Journal of the American Academy of Dermatology
Volume 62, Issue 2 , Pages 177-188 , February 2010

Alopecia areata update: Part I. Clinical picture, histopathology, and pathogenesis

  • Abdullah Alkhalifah, MD

      Affiliations

    • Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada
    • ,
  • Adel Alsantali, MD

      Affiliations

    • Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada
    • ,
  • Eddy Wang, BSc

      Affiliations

    • Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada
    • ,
  • Kevin J. McElwee, PhD

      Affiliations

    • Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada
    • ,
  • Jerry Shapiro, MD

      Affiliations

    • Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Dermatology, New York University, New York, New York
    • Corresponding Author InformationReprint requests: Jerry Shapiro, MD, University of British Columbia Skin Care Center, 835 W 10th Ave, Vancouver, BC, V5Z 4E8, Canada.

References 

  1. Sharma VK, Dawn G, Kumar B. Profile of alopecia areata in Northern India. Int J Dermatol. 1996;35:22–27
  2. Tan E, Tay YK, Goh CL, Chin Giam Y. The pattern and profile of alopecia areata in Singapore—a study of 219 Asians. Int J Dermatol. 2002;41:748–753
  3. Safavi K. Prevalence of alopecia areata in the First National Health and Nutrition Examination Survey. Arch Dermatol. 1992;128:702
  4. Safavi KH, Muller SA, Suman VJ, Moshell AN, Melton LJ. Incidence of alopecia areata in Olmsted County, Minnesota, 1975 through 1989. Mayo Clin Proc. 1995;70:628–633
  5. Wasserman D, Guzman-Sanchez DA, Scott K, McMichael A. Alopecia areata. Int J Dermatol. 2007;46:121–131
  6. Kyriakis KP, Paltatzidou K, Kosma E, Sofouri E, Tadros A, Rachioti E. Alopecia areata prevalence by gender and age. J Eur Acad Dermatol Venereol. 2009;23:572–573
  7. Kavak A, Yesildal N, Parlak A, Gokdemir G, Aydogan I, Anul H, et al. Alopecia areata in Turkey: demographic and clinical features. J Eur Acad Dermatol Venereol. 2008;22:977–981
  8. Nanda A, Al-Fouzan AS, Al-Hasawi F. Alopecia areata in children: a clinical profile. Pediatr Dermatol. 2002;19:482–485
  9. Price VH. Alopecia areata: clinical aspects. J Invest Dermatol. 1991;96:68S
  10. de Berker DAR, Messenger AG, Sinclair RD. Disorders of hair. In:  Burns DA,  Breathnach SM,  Cox N,  Griffiths CE editor. 7th ed. Rook's textbook of dermatology. Vol. 4:Oxford: Wiley-Blackwell; 2004;p. 63.1-63.120
  11. Madani S, Shapiro J. Alopecia areata update. J Am Acad Dermatol. 2000;42:549–566
  12. Shapiro J, Madani S. Alopecia areata: diagnosis and management. Int J Dermatol. 1999;38(suppl 1):19–24
  13. Price VH. Therapy of alopecia areata: on the cusp and in the future. J Investig Dermatol Symp Proc. 2003;8:207–211
  14. Sato-Kawamura M, Aiba S, Tagami H. Acute diffuse and total alopecia of the female scalp. A new subtype of diffuse alopecia areata that has a favorable prognosis. Dermatology. 2002;205:367–373
  15. Lew BL, Shin MK, Sim WY. Acute diffuse and total alopecia: a new subtype of alopecia areata with a favorable prognosis. J Am Acad Dermatol. 2009;60:85–93
  16. Tosti A, Whiting D, Iorizzo M, Pazzaglia M, Misciali C, Vincenzi C, et al. The role of scalp dermoscopy in the diagnosis of alopecia areata incognita. J Am Acad Dermatol. 2008;59:64–67
  17. Ross EK, Vincenzi C, Tosti A. Videodermoscopy in the evaluation of hair and scalp disorders. J Am Acad Dermatol. 2006;55:799–806
  18. Rakowska A, Slowinska M, Kowalska-Oledzka E, Olszewska M, Czuwara J, Rudnicka L. Alopecia areata incognita: true or false?. J Am Acad Dermatol. 2009;60:162–163
  19. Tobin DJ, Fenton DA, Kendall MD. Ultrastructural study of exclamation-mark hair shafts in alopecia areata. J Cutan Pathol. 1990;17:348–354
  20. Zlotogorski A, Panteleyev AA, Aita VM, Christiano AM. Clinical and molecular diagnostic criteria of congenital atrichia with papular lesions. J Invest Dermatol. 2002;118:887–890
  21. Tosti A, Bellavista S, Iorizzo M. Alopecia areata: a long term follow-up study of 191 patients. J Am Acad Dermatol. 2006;55:438–441
  22. Walker SA, Rothman S. A statistical study and consideration of endocrine influences. J Invest Dermatol. 1950;14:403–413
  23. Gandhi V, Baruah MC, Bhattacharaya SN. Nail changes in alopecia areata: incidence and pattern. Indian J Dermatol Venereol Leprol. 2003;69:114–115
  24. Kasumagic-Halilovic E, Prohic A. Nail changes in alopecia areata: frequency and clinical presentation. J Eur Acad Dermatol Venereol. 2009;23:240–241
  25. Seyrafi H, Akhiani M, Abbasi H, Mirpour S, Gholamrezanezhad A. Evaluation of the profile of alopecia areata and the prevalence of thyroid function test abnormalities and serum autoantibodies in Iranian patients. BMC Dermatol. 2005;5:11
  26. Kasumagic-Halilovic E. Thyroid autoimmunity in patients with alopecia areata. Acta Dermatovenerol Croat. 2008;16:123–125
  27. Hordinsky M, Ericson M. Autoimmunity: alopecia areata. J Investig Dermatol Symp Proc. 2004;9:73–78
  28. Goh C, Finkel M, Christos PJ, Sinha AA. Profile of 513 patients with alopecia areata: associations of disease subtypes with atopy, autoimmune disease and positive family history. J Eur Acad Dermatol Venereol. 2006;20:1055–1060
  29. Wang SJ, Shohat T, Vadheim C, Shellow W, Edwards J, Rotter JI. Increased risk for type I (insulin-dependent) diabetes in relatives of patients with alopecia areata (AA). Am J Med Genet. 1994;51:234–239
  30. Ruiz-Doblado S, Carrizosa A, García-Hernández MJ. Alopecia areata: psychiatric comorbidity and adjustment to illness. Int J Dermatol. 2003;42:434–437
  31. Recupero SM, Abdolrahimzadeh S, De Dominicis M, Mollo R, Carboni I, Rota L, et al. Ocular alterations in alopecia areata. Eye. 1999;13(pt 5):643–646
  32. MacDonald Hull SP, Wood ML, Hutchinson PE, Sladden M, Messenger AG. British Association of Dermatologists. Guidelines for the management of alopecia areata. Br J Dermatol. 2003;149:692–699
  33. Messenger AG, Slater DN, Bleehen SS. Alopecia areata: alterations in the hair growth cycle and correlation with the follicular pathology. Br J Dermatol. 1986;114:337–347
  34. Weedon D. Diseases of cutaneous appendages. In:  Weedon D editors. Weedon's skin pathology. London: Churchill Livingstone; 2002;
  35. Elston DM, McCollough ML, Bergfeld WF, Liranzo MO, Heibel M. Eosinophils in fibrous tracts and near hair bulbs: a helpful diagnostic feature of alopecia areata. J Am Acad Dermatol. 1997;37:101–106
  36. El Darouti M, Marzouk SA, Sharawi E. Eosinophils in fibrous tracts and near hair bulbs: a helpful diagnostic feature of alopecia areata. J Am Acad Dermatol. 2000;42:305–307
  37. Todes-Taylor N, Turner R, Wood GS, Stratte PT, Morhenn VB. T cell subpopulations in alopecia areata. J Am Acad Dermatol. 1984;11(2 pt 1):216–223
  38. Whiting DA. Histopathologic features of alopecia areata: a new look. Arch Dermatol. 2003;139:1555–1559
  39. Tobin DJ. Morphological analysis of hair follicles in alopecia areata. Microsc Res Tech. 1997;38:443–451
  40. Sperling LC. Alopecia areata. In:  Sperling LC editors. An atlas of hair pathology with clinical correlations. 1st ed. New York: Parthenon Publishing; 2003;p. 109–138
  41. Tobin DJ, Fenton DA, Kendall MD. Cell degeneration in alopecia areata. An ultrastructural study. Am J Dermatopathol. 1991;13:248–256
  42. Whiting DA. Histopathology of alopecia areata in horizontal sections of scalp biopsies. J Invest Dermatol. 1995;104(suppl 5):26S-7S
  43. Vogt A, McElwee KJ, Blume-Peytavi U. Biology of the hair follicle. In:  Whiting DA,  Blume-Peytavi U,  Tosti A editor. Hair growth and disorders. Berlin: Springer; 2008;p. 1–22
  44. McElwee KJ, Sinclair R. Hair physiology and its disorders. Drug Discovery Today: Disease Mechanisms. 2008;5:e163–e171
  45. Freyschmidt-Paul P, McElwee KJ, Hoffmann R. Alopecia areata. In:  Whiting DA,  Blume-Peytavi U,  Tosti A editor. Hair growth and disorders. Berlin: Springer; 2008;p. 311–332
  46. King LE, McElwee KJ, Sundberg JP. Alopecia areata. Curr Dir Autoimmun. 2008;10:280–312
  47. Lu W, Shapiro J, Yu M, Barekatain A, Lo B, Finner A, et al. Alopecia areata: pathogenesis and potential for therapy. Expert Rev Mol Med. 2006;8:1–19
  48. McDonagh AJ, Tazi-Ahnini R. Epidemiology and genetics of alopecia areata. Clin Exp Dermatol. 2002;27:405–409
  49. Paus R, Slominski A, Czarnetzki BM. 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. 1993;66:541–554
  50. McElwee KJ, Tobin DJ, Bystryn JC, King LE, Sundberg JP. Alopecia areata: an autoimmune disease?. Exp Dermatol. 1999;8:371–379
  51. Sundberg JP, McElwee KJ, Whiting DA, King LE. Alopecia areata: spontaneous and skin graft-induced mouse models. In:  Chan LS editors. Animal models of human inflammatory skin diseases. Vol V:Boca Raton, FL: CRC Press; 2003;p. 429–450
  52. McElwee KJ. Alopecia areata: spontaneous rat model of alopecia areata. In:  Chan LS editors. Animal models of human inflammatory skin diseases. Vol V:Boca Raton, FL: CRC Press; 2003;p. 451–468
  53. Sundberg JP, Cordy WR, King LE. Alopecia areata in aging C3H/HeJ mice. J Invest Dermatol. 1994;102:847–856
  54. Zhang JG, Oliver RF. Immunohistological study of the development of the cellular infiltrate in the pelage follicles of the DEBR model for alopecia areata. Br J Dermatol. 1994;130:405–414
  55. McElwee KJ, Boggess D, King LE, Sundberg JP. Experimental induction of alopecia areata-like hair loss in C3H/HeJ mice using full-thickness skin grafts. J Invest Dermatol. 1998;111:797–803
  56. McElwee KJ, Silva K, Boggess D, Bechtold L, King LE, Sundberg JP. Alopecia areata in C3H/HeJ mice involves leukocyte-mediated root sheath disruption in advance of overt hair loss. Vet Pathol. 2003;40:643–650
  57. Carroll JM, McElwee KJ, King LE, Byrne MC, Sundberg JP. 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. 2002;119:392–402
  58. Freyschmidt-Paul P, Seiter S, Zoller M, Konig A, Ziegler A, Sundberg JP, et al. Treatment with an anti-CD44v10-specific antibody inhibits the onset of alopecia areata in C3H/HeJ mice. J Invest Dermatol. 2000;115:653–657
  59. McElwee KJ, Spiers EM, Oliver RF. Partial restoration of hair growth in the DEBR model for alopecia areata after in vivo depletion of CD4+ T cells. Br J Dermatol. 1999;140:432–437
  60. McElwee KJ, Spiers EM, Oliver RF. In vivo depletion of CD8+ T cells restores hair growth in the DEBR model for alopecia areata. Br J Dermatol. 1996;135:211–217
  61. McElwee KJ, Freyschmidt-Paul P, Hoffmann R, Kissling S, Hummel S, Vitacolonna M, 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. 2005;124:947–957
  62. Gilhar A, Landau M, Assy B, Shalaginov R, Serafimovich S, Kalish RS. Mediation of alopecia areata by cooperation between CD4+ and CD8+ T lymphocytes: transfer to human scalp explants on Prkdc(scid) mice. Arch Dermatol. 2002;138:916–922
  63. Sun J, Silva KA, McElwee KJ, King LE, Sundberg JP. The C3H/HeJ mouse and DEBR rat models for alopecia areata: review of preclinical drug screening approaches and results. Exp Dermatol. 2008;17:793–805
  64. Zoller M, Gupta P, Marhaba R, Vitacolonna M, Freyschmidt-Paul P. Anti-CD44-mediated blockade of leukocyte migration in skin-associated immune diseases. J Leukoc Biol. 2007;82:57–71
  65. Marhaba R, Vitacolonna M, Hildebrand D, Baniyash M, Freyschmidt-Paul P, Zoller M. The importance of myeloid-derived suppressor cells in the regulation of autoimmune effector cells by a chronic contact eczema. J Immunol. 2007;179:5071–5081
  66. Stankler L. Synchronous alopecia areata in two siblings: a possible viral aetiology. Lancet. 1979;1:1303–1304
  67. Alsaleh QA, Nanda A, al-Hasawi F, el-Kashlan M. Concurrent appearance of alopecia areata in siblings. Pediatr Dermatol. 1995;12:285–286
  68. McElwee K, Freyschmidt-Paul P, Ziegler A, Happle R, Hoffmann R. Genetic susceptibility and severity of alopecia areata in human and animal models. Eur J Dermatol. 2001;11:11–16
  69. Akar A, Arca E, Erbil H, Akay C, Sayal A, Gur AR. Antioxidant enzymes and lipid peroxidation in the scalp of patients with alopecia areata. J Dermatol Sci. 2002;29:85–90
  70. Sundberg JP, Silva KA, Li R, Cox GA, King LE. Adult-onset alopecia areata is a complex polygenic trait in the C3H/HeJ mouse model. J Invest Dermatol. 2004;123:294–297
  71. Martinez-Mir A, Zlotogorski A, Gordon D, Petukhova L, Mo J, Gilliam TC, et al. Genomewide scan for linkage reveals evidence of several susceptibility loci for alopecia areata. Am J Hum Genet. 2007;80:316–328
  72. Duvic M, Norris D, Christiano A, Hordinsky M, Price V. Alopecia areata registry: an overview. J Investig Dermatol Symp Proc. 2003;8:219–221
  73. Rodriguez TA, Duvic M. Onset of alopecia areata after Epstein-Barr virus infectious mononucleosis. J Am Acad Dermatol. 2008;59:137–139
  74. Ikeda T. Produced alopecia areata based on the focal infection theory and mental motive theory. Dermatologica. 1967;134:1–11
  75. Brauner GJ, Goodheart HP. Dermatologic care behind bars. J Am Acad Dermatol. 1988;18:1066–1073
  76. Gupta MA, Gupta AK, Watteel GN. Stress and alopecia areata: a psychodermatologic study. Acta Derm Venereol. 1997;77:296–298
  77. Perini GI, Veller Fornasa C, Cipriani R, Bettin A, Zecchino F, Peserico A. Life events and alopecia areata. Psychother Psychosom. 1984;41:48–52
  78. Brajac I, Tkalcic M, Dragojevic DM, Gruber F. Roles of stress, stress perception and trait-anxiety in the onset and course of alopecia areata. J Dermatol. 2003;30:871–878
  79. Gulec AT, Tanriverdi N, Duru C, Saray Y, Akcali C. The role of psychological factors in alopecia areata and the impact of the disease on the quality of life. Int J Dermatol. 2004;43:352–356
  80. Picardi A, Pasquini P, Cattaruzza MS, Gaetano P, Baliva G, Melchi CF, et al. Psychosomatic factors in first-onset alopecia areata. Psychosomatics. 2003;44:374–381
  81. 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. 2007;21:356–359
  82. Liakopoulou M, Alifieraki T, Katideniou A, Kakourou T, Tselalidou E, Tsiantis J, et al. Children with alopecia areata: psychiatric symptomatology and life events. J Am Acad Child Adolesc Psychiatry. 1997;36:678–684
  83. Siebenhaar F, Sharov AA, Peters EM, Sharova TY, Syska W, Mardaryev AN, et al. Substance P as an immunomodulatory neuropeptide in a mouse model for autoimmune hair loss (alopecia areata). J Invest Dermatol. 2007;127:1489–1497
  84. Toyoda M, Makino T, Kagoura M, Morohashi M. Expression of neuropeptide-degrading enzymes in alopecia areata: an immunohistochemical study. Br J Dermatol. 2001;144:46–54
  85. Zhang X, Yu M, Yu W, Weinberg J, Shapiro J, McElwee KJ. Development of alopecia areata is associated with higher central and peripheral hypothalamic-pituitary-adrenal tone in the skin graft induced C3H/HeJ mouse model. J Invest Dermatol. 2009;129:1527–1538
  86. Theofilopoulos AN. The basis of autoimmunity: part II. Genetic predisposition. Immunol Today. 1995;16:150–159
  87. Theofilopoulos AN. The basis of autoimmunity: part I. Mechanisms of aberrant self-recognition. Immunol Today. 1995;16:90–98
  88. Goodnow CC, Sprent J. Fazekas de St Groth B, Vinuesa CG. Cellular and genetic mechanisms of self tolerance and autoimmunity. Nature. 2005;435:590–597
  89. Goodnow CC. Multistep pathogenesis of autoimmune disease. Cell. 2007;130:25–35
  90. Paus R, Nickoloff BJ, Ito T. A “hairy” privilege. Trends Immunol. 2005;26:32–40
  91. Ito T, Meyer KC, Ito N, Paus R. Immune privilege and the skin. Curr Dir Autoimmun. 2008;10:27–52
  92. Ito T, Ito N, Bettermann A, Tokura Y, Takigawa M, Paus R. Collapse and restoration of MHC class-I-dependent immune privilege: exploiting the human hair follicle as a model. Am J Pathol. 2004;164:623–634
  93. Botchkareva NV, Ahluwalia G, Shander D. Apoptosis in the hair follicle. J Invest Dermatol. 2006;126:258–264
  94. Weedon D, Strutton G. Apoptosis as the mechanism of the involution of hair follicles in catagen transformation. Acta Derm Venereol. 1981;61:335–339
  95. Lindner G, Botchkarev VA, Botchkareva NV, Ling G, van der Veen C, Paus R. Analysis of apoptosis during hair follicle regression (catagen). Am J Pathol. 1997;151:1601–1617
  96. Eichmuller S, van der Veen C, Moll I, Hermes B, Hofmann U, Muller-Rover S, et al. Clusters of perifollicular macrophages in normal murine skin: physiological degeneration of selected hair follicles by programmed organ deletion. J Histochem Cytochem. 1998;46:361–370
  97. Parakkal PF. Role of macrophages in collagen resorption during hair growth cycle. J Ultrastruct Res. 1969;29:210–217
  98. McElwee KJ, Pickett P, Oliver RF. The DEBR rat, alopecia areata and autoantibodies to the hair follicle. Br J Dermatol. 1996;134:55–63
  99. Tobin DJ, Sundberg JP, King LE, Boggess D, Bystryn JC. Autoantibodies to hair follicles in C3H/HeJ mice with alopecia areata-like hair loss. J Invest Dermatol. 1997;109:329–333
  100. Tobin DJ, Orentreich N, Fenton DA, Bystryn JC. Antibodies to hair follicles in alopecia areata. J Invest Dermatol. 1994;102:721–724
  101. Ueno H, Klechevsky E, Morita R, Aspord C, Cao T, Matsui T, et al. Dendritic cell subsets in health and disease. Immunol Rev. 2007;219:118–142
  102. Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature. 1998;392:86–89
  103. Mehling A, Beissert S. Dendritic cells under investigation in autoimmune disease. Crit Rev Biochem Mol Biol. 2003;38:1–21
  104. Zoller M, McElwee KJ, Engel P, Hoffmann R. Transient CD44 variant isoform expression and reduction in CD4(+)/CD25(+) regulatory T cells in C3H/HeJ mice with alopecia areata. J Invest Dermatol. 2002;118:983–992

 Funding sources: None.

 Conflicts of interest: Dr Shapiro is a consultant for Johnson and Johnson Inc. Drs Shapiro and McElwee are cofounders of TrichoScience Innovations Inc. The other authors, editors, and peer reviewers have no relevant financial relationships.

PII: S0190-9622(09)01363-2

doi: 10.1016/j.jaad.2009.10.032

Journal of the American Academy of Dermatology
Volume 62, Issue 2 , Pages 177-188 , February 2010

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