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Published in: Advances in Therapy 7/2017

Open Access 01-07-2017 | Review

The Changing Landscape of Alopecia Areata: The Translational Landscape

Authors: Etienne C. E. Wang, Angela M. Christiano

Published in: Advances in Therapy | Issue 7/2017

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Abstract

Recent genetic and preclinical studies have increased our understanding of the immunopathogenesis of alopecia areata (AA). This has allowed expedited development of targeted therapies for the treatment of AA, and a paradigm shift in our approach and understanding of autoimmunity and the hair follicle. The synergy between preclinical studies, animal models, and translational studies has led to unprecedented advances in the treatment options for AA, ultimately benefiting patients who have had little recourse. In this review, we summarize the scientific field of contemporary AA research, and look forward to potential new technologies and developments.
Literature
1.
go back to reference Safavi KH, et al. Incidence of alopecia areata in Olmsted County, Minnesota, 1975 through 1989. Mayo Clin Proc. 1995;70(7):628–33.CrossRefPubMed Safavi KH, et al. Incidence of alopecia areata in Olmsted County, Minnesota, 1975 through 1989. Mayo Clin Proc. 1995;70(7):628–33.CrossRefPubMed
2.
go back to reference Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: a systematic review. Clin Cosmet Investig Dermatol. 2015;8:397–403.PubMedPubMedCentral Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: a systematic review. Clin Cosmet Investig Dermatol. 2015;8:397–403.PubMedPubMedCentral
3.
go back to reference Petukhova L, Christiano AM. The genetic architecture of alopecia areata. J Investig Dermatol Symp Proc. 2013;16(1):S16–22.CrossRefPubMed Petukhova L, Christiano AM. The genetic architecture of alopecia areata. J Investig Dermatol Symp Proc. 2013;16(1):S16–22.CrossRefPubMed
4.
5.
go back to reference Colombe BW, et al. HLA class II antigen associations help to define two types of alopecia areata. J Am Acad Dermatol. 1995;33(5 Pt 1):757–64.PubMed Colombe BW, et al. HLA class II antigen associations help to define two types of alopecia areata. J Am Acad Dermatol. 1995;33(5 Pt 1):757–64.PubMed
6.
go back to reference Barahmani N, et al. Major histocompatibility complex class I chain-related gene A polymorphisms and extended haplotypes are associated with familial alopecia areata. J Invest Dermatol. 2006;126(1):74–8.CrossRefPubMed Barahmani N, et al. Major histocompatibility complex class I chain-related gene A polymorphisms and extended haplotypes are associated with familial alopecia areata. J Invest Dermatol. 2006;126(1):74–8.CrossRefPubMed
7.
go back to reference Moftah NH, et al. ULBP3: a marker for alopecia areata incognita. Arch Dermatol Res. 2016;308(6):415–21.CrossRefPubMed Moftah NH, et al. ULBP3: a marker for alopecia areata incognita. Arch Dermatol Res. 2016;308(6):415–21.CrossRefPubMed
8.
go back to reference Betz RC, et al. Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci. Nat Commun. 2015;6:5966.CrossRefPubMedPubMedCentral Betz RC, et al. Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci. Nat Commun. 2015;6:5966.CrossRefPubMedPubMedCentral
9.
go back to reference Petukhova L, Christiano AM. Functional interpretation of genome-wide association study evidence in alopecia areata. J Invest Dermatol. 2016;136(1):314–7.CrossRefPubMedPubMedCentral Petukhova L, Christiano AM. Functional interpretation of genome-wide association study evidence in alopecia areata. J Invest Dermatol. 2016;136(1):314–7.CrossRefPubMedPubMedCentral
11.
go back to reference Kuwano Y, et al. Serum chemokine profiles in patients with alopecia areata. Br J Dermatol. 2007;157(3):466–73.CrossRefPubMed Kuwano Y, et al. Serum chemokine profiles in patients with alopecia areata. Br J Dermatol. 2007;157(3):466–73.CrossRefPubMed
12.
go back to reference Sadeghi S, et al. Study of Th1/Th2 balance in peripheral blood mononuclear cells of patients with alopecia areata. Acta Microbiol Immunol Hung. 2015;62(3):275–85.CrossRefPubMed Sadeghi S, et al. Study of Th1/Th2 balance in peripheral blood mononuclear cells of patients with alopecia areata. Acta Microbiol Immunol Hung. 2015;62(3):275–85.CrossRefPubMed
13.
go back to reference Suarez-Farinas M, et al. Alopecia areata profiling shows TH1, TH2, and IL-23 cytokine activation without parallel TH17/TH22 skewing. J Allergy Clin Immunol. 2015;136(5):1277–87.CrossRefPubMed Suarez-Farinas M, et al. Alopecia areata profiling shows TH1, TH2, and IL-23 cytokine activation without parallel TH17/TH22 skewing. J Allergy Clin Immunol. 2015;136(5):1277–87.CrossRefPubMed
15.
go back to reference Paus R, Bertolini M. The role of hair follicle immune privilege collapse in alopecia areata: status and perspectives. J Investig Dermatol Symp Proc. 2013;16(1):S25–7.CrossRefPubMed Paus R, Bertolini M. The role of hair follicle immune privilege collapse in alopecia areata: status and perspectives. J Investig Dermatol Symp Proc. 2013;16(1):S25–7.CrossRefPubMed
16.
go back to reference Wang EH, et al. Identification of autoantigen epitopes in alopecia areata. J Invest Dermatol. 2016;136(8):1617–26. Wang EH, et al. Identification of autoantigen epitopes in alopecia areata. J Invest Dermatol. 2016;136(8):1617–26.
17.
go back to reference Tobin DJ, et al. Autoantibodies to hair follicles in C3H/HeJ mice with alopecia areata-like hair loss. J Invest Dermatol. 1997;109(3):329–33.CrossRefPubMed Tobin DJ, et al. Autoantibodies to hair follicles in C3H/HeJ mice with alopecia areata-like hair loss. J Invest Dermatol. 1997;109(3):329–33.CrossRefPubMed
18.
go back to reference Leung MC, et al. Trichohyalin is a potential major autoantigen in human alopecia areata. J Proteome Res. 2010;9(10):5153–63.CrossRefPubMed Leung MC, et al. Trichohyalin is a potential major autoantigen in human alopecia areata. J Proteome Res. 2010;9(10):5153–63.CrossRefPubMed
19.
go back to reference Sundberg JP, et al. C3H/HeJ mouse model for alopecia areata. J Invest Dermatol. 1995;104(5 Suppl):16S–7S.CrossRefPubMed Sundberg JP, et al. C3H/HeJ mouse model for alopecia areata. J Invest Dermatol. 1995;104(5 Suppl):16S–7S.CrossRefPubMed
20.
go back to reference McElwee KJ, et al. Experimental induction of alopecia areata-like hair loss in C3H/HeJ mice using full-thickness skin grafts. J Invest Dermatol. 1998;111(5):797–803.CrossRefPubMed McElwee KJ, et al. Experimental induction of alopecia areata-like hair loss in C3H/HeJ mice using full-thickness skin grafts. J Invest Dermatol. 1998;111(5):797–803.CrossRefPubMed
21.
go back to reference Wang EH, et al. Transfer of alopecia areata to C3H/HeJ mice using cultured lymph node-derived cells. J Invest Dermatol. 2015;135(10):2530–2.CrossRefPubMed Wang EH, et al. Transfer of alopecia areata to C3H/HeJ mice using cultured lymph node-derived cells. J Invest Dermatol. 2015;135(10):2530–2.CrossRefPubMed
22.
go back to reference Gilhar A, Keren A, Paus R. A new humanized mouse model for alopecia areata. J Investig Dermatol Symp Proc. 2013;16(1):S37–8.CrossRefPubMed Gilhar A, Keren A, Paus R. A new humanized mouse model for alopecia areata. J Investig Dermatol Symp Proc. 2013;16(1):S37–8.CrossRefPubMed
23.
24.
go back to reference Estefan J, et al. Alopecia areata–Part II: diagnosis and pathology. Skinmed. 2015;13(2):121–6.PubMed Estefan J, et al. Alopecia areata–Part II: diagnosis and pathology. Skinmed. 2015;13(2):121–6.PubMed
25.
go back to reference Tosti A, et al. The role of scalp dermoscopy in the diagnosis of alopecia areata incognita. J Am Acad Dermatol. 2008;59(1):64–7.CrossRefPubMed Tosti A, et al. The role of scalp dermoscopy in the diagnosis of alopecia areata incognita. J Am Acad Dermatol. 2008;59(1):64–7.CrossRefPubMed
26.
go back to reference Ardigo M, et al. Reflectance confocal microscopy of the yellow dot pattern in alopecia areata. Arch Dermatol. 2011;147(1):61–4.CrossRefPubMed Ardigo M, et al. Reflectance confocal microscopy of the yellow dot pattern in alopecia areata. Arch Dermatol. 2011;147(1):61–4.CrossRefPubMed
27.
go back to reference Hordinsky M, Donati A. Alopecia areata: an evidence-based treatment update. Am J Clin Dermatol. 2014;15(3):231–46.CrossRefPubMed Hordinsky M, Donati A. Alopecia areata: an evidence-based treatment update. Am J Clin Dermatol. 2014;15(3):231–46.CrossRefPubMed
28.
go back to reference Hordinsky MK. Current treatments for alopecia areata. J Investig Dermatol Symp Proc. 2015;17(2):44–6.CrossRefPubMed Hordinsky MK. Current treatments for alopecia areata. J Investig Dermatol Symp Proc. 2015;17(2):44–6.CrossRefPubMed
29.
go back to reference Pieri L, Guglielmelli P, Vannucchi AM. Ruxolitinib-induced reversal of alopecia universalis in a patient with essential thrombocythemia. Am J Hematol. 2015;90(1):82–3.CrossRefPubMed Pieri L, Guglielmelli P, Vannucchi AM. Ruxolitinib-induced reversal of alopecia universalis in a patient with essential thrombocythemia. Am J Hematol. 2015;90(1):82–3.CrossRefPubMed
30.
go back to reference Higgins E, et al. Use of ruxolitinib to successfully treat chronic mucocutaneous candidiasis caused by gain-of-function signal transducer and activator of transcription 1 (STAT1) mutation. J Allergy Clin Immunol. 2015;135(2):551–3.CrossRefPubMed Higgins E, et al. Use of ruxolitinib to successfully treat chronic mucocutaneous candidiasis caused by gain-of-function signal transducer and activator of transcription 1 (STAT1) mutation. J Allergy Clin Immunol. 2015;135(2):551–3.CrossRefPubMed
31.
go back to reference Kennedy Crispin M, et al. Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight. 2016;1(15):e89776.CrossRefPubMedPubMedCentral Kennedy Crispin M, et al. Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight. 2016;1(15):e89776.CrossRefPubMedPubMedCentral
32.
33.
go back to reference Patel H, et al. Association of cytotoxic T-lymphocyte antigen 4 (CTLA4) and thyroglobulin (TG) genetic variants with autoimmune hypothyroidism. PLoS One. 2016;11(3):e0149441.CrossRefPubMedPubMedCentral Patel H, et al. Association of cytotoxic T-lymphocyte antigen 4 (CTLA4) and thyroglobulin (TG) genetic variants with autoimmune hypothyroidism. PLoS One. 2016;11(3):e0149441.CrossRefPubMedPubMedCentral
34.
go back to reference Benhatchi K, et al. CTLA4 exon1 A49G polymorphism in Slovak patients with rheumatoid arthritis and Hashimoto thyroiditis-results and the review of the literature. Clin Rheumatol. 2011;30(10):1319–24.CrossRefPubMed Benhatchi K, et al. CTLA4 exon1 A49G polymorphism in Slovak patients with rheumatoid arthritis and Hashimoto thyroiditis-results and the review of the literature. Clin Rheumatol. 2011;30(10):1319–24.CrossRefPubMed
35.
go back to reference Repnik K, Potocnik U. CTLA4 CT60 single-nucleotide polymorphism is associated with Slovenian inflammatory bowel disease patients and regulates expression of CTLA4 isoforms. DNA Cell Biol. 2010;29(10):603–10.CrossRefPubMed Repnik K, Potocnik U. CTLA4 CT60 single-nucleotide polymorphism is associated with Slovenian inflammatory bowel disease patients and regulates expression of CTLA4 isoforms. DNA Cell Biol. 2010;29(10):603–10.CrossRefPubMed
36.
go back to reference Megiorni F, et al. Cytotoxic T-lymphocyte antigen 4 (CTLA4) +49AG and CT60 gene polymorphisms in alopecia areata: a case-control association study in the Italian population. Arch Dermatol Res. 2013;305(7):665–70.CrossRefPubMed Megiorni F, et al. Cytotoxic T-lymphocyte antigen 4 (CTLA4) +49AG and CT60 gene polymorphisms in alopecia areata: a case-control association study in the Italian population. Arch Dermatol Res. 2013;305(7):665–70.CrossRefPubMed
37.
go back to reference Nusslein HG, et al. Efficacy and prognostic factors of treatment retention with intravenous abatacept for rheumatoid arthritis: 24-month results from an international, prospective, real-world study. Clin Exp Rheumatol. 2016;34(3):489–99.PubMed Nusslein HG, et al. Efficacy and prognostic factors of treatment retention with intravenous abatacept for rheumatoid arthritis: 24-month results from an international, prospective, real-world study. Clin Exp Rheumatol. 2016;34(3):489–99.PubMed
38.
go back to reference Petukhova L, et al. The genetics of alopecia areata: what’s new and how will it help our patients? Dermatol Ther. 2011;24(3):326–36.CrossRefPubMed Petukhova L, et al. The genetics of alopecia areata: what’s new and how will it help our patients? Dermatol Ther. 2011;24(3):326–36.CrossRefPubMed
39.
go back to reference Ali A, Martin JMT. Hair growth in patients alopecia areata totalis after treatment with simvastatin and ezetimibe. J Drugs Dermatol. 2010;9(1):62–4.PubMed Ali A, Martin JMT. Hair growth in patients alopecia areata totalis after treatment with simvastatin and ezetimibe. J Drugs Dermatol. 2010;9(1):62–4.PubMed
40.
go back to reference Lattouf C, et al. Treatment of alopecia areata with simvastatin/ezetimibe. J Am Acad Dermatol. 2015;72(2):359–61.CrossRefPubMed Lattouf C, et al. Treatment of alopecia areata with simvastatin/ezetimibe. J Am Acad Dermatol. 2015;72(2):359–61.CrossRefPubMed
41.
go back to reference Loi C, Starace M, Piraccini BM. Alopecia areata (AA) and treatment with simvastatin/ezetimibe: experience of 20 patients. J Am Acad Dermatol. 2016;74(5):e99–100.CrossRefPubMed Loi C, Starace M, Piraccini BM. Alopecia areata (AA) and treatment with simvastatin/ezetimibe: experience of 20 patients. J Am Acad Dermatol. 2016;74(5):e99–100.CrossRefPubMed
42.
go back to reference Moreira FT, et al. Effects of two lipid lowering therapies on immune responses in hyperlipidemic subjects. Life Sci. 2014;98(2):83–7.CrossRefPubMed Moreira FT, et al. Effects of two lipid lowering therapies on immune responses in hyperlipidemic subjects. Life Sci. 2014;98(2):83–7.CrossRefPubMed
43.
go back to reference Bolduc C, Bissonnette R. Safety and efficacy of adalimumab for the treatment of severe alopecia areata: case series of three patients. J Cutan Med Surg. 2012;16(4):257–60.CrossRefPubMed Bolduc C, Bissonnette R. Safety and efficacy of adalimumab for the treatment of severe alopecia areata: case series of three patients. J Cutan Med Surg. 2012;16(4):257–60.CrossRefPubMed
44.
go back to reference Hernandez MV, et al. Development of alopecia areata after biological therapy with TNF-alpha blockers: description of a case and review of the literature. Clin Exp Rheumatol. 2009;27(5):892–3.PubMed Hernandez MV, et al. Development of alopecia areata after biological therapy with TNF-alpha blockers: description of a case and review of the literature. Clin Exp Rheumatol. 2009;27(5):892–3.PubMed
46.
go back to reference Freyschmidt-Paul P, et al. Interferon-gamma-deficient mice are resistant to the development of alopecia areata. Br J Dermatol. 2006;155(3):515–21.CrossRefPubMed Freyschmidt-Paul P, et al. Interferon-gamma-deficient mice are resistant to the development of alopecia areata. Br J Dermatol. 2006;155(3):515–21.CrossRefPubMed
47.
go back to reference Freyschmidt-Paul P, et al. The functional relevance of the type 1 cytokines IFN-gamma and IL-2 in alopecia areata of C3H/HeJ mice. J Investig Dermatol Symp Proc. 2005;10(3):282–3.CrossRefPubMed Freyschmidt-Paul P, et al. The functional relevance of the type 1 cytokines IFN-gamma and IL-2 in alopecia areata of C3H/HeJ mice. J Investig Dermatol Symp Proc. 2005;10(3):282–3.CrossRefPubMed
48.
go back to reference Pham MN, von Herrath MG, Vela JL. Antigen-specific regulatory T cells and low dose of IL-2 in treatment of type 1 diabetes. Front Immunol. 2015;6:651.PubMed Pham MN, von Herrath MG, Vela JL. Antigen-specific regulatory T cells and low dose of IL-2 in treatment of type 1 diabetes. Front Immunol. 2015;6:651.PubMed
49.
go back to reference Castela E, et al. Effects of low-dose recombinant interleukin 2 to promote T-regulatory cells in alopecia areata. JAMA Dermatol. 2014;150(7):748–51.CrossRefPubMed Castela E, et al. Effects of low-dose recombinant interleukin 2 to promote T-regulatory cells in alopecia areata. JAMA Dermatol. 2014;150(7):748–51.CrossRefPubMed
50.
go back to reference Guttman-Yassky E, et al. Extensive alopecia areata is reversed by IL-12/IL-23p40 cytokine antagonism. J Allergy Clin Immunol. 2016;137(1):301–4.CrossRefPubMed Guttman-Yassky E, et al. Extensive alopecia areata is reversed by IL-12/IL-23p40 cytokine antagonism. J Allergy Clin Immunol. 2016;137(1):301–4.CrossRefPubMed
Metadata
Title
The Changing Landscape of Alopecia Areata: The Translational Landscape
Authors
Etienne C. E. Wang
Angela M. Christiano
Publication date
01-07-2017
Publisher
Springer Healthcare
Published in
Advances in Therapy / Issue 7/2017
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-017-0540-9

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