title: Cutaneous manifestations of DOCK8 deficiency syndrome.
abstract: BACKGROUND
  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. 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.
  
  
  METHODS
  Twenty-one patients from 14 families with confirmed homozygous or compound heterozygous mutations in DOCK8 were evaluated. 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 5 patients during adolescence and young adulthood.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dermatology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA. emily.chu@uphs.upenn.edu
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chu
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Freeman
authors.forename: Huie
authors.initials: H
authors.lastname: Jing
authors.forename: Edward W
authors.initials: EW
authors.lastname: Cowen
authors.forename: Joie
authors.initials: J
authors.lastname: Davis
authors.forename: Helen C
authors.initials: HC
authors.lastname: Su
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.forename: Maria L Chanco
authors.initials: ML
authors.lastname: Turner
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007589:Job Syndrome / Q000175:diagnosis*; D008297:Male; D009154:Mutation; D012871:Skin Diseases / Q000175:diagnosis* / Q000235:genetics*; D013577:Syndrome; D055815:Young Adult
chemical_list: C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors