 Lesions were chronic or progressive ulcers treated empirically with antibacterials, corticosteroids, antifungals, or antivirals before fungal identification.^1,5-7 Initially, in 60% patients, the lesions were misattributed to neutropenic complications, herpes zoster, and decubitus ulcer.^1,6,7 Our case highlights a diagnostic pitfall, where isolating a non-causative fungal species, as in our case, or defaulting to a likely explanation may lead to premature diagnostic closure and delayed identification of the actual pathogen.

Similar to our case, a patient who underwent two biopsies at an early stage of disease manifesting with erythematous papules, showed no fungal elements, however, biopsies undertaken at a later stage from the necrotic plaque revealed fungal budding yeasts and suppurative granulomatous dermal inflammation.⁶ This suggests timing and repetition of biopsies at different ulcer stages may be important. In all cases, fungal culture from tissue or blood, was positive for C. tropicalis and is essential for diagnosis.^1,4-7

Although 80% of the studies did not explicitly report azole resistance,^1,4-6 42.9% of all patients responded to azole therapy, suggesting susceptibility.^1,5,6 Ulcers responded to itraconazole (200 mg oral daily for 3 weeks, interrupted, then another 2 weeks; healed with mild scarring), voriconazole (dosage and duration not reported), or fluconazole (200 mg oral daily for 2 weeks, then weekly for 6 weeks; complete resolution).^1,5,6 Topical bifonazole cream was used with oral itraconazole, though its stand alone effectiveness was not established.⁵ Our case confirmed fluconazole-resistant C. tropicalis on tissue culture, and responded completely with 6 weeks of caspofungin.

This study illustrates the features of Candida tropicalis- induced cutaneous ulcers and the importance of considering this pathogen in the differential diagnosis of chronic, atypical or non-healing ulcers, even in immunocompetent individuals. We recommend biopsies and fungal cultures from multiple sites at early and later/necrotic lesion stages, along with AFSTs. Timely and repeat sampling may prevent false negatives and treatment delays, particularly in the setting of antifungal resistance.