title: Distinct Cutaneous Manifestations and Cold-Induced Leukocyte Activation Associated With PLCG2 Mutations.
abstract: OBJECTIVE
  PLCG2-associated antibody deficiency and immune dysregulation (PLAID) is a newly characterized immunodeficiency syndrome associated with distinct cutaneous features. Awareness of the cutaneous skin findings associated with PLAID may facilitate diagnosis and improve patient care.
  
  
  OBJECTIVE
  To characterize the cutaneous manifestations of PLAID and identify potential cellular mechanisms of the disease.
  
  
  METHODS
  In this retrospective analysis of patients with PLAID and PLAID-like disease evaluated at the National Institutes of Health from January 1, 2005, through December 31, 2014, patients with deletions in PLCG2 leading to PLAID and patients with PLAID-like disease for whom a PLAID mutation was not identified were studied.
  
  
  METHODS
  Characterization of cutaneous manifestations of PLAID and PLAID-like disease and analysis of PLAID immune cell activation.
  
  
  RESULTS
  Among 36 patients with PLAID and PLAID-like phenotypes, all of whom had evaporative cold urticaria, 8 patients had a history of unique neonatal-onset ulcerative and cutaneous lesions in cold-sensitive regions of the body. Granulomatous skin lesions sparing warm regions (eg, flexural surfaces and skinfolds) were identified in 4 patients. Neutrophils and monocytes from patients with PLAID exhibited enhanced baseline activation in vitro, which was potentiated by ambient temperature exposure.
  
  
  CONCLUSIONS
  Collectively, these findings suggest that early identification of neonatal lesions may help in the diagnosis of PLAID and that leukocyte hyperactivation may underlie cutaneous lesions in patients with PLAID. Further characterization of mechanisms underlying leukocyte hyperactivation may contribute to the fundamental understanding of granuloma formation.
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Oyinade M
authors.initials: OM
authors.lastname: Aderibigbe
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Debra Long
authors.initials: DL
authors.lastname: Priel
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Chyi-Chia Richard
authors.initials: CC
authors.lastname: Lee
authors.affiliation: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ombrello
authors.affiliation: Pediatric Dermatology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Vimal H
authors.initials: VH
authors.lastname: Prajapati
authors.affiliation: Pediatric Dermatology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Marilyn G
authors.initials: MG
authors.lastname: Liang
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Lyons
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kuhns
authors.affiliation: Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Cowen
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Milner
mesh_terms: D003080:Cold Temperature; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D009154:Mutation; D051966:Phospholipase C gamma / Q000235:genetics*; D012189:Retrospective Studies; D012871:Skin Diseases / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D014581:Urticaria / Q000209:etiology*
chemical_list: D051966:Phospholipase C gamma