Treatment options for DOCK8 deficiency-related severe dermatitis

Background Cutaneous manifestations of dedicator of cytokinesis 8 gene (DOCK8) deficiency, a combined type of T and B cell immunodeficiency, previously designated as autosomal recessive hyper IgE syndrome, includes dermatitis and skin infections. There are limited treatment options for dermatitis related to the syndrome. Objective To describe a cohort of patients with DOCK8 deficiency with a focus on the treatment of their cutaneous manifestations. Methods A retrospective study on all children with the genetic diagnosis of DOCK8 deficiency treated at the Sheba Medical Center between 1/1/2003 and 1/1/2021 was preformed. Collected data included: demographic features, family history, laboratory, genetic testing, skin manifestations, treatment, and disease course. Description of two cases of severe recalcitrant dermatitis treated with dupilumab is detailed. Results Nine children with a genetic diagnosis of DOCK8 deficiency were included, of whom six were girls (66%) with a median age of 8.5 (+/- 2.2 SD) years. The median age at diagnosis was 2.8 (+/- 2.6 SD) years. Six patients were born to consanguineous parents. Five out of six patients who received hematopoietic stem cell transplantation (HSCT) had a complete response, and one was recently transplanted. Of note, two patients, while awaiting HSCT, were treated with dupilumab for their severe dermatitis resulting in a marked improvement of the cutaneous manifestations and pruritus. Conclusions Hematopoietic stem cell transplantation is the gold standard and most effective therapy for patients with DOCK8 deficiency. Dupilumab, a biological therapy indicated for atopic dermatitis and other Th2 derived dermatoses, is an excellent option for dermatitis in patients with DOCK8 deficiency and can be used as a bridge before HSCT. Larger studies are needed to confirm this observation.

Automated summary

DOCK8 deficiency is a combined type of T and B cell immunodeficiency with limited treatment options for dermatitis. Hematopoietic stem cell transplantation is the gold standard therapy, while dupilumab can be an excellent option for dermatitis in patients with DOCK8 deficiency, potentially serving as a bridge before transplantation. Larger studies are needed to confirm the efficacy of dupilumab in this population.