Distinct cutaneous manifestations and cold-induced leukocyte activation associated with PLCG2 mutations

Oyinade M Aderibigbe, Debra Long Priel, Chyi Chia Richard Lee, Michael J. Ombrello, Vimal H. Prajapati, Marilyn G. Liang, Jonathan J. Lyons, Douglas B. Kuhns, Edward W. Cowen, Joshua D. Milner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


IMPORTANCE: 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. OBJECTIVES: To characterize the cutaneous manifestations of PLAID and identify potential cellular mechanisms of the disease. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.

Original languageEnglish (US)
Pages (from-to)627-634
Number of pages8
JournalJAMA dermatology
Issue number6
StatePublished - Jun 1 2015

ASJC Scopus subject areas

  • Dermatology


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