Editing Alopecia areata (section)

== Causes ==
[[File:Alopecia areata.svg|thumb|In alopecia areata, a hair follicle is attacked by the immune system. T-cells swarm the roots, killing the follicle. This causes the hair to fall out and parts of the head to become bald.]]

Alopecia areata is thought to be a systemic autoimmune disorder in which the body attacks its own anagen [[hair follicle]]s and suppresses or stops hair growth.<ref name=draelos/> For example, [[T cell]] [[lymphocytes]] cluster around affected follicles, causing inflammation and subsequent hair loss. Hair follicles in a normal state are thought to be kept secure from the immune system, a phenomenon called immune privilege. A breach in this immune privilege state is considered as the cause of alopecia areata.<ref name=BJD2018/> A few cases of babies being born with [[congenital]] alopecia areata have been reported.<ref name=LenanePope2005>{{cite journal | vauthors = Lenane P, Pope E, Krafchik B | title = Congenital alopecia areata | journal = Journal of the American Academy of Dermatology | volume = 52 | issue = 2 Suppl 1 | pages = 8–11 | date = February 2005 | pmid = 15692503 | doi = 10.1016/j.jaad.2004.06.024 | type = Case Reports. Review | quote = We believe AA should be classified not only as an acquired, but also a congenital form of nonscarring hair loss. It may well be more common than is thought because of lack of recognition }}</ref> It is recognized as a type 1 inflammatory disease.<ref name="Fukuyama Ito Ohyama 2021 pp. 19–36">{{cite journal | vauthors = Fukuyama M, Ito T, Ohyama M | title = Alopecia areata: Current understanding of the pathophysiology and update on therapeutic approaches, featuring the Japanese Dermatological Association guidelines | journal = The Journal of Dermatology | volume = 49 | issue = 1 | pages = 19–36 | date = January 2022 | pmid = 34709679 | doi = 10.1111/1346-8138.16207 | s2cid = 240073350 }}</ref>

Alopecia areata is not [[Infectious disease|contagious]].<ref name=draelos/> It occurs more frequently in people who have affected family members, suggesting [[heredity]] may be a factor.<ref name=draelos/> Strong evidence of genetic association with increased risk for alopecia areata was found by studying families with two or more affected members. This study identified at least four regions in the genome that are likely to contain these genes.<ref>{{cite journal | vauthors = Martinez-Mir A, Zlotogorski A, Gordon D, Petukhova L, Mo J, Gilliam TC, Londono D, Haynes C, Ott J, Hordinsky M, Nanova K, Norris D, Price V, Duvic M, Christiano AM | title = Genomewide scan for linkage reveals evidence of several susceptibility loci for alopecia areata | journal = American Journal of Human Genetics | volume = 80 | issue = 2 | pages = 316–328 | date = February 2007 | pmid = 17236136 | pmc = 1785354 | doi = 10.1086/511442 }}</ref> In addition, alopecia areata shares genetic risk factors with other autoimmune diseases, including [[rheumatoid arthritis]], [[diabetes mellitus type 1|type 1 diabetes]], and [[celiac disease]].<ref name=HordinskyJunqueira2015>{{cite journal | vauthors = Hordinsky M, Junqueira AL | title = Alopecia areata update | journal = Seminars in Cutaneous Medicine and Surgery | volume = 34 | issue = 2 | pages = 72–75 | date = June 2015 | pmid = 26176283 | doi = 10.12788/j.sder.2015.0160 | doi-broken-date = 1 November 2024 | type = Review | doi-access = free }}{{open access}}</ref> It may be the only manifestation of celiac disease.<ref name=CaproniBonciolini2012>{{cite journal | vauthors = Caproni M, Bonciolini V, D'Errico A, Antiga E, Fabbri P | title = Celiac disease and dermatologic manifestations: many skin clue to unfold gluten-sensitive enteropathy | journal = Gastroenterology Research and Practice | volume = 2012 | pages = 952753 | year = 2012 | pmid = 22693492 | pmc = 3369470 | doi = 10.1155/2012/952753 | doi-access = free | type = Review }}</ref><ref name=TackVerbeek2010>{{cite journal | vauthors = Tack GJ, Verbeek WH, Schreurs MW, Mulder CJ | title = The spectrum of celiac disease: epidemiology, clinical aspects and treatment | journal = Nature Reviews. Gastroenterology & Hepatology | volume = 7 | issue = 4 | pages = 204–213 | date = April 2010 | pmid = 20212505 | doi = 10.1038/nrgastro.2010.23 | type = Review | s2cid = 7951660 }}</ref>

Lifestyle factors such as smoking, sleep quality, and obesity may also contribute to the onset and progression of alopecia areata.<ref name="Sánchez-Pellicer 1860">{{cite journal | vauthors = Sánchez-Pellicer P, Navarro-Moratalla L, Núñez-Delegido E, Agüera-Santos J, Navarro-López V | title = How Our Microbiome Influences the Pathogenesis of Alopecia Areata | journal = Genes | volume = 13 | issue = 10 | pages = 1860 | date = October 2022 | pmid = 36292745 | pmc = 9601531 | doi = 10.3390/genes13101860 | doi-access = free }}</ref> Studies indicate that smokers have a higher risk of developing the condition, potentially due to tobacco-induced [[T helper 17 cell|Th17-mediated inflammation]] in hair follicles.<ref>{{cite journal | vauthors = Dai YX, Yeh FY, Shen YJ, Tai YH, Chou YJ, Chang YT, Chen TJ, Li CP, Wu CY | title = Cigarette Smoking, Alcohol Consumption, and Risk of Alopecia Areata: A Population-Based Cohort Study in Taiwan | journal = American Journal of Clinical Dermatology | volume = 21 | issue = 6 | pages = 901–911 | date = December 2020 | pmid = 32761499 | doi = 10.1007/s40257-020-00547-7 }}</ref><ref>{{cite journal | vauthors = Melnik BC, John SM, Chen W, Plewig G | title = T helper 17 cell/regulatory T-cell imbalance in hidradenitis suppurativa/acne inversa: the link to hair follicle dissection, obesity, smoking and autoimmune comorbidities | journal = The British Journal of Dermatology | volume = 179 | issue = 2 | pages = 260–272 | date = August 2018 | pmid = 29573406 | doi = 10.1111/bjd.16561 }}</ref> While some research suggests a link between [[sleep disorder]]s and alopecia areata, findings remain inconclusive.<ref name="Sánchez-Pellicer 1860"/> However, since sleep disturbances impact immune function, they may play a role in disease pathogenesis.<ref>{{cite journal | vauthors = Besedovsky L, Lange T, Haack M | title = The Sleep-Immune Crosstalk in Health and Disease | journal = Physiological Reviews | volume = 99 | issue = 3 | pages = 1325–1380 | date = July 2019 | pmid = 30920354 | doi = 10.1152/physrev.00010.2018 }}</ref> Additionally, obesity is associated with an increased risk of alopecia areata, likely due to [[adipokine]] dysregulation, which promotes chronic low-grade inflammation and alters immune response, as seen in other inflammatory skin conditions.<ref>{{cite journal | vauthors = Hagino T, Okazaki S, Serizawa N, Suzuki K, Kaga M, Otsuka Y, Mikami E, Hoashi T, Saeki H, Matsuda H, Mitsui H, Kanda N | title = Dietary Habits in Japanese Patients with Alopecia Areata | journal = Clinical, Cosmetic and Investigational Dermatology | volume = 14 | pages = 1579–1591 | date = October 2021 | pmid = 34737597 | doi = 10.2147/CCID.S335440 | doi-access = free | pmc = 8560057 }}</ref><ref>{{cite journal | vauthors = Taylor EB | title = The complex role of adipokines in obesity, inflammation, and autoimmunity | journal = Clinical Science | volume = 135 | issue = 6 | pages = 731–752 | date = March 2021 | pmid = 33729498 | doi = 10.1042/CS20200895 | pmc = 7969664 }}</ref>

Endogenous [[retinoid]]s metabolic defect is a key part of the pathogenesis of the alopecia areata.<ref>{{cite journal | vauthors = Duncan FJ, Silva KA, Johnson CJ, King BL, Szatkiewicz JP, Kamdar SP, Ong DE, Napoli JL, Wang J, King LE, Whiting DA, McElwee KJ, Sundberg JP, Everts HB | title = Endogenous retinoids in the pathogenesis of alopecia areata | journal = The Journal of Investigative Dermatology | volume = 133 | issue = 2 | pages = 334–343 | date = February 2013 | pmid = 23014334 | pmc = 3546144 | doi = 10.1038/jid.2012.344 }}</ref>

In 2010, a genome-wide association study was completed that identified 129 single nucleotide polymorphisms that were associated with alopecia areata. The genes that were identified include those involved in
controlling the activation and proliferation of regulatory T cells, cytotoxic T lymphocyte-associated antigen 4, interleukin-2, interleukin-2 receptor A, and Eos (also known as Ikaros family zinc finger 4), as well as the human leukocyte antigen. The study also identified two genes, ''PRDX5'' and ''STX17'', that are expressed in the hair follicle.<ref>{{cite journal | vauthors = Petukhova L, Duvic M, Hordinsky M, Norris D, Price V, Shimomura Y, Kim H, Singh P, Lee A, Chen WV, Meyer KC, Paus R, Jahoda CA, Amos CI, Gregersen PK, Christiano AM | title = Genome-wide association study in alopecia areata implicates both innate and adaptive immunity | journal = Nature | volume = 466 | issue = 7302 | pages = 113–117 | date = July 2010 | pmid = 20596022 | pmc = 2921172 | doi = 10.1038/nature09114 | bibcode = 2010Natur.466..113P }}</ref>

There is emerging evidence suggesting a possible link between AA and vaccinations, including influenza, zoster, and [[Human papillomavirus infection|human papillomavirus (HPV)]] vaccines.<ref>{{cite journal | vauthors = Chu CH, Cheng YP, Chan JY | title = Alopecia Areata After Vaccination: Recurrence with Rechallenge | journal = Pediatric Dermatology | volume = 33 | issue = 3 | pages = e218-e219 | date = May 2016 | pmid = 27071855 | doi = 10.1111/pde.12849 }}</ref> One possible explanation is that vaccinations could trigger immune system activation, which has been observed to exacerbate preexisting autoimmune or autoinflammatory conditions in at-risk populations.<ref>{{cite journal | vauthors = Terracina KA, Tan FK | title = Flare of rheumatoid arthritis after COVID-19 vaccination | journal = The Lancet. Rheumatology | volume = 3 | issue = 7 | pages = e469-e470 | date = July 2021 | pmid = 33817664 | pmc = 8009616 | doi = 10.1016/S2665-9913(21)00108-9 }}</ref> A small study observed hair loss exacerbation in three patients following COVID-19 [[MRNA vaccine|mRNA vaccinations]] ([[Pfizer–BioNTech COVID-19 vaccine|Pfizer-BioNTech]] and [[Moderna COVID-19 vaccine|Moderna]]).<ref name="COVID-19 vaccination related exacer">{{cite journal | vauthors = Babadjouni A, Phong CH, Nguyen C, Mesinkovska NA | title = COVID-19 vaccination related exacerbations of hair loss in patients with moderate-to-severe alopecia areata on systemic therapy | journal = JAAD Case Reports | volume = 29 | pages = 181–185 | date = November 2022 | pmid = 36035747 | pmc = 9391088 | doi = 10.1016/j.jdcr.2022.08.016 }}</ref> These patients, who were younger on average (30.6 years) compared to unaffected individuals (37.2 years), experienced worsening hair loss within two weeks post-vaccination.<ref name="COVID-19 vaccination related exacer"/> Similar cases have been reported with the [[Oxford–AstraZeneca COVID-19 vaccine|AstraZeneca]] and [[Janssen COVID-19 vaccine|Johnson & Johnson]] COVID-19 vaccines.<ref>{{cite journal | vauthors = Essam R, Ehab R, Al-Razzaz R, Khater MW, Moustafa EA | title = Alopecia areata after ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca): a potential triggering factor? | journal = Journal of Cosmetic Dermatology | volume = 20 | issue = 12 | pages = 3727–3729 | date = December 2021 | pmid = 34559937 | pmc = 8661988 | doi = 10.1111/jocd.14459 }}</ref> However, AA flares have also been linked to [[COVID-19|SARS-CoV-2 infection]], either as an exacerbation of preexisting disease or a new diagnosis.<ref name="COVID-19 vaccination related exacer"/> In the study's non-vaccinated AA cohort, the only observed case of hair loss worsening occurred after a COVID-19 infection.<ref name="COVID-19 vaccination related exacer"/> While causality remains unclear, these findings emphasize the need for further research into the relationship between vaccinations and AA progression.

A psychodermatological connection is noted with impairment in psychiatric comorbidities including mental well-being, self esteem and mental disorders acting as pathogenic triggers for alopecia areata.<ref name="Strazzulla Wang Avila Lo Sicco 2018 pp. 1–12">{{cite journal | vauthors = Strazzulla LC, Wang EH, Avila L, Lo Sicco K, Brinster N, Christiano AM, Shapiro J | title = Alopecia areata: Disease characteristics, clinical evaluation, and new perspectives on pathogenesis | journal = Journal of the American Academy of Dermatology | volume = 78 | issue = 1 | pages = 1–12 | date = January 2018 | pmid = 29241771 | doi = 10.1016/j.jaad.2017.04.1141 | publisher = Elsevier BV }}</ref><ref name="Lee Lee Lee Lee 2019 pp. 466–477.e16">{{cite journal | vauthors = Lee S, Lee H, Lee CH, Lee WS | title = Comorbidities in alopecia areata: A systematic review and meta-analysis | journal = Journal of the American Academy of Dermatology | volume = 80 | issue = 2 | pages = 466–477.e16 | date = February 2019 | pmid = 30031145 | doi = 10.1016/j.jaad.2018.07.013 | publisher = Elsevier BV | s2cid = 51707882 }}</ref><ref name="Torales Castaldelli-Maia Ventriglio Almirón-Santacruz 2021 pp. 2318–2323">{{cite journal | vauthors = Torales J, Castaldelli-Maia JM, Ventriglio A, Almirón-Santacruz J, Barrios I, O'Higgins M, García O, Navarro R, Melgarejo O, Jafferany M | title = Alopecia areata: A psychodermatological perspective | journal = Journal of Cosmetic Dermatology | volume = 21 | issue = 6 | pages = 2318–2323 | date = June 2022 | pmid = 34449973 | doi = 10.1111/jocd.14416 | s2cid = 237340798 }}</ref><ref name="Minokawa Sawada Nakamura 2022 p=1038">{{cite journal | vauthors = Minokawa Y, Sawada Y, Nakamura M | title = Lifestyle Factors Involved in the Pathogenesis of Alopecia Areata | journal = International Journal of Molecular Sciences | volume = 23 | issue = 3 | page = 1038 | date = January 2022 | pmid = 35162962 | pmc = 8835065 | doi = 10.3390/ijms23031038 | doi-access = free }}</ref>