IDDT Journal

Table 1: Characteristics of Previously Published Cases of Infections with Emergomyces Spp

For the clinicians and microbiologists, diagnosis of emergomycosis is challenging. Studies indicate that three-quarters of patients with emergomycosis get misdiagnosed as TB and receive treatment for the same as pulmonary lesions on chest radiograph may mimic pulmonary TB [1]. The cutaneous lesions of emergomycosis may simulate cutaneous lesions of secondary syphilis, drug reactions, guttate psoriasis, Kaposi sarcoma, papular eruption of HIV, pyoderma gangrenosum, scrofuloderma or varicella [1]. Additionally, morphological intracellular yeast form of Emergomyces resembles to Histoplasma capsulatum [4]. In skin biopsy specimens, it can be mislabelled as Sporothrix schenckii [4]. Histopathology can detect yeasts, but cannot differentiate between the different fungal genera or give a species level identification. Therefore, fungal culture and isolation are imperative for differentiating between these dimorphic fungi followed by molecular identification to confirm the diagnosis [1,4]. In most reported cases, identification of the species was confirmed by sequencing (Table 1). In the present report, fungal culture and genomic sequencing helped us to reach a species level identification. MALDI TOF MS could not identify the causal fungus. Possibly, a library update can help with this.

At present no treatment guidelines are available for emergomycosis. The IDSA recommendations for management of histoplasmosis and blastomycosis are being followed for emergomycosis [1]. Multiple treatment courses have been used with varying outcomes (Table 1). Maphanga TG et al, studied AFST by BMD for 50 isolates of E. africanus in order to guide clinical management. Amphotericin B was reported to be a best therapeutic option, followed by the azoles (itraconazole > voriconazole/posaconazole). Fluconazole was found to be relatively less potent. Echinocandins showed almost no activity with higher minimum effective concentrations (MECs) [33]. Similar results were obtained by Dukik et al, for anidulafungin and micafungin. However, they observed posaconazole to be most effective, followed by amphotericin B, itraconazole, voriconazole, and isavuconazole [34]. A disseminated emegomycosis by E. pasteurianus in Netherlands was also reported to be successfully treated with 14 months of posaconazole therapy indicating that posaconazole could be a possible treatment option [35]. However, for isavuconazole, is a novel triazole, studies have reported comparatively higher MIC values [34,35] and therefore, not a preferred treatment option. Our AFST findings are in accordance with the previously published findings of Maphanga TG et al, [33]. Though fluconazole was considered as relatively less potent agent, our isolate was susceptible. The current case was successfully treated with amphotericin B deoxycholate followed by itraconazole. The optimal timing of ART initiation following diagnosis of emergomycosis has not been established [4]. In the present case, ART was started 2 weeks after antifungal therapy and deterioration of cutaneous or lung lesions after ART therapy was not noted.

Despite the good susceptibility data, high death rates had been reported in emergomycosis (Table 1, 2). The mortality rate in emergomycosis patients ranges from 48 to 51% [7,36]. Late clinical suspicion after the appearance or deterioration of widespread cutaneous lesions after initiation ART may be the reason. Additionally, comorbid factors, poor control of the underlying condition, late or missed diagnosis, drug to drug interactions, emergence of resistance and intolerance to the available antifungals might be the proximate causes. Considering the host toxicity profile of currently available antifungal drugs and the endogenous resistance of dimorphic fungi to the less toxic echinocandins, new and alternative antifungal drugs, preferably with novel modes of action (to avoid cross-resistance and/or cross-toxicities) need to be explored. Also, the availability of oral formulations would enable ambulatory treatment resulting in improved patient compliance and adherence to treatment.

Table 2: Antifungal Drugs Breakpoints of Emergomyces Spp Isolates in Previously Published Cases Report

Conclusion

Emergomycosis is a fatal systemic fungal disease among immunocompromised patients in endemic regions and diagnosis is challenging, particularly in resource limited settings. A high index of suspicion is needed, especially in countries where tuberculosis infections are endemic. Fungal culture and isolation are imperative followed by molecular identification to confirm the diagnosis. Close scrutiny of histoplasmosis cases diagnosed only by histopathology in immunosuppressed patients is required. For the management of emergomycosis, amphotericin B appeared to be the best therapeutic option, followed by the azoles.

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