Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle. Hair loss can take many forms ranging from loss in well-defined patches to diffuse or total hair loss, which can affect all hair-bearing sites. Patchy alopecia areata affecting the scalp is the most common type. Alopecia areata affects nearly 2% of the general population at some point during their lifetime. Skin biopsies of affected skin show a lymphocytic infiltrate in and around the bulb or the lower part of the hair follicle in the anagen (hair growth) phase. A breakdown of immune privilege of the hair follicle is thought to be an important driver of alopecia areata. Genetic studies in patients and mouse models have shown that alopecia areata is a complex, polygenic disease. Several genetic susceptibility loci were identified to be associated with signalling pathways that are important to hair follicle cycling and development. Alopecia areata is usually diagnosed based on clinical manifestations, but dermoscopy and histopathology can be helpful. Alopecia areata is difficult to manage medically, but recent advances in understanding the molecular mechanisms have revealed new treatments and the possibility of remission in the near future.
Subscribe to Journal
Get full journal access for 1 year
only $59.00 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
McElwee, K. J. et al. Comparison of alopecia areata in human and nonhuman mammalian species. Pathobiology 66, 90–107 (1998).
Xing, L. et al. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat. Med. 20, 1043–1049 (2014). On the basis of human GWAS, the JAK pathway was determined to be a therapeutic target. These initial studies reveal a potentially efficacious approach to treating patients with alopecia areata using already FDA-approved drugs.
Duvic, M. et al. The National Alopecia Areata Registry — update. J. Investig. Dermatol. Symp. Proc. 16, S53 (2013).
Petukhova, L. et al. Genome-wide association study in alopecia areata implicates both innate and adaptive immunity. Nature 466, 113–117 (2010). This is the first large-scale human genetics study on alopecia areata. It demonstrates the complexity of the genetic basis of alopecia areata. Many of the discoveries confirmed findings in mouse QTL studies reported almost a decade earlier.
Shi, Q. et al. Health-related quality of life (HRQoL) in alopecia areata patients — a secondary analysis of the National Alopecia Areata Registry data. J. Investig. Dermatol. Symp. Proc. 16, S49–S50 (2013).
Michie, H. J., Jahoda, C. A. B., Oliver, R. F. & Johnson, B. E. The DEBR rat: an animal model of human alopecia areata. Br. J. Dermatol. 125, 94–100 (1991). This is the first useable animal model reported to develop alopecia areata, which seems to have a genetic basis.
Oliver, R. et al. The DEBR rat model for alopecia areata. J. Invest. Dermatol. 96, 97S (1991).
Sundberg, J. P., Cordy, W. R. & King, L. E. Alopecia areata in aging C3H/HeJ mice. J. Invest. Dermatol. 102, 847–856 (1994). This is the first description of an inbred laboratory mouse model for alopecia areata. The disease is spontaneous, is associated with a relatively low frequency within the colony and lesions that wax and wane, making it an interesting observation but not a model that is readily amenable to experimental manipulation. Later work with full-thickness skin grafts followed by cell transfer methods provided a very useful model that remains the standard in the field.
Sundberg, J. P. et al. Major locus on mouse chromosome 17 and minor locus on chromosome 9 are linked with alopecia areata in C3H/HeJ mice. J. Invest. Dermatol. 120, 771–775 (2003). This is the first genome-wide evaluation of the complex genetics of alopecia areata in any species. Discoveries made here were later confirmed in human genetic studies.
Sundberg, J. P., Silva, K. A., Li, R., King, L. E. & Cox, G. A. Adult onset alopecia areata is a complex polygenic trait in the C3H/HeJ mouse model. J. Invest. Dermatol. 123, 294–297 (2004). This is a follow-up study on the earlier studies that expanded the number of loci.
Jabbari, A. et al. Molecular signatures define alopecia areata subtypes and transcriptional biomarkers. EBioMedicine 7, 240–247 (2016).
Gip, L., Lodin, A. & Molin, L. Alopecia areata. A follow-up investigation of outpatient material. Acta Derm. Venereol. 49, 180–188 (1969).
Walker, S. A. & Rothman, S. A statistical study and consideration of endocrine influences. J. Invest. Dermatol. 14, 403–413 (1950).
Ikeda, T. A new classification of alopecia areata. Dermatologica 131, 421–445 (1965).
Ro, B. I. Alopecia areata in Korea (1982–1994). J. Dermatol. 22, 858–864 (1995).
Safavi, K. Prevalence of alopecia areata in the First National Health and Nutrition Examination Survey. Arch. Dermatol. 128, 702 (1992). This is the most quoted publication on the epidemiology of alopecia areata.
Safavi, K. H., Muller, S. A., Suman, V. J., Moshell, A. N. & Melton, L. J. Incidence of alopecia areata in Olmstead County, Minnesota, 1975 through 1989. Mayo Clin. Proc. 70, 628–633 (1995).
Mirzoyev, S. A., Schrum, A. G., Davis, M. D. & Torgerson, R. R. Lifetime incidence risk of alopecia areata estimated at 2.1% by Rochester Epidemiology Project, 1990–2009. J. Invest. Dermatol. 134, 1141–1142 (2014).
Fricke, A. C. V. & Miteva, M. Epidemiology and burden of alopecia areata: a systematic review. Clin. Cosmet. Investig. Dermatol. 8, 397–403 (2015).
Whiting, D. A. Histopathologic features of alopecia areata. Arch. Dermatol. 139, 1555–1559 (2003).
Lundin, M. et al. Gender differences in alopecia areata. J. Drugs Dermatol. 13, 409–413 (2014).
Ranawaka, R. R. An observational study of alopecia areata in Sri Lankan adult patients. Ceylon Med. J. 59, 128–131 (2014).
Burns, T., Breathnach, S., Cox, N. & Griffiths, C. (eds) Rook's Textbook of Dermatology 8th edn (Blackwell, 2010).
Rocha, J. et al. Alopecia areata: a retrospective study of the paediatric dermatology department (2000–2008). Acta Med. Port. 24, 207–214 (in Portuguese) (2011).
Nanda, A., Al-Fouzan, A. S. & Al-Hasawi, F. Alopecia areata in children: a clinical profile. Pediatr. Dermatol. 19, 482–485 (2002).
Xiao, F. L. et al. The epidemiology of childhood alopecia areata in China: a study of 226 patients. Pediatr. Dermatol. 23, 13–18 (2006).
Kakourou, T., Karachristou, K. & Chrousos, G. A case series of alopecia areata in children: impact of personal and family history of stress and autoimmunity. J. Eur. Acad. Dermatol. Venereol. 21, 356–359 (2007).
Guzmán-Sánchez, D. A., Villanueva-Quintero, G. D., Alfaro, N. & McMichael, A. A clinical study of alopecia areata in Mexico. Int. J. Dermatol. 46, 1308–1310 (2007).
Yang, S. et al. The genetic epidemiology of alopecia areata in China. Br. J. Dermatol. 151, 16–23 (2004).
Tan, E., Tay, Y. K. & Giam, Y. C. A clinical study of childhood alopecia in Singapore. Pediatr. Dermatol. 19, 298–301 (2002).
Barsky, S. & Gigli, I. Alopecia areata in twins. Arch. Dermatol. 83, 224–225 (1961).
Bonjean, M., Prime, A. & Avon, P. Pelada in 2 homozygotic twins. Lyon Med. 219, 1852–1853 (in French) (1968).
Cole, G. W. & Herzlinger, D. Alopecia universalis in identical twins. Int. J. Dermatol. 23, 283 (1984).
Hendren, S. Identical alopecia areata in identical twins. Arch. Dermatol. 60, 793–795 (1949).
Weidman, A. I., Zion, L. S. & Mamelok, A. E. Alopecia areata occurring simultaneously in identical twins. Arch. Dermatol. 74, 424–426 (1956).
Werth, V. P., White, W. L., Sanchez, M. R. & Franks, A. G. Incidence of alopecia areata and lupus erythematosus. Arch. Dermatol. 128, 368–371 (1992).
Insler, M. S. & Helm, C. J. Alopecia areata including the cilia and eyebrows of two sisters. Ann. Ophthalmol. 21, 451–453 (1989).
Hordinsky, M. K., Hallgren, H., Nelsen, D. & Filipovich, A. H. Familial alopecia areata. HLA antigens and autoimmunity formation in an American family. Arch. Dermatol. 120, 464–468 (1984).
Van der Steen, P. et al. The genetic risk for alopecia areata in first degree relatives of severely affected patients. An estimate. Acta Derm. Venereol. 72, 373–375 (1992).
Dawn, G. & Kumar, B. Profile of alopecia areata in northern India. Int. J. Dermatol. 35, 22–27 (1996).
Barahmani, N. et al. Human leukocyte antigen class II alleles are associated with risk of alopecia areata. J. Invest. Dermatol. 128, 240–243 (2008).
Betz, R. C. et al. Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci. Nat. Commun. 6, 5966 (2015).
Chu, S. Y. et al. Comorbidity profiles among patients with alopecia areata: the importance of onset age, a nationwide population-based study. J. Am. Acad. Dermatol. 65, 949–956 (2011).
Chen, C.-H., Wang, K.-H., Lin, H.-C. & Chung, S.-D. Follow-up study on the relationship between alopecia areata and risk of autoimmune diseases. J. Dermatol. 43, 228–229 (2015).
Garzorz, N. et al. Dissecting susceptibility from exogenous triggers: the model of alopecia areata and associated inflammatory skin diseases. J. Eur. Acad. Dermatol. Venereol. 29, 2429–2435 (2015).
Lee, N. R. et al. Differences in comorbidity profiles between early-onset and late-onset alopecia areata patients: a retrospective study of 871 Korean patients. Ann. Dermatol. 26, 722–726 (2014).
Mohan, G. C. & Silverberg, J. I. Association of vitiligo and alopecia areata with atopic dermatitis: a systematic review and meta-analysis. JAMA Dermatol. 151, 522–528 (2015).
Chen, C.-H. et al. Association between herpes zoster and alopecia areata: a population-based study. J. Dermatol. 42, 824–825 (2015).
Diaz-Angulo, S., Lopez-Hoyos, M., Munoz-Cacho, P., Lopez-Escobar, M. & Gonzalez-Lopez, M. A. High prevalence of thyroid autoimmunity in patients with alopecia areata and vitiligo: a controlled study. Australas. J. Dermatol. 56, 142–143 (2015).
Kurtipek, G. S., Cihan, F. G., Demirbas, S. E. & Ataseven, A. The frequency of autoimmune thyroid disease in alopecia areata and vitiligo patients. Biomed. Res. Int. 2015, 435947 (2015).
Petukhova, L. & Christiano, A. M. The genetic architecture of alopecia areata. J. Investig. Dermatol. Symp. Proc. 16, S16–S22 (2013).
Kavak, A., Baykal, C., Ozarmagan, G. & Akar, U. HLA and alopecia areata. Int. J. Dermatol. 39, 589–592 (2000).
Hordinsky, M. K. Overview of alopecia areata. J. Investig. Dermatol. Symp. Proc. 16, S13–S15 (2013).
Colombe, B. W., Lou, C. D. & Price, V. H. The genetic basis of alopecia areata: HLA associations with patchy alopecia areata versus alopecia totalis and alopecia universalis. J. Investig. Dermatol. Symp. Proc. 4, 216–219 (1999).
Gough, S. C. & Simmonds, M. J. The HLA region and autoimmune disease: associations and mechanisms of action. Curr. Genomics 8, 453–465 (2007).
Petukhova, L. & Christiano, A. M. Functional interpretation of genome-wide association study evidence in alopecia areata. J. Invest. Dermatol. 136, 314–317 (2016).
Carroll, J., McElwee, K. J., King, L. E., Byrne, M. C. & Sundberg, J. P. Gene array profiling and immunomodulation studies define a cell mediated immune response underlying the pathogenesis of alopecia areata in a mouse model and humans. J. Invest. Dermatol. 119, 392–402 (2002). This is the first transcriptome analysis of alopecia areata in both humans and laboratory mice. The lymphocyte co-stimulatory cascade was identified as the underlying molecular pathway and was blocked at several points with monoclonal antibodies, pointing towards novel therapeutic approaches, some of which are now in clinical trials.
McPhee, C. G. et al. Gene expression studies identify Cxcr3 and its ligands. Cxcl9, Cxcl10, andCxcl11in the pathogenesis of alopecia areata in the mouse. J. Invest. Dermatol. 132, 1736–1738 (2012).
Fischer, J. et al. Genome-wide analysis of copy number variants in alopecia areata in a Central European cohort reveals association with MCHR2. Exp. Dermatol. http://dx.doi.org/10.1111/exd.13123 (2016).
Rice, R. H. et al. Differentiating inbred mouse strains from each other and those with single gene mutations using hair proteomics. PLoS ONE 7, e51956 (2012).
Rice, R. H. et al. Distinguishing mouse strains by proteomic analysis of pelage hair. J. Invest. Dermatol. 129, 2120–2125 (2009).
Sundberg, J. P. et al. Crisp1 and alopecia areata in C3H/HeJ mice. Exp. Mol. Pathol. 97, 525–528 (2014).
Eckert, J., Church, R. E. & Ebling, F. J. The pathogenesis of alopecia areata. Br. J. Dermatol. 80, 203–210 (1968).
Messenger, A. G., Slater, D. N. & Bleehen, S. S. Alopecia areata: alterations in the hair growth cycle and correlation with the follicular pathology. Br. J. Dermatol. 114, 337–347 (1986).
VanScott, E. J. Morphologic changes in pilosebaceous units and anagen hairs in alopecia areata. J. Invest. Dermatol. 31, 35–43 (1958).
Chase, H. B., Rauch, H. & Smith, V. W. Critical stages of hair development and pigmentation in the mouse. Physiol. Zool. 24, 1–8 (1951).
Thies, W. Comparative histologic studies in alopecia areata and scar-atrophy alopecia. Arch. Klin. Exp. Dermatol. 227, 541–549 (in German) (1966).
Messenger, A. G. & Bleehen, S. S. Alopecia areata: light and electron microscopic pathology of the regrowing white hair. Br. J. Dermatol. 110, 155–162 (1984).
Paus, R., Slominski, A. & Czarnetzki, B. M. Is alopecia areata an autoimmune-response against melanogenesis-related proteins exposed by abnormal MHC class I expression in the anagen hair bulb? Yale J. Biol. Med. 66, 541–554 (1993). Although this is primarily an opinion paper, it set the focus of research for the next two decades. Much of the work was proven to be correct in both patients and animal models.
Tharumanathan, S. Understanding the biological mechanism of alopecia areata. Am. J. Dermatol. Venereol. 4, 1–4 (2015).
Paus, R. & Bertolini, M. The role of hair follicle immune privilege collapse in alopecia areata: status and perspectives. J. Investig. Dermatol. Symp. Proc. 16, S25–S27 (2013).
Paus, R., Nickoloff, B. J. & Ito, T. A “hairy” privilege. Trends Immunol. 26, 32–40 (2005).
Meyer, K. C. et al. Evidence that the bulge region is a site of relative immune privilege in human hair follicles. Br. J. Dermatol. 159, 1077–1085 (2008).
Ito, T., Meyer, K. C., Ito, N. & Paus, R. Immune privilege and the skin. Curr. Dir. Autoimmun. 10, 27–52 (2008).
Trautman, S., Thompson, M., Roberts, J. & Thompson, C. T. Melanocytes: a possible autoimmune target in alopecia areata. J. Am. Acad. Dermatol. 61, 529–530 (2009).
Ito, T. et al. Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack. J. Invest. Dermatol. 128, 1196–1206 (2008).
Bertolini, M. et al. Vasoactive intestinal peptide, whose receptor-mediated signalling may be defective in alopecia areata, provides protection from hair follicle immune privilege collapse. Br. J. Dermatol. 175, 531–541 (2016).
Finner, A. M. Alopecia areata: clinical presentation, diagnosis, and unusual cases. Dermatol. Ther. 24, 348–354 (2011).
Messenger, A. G. & Bleehen, S. S. Expression of HLA-DR by anagen hair follicles in alopecia areata. J. Invest. Dermatol. 85, 569–572 (1985).
Paus, R., Slominski, A. & Czarnetzki, B. M. Is alopecia areata an autoimmune-response against melanogenesis-related proteins, exposed by abnormal MHC class I expression in the anagen hair bulb? Yale J. Biol. Med. 66, 541–554 (1993).
Gilhar, A. et al. Melanocyte-associated T cell epitopes can function as autoantigens for transfer of alopecia areata to human scalp explants on Prkdcscid mice. J. Invest. Dermatol. 117, 1357–1362 (2001).
Erb, U., Freyschmidt-Paul, P. & Zö ller, M. Tolerance induction by hair-specific keratins in murine alopecia areata. J. Leukoc. Biol. 94, 845–857 (2013).
Wang, E. H. et al. Identification of autoantigen epitopes in alopecia areata. J. Invest. Dermatol. 136, 1617–1626 (2016).
Alzolibani, A. A. Preferential recognition of hydroxyl radical-modified superoxide dismutase by circulating autoantibodies in patients with alopecia areata. Ann. Dermatol. 26, 576–583 (2014).
Kalkan, G. et al. Relationship between manganese superoxide dismutase (MnSODAla-9Val) and glutathione peroxidase (GPx1 Pro 197 Leu) gene polymorphisms and alopecia areata. Int. J. Exp. Med. 8, 21533–21540 (2015).
Fattah, N. S. A., Ebrahim, A. & Okda, E. S. E. Lipid peroxidation/antioxidant activity in patients with alopecia areata. J. Eur. Acad. Dermatol. Venereol. 25, 403–408 (2011).
Mijailović, B., Mladenović, T., Hrnjak, M., Karadaglić, D. & Nikolić, B. Contact thermometry of lesions in alopecia areata. Vojnosanit. Pregl. 54, 31–33 (in Serbian) (1997).
Skoutelis, A., Freinkel, R. K., Kaufman, D. S. & Leibovich, S. J. Angiogenic activity is defective in monocytes from patients with alopecia universalis. J. Invest. Dermatol. 95, 139–143 (1990).
Popchristov, P., Konstantinov, A. & Obreshkova, E. The blood vessels of the scalp in patients with alopecia areata before and after corticosteroid therapy. Br. J. Dermatol. 80, 753–757 (1968).
Karaman, S. et al. Decline of lymphatic vessel density and function in murine skin during aging. Angiogenesis 18, 489–498 (2015).
Sundberg, J. P. et al. Dermal lymphatic dilation in a mouse model of alopecia areata. Exp. Mol. Pathol. 100, 332–336 (2016).
Sundberg, J. P., Elson, C. O., Bedigian, H. & Birkenmeier, E. H. Spontaneous, heritable colitis in a new substrain of C3H/HeJ mice. Gastroenterology 107, 1726–1735 (1994).
Safina, D. D., Abdulkhakov, R. A., Abdulkhakov, S. R., Odintsova, A. K. & Cheremina, N. A. Clinical case of a combination of ulcerative colitis and alopecia areata. Eksp. Klin. Gastroenterol. 2013, 92–96 (in Russian) (2013).
McElwee, K. J., Boggess, D., King, L. E. & Sundberg, J. P. Experimental induction of alopecia areata-like hair loss in C3H/HeJ mice using full-thickness skin grafts. J. Invest. Dermatol. 111, 797–803 (1998). This paper describes the methods of using full-thickness skin grafts to induce or transfer alopecia areata from an affected inbred mouse to another histocompatible inbred mouse in a reproducible manner. Disease progressed in a predictable manner, which allowed experimental manipulation. Later studies refined this method with various cell transfer methods.
McElwee, K. J. et al. Dietary soy oil content and soy derived phytoestrogen genistein increase resistance to alopecia areata onset in C3H/HeJ mice. Exp. Dermatol. 12, 30–36 (2003).
Chu, C.-H., Cheng, Y.-P. & Chan, J.-Y. L. Alopecia areata after vaccination: recurrence with rechallenge. Pediatr. Dermatol. 33, e218–e219 (2016).
Wise, R., Kiminyo, K. & Salive, M. Hair loss after routine vaccination. JAMA 278, 1176–1178 (1997).
Sánchez-Ramón, S., Gil, J., Cianchetta-Sí vori, M. & Ferná ndez-Cruz, E. Alopecia universalis in an adult after routine tetanus toxoid vaccine. Med. Clin. (Barc.) 136, 318 (in Spanish) (2011).
Lai, Y. C. & Yew, Y. W. Severe autoimmune adverse events post herpes zoster vaccine: a case–control study of adverse events in a national database. J. Drugs Dermatol. 14, 681–684 (2015).
Geier, D. A. & Geier, M. R. A case–control study of quadrivalent human papillomavirus vaccine-associated autoimmune adverse events. Clin. Rheumatol. 34, 1225–1231 (2015).
Ito, T. & Tokura, Y. Alopecia areata triggered or exacerbated by swine flu virus infection. J. Dermatol. 39, 863–864 (2012).
Sundberg, J. P. et al. Recombinant human hepatitis B vaccine initiating alopecia areata: testing the hypothesis using the C3H/HeJ mouse model. Vet. Dermatol. 20, 99–104 (2009).
Sundberg, J. P., McElwee, K. J., Brehm, M. A., Su, L. & King, L. E. Animal models for alopecia areata: what and where? J. Investig. Dermatol. Symp. Proc. 17, 23–26 (2015).
Gilhar, A., Schrum, A. G., Etzioni, A., Waldman, H. & Paus, R. Alopecia areata: animal models illuminate autoimmune pathogenesis and novel immunotherapeutic strategies. Autoimmun. Rev. 15, 726–735 (2016).
Sundberg, J. P., Nanney, L. B., Fleckman, P. & King, L. E. Jr in Comparative Anatomy and Histology. A Mouse and Human Atlas (eds Treuting, P., Dintzis, S., Fervert, C. W., Liggitt, D. & Montine, K. S. ) 433–455 (Academic Press, 2012).
Sundberg, J. P. & King, L. E. in Pathology of Genetically Engineered Mice (eds Ward, J. M., Mahler, J. F., Maronpot, R. R. & Sundberg, J. P. ) 181–213 (Iowa State University Press, 2000).
Freyschmidt-Paul, P. et al. Treatment of alopecia areata in C3H/HeJ mice with the topical immunosuppressant FK506 (Tacrolimus). Eur. J. Dermatol. 11, 405–409 (2001).
Sun, J., Silva, K. A., McElwee, K. J., King, L. E. & Sundberg, J. P. The C3H/HeJ mouse and DEBR rat models for alopecia areata: preclinical drug screening tools. Exp. Dermatol. 17, 793–805 (2008).
Harries, M. J., Sun, J., Paus, R. & King, L. E. Management of alopecia areata. BMJ 341, c3671 (2010).
McElwee, K., Boggess, D., Miller, J., King, L. & Sundberg, J. Spontaneous alopecia areata-like hair loss in one congenic and seven inbred laboratory mouse strains. J. Investig. Dermatol. Symp. Proc. 4, 202–206 (1999).
Sundberg, J. P. et al. Mouse alopecia areata and heart disease: know your mouse! J. Invest. Dermatol. 134, 279–281 (2014).
Poltorak, A. et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085–2088 (1998).
Berning, A. K., Eicher, E. M., Paul, W. E. & Scher, I. Mapping of the X-linked immune deficiency mutation (xid) of CBA/N mice. J. Immunol. 124, 1875–1877 (1980).
King, L. E., McElwee, K. J. & Sundberg, J. P. in Dermatologic Immunity: Current Directions in Autoimmunity (eds Nickoloff, B. J. & Nestle, F. O. ) 280–312 (Karger, 2008).
Alli, R., Nguyen, P., Boyd, K., Sundberg, J. P. & Geiger, T. L. A mouse model of clonal CD8+ T lymphocyte-mediated alopecia areata progressing to alopecia universalis. J. Immunol. 188, 477–486 (2012).
McElwee, K. J. et al. Alopecia areata in C3H/HeJ mice involves leucocyte-mediated root sheath disruption in advance of overt hair loss. Vet. Pathol. 40, 643–650 (2003).
Silva, K. A. & Sundberg, J. P. Surgical methods for full thickness skin grafts to induce alopecia areata in C3H/HeJ mice. Comp. Med. 63, 392–397 (2013).
McElwee, K. J. et al. Transfer of CD8+ cells induces localized hair loss whereas CD4+/CD25− cells promote systemic alopecia areata and CD4+/CD25+ cells blockade disease onset in the C3H/HeJ mouse model. J. Invest. Dermatol. 124, 947–957 (2005).
Gilhar, A. et al. Autoimmune disease induction in a healthy human organ: a humanized mouse model of alopecia areata. J. Invest. Dermatol. 133, 844–847 (2013).
Restrepo, R. & Calonje, E. in McKee's Pathologyof the Skin (eds Calonje, E., Brenn, T., Lazar, A. & McKee, P. H. ) 967–1050 (Elsevier, 2012).
Messenger, A. G., Sinclair, R. D., Farrant, P. & de Berker, D. A. R. in Rook's Textbook of Dermatology 9th edn (eds Griffiths, C., Barker, J., Bleiker, T., Chalmers, R. & Creamer, D. ) 1–88 (Wiley-Blackwell, 2016).
McElwee, K. J., Silva, K., Beamer, W. G., King, L. E. & Sundberg, J. P. Melanocyte and gonad activity as potential modifying factors in C3H/HeJ mouse alopecia areata. Exp. Dermatol. 10, 420–429 (2001).
Gandhi, V., Baruah, M. C. & Bhattacharaya, S. N. Nail changes in alopecia areata: incidence and pattern. Indian J. Dermatol. Venereol. Leprol. 69, 114–115 (2003).
Kasumagic-Halilovic, E. & Prohic, A. Nail changes in alopecia areata: frequency and clinical presentation. J. Eur. Acad. Dermatol. Venereol. 23, 240–241 (2009).
Sharma, V. K., Dawn, G., Muralidhar, S. & Kumar, B. Nail changes in 1000 Indian patients with alopecia areata. Eur. J. Acad. Dermatol. Venereol. 10, 189–191 (1998).
Tosti, A., Bellavista, S. & Iorizzo, M. Alopecia areata: a long term follow-up study of 191 patients. J. Am. Acad. Dermatol. 55, 438–441 (2006).
De Waard-van der Spek, F. B., Oranje, A. P., De Raeymaecker, D. M. & Peereboom-Wynia, J. D. Juvenile versus maturity-onset alopecia areata — a comparative retrospective clinical study. Clin. Exp. Dermatol. 14, 429–433 (1989).
Sharma, V. K., Dawn, G. & Kumar, B. Profile of alopecia areata in northern India. Int. J. Dermatol. 35, 22–27 (1996).
Tan, E., Tay, Y. K., Goh, C. L. & Giam, Y. C. The pattern and profile of alopecia areata in Singapore — a study of 219 Asians. Int. J. Dermatol. 41, 748–753 (2002).
Goh, C., Finkel, M., Christos, P. J. & Sinha, A. A. Profile of 513 patients with alopecia areata: associations of disease subtypes with atopy, autoimmune disease and positive family history. J. Eur. Acad. Dermatol. Venereol. 20, 1055–1060 (2006).
Olsen, E. A. et al. Alopecia areata investigational assessment guidelines — part II. National Alopecia Areata Foundation. J. Am. Acad. Dermatol. 51, 440–447 (2004).
Jang, Y. H. et al. Alopecia areata progression index, a scoring system for evaluating overall hair loss activity in alopecia areata patients with pigmented hair: a development and reliability assessment. Dermatology 232, 143–149 (2016).
Mubki, T., Rudnicka, L., Olszewska, M. & Shapiro, J. Evaluation and diagnosis of the hair loss patient: part II. Trichoscopic and laboratory evaluations. J. Am. Acad. Dermatol. 71, 431.e1–431.e11 (2014).
Zlotogorski, A., Panteleyev, A. A., Aita, V. M. & Christiano, A. M. Clinical and molecular diagnostic criteria of congenital atrichia with papular lesions. J. Invest. Dermatol. 118, 887–890 (2002).
Miller, J. et al. Atrichia caused by mutations in the vitamin D receptor gene is a phenocopy of generalized atrichia caused by mutations in the hairless gene. J. Invest. Dermatol. 117, 612–617 (2001).
Delamere, F. M., Sladden, M. M., Dobbins, H. M. & Leonardi-Bee, J. Interventions for alopecia areata. Cochrane Database Syst. Rev. 16, CD004413 (2008).
Messenger, A. G., McKillop, J., Farrant, P., McDonagh, A. J. & Sladden, M. British Association of Dermatologists' guidelines for the management of alopecia areata 2012. Br. J. Dermatol. 166, 916–926 (2012).
Charuwichitratana, S., Wattanakrai, P. & Tanrattanakorn, S. Randomized double-blind placebo-controlled trial in the treatment of alopecia areata with 0.25% desoximetasone cream. Arch. Dermatol. 136, 1276–1277 (2000).
Tosti, A., Piraccini, B. M., Pazzaglia, M. & Vincenzi, C. Clobetasol propionate 0.05% under occlusion in the treatment of alopecia totalis/universalis. J. Am. Acad. Dermatol. 49, 96–98 (2003).
Tosti, A., Iorizzo, M., Botta, G. L. & Milani, M. Efficacy and safety of a new clobetasol propionate 0.05% foam in alopecia areata: a randomized, double-blind placebo-controlled trial. J. Eur. Acad. Dermatol. Venereol. 20, 1243–1247 (2006).
Solomon, I. L. & Green, O. C. Monilethrix: its occurrence in seven generations, with one case that responded to endocrine therapy. N. Engl. J. Med. 269, 1279–1282 (1963).
Kubeyinje, E. P. Intralesional triamcinolone acetonide in alopecia areata amongst 62 Saudi Arabs. East Afr. Med. J. 71, 674–675 (1994).
Fuentes-Duculan, J. et al. Biomarkers of alopecia areata disease activity and response to corticosteroid treatment. Exp. Dermatol. 25, 282–286 (2016).
Olsen, E. A., Carson, S. C. & Turney, E. A. Systemic steroids with or without 2% topical minoxidil in the treatment of alopecia areata. Arch. Dermatol. 128, 1467–1473 (1992).
Sharma, V. K. & Gupta, S. Twice weekly 5 mg dexamethasone oral pulse in the treatment of extensive alopecia areata. J. Dermatol. 26, 562–565 (1999).
Nakajima, T., Inui, S. & Itami, S. Pulse corticosteroid therapy for alopecia areata: study of 139 patients. Dermatology 215, 320–324 (2007).
Yang, C. C. et al. Early intervention with high-dose steroid pulse therapy prolongs disease-free interval of severe alopecia areata: a retrospective study. Ann. Dermatol. 25, 471–474 (2013).
Kar, B. R., Handa, S., Dogra, S. & Kumar, B. Placebo-controlled oral pulse prednisolone therapy in alopecia areata. J. Am. Acad. Dermatol. 52, 287–290 (2005).
Happle, R. Antigenic competition as a therapeutic concept for alopecia areata. Arch. Dermatol. Res. 267, 109–114 (1980). This paper provides an early approach to treating alopecia areata; the topical application of potent allergens has been used extensively in Europe and Canada for decades.
Bröcker, E. B., Echternacht-Happle, K., Hamm, H. & Happle, R. Abnormal expression of class I and class II major histocompatibility antigens in alopecia areata: modulation by topical immunotherapy. J. Invest. Dermatol. 88, 564–568 (1987).
Hoffmann, R. et al. Growth factor mRNA in alopecia areata before and after treatment with the contact allergen diphenylcyclopropenone. Acta Derm. Venereol. 76, 17–20 (1996).
Marhaba, R. et al. The importance of myeloid-derived suppressor cells in the regulation of autoimmune effector cells by a chronic contact eczema. J. Immunol. 179, 5071–5081 (2007).
Rokhsar, C. K., Shupack, J. L., Vafai, J. J. & Washenik, K. Efficacy of topical sensitizers in the treatment of alopecia areata. J. Am. Acad. Dermatol. 39, 751–761 (1998).
Van der Steen, P. H. M., Van Baar, H. M. J., Happle, R., Boezeman, J. B. M. & Perret, C. M. Prognostic factors in the treatment of alopecia areata with diphenylcyclopropenone. J. Am. Acad. Dermatol. 24, 227–230 (1991).
Gordon, P. M., Aldrige, R. D., McVittie, E. & Hunter, J. A. Topical diphencyprone for alopecia areata: evaluation of 48 cases after 30 months' follow-up. Br. J. Dermatol. 134, 869–871 (1996).
Wiseman, M. C., Shapiro, J., MacDonald, N. & Lui, H. Predictive model for immunotherapy of alopecia areata with diphencyprone. Arch. Dermatol. 137, 1063–1068 (2001).
Hull, S. M., Pepall, L. & Cunliffe, W. J. Alopecia areata in children: response to treatment with diphencyprone. Br. J. Dermatol. 125, 164–168 (1991).
Schuttelaar, M. L. et al. Alopecia areata in children: treatment with diphencyprone. Br. J. Dermatol. 135, 581–585 (1996).
Tosti, A., Guidetti, M. S., Bardazzi, F. & Misciali, C. Long-term results of topical immunotherapy in children with alopecia totalis or alopecia universalis. J. Am. Acad. Dermatol. 35, 199–201 (1996).
Tosti, A., Guerra, L. & Bardazzi, F. Contact urticaria during topical immunotherapy. Contact Dermatitis 21, 196–197 (1989).
MacDonald-Hull, S. P., Cotterill, J. A. & Norris, J. F. Vitiligo following diphencyprone dermatitis. Br. J. Dermatol. 120, 323 (1989).
Joly, P. The use of methotrexate alone or in combination with low doses of oral corticosteroids in the treatment of alopecia totalis or universalis. J. Am. Acad. Dermatol. 55, 632–636 (2006).
Hammerschmidt, M. & Brenner, F. M. Efficacy and safety of methotrexate in alopecia areata. An. Bras. Dermatol. 89, 729–734 (2014).
Anuset, D., Perceau, G., Bernard, P. & Reguiai, Z. Efficacy and safety of methotrexate combined with low- to moderate-dose corticosteroids for severe alopecia areata. Dermatology 232, 242–248 (2016).
Shapiro, J., Lui, H., Tron, V. & Ho, V. Systemic cyclosporine and low-dose prednisone in the treatment of chronic severe alopecia areata. J. Am. Acad. Dermatol. 36, 114–117 (1997).
Price, V. H., Willey, A. & Chen, B. K. Topical tacrolimus in alopecia areata. J. Am. Acad. Dermatol. 52, 138–139 (2005).
Strober, B. E. et al. Etanercept does not effectively treat moderate to severe alopecia areata: an open-label study. J. Am. Acad. Dermatol. 52, 1082–1084 (2005).
Ferran, M., Calvet, J., Almirall, M., Pujol, R. M. & Maymó, J. Alopecia areata as another immune-mediated disease developed in patients treated with tumour necrosis factor-α blocker agents: report of five cases and review of the literature. J. Eur. Acad. Dermatol. Venereol. 25, 479–484 (2011).
Tauber, M. et al. Alopecia areata occurring during anti-TNF therapy: a national multicenter prospective study. J. Am. Acad. Dermatol. 70, 1146–1149 (2014).
Price, V. H. et al. Subcutaneous efalizumab is not effective in the treatment of alopecia areata. J. Am. Acad. Dermatol. 58, 395–402 (2008).
Strober, B. E. et al. Alefacept for severe alopecia areata: a randomized, double-blind, placebo-controlled study. Arch. Dermatol. 145, 262–266 (2009).
Byun, J. W., Moon, J. H., Bang, C. Y., Shin, J. & Choi, G. S. Effectiveness of 308-nm excimer laser therapy in treating alopecia areata, determined by examining the treated sides of selected alopecic patches. Dermatology 231, 70–76 (2015).
Mlacker, S. et al. A review on laser and light-based therapies for alopecia areata. J. Cosmet. Laser Ther. http://dx.doi.org/10.1080/14764172.2016.1248440 (2017).
King, L. E., Silva, K. A., Kennedy, V. E. & Sundberg, J. P. Lack of response to laser comb in spontaneous and graft-induced alopecia areata in C3H/HeJ mice. J. Invest. Dermatol. 134, 264–266 (2014).
Claudy, A. L. & Gagnaire, D. PUVA treatment of alopecia areata. Arch. Dermatol. 119, 975–978 (1983).
Lassus, A., Eskelinen, A. & Johansson, E. Treatment of alopecia areata with three different PUVA modalities. Photodermatology 1, 141–144 (1984).
Mitchell, A. J. & Douglass, M. C. Topical photochemotherapy for alopecia areata. J. Am. Acad. Dermatol. 12, 644–649 (1985).
Taylor, C. R. & Hawk, J. L. PUVA treatment of alopecia areata partialis, totalis and universalis: audit of 10 years' experience at St John's Institute of Dermatology. Br. J. Dermatol. 133, 914–918 (1995).
Healy, E. & Rogers, S. PUVA treatment for alopecia areata — does it work? A retrospective review of 102 cases. Br. J. Dermatol. 129, 42–44 (1993).
Hunt, N. & McHale, S. The psychological impact of alopecia. BMJ 331, 951–953 (2005).
Bilgiç, Ö. et al. Psychiatric symptomatology and health-related quality of life in children and adolescents with alopecia areata. J. Eur. Acad. Dermatol. Venereol. 28, 1463–1468 (2014).
Karimkhani, C. et al. Global burden of skin disease as reflected in Cochrane Database of Systematic Reviews. JAMA Dermatol. 150, 945–951 (2014).
Rencz, F. et al. Alopecia areata and health-related quality of life: a systematic review and meta-analysis. Br. J. Dermatol. 175, 561–571 (2016).
Liu, L. Y., King, B. A. & Craiglow, B. G. Health-related quality of life (HRQoL) among patients with alopecia areata (AA): a systematic review. J. Am. Acad. Dermatol. 75, 806–812 (2016).
Cartwright, T., Endean, N. & Porter, A. Illness perceptions, coping and quality of life in patients with alopecia. Br. J. Dermatol. 160, 1034–1039 (2009).
Lebwohl, M., Heymann, W., Berth-Jones, J. & Coulson, I. Treatment of Skin Disease: Comprehensive Therapeutic Strategies (Expert Consult — Online and Print) 4th edn (Saunders, 2014).
Sundberg, J. P., McElwee, K. J., Carroll, J. M. & King, L. E. Jr. Hypothesis testing: CTLA4 costimulatory pathways critical in pathogenesis of human and mouse alopecia areata. J. Invest. Dermatol. 131, 2323–2324 (2011).
John, K. K.-G. et al. Genetic variants in CTLA4 are strongly associated with alopecia areata. J. Invest. Dermatol. 131, 1169–1172 (2011).
Ghoreishi, M., Martinka, M. & Dutz, J. P. Type 1 interferon signature in the scalp lesions of alopecia areata. Br. J. Dermatol. 163, 57–62 (2010).
Subramanya, R. D., Coda, A. B. & Sinha, A. A. Transcriptional profiling in alopecia areata defines immune and cell cycle control related genes within disease-specific signatures. Genomics 96, 146–153 (2010).
Dai, Z. et al. CXCR3 blockade inhibits T cell migration into the skin and prevents development of alopecia areata. J. Immunol. 197, 1089–1099 (2016).
Guttman-Yassky, E. et al. Extensive alopecia areata is reversed by IL-12/IL-23p40 cytokine antagonism. J. Allergy Clin. Immunol. 137, 301–304 (2016).
US National Library of Medicine. ClinicalTrials.govhttps://clinicaltrials.gov/ct2/show/NCT02599129 (2017).
Craiglow, B. G. & King, B. A. Killing two birds with one stone: oral tofacitinib reverses alopecia universalis in a patient with plaque psoriasis. J. Invest. Dermatol. 134, 2988–2990 (2014).
Dhayalan, A. & King, B. A. Tofacitinib citrate for the treatment of nail dystrophy associated with alopecia universalis. JAMA Dermatol. 152, 492–493 (2016).
Gupta, A. K., Carviel, J. L. & Abramovits, W. Efficacy of tofacitinib in treatment of alopecia universalis in two patients. J. Eur. Acad. Dermatol. Venereol. 30, 1373–1378 (2016).
Crispin, M. K. et al. Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight 1, e89776 (2016).
Liu, L. Y., Craiglow, B. G., Dai, F. & King, B. A. Tofacitinib for the treatment of severe alopecia areata and variants: a study of 90 patients. J. Eur. Acad. Dermatol. Venereol. 76, 22–28 (2016).
Pieri, L., Guglielmelli, P. & Vannucchi, A. M. Ruxolitinib-induced reversal of alopecia universalis in a patient with essential thrombocythemia. Am. J. Hematol. 90, 82–83 (2015).
Mackay-Wiggan, J. et al. Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. JCI Insight 1, e89790 (2016).
Jabbari, A. et al. Reversal of alopecia areata following treatment with the JAK1/2 inhibitor baricitinib. EBioMedicine 2, 351–355 (2015).
Anzengruber, F. et al. Transient efficacy of tofacitinib in alopecia areata universalis. Case Rep. Dermatol. 8, 102–106 (2016).
Li, Y. et al. Hair regrowth in alopecia areata patients following stem cell educator therapy. BMC Med. 13, 87 (2015).
Sperling, L. C., Cowper, S. E. & Knopp, E. A. An Atlas of Hair Pathology with Clinical Correlations 2nd edn (CRC Press, 2012).
Navarini, A. A., Nobbe, S. & Trü eb, R. M. Marie Antoinette syndrome. Arch. Dermatol. 145, 656 (2009).
Forstbauer, L. M. et al. Genome-wide pooling approach identifies SPATA5 as a new susceptibility locus for alopecia areata. Eur. J. Hum. Genet. 20, 326–332 (2012).
Jagielska, D. et al. Follow-up study of the first genome-wide association scan in alopecia areata: IL13 and KIAA0350 as susceptibility loci supported with genome-wide significance. J. Invest. Dermatol. 132, 2192–2197 (2012).
Messenger, A. G., Sinclair, R. D., Farrant, P. & de Berker, D. A. R. in Rook's Textbook of Dermatology 9th edn (eds Griffiths, C., Barker, J., Bleiker, T., Chalmers, R. & Creamer, D. ) 89 (Wiley-Blackwell, 2016).
Bohm, M. in European Handbook of Dermatological Treatments (eds Katsambas, A. D., Lotti, T. M., Dessinioti, C, & D'Erme, A. M. ) 45–53 (Springer Berlin Heidelberg, 2015).
This work was supported in part by grants from the US NIH (R01AR056635 to J.P.S.; and P50AR070588, R01AR065963, R01AR056016, U01AR067173 and R21AR061881 to A.M.C.) and the National Alopecia Areata Foundation (L.E.K., A.M.C. and J.P.S.). Core facilities at The Jackson Laboratory were supported by the US National Cancer Institute (CA034196).
L.E.K. is on the scientific advisory committee for the National Alopecia Areata Foundation (NAAF) and the Cicatricial Alopecia Research Foundation (CARF). A.M.C. is on the scientific advisory committee for the NAAF and is a consultant for Aclaris Therapeutics, Inc. J.P.S. has or has had sponsored research contract with Biocon and the NAAF for preclinical trials using mouse models for alopecia areata, and is on the scientific advisory committee for the NAAF and is Chairman for the CARF. C.H.P. and A.G.M. have no competing interests.
About this article
Cite this article
Pratt, C., King, L., Messenger, A. et al. Alopecia areata. Nat Rev Dis Primers 3, 17011 (2017). https://doi.org/10.1038/nrdp.2017.11
Efficacy of systemic minoxidil and tofacitinib combination in treatment‐resistant alopecia universalis
Journal of Cosmetic Dermatology (2020)
NFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices
Nature Cell Biology (2020)
Alopecia areata in patients with systemic lupus erythematosus treated with belimumab: a plausible association
Journal of Investigative Dermatology Symposium Proceedings (2020)
British Journal of Dermatology (2020)