Introduction. Invasive fungal diseases (IFDs) are life-threatening infections that require rapid diagnostic and frequently occur in patients with either iatrogenic or acquired immunodeficiencies and Inborn Errors of Immunity (IEI). CARD9 deficiency is an autosomal recessive IEI that causes susceptibility to invasive fungal infections by ascomycetes.
Materials and methods. Clinical history was reviewed and serum immunoglobulins (Ig) and peripheral blood (PB) lymphocyte populations were evaluated by flow cytometry. Whole exome sequencing was performed on genomic DNA.
Results. Female patient, 60 years old, parents apparently not consanguineous, born and living in a rural area of northern Colombia, working in cotton crops. In 2008 she started a violaceous plaque on the left elbow that progressed to arms, trunk, back and lower limbs; some lesions were bleeding and painful ulcers. She consulted multiple times and received treatments “without improvement”.Between 2017 and 2019 they performed skin biopsies that reported “molds” and prescribed itraconazole and terbinafine with partial improvement but poor adherence to treatment. Referred in December 2022 to 4th level institution in Medellin for weight loss (6-7 kg), hyporexia, odynophagia and dysphagia for solids, and skin with disseminated hyperpigmented and ulcerated warty plaques.Upper gastrointestinal endoscopy revealed Candida spp. esophagitis. Skin biopsy showed extensive acute necrosis and chronic granulomatous inflammation, and methenamine silver staining identified multiple branching and pigmented filamentous fungal structures. Skin biopsy culture (Sabouraud dextrose agar) grew black and gray velvety colonies and Universal Panfungal PCR identified Cyphellophora sp. All determinations of leukocyte subpopulations in peripheral blood, as well as dihydrorhodamine and serum immunoglobulin tests were normal. IEI was suspected and the exome revealed a deleterious homozygous variant in CARD9 (p.Gln289*) which predicts a loss of the CC2 domain of the protein.. According to sensitivity testing, she was started on posaconazole with significant clinical response and was discharged to continue therapy for one year.