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Phialophora americana infection in a patient with a compound heterozygous CARD9 mutation
Jie Wu1, Yang Xiang2, Fengming Li1
1Department of Dermatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No.324 Jingwuweiqi Road, Huaiyin District, Jinan, Shandong Province, 250000, P.R. China.
Insights
A rare Phialophora americana fungal infection was successfully treated in a patient with CARD9 deficiency. Novel mutations in the CARD9 gene were identified, leading to increased susceptibility to this opportunistic fungal pathogen.
Area of Science:
- Medical Mycology
- Human Genetics
- Immunology
Background:
- Phaeohyphomycosis, a fungal infection, is uncommon, particularly when caused by Phialophora americana.
- Caspase recruitment domain-containing protein 9 (CARD9) deficiency is linked to Phialophora americana infections.
- Patients with CARD9 deficiency are susceptible to deep fungal infections.
Purpose of the Study:
- To report a rare case of invasive Phialophora americana infection in a patient with CARD9 deficiency.
- To identify the genetic basis of CARD9 deficiency in the affected patient.
- To describe the clinical presentation, treatment, and outcome of this rare infection.
Main Methods:
- Metagenomic next-generation sequencing (mNGS) was used to identify the causative fungal pathogen.
- Whole exome sequencing (WES) was performed to detect genetic mutations.
- Clinical data, including treatment response and cytokine levels (IL-17, IFN-γ), were analyzed.
Main Results:
- Phialophora americana was identified as the pathogen causing a deep subcutaneous infection.
- The patient was found to have novel compound heterozygous mutations in the CARD9 gene.
- Treatment with voriconazole was effective, leading to successful resolution of symptoms.
Conclusions:
- Novel compound heterozygous mutations in CARD9 can lead to CARD9 deficiency.
- CARD9 deficiency increases susceptibility to Phialophora americana infections.
- Antifungal therapy with voriconazole is a viable treatment option for Phialophora americana infections in CARD9-deficient individuals.
Abstract:
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.
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