LB1565 Primary cutaneous aspergillosis in a patient with CARD9 deficiency

Abstract

Aspergillus species, a common saprophytic mold, seldom acts as a pathogen in immunocompetent hosts, and primary cutaneous involvement is even less. Herein, we report a patient of primary cutaneous aspergillosis harboring CARD9 mutations. The 45-year-old patient presented with a 37-year history of skin lesions on the face. The lesion was a soy-sized rash on his left eyelid at the age of 8, which slowly enlarged and progressed during the past 3 years. Physical examination revealed erythematous plaques with clear border on his face and nose. Direct microscopic examination showed slender, septate, branched hyphae. A biopsy specimen revealed mixed inflammatory infiltrations with septate hyphae noted in multinuclear giant cells. From tissue cultures, Aspergillus fumigatus was isolated and identified. The patient denied any immunosuppressive conditions, and results of routine laboratory examinations were generally normal. A CT scan excluded pulmonary aspergillosis. Therefore, the diagnosis of primary cutaneous aspergillosis was made on the basis of the above findings. The patient responds well to oral itraconazole and is still under treatment. To study the reason for the prolonged infection and identify the genetic background in this seemingly immunocompetent patient, we screened mutations in several related genes. Sanger sequencing of CARD9 showed that the patient harbored a homozygous frame shift mutation in exon 6 (c.819_820insG, p.D274fsX60), leading to premature termination codons. His son was asymptomatic and heterozygous carrier of the same mutation. CARD9, mainly expressed in myeloid cells, is a key adaptor in the downstream signaling of several C-type lectin receptors, and mediates anti-fungal immunity by forming a complex with BCL10 and MALT1. This is, to our knowledge, the first report that linked cutaneous aspergillosis to CARD9 mutations. This work enriches both the phenotypic spectrum of CARD9 deficiencies and the genetic background of primary cutaneous aspergillosis.