A CASE OF DOCK8 DEFICIENCY TREATED WITH DUPILUMAB

Abstract

<h3>Introduction</h3> Dedicator of cytokinesis 8 gene (DOCK8) deficiency is an immune disorder associated with autosomal recessive hyper-IgE syndrome, characterized by elevated IgE levels, atopic dermatitis, and predisposition to recurrent skin and lung infections. <h3>Case Description</h3> A 12-year-old male presented to Immunology clinic for DOCK8 deficiency. He was diagnosed in infancy due to diffuse papulopustular eruption positive for candidiasis and known family history. Past medical history included severe eczematous dermatitis, asthma, interstitial lung disease, food allergies, and poor growth, with cutaneous HSV and fungal infections, HSV keratitis, and MRSA bacteremia. Family history was notable for two siblings with DOCK8 deficiency, both deceased. Physical exam demonstrated severe generalized eczematous papules and plaques and intermittent coarse breath sounds. IgE ranged from 22.9–14,730 kU/L. Absolute eosinophil count fluctuated between 30–10,350 cells/mcL. Sequencing of the <i>DOCK8</i> gene revealed a novel 2 base pair deletion resulting in a frame shift mutation in exon 14 at codon 510. He was managed on weekly subcutaneous immunoglobulin replacement, prophylactic Bactrim and valacyclovir, and followed by Immunology, Dermatology, Pulmonology, and Ophthalmology. Family declined bone marrow transplantation. Due to the severity of his eczematous dermatitis, monthly dupilumab injections were initiated. Within a year, he reported significant improvement in cutaneous and respiratory symptoms, with increase in lung function from FEV1 of 32% to 63%. <h3>Discussion</h3> In patients with DOCK8 deficiency, hematopoietic stem cell transplantation is curative. For patients who are unable or unwilling to undergo or awaiting transplant, dupilumab is a treatment option for improvement of both cutaneous and respiratory manifestations.