Phialophora americana infection in a patient with a compound heterozygous CARD9 mutation

Phaeohyphomycosis caused by Phialophora americana is relatively rare in clinical practice. Deficiency in the human caspase recruitment domain-containing protein 9 (CARD9) is associated with infections caused by Phialophora americana. In this case, the patient has had a decade-long history of recurrent tinea corporis and recently presented with an invasive, deep subcutaneous infection in the right axilla caused by Phialophora americana. Metagenomic next-generation sequencing (mNGS) confirmed that the pathogen infecting the patient was Phialophora americana. Whole exome sequencing (WES) revealed that the patient had compound heterozygous CARD9 gene mutations, with a c.952-1G > A mutation in intron 6 and a c.184 + 5G > T mutation in intron 2. The expression of the CARD9 protein and the levels of cytokines, including IL-17 and IFN-γ, were observed to be decreased in the patient. After an ineffective treatment with amphotericin B, voriconazole was administered for antifungal therapy and yielded satisfactory results. Following discharge, the patient continued oral voriconazole for ongoing antifungal treatment. One month after discharge, the patient returned to the hospital for a follow-up examination, during which it was observed that the symptoms had been successfully resolved. The novel compound heterozygous mutations may lead to CARD9 deficiency, which in turn results in susceptibility to Phialophora americana infection.