Anete S Grumach, MD, PhD 1,4; Flavio de Queiroz-Telles Filho, MD, PhD 2; Nelson Rosario Filho, MD, PhD 3; Rosemeire Navickas Constantino-Silva, PhD 4; Mélanie Migaud, BSc 5; Fanny Lanternier, MD, PhD 5; Jean Laurent Casanova, MD, PhD 5,6,7; Anne Puel, PhD 5,6.
1) Outpatient group of Recurrent Infections, Department of Pediatrics and Clinical Medicine, Faculty of Medicine ABC, Santo Andre, SP, Brazil; 2) Department of Health Community, Federal University of Parana, Curitiba, PR, Brazil; 3) Department of Pediatrics, Federal University of Paraná, Curitiba, PR, Brazil; 4) Laboratory of Clinical Immunology, Center of Research, Faculty of Medicine ABC, Santo Andre, SP, Brazil; 5) Laboratory of Human Genetics of Infectious Diseases, Université Paris Descartes-Sorbonne, Paris, France; 6) St Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY, USA; 7) Howard Hughes Medical Institute, Rockefeller Foundation, New York, USA
Background: Deep dermatophytosis had been described in HIV and immunosupressed patients. Recently, the association with autosomal recessive CARD9 deficiency was found in individuals previously classified as “immunocompetent”. We describe a new CARD9 mutation associated with dermatophytosis.
Methods: We report a 24-year-old Brazilian male with deep dermatophytosis with Trichophyton mentagrophytes isolated from the skin lesions. Opsonophagocyosis of Candida was performed. CARD9was amplified with specific primers.
Results: The symptoms initiated with oral candidiasis at 3 years old, generalized afterwars and treated with oral and local therapy. At 11 years old well delimitated, descamative and pruriginosus skin lesions appeared; ketoconazol and itraconazole were maintained for 5 years. At 14 years old, the lesions were ulcerative, secretive and painful in the shoulders (15cm of diameter); terbinafine and posaconazole were used without result. His brother presents superficial dermatophytosis. A homozygous mutation in CARD9 exon 3(R101S) was identified in the patient. His parents, one brother (with superficial dermatophytosis) and one sister are heterozygous for this mutation. Laboratory evaluations showed eosinophilia and high IgE levels; Candida killing was clearly impaired in the patient.
Conclusions: This is the first report of CARD9 deficiency in a Brazilian family and the first report of a CARD9 R101S mutation. A different mutation affecting the same amino-acid (R101C) had been previously described in two Moroccan siblings with deep dermatophytosis.