title: Cutaneous manifestations of primary immunodeficiency.
abstract: OBJECTIVE
  To show that skin symptoms help in the recognition of primary immunodeficiencies (PIDs). To analyze whether recent molecular data help in understanding genotype/phenotype relations.
  
  
  RESULTS
  Erythroderma in Omenn syndrome may be caused by either mutations in genes associated with severe combined immunodeficiency (SCID) in which the generation of some T cells is possible, which results in potentially autoreactive lymphoid clones, or by selective proliferation of revertant CD8 T cells in the skin due to clonal expansion in response to infections or autoantigens.The newborn eczematous eruption, which occurs mainly in the signal-transducer-and-activator-of-transcription-3 (STAT3) variant, helps to differentiate STAT3 from Dedicator of Cytokinesis 8-related Hyper-IgE-syndrome (HIES).Impaired T helper 17 cell (TH17) immunity [HIES and defects of autoimmune regulator element (AIRE), STAT-1, and interleukin17 receptor(IL17(R))] may give rise to localized chronic mucocutaneous candidiasis, whereas a defective innate immune system predisposes to systemic candidiasis [congenital neutropenia, neutrophil dysfunction, and caspase recruitment domain 9 (CARD9) deficiency].Noninfectious granulomas may be the presenting symptom in innate immunity defects [such as chronic granulomatous disease (CGD) or in predominantly humoral immunodeficiencies such as common variable immunodeficiency], as well as ataxia teleangiectasia or rare recombination-activating gene-deficient cases.
  
  
  CONCLUSIONS
  The skin is important in the diagnosis of PIDs. In particular eczematous lesions, erythroderma, noninfectious granuloma, and microbial manifestations may help to direct further diagnostic laboratory analysis.
authors.affiliation: Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. j.h.sillevissmitt@amc.uva.nl
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Sillevis Smitt
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D003872:Dermatitis / Q000209:etiology; D003873:Dermatitis, Exfoliative / Q000209:etiology; D006099:Granuloma / Q000150:complications; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications* / Q000175:diagnosis*; D009894:Opportunistic Infections / Q000150:complications; D012871:Skin Diseases / Q000209:etiology*; D012874:Skin Diseases, Infectious / Q000150:complications