Early-Onset Invasive Infection Due to Corynespora cassiicola Associated with Compound Heterozygous CARD9 Mutations in a Colombian Patient.

PURPOSE: CARD9 deficiency is an inborn error of immunity that predisposes otherwise healthy humans to mucocutaneous and invasive fungal infections, mostly caused by Candida, but also by dermatophytes, Aspergillus, and other fungi. Phaeohyphomycosis are an emerging group of fungal infections caused by dematiaceous fungi (phaeohyphomycetes) and are being increasingly identified in patients with CARD9 deficiency. The Corynespora genus belongs to phaeohyphomycetes and only one adult patient with CARD9 deficiency has been reported to suffer from invasive disease caused by C. cassiicola. We identified a Colombian child with an early-onset, deep, and destructive mucocutaneous infection due to C. cassiicola and we searched for mutations in CARD9. METHODS: We reviewed the medical records and immunological findings in the patient. Microbiologic tests and biopsies were performed. Whole-exome sequencing (WES) was made and Sanger sequencing was used to confirm the CARD9 mutations in the patient and her family. Finally, CARD9 protein expression was evaluated in peripheral blood mononuclear cells (PBMC) by western blotting. RESULTS: The patient was affected by a large, indurated, foul-smelling, and verrucous ulcerated lesion on the left side of the face with extensive necrosis and crusting, due to a C. cassiicola infectious disease. WES led to the identification of compound heterozygous mutations in the patient consisting of the previously reported p.Q289* nonsense (c.865C > T, exon 6) mutation, and a novel deletion (c.23_29del; p.Asp8Alafs10*) leading to a frameshift and a premature stop codon in exon 2. CARD9 protein expression was absent in peripheral blood mononuclear cells from the patient. CONCLUSION: We describe here compound heterozygous loss-of-expression mutations in CARD9 leading to severe deep and destructive mucocutaneous phaeohyphomycosis due to C. cassiicola in a Colombian child.

Subcutaneous phaeohyphomycosis (mycotic cyst).

Phaeohyphomycosis designates fungal infections caused by pheoid or melanized fungi and characterized histopathologically by the presence of septate hyphae, pseudohyphae, and yeasts. Etiologic agents include Exophiala, Phoma, Bipolaris, Phialophora, Colletotrichum, Curvularia, Alternaria, Exserohilum, and Phialemonium sp. The most common are Exophiala jeanselmei and Wangiella dermatitidis. The clinical presentation depends on the immune status of the host: superficial (tinea nigra and black piedra); cutaneous (scytalidiosis) and corneal; subcutaneous (mycotic cyst); and systemic phaeohyphomycosis in the immunocompromised host. The mycotic cyst is a localized form, characterized by subcutaneous asymptomatic nodular lesions that develop after traumatic implantation of fungi, especially on the extremities. The average size of the cysts is 2.5 cm. KOH examination reveals pigmented yeasts, pseudohyphae, and hyphae. A cutaneous biopsy specimen usually shows an abscess or a suppurative granuloma with pigmented yeasts and pseudohyphae. The treatment of choice is surgical excision, but additional anti-fungal therapy is recommended for recurrent cases and immunocompromised patients.