Thursday 30 June 2011
Mutations in the dedicator of cytokinesis 8 gene (DOCK8) cause a combined primary immunodeficiency syndrome that is characterized by elevated serum IgE levels, depressed IgM levels, eosinophilia, sinopulmonary infections, cutaneous viral infections, and lymphopenia.
Clinical findings included dermatitis, asthma, food and environmental allergies, recurrent sinopulmonary infections, staphylococcal skin abscesses, and severe cutaneous viral infections.
Malignant neoplasms, including aggressive cutaneous T-cell lymphoma, anal and vulvar squamous cell carcinomas, and diffuse large B-cell lymphoma, developed in patients during adolescence and young adulthood.
Many patients with DOCK8 deficiency were previously thought to have a variant of Job’s syndrome.
Distinguishing between DOCK8 deficiency and Job’s syndrome, also referred to as autosomal dominant hyper-IgE syndrome, on the basis of clinical findings alone is challenging.
The discovery of the DOCK8 mutation has made it possible to differentiate the cutaneous manifestations of these hyper-IgE syndromes.
DOCK8 deficiency and Job’s syndrome share several clinical features, including elevated serum IgE levels, dermatitis, recurrent sinopulmonary infections, and cutaneous staphylococcal abscesses.
However, the presence of recalcitrant, widespread cutaneous viral infections, asthma, and food and environmental allergies, as well as the absence of newborn rash and coarse facies, favors the clinical diagnosis of DOCK8 deficiency.
Rates of malignancy and overall mortality in patients with DOCK8 deficiency were higher than in those with Job’s syndrome, highlighting the value of distinguishing between these conditions and the importance of close monitoring for neoplasia.
hyper-IgE syndrome (HIE syndrome, HIES)
DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice. Randall KL, Chan SS, Ma CS, Fung I, Mei Y, Yabas M, Tan A, Arkwright PD, Al Suwairi W, Lugo Reyes SO, Yamazaki-Nakashimada MA, Garcia-Cruz Mde L, Smart JM, Picard C, Okada S, Jouanguy E, Casanova JL, Lambe T, Cornall RJ, Russell S, Oliaro J, Tangye SG, Bertram EM, Goodnow CC. J Exp Med. 2011 Oct 24;208(11):2305-20. PMID: 22006977
Cutaneous Manifestations of DOCK8 Deficiency Syndrome. Chu EY, Freeman AF, Jing H, Cowen EW, Davis J, Su HC, Holland SM, Turner ML. Arch Dermatol. 2011 Sep 19. PMID: 21931011