title: Dissecting susceptibility from exogenous triggers: the model of alopecia areata and associated inflammatory skin diseases.
abstract: BACKGROUND
  Alopecia areata (AA) is a T-cell-driven autoimmune disease of the hair follicle and frequently reported to be associated with inflammatory skin diseases (ISD) such as atopic eczema (AE) or psoriasis. Interestingly, AA on the one hand and both AE and psoriasis on the other hand are believed to be driven by mutually antagonistic T-cell subsets.
  
  
  OBJECTIVE
  To characterize AA-specific T-cell profiles and inflammatory pattern by intra-individual comparison of AA and coexistent ISD.
  
  
  METHODS
  112 patients with AA were recruited and investigated for coexisting ISD. In-depth analyses were performed in patients with AA and AE (n = 2), AA and psoriasis (n = 1), AA and psoriasis and AE (n = 1) and AA and lichen planus (n = 1), using histology, immunohistochemistry and cytokine staining of T cells isolated from lesional skin.
  
  
  RESULTS
  Of 112 AA patients investigated, 23 suffered from an ISD. The prevalence of AE, vitiligo, psoriasis and lichen planus was higher in the investigated AA cohort than in the normal population. The clinical as well as histological phenotype of AA the coexistent ISD were unequivocal. In line with this, T-cell infiltrates were found to be disease-characteristics with AA and lichen planus dominated by CD8+ and IFN-γ+ TNF-α+ producing T cells while psoriasis lesions in the same patients were dominated by IL-17+ and AE by IL-4+ T cells.
  
  
  CONCLUSIONS
  AA patients have a higher incidence of various T-cell-driven inflammatory skin diseases than the normal population, a phenomenon which might relate to over-activation of skin-homing T cells and to specific immune triggers as the primary cause of inflammation. More importantly, we showed that by using AA as a model disease, our approach of intra-individual comparison of distinct inflammatory responses in the same patient is feasible and offers the unique possibility to gain insights into disease pathogenesis independent from genetic susceptibilities.
authors.affiliation: Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Garzorz
authors.affiliation: Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Alsisi
authors.affiliation: Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Todorova
authors.affiliation: ZAUM - Center of Allergy and Environment, Technical University of Munich and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Atenhan
authors.affiliation: ZAUM - Center of Allergy and Environment, Technical University of Munich and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Thomas
authors.affiliation: Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Lauffer
authors.affiliation: Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Ring
authors.affiliation: ZAUM - Center of Allergy and Environment, Technical University of Munich and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schmidt-Weber
authors.affiliation: Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Biedermann
authors.affiliation: ZAUM - Center of Allergy and Environment, Technical University of Munich and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Eyerich
authors.affiliation: Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Eyerich
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000506:Alopecia Areata / Q000150:complications / Q000276:immunology* / Q000473:pathology; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry* / Q000473:pathology; D002648:Child; D003876:Dermatitis, Atopic / Q000150:complications / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D020381:Interleukin-17 / Q000032:analysis; D008010:Lichen Planus / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010641:Phenotype; D011565:Psoriasis / Q000150:complications / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D055815:Young Adult
chemical_list: D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma