Introduction: Caspase Recruitment Domain-containing protein 9 (CARD9) is an autosomal-recessive primary immunodeficiency which is associated invasive or chronic fungal infections including candidiais, phaeohyphomycosis and deep dermatoohytosis. We describe a case of inavise CARD 9 deficiency succesfully treated with HSCT. Case report: A 26-yearold Caucasian male patient, living in rural area in the south of Brazil. He is from italian origin, without consanguinity. Developed in the age of 3, erythematous scaly cutaneous lesions in mandibular area. In the following years, the lesions spread to whole body and scalp, with loose of hair. During the last 20 years the patient received several topic and systemic antifungals, including ketoconazole, itraconazole, terbinafine, posaconazole and lipid amphotericin B(L-AMB). Transient response was observed after each treatment. In the last 2 years, the lesions progressed with poor response to combined antifungal treatment, consisting of voriconazole and L-AMB. Direct mycologic examination and biopsy identified hyaline septated hyphae and culture yelded T. mentagrophytes (phenotypically) and later T. interdigitalis (gen sequency). In 2013, he had the diagnosis of CARD 9 deficiency (J Clin Immunol 2015,35:486-90). He was found to be homozygous for a novel c.302G>T variation in the exon 3 of the CARD9 gene (R101L). An identical sibling was found. The donor was his 32-yearold sister, with no pregnancies and heterozygosis for the CARD 9 mutation without skin lesions. The patient was submitted to HSCT in August 2015. At this time the patient presented severe tegumental and lymphonode involvement. He was clondictioned with fludarabine, oral Bussulfan and antithymocitic globuline. Immunoprophylaxis was with cyclosporine and oral mycofenolate and the source of cells was bone marrow. He had mucositis grade 3 and febrile neutropenia that was treated with meropenen and vancomicine (coagulase negative staphylococcus in blood culture) and L-AMB and terbinafine for the fungal infection. Granulocytes infusions were done in days +6,10,11 of HSCT. After the engraftment, lesions started to reduce and a new skin biopsy showed no fungal involvement. Neutrophilic and platelets engraftment occurred on days +16 and 35, retrospectively. He was discharged on day + 26 with oral cyclosporine and mycofenolate mofetila, L-AMB and terbinafine. Mycofenolate was tapped on day +35. On day+ 40 CMV became positive and Gancyclovir was given for 14 days. On day 80, he presented with erithematosus rash in 50% of body surface and metilprednisolone 1mg/kg was started with good response and was tappered and stopped on day 100. L-AMB was stopped on D+45 and terfinafine on day+ 100. Immune recontitution on day 100 showed CD4 488/uL; CD8 1151/uL; B lymphocytes 16 /uL; and NK cells 333/uL. Immunoglobuline levels were normal and chemerism was 100% of donor cells. Cyclosporine was stopped after 8 months of transplantation. Skin lesions continue to improve without evidence of active infection. After two years follow up the patient is clinically and mycologically cured. Conclusion: Patients with CARD 9 associated mycoses are usually refractory to antifungal therapy and the mortality rates are high, including for deep dermatophytosis. This is the first patient with CARD 9 deffciency and severe fungal infection successfully treated with HSCT.
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- TIMM 8th (2017)