Abstract
Alopecia areata (AA) is a kind of alopecia that affects hair follicles and nails. It typically comes with round patches and is a type of nonscarring hair loss. Various therapies are accessible for the management and treatment of AA, including topical, systemic and injectable modalities. It is a very complex type of autoimmune disease and is identified as round patches of hair loss and may occur at any age. This review paper highlights the epidemiology, clinical features, pathogenesis and new treatment options for AA, with a specific emphasis on nanoparticulate drug-delivery systems. By exploring these innovative treatment approaches, researchers aim to enhance the effectiveness and targeted delivery of therapeutic agents, ultimately improving outcomes for individuals living with AA.
Papers of special note have been highlighted as: • of interest
References
- 1. . Epidemiology and burden of alopecia areata: a systematic review. Clin. Cosmet. Investig. Dermatol. 8, 397–403 (2015). • This type of systematic review is crucial for understanding the prevalence, risk factors and impact of alopecia areata on individuals and populations.
- 2. Hair follicle targeting with nanoparticles. Nanotechnology in Dermatology. Springer (2013).95–107
- 3. . Profile of alopecia areata in Northern India. Int. J. Dermatol. 35(1), 22–27 (1996).
- 4. . Prevalence of alopecia areata in the first national health and nutrition examination survey. Arch. Dermatol. 128(5), 702 (1992).
- 5. Incidence of alopecia areata in Olmsted County, Minnesota, 1975 Through 1989. Mayo Clin. Proc. 70(7), 628–633 (1995).
- 6. . Lifetime incidence risk of alopecia areata estimated at 2.1% by Rochester Epidemiology Project, 1990–2009. J. Invest. Dermatol. 134(4), 1141–1142 (2014).
- 7. , Messenger Alopecia areata. Nat. Rev. Dis. Primers. 3, 17011 (2017).
- 8. What causes alopecia areata? Exp. Dermatol. 22(9), 609–626 (2013).
- 9. . Alopecia areata. N. Engl. J. Med. 366(16), 1515–1525 (2012).
- 10. . Alopecia areata: a review of disease pathogenesis. Br. J. Dermatol. 179(5), 1033–1048 (2018).
- 11. . Immune privilege collapse and alopecia development: is stress a factor. Skin Appendage Disord. 4(4), 236–244 (2018).
- 12. . Treatment of alopecia areata: “what is new on the horizon?”. Dermatol. Ther. 24(3), 364–368 (2011).
- 13. . Alopecia areata: a new treatment plan. Clin. Cosmet. Investig. Dermatol. 4, 107–115 (2011).
- 14. . Clobetasol propionate 0.05% under occlusion in the treatment of alopecia totalis/universalis. J. Am. Acad. Dermatol. 49(1), 96–98 (2003).
- 15. . Minoxidil and its use in hair disorders: a review. Drug Des. Dev. Ther. 13, 2777–2786 (2019).
- 16. . Liposomes and niosomes as potential carriers for dermal delivery of minoxidil. J. Drug Target. 15(2), 101–108 (2007).
- 17. . Penetration profile of microspheres in follicular targeting of terminal hair follicles. J. Invest. Dermatol. 123(1), 168–176 (2004).
- 18. Roxithromycin-loaded lipid nanoparticles for follicular targeting. Int. J. Pharm. 495(2), 807–815 (2015).
- 19. . Human hair follicle: reservoir function and selective targeting. Br. J. Dermatol. 165(Suppl. 2), 13–17 (2011).
- 20. . Transfollicular drug delivery: current perspectives. Res. Rep. Transdermal Drug Deliv. 5, 1 (2016). • Explores the current perspectives on delivering drugs through hair follicles, which can be a fascinating avenue for enhancing topical drug delivery.
- 21. . Nanocarriers and nanoparticles for skin care and dermatological treatments. Indian Dermatol. Online J. 4(4), 267–272 (2013). • Delves into the world of nanocarriers and nanoparticles designed for skin care and dermatological treatments.
- 22. . Nanoparticles--an efficient carrier for drug delivery into the hair follicles. Eur. J. Pharm. Biopharm. 66(2), 159–164 (2007).
- 23. . Nanomedicine in dermatology: nanotechnology in prevention, diagnosis, and therapy. Nanosci. Nanotechnol. Hum. Health (2006). https://doi.org/10.1002/9783527692057.ch16 • Explores the diverse applications of nanomedicine in dermatology, covering everything from prevention and diagnosis to therapy.
- 24. . Ratchet effect for nanoparticle transport in hair follicles. Eur. J. Pharm. Biopharm. 116, 125–130 (2017).
- 25. . Alopecia areata and autoimmunity: a clinical study. Indian J. Dermatol. 53(2), 70–74 (2008).
- 26. . Utility of horizontal sections of scalp biopsies in differentiating between androgenetic alopecia and alopecia areata. Dermatol. [BaselSwitzerland] 234(3–4), 137–147 (2018).
- 27. . Prevalence and Clinical Characteristics of Alopecia Areata at a Tertiary Care Center in Saudi Arabia. Dermatol. Res. Pract. 2020, 7194270 (2020).
- 28. Prevalence of Dermatological Disorders in Japan: A Nationwide, Cross-Sectional, Seasonal, Multicenter, Hospital-Based Study. J. Dermatol. 38(4), 310–320 (2011).
- 29. Alopecia Areata Prevalence by Gender and Age. J. Eur. Acad. Dermatol. Venereol. 23(5), 572–573 (2009).
- 30. . The Color Atlas and Synopsis of Family Medicine McGraw-Hill Professional (2019).
- 31. “Stem cell therapy as a novel therapeutic intervention for resistant cases of alopecia areata and androgenetic alopecia.”. The Journal of Dermatological Treatment 29(5), 431–440 (2018).
- 32. . 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(6), 541–554 (1993).
- 33. . Novel Aspects of Hair Follicle Immune Privilege and Their Relevance to Alopecia Areata. J. Invest. Dermatol. Blackwell Publishing Inc, U.S.02148 (2005).
- 34. . The Psychological Impact of Alopecia. BMJ 331(7522), 951–953 (2005).
- 35. Neuropeptide Control Mechanisms in Cutaneous Biology: Physiological and Clinical Significance. J. Invest. Dermatol. 126(9), 1937–19479 (2006).
- 36. . An In Vitro Model for the Exploration of Cutaneous Stress Responses: Substance P Inhibits Hair Growth, Induces Mast Cell Degranulation, Up-Regulates p75NTR Expression and Causes Immune Privilege Collapse In Vitro. J. Investig. Dermatol. 127, S109– (2007).
- 37. . Stress and the Hair Follicle: Exploring the Connections. Am. J. Pathol. 162(3), 709–712 (2003).
- 38. The Epidemiology of Childhood Alopecia Areata in China: A Study of 226 Patients. Pediatr. Dermatol. 23(1), 13–18 (2006).
- 39. Scan for Linkage Reveals Evidence of Several Susceptibility Loci for Alopecia Areata. Am. J. Hum. Genet. 80(2), 316–3289 (2007).
- 40. . Immune Privilege Collapse and Alopecia Development: Is Stress a Factor. Skin Appendage Disord. 4(4), 236–244 (2018).
- 41. . Alopecia Areata: Review of Epidemiology, Clinical Features, Pathogenesis, and New Treatment Options. Int. J. Trichology 10(2), 51–60 (2018).
- 42. . Alopecia Areata: News on Diagnosis, Pathogenesis and Treatment. G. Ital. Dermatol. Venereol. 149(1), 25–45 (2014).
- 43. . Management of Alopecia Areata. BMJ 341, c3671 (2010).
- 44. . Management of Alopecia Areata. BMJ 341, c3671 (2010).
- 45. . New Aspects of the Treatment of Alopecia Areata. Postepy Dermatol. Alergol. 31(4), 262–265 (2014).
- 46. . Alopecia Areata Treated with Oral Azathioprine: A Case Series. Int. J. Trichology 11(5), 219–222 (2019).
- 47. . Minoxidil and Its Use in Hair Disorders: A Review. Drug Des. Dev. Ther. 13, 2777–2786 (2019). • Comprehensively examines minoxidil, a medication widely used for treating various hair disorders.
- 48. . Topical Immunotherapy in Alopecia Areata. Int. J. Trichology 2(1), 36–39 (2010).
- 49. . The Efficacy and Safety of Targeted Narrowband UVB Therapy: A Retrospective Cohort Study. Turk. J. Med. Sci. 49(2), 595–603 (2019).
- 50. 308-nm Excimer Lamp for the Treatment of Alopecia Areata: Clinical Trial on 16 Cases. Indian J. Dermatol. 58(4), 326 (2013).
- 51. . 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(10), 1243–1247 (2006).
- 52. . Clobetasol Propionate, 0.05%, vs Hydrocortisone, 1%, for Alopecia Areata in Children: A Randomized Clinical Trial. JAMA Dermatol. 150(1), 47–50 (2014).
- 53. . Management of Alopecia Areata: An Update. Br. J. Med. Pract. 5(3), (2012).
- 54. . Are Ointments Better than Other Vehicles for Corticosteroid Treatment of Psoriasis? J. Drugs Dermatol. 8(6), 570–572 (2009).
- 55. . Innovative Topical Formulations for Treatment of Dermatitis. Recent Pat. Inflamm. Allergy Drug Discov. 6(3), 186–201 (2016).
- 56. . A Tutorial for Developing a Topical Cream Formulation Based on the Quality by Design Approach. J. Pharm. Sci. 107(10), 2653–2662 (2018).
- 57. . Penetration of Drugs Through Skin, a Complex Rate-Controlling Membrane. Curr. Opin. Colloid Interface Sci. 17(3), 156–165 (2012).
- 58. . Efficacy of Combination Therapy for the Management Regime of Alopecia Areata. Mymensingh Med. J. 16(Suppl. 2), S19–S22 (2007).
- 59. . Recent Advances in Follicular Drug Delivery of Nanoparticles. Expert Opin. Drug Deliv. 17(1), 49–60 (2020).
- 60. Transdermal Delivery of Minoxidil Using HA-PLGA Nanoparticles for the Treatment in Alopecia. Biomater. Res. 23, 16 (2019).
- 61. . Erythema multiforme Following Topical Minoxidil. Indian J. Dermatol. Venereol. Leprol. 59(6), 313–314 (1993).
- 62. Drug Delivery System Based on Minoxidil Nanoparticles Promotes Hair Growth in C57BL/6 Mice. Int. J. Nanomedicine 14, 7921–7931 (2019).
- 63. . Allergic Contact Dermatitis to Topical Minoxidil Solution: Etiology and Treatment. J. Am. Acad. Dermatol. 46(2), 309–312 (2002).
- 64. . Solid Lipid Nanoparticles [SLNs] and Nanostructured Lipid Carriers [NLCs]: Recent Advances in Drug Delivery. J. Pharm. Investig. 43(5), 353–362 (2013).
- 65. Nanocarriers for Optimizing the Balance Between Interfollicular Permeation and Follicular Uptake of Topically Applied Clobetasol to Minimize Adverse Effects. J. Control. Release 223, 207–214 (2016).
- 66. Nanoparticles–an Efficient Carrier for Drug Delivery into the Hair Follicles. Eur. J. Pharm. Biopharm. 66(2), 159–164 (2007).
- 67. . Formulations Based on Solid Lipid Nanoparticles [SLN] and Nanostructured Lipid Carriers [NLC] for Cutaneous Use: A Review. Eur. J. Pharm. Sci. 112, 159–167 (2018).
- 68. . Follicular-targeted delivery of spironolactone provided by polymeric nanoparticles . Colloids Surf B Biointerfaces. 208, 112101 (2021). • This reference explores an innovative approach to hair loss treatment using spironolactone-loaded polymeric nanoparticles.
- 69. . Latanoprost Loaded in Polymeric Nanocapsules for Effective Topical Treatment of Alopecia. A.A.P.S. PharmSciTech 21(8), 305 (2020).
- 70. . Chitosan Nanoparticles for Targeting and Sustaining Minoxidil Sulphate Delivery to Hair Follicles. Int. J. Biol. Macromol. 75, 225–229 (2015).
- 71. . Transdermal Delivery of Mixnoxidil with Block Copolymer Nanoparticles. J. Control. Release 97(3), 477–484 (2004).
- 72. . Design of Finasteride-Loaded Nanoparticles for Potential Treatment of Alopecia. Skin Pharmacol. Physiol. 30(4), 197–204 (2017).
- 73. . Novel Iron Oxide Nanocarriers Loading Finasteride or Dutasteride: Enhanced Skin Penetration for Topical Treatment of Alopecia. Int. J. Pharm 587, 119709 (2020).
- 74. Drug Delivery System Based on Minoxidil Nanoparticles Promotes Hair Growth in C57BL/6 Mice. Int. J. Nanomedicine 14, 7921–7931 (2019).
- 75. Minoxidil. J. Drug Target. 15(2), 101–108 (2007).
- 76. . Preparation and Characterization of Minoxidil Loaded Nanostructured Lipid Carriers. A.A.P.S. PharmSciTech 18(2), 509–516 (2017). • Explores how these nanoparticles can target and sustain the delivery of minoxidil sulfate specifically to hair follicles.
- 77. . Solid Lipid Nanoparticles Suspension Versus Commercial Solutions for Dermal Delivery of Minoxidil. Int. J. Pharm. 416(1), 300–304 (2011).
- 78. . Histological Assessment of Follicular Delivery of Flutamide by Solid Lipid Nanoparticles: Potential Tool for the Treatment of Androgenic Alopecia. Drug Dev. Ind. Pharm. 42(6), 846–853 (2016).
- 79. Effect of Physical Stimuli on Hair Follicle Deposition of Clobetasol-Loaded Lipid Nanocarriers. Sci. Rep. 10(1), 176 (2020).
- 80. . Squalene-Containing Nanostructured Lipid Carriers Promote Percutaneous Absorption and Hair Follicle Targeting of Diphencyprone for Treating Alopecia Areata. Pharm. Res. 30(2), 435–446 (2013).
- 81. . Squarticles as a Lipid Nanocarrier for Delivering Diphencyprone and Minoxidil to Hair Follicles and Human Dermal Papilla Cells. A.A.P.S. J. 16(1), 140–150 (2014).
- 82. . Hair Follicle Targeting and Dermal Drug Delivery with Curcumin Drug Nanocrystals-Essential Influence of Excipients. Nanomaterials [Basel] 10(11), (2010).
- 83. . Alopecia Areata. Indian J. Dermatol. Venereol. Leprol. 67(4), 188 (2001).
- 84. Alopecia Areata: Topical Immunotherapy Treatment with Diphencyprone. J. Eur. Acad. Dermatol. Venereol. 22(3), 320–323 (2008). • Explores the use of diphencyprone in topical immunotherapy for alopecia areata.
- 85. . Bimatoprost for the Treatment of Eyelash, Eyebrow and Scalp Alopecia. Expert Opin. Investig. Drugs 26(4), 515–522 (2017).
- 86. . A Comparison of the Efficacy, Relapse Rate and Side Effects Among Three Modalities of Systemic Corticosteroid Therapy for Alopecia Areata. Dermatology 212(4), 361–3z65 (2006).
- 87. . [Long-Term Follow-Up of the Efficacy of Methotrexate Alone or in Combination with Low Doses of Oral Corticosteroids in the Treatment of Alopecia Areata Totalis or universalis]. Ann. Dermatol. Venereol. 137(8–9), 507–513 (2010).
- 88. . Topical Minoxidil Therapy and Hair Regrowth. Arch. Dermatol. 121(2), 191–192 (1985).
- 89. . Immunohistochemical Characterization of the Cellular Infiltrate in Severe Alopecia Areata Before and After Minoxidil Treatment. Dermatologica 175(Suppl. 2), 29–35 (1987).
- 90. . Topical Minoxidil in Alopecia Areata: No Effect on the Perifollicular Lymphoid Infiltration. J. Invest. Dermatol. 99(1), 40–47 (1992).
- 91. . Double-blind, placebo-controlled evaluation of topical minoxidil in extensive alopecia areata. J. Am. Acad. Dermatol. 16(3 Pt. 2), 730–736 (1987).
- 92. . Systemic Steroids with or Without 2% Topical Minoxidil in the Treatment of Alopecia Areata. Arch. Dermatol. 128(11), 1467–1473 (1992).
- 93. . Treatments Options for Alopecia. Expert Opin. Pharmacother. 16(15), 2343–2354 (2015).
- 94. A Randomized, Placebo-Controlled Trial of 5% and 2% Topical Minoxidil Solutions in the Treatment of Female Pattern Hair Loss. J. Am. Acad. Dermatol. 50(4), 541–553 (2004).
- 95. . Ocular Complications of Topical, Peri-ocular, and Systemic Corticosteroids. Curr. Opin. Ophthalmol. 11(6), 478–483 (2000).
- 96. . Minoxidil's Action in Hair Follicles. J. Invest. Dermatol. 96(5), S73–74S (1991).
- 97. . Evaluation of Anthralin in the Treatment of Alopecia Areata. Arch. Dermatol. 123(11), 1491–1493 (1987).
- 98. . Latanoprost in the Treatment of Eyelash Alopecia in Alopecia Areata universalis. J. Eur. Acad. Dermatol. Venereol. 24(4), 481–485 (2010).
- 99. . Comparative Assessment of Topical Steroids, Topical Tretenoin [0.05%] and Dithranol Paste in Alopecia Areata. Indian J. Dermatol. 55(2), 148–149 (2010).
- 100. Dermatol. Surg. 33(12), 1483–1487 (2007).
- 101. . 308-nm Excimer Laser for the Treatment of Alopecia Areata in Children. Pediatr. Dermatol. 26(5), 547–550 (2009).
- 102. . Placebo-Controlled Oral Pulse Prednisolone Therapy in Alopecia Areata. J. Am. Acad. Dermatol. 52(2), 287–290 (2005).
- 103. . Evaluation of oral minoxidil in the treatment of alopecia areata. Arch. Dermatol. 123(11), 1488–1490 (1987).
- 104. . Topical minoxidil [3%] in extensive alopecia areata, including long-term efficacy. J. Am. Acad. Dermatol. 16(3 Pt. 2), 737–744 (1987).
- 105. . Minoxidil-induced hypertrichosis in a child with alopecia areata. Indian Dermatol. Online J. 8(2), 147–148 (2017).
- 106. . The comparison of treatment with clobetasol propionate 0.05% and topical pimecrolimus 1% treatment in the treatment of alopecia areata. J. Dermatolog. Treat. 23(6), 410–420 (2012).