Epidemiology, management and the associated burden of mental health illness, atopic and autoimmune conditions, and common infections in alopecia areata: protocol for an observational study series

Matthew Harries, Abby E Macbeth, Susan Holmes, Andrew R Thompson, Wing Sin Chiu, William Romero Gallardo, Andrew G Messenger, Christos Tziotzios, Simon de Lusignan, Matthew Harries, Abby E Macbeth, Susan Holmes, Andrew R Thompson, Wing Sin Chiu, William Romero Gallardo, Andrew G Messenger, Christos Tziotzios, Simon de Lusignan

Abstract

Introduction: Alopecia areata (AA) is a common cause of immune-mediated non-scarring hair loss. Links between AA and common mental health, autoimmune and atopic conditions, and common infections have previously been described but remain incompletely elucidated and contemporary descriptions of the epidemiology of AA in the UK are lacking.

Methods and analysis: Retrospective study series using a large population-based cohort (5.2 million) from the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database, exploring four themes: AA epidemiology, mental health comorbidities, autoimmune/atopic associations and common infections.In the epidemiology theme, we will describe the incidence and point prevalence of AA overall and by age, sex and sociodemographic factors. Healthcare utilisation (primary care visits and secondary care referrals) and treatments for AA will also be assessed. In the mental health theme, we will explore the prevalence and incidence of mental health conditions (anxiety, depressive episodes, recurrent depressive disorder, adjustment disorder, agoraphobia, self-harm and parasuicide) in people with AA compared with matched controls. We will also explore the mental health treatment patterns (medication and psychological interventions), time off work and unemployment rates. Within the autoimmune/atopic associations theme, we will examine the prevalence of atopic (atopic dermatitis, allergic rhinitis, asthma) and autoimmune conditions (Crohn's disease, ulcerative colitis, coeliac disease, type 1 diabetes, Hashimoto's thyroiditis, Graves' disease, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus (SLE), polymyalgia rheumatica, Sjögren's syndrome, psoriasis, vitiligo, multiple sclerosis, pernicious anaemia) in people with AA compared with matched controls. We will also estimate the incidence of new-onset atopic and autoimmune conditions after AA diagnosis. Within the common infections theme, we will examine the incidence of common infections (respiratory tract infection, pneumonia, acute bronchitis, influenza, skin infection, urinary tract infection, genital infections, gastrointestinal infection, herpes simplex, herpes zoster, meningitis, COVID-19) in people with AA compared with matched controls.

Ethics and dissemination: The Health Research Authority decision tool classed this a study of usual practice, ethics approval was not required. Study approval was granted by the RCGP RSC Study Approval Committee. Results will be disseminated through peer-reviewed publications.

Observational study registration number: NCT04239521.

Keywords: dermatology; epidemiology; immunology; infectious diseases; mental health; primary care.

Conflict of interest statement

Competing interests: SdL is Director of RCGP RSC. He has received funding for projects from Eli Lilly, AstraZeneca, GSK, Seqirus and Takeda—all through his universities and none related to this study. WSC and WRG are employees of Pfizer. SH and CT are investigators on the Pfizer-funded Allegro clinical trial.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

References

    1. Hordinsky MK. Overview of alopecia areata. J Investig Dermatol Symp Proc 2013;16:S13–15. 10.1038/jidsymp.2013.4
    1. Alkhalifah A, Alsantali A, Wang E, et al. . Alopecia areata update: Part I. clinical picture, histopathology, and pathogenesis. J Am Acad Dermatol 2010;62:177-88, quiz 189-90. 10.1016/j.jaad.2009.10.032
    1. Madani S, Shapiro J. Alopecia areata update. J Am Acad Dermatol 2000;42:549-66; quiz 567-70.
    1. Mirzoyev SA, Schrum AG, Davis MDP, et al. . Lifetime incidence risk of alopecia areata estimated at 2.1% by Rochester Epidemiology Project, 1990-2009. J Invest Dermatol 2014;134:1141–2. 10.1038/jid.2013.464
    1. Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: a systematic review. Clin Cosmet Investig Dermatol 2015;8:397–403. 10.2147/CCID.S53985
    1. Richard M-A, Corgibet F, Beylot-Barry M, et al. . Sex- and age-adjusted prevalence estimates of five chronic inflammatory skin diseases in France: results of the « OBJECTIFS Peau » study. J Eur Acad Dermatol Venereol 2018;32:1967–71. 10.1111/jdv.14959
    1. Harries MJ, Sun J, Paus R, et al. . Management of alopecia areata. BMJ 2010;341:c3671. 10.1136/bmj.c3671
    1. Cochrane . Treatments for alopecia aerate, alopecia totalis and alopecia universalis, 2008.
    1. Lee S, Lee H, Lee CH, et al. . Comorbidities in alopecia areata: a systematic review and meta-analysis. J Am Acad Dermatol 2019;80:466–77. 10.1016/j.jaad.2018.07.013
    1. Montgomery K, White C, Thompson A. A mixed methods survey of social anxiety, anxiety, depression and Wig use in alopecia. BMJ Open 2017;7:e015468. 10.1136/bmjopen-2016-015468
    1. Huang KP, Mullangi S, Guo Y, et al. . Autoimmune, atopic, and mental health comorbid conditions associated with alopecia areata in the United States. JAMA Dermatol 2013;149:789–94. 10.1001/jamadermatol.2013.3049
    1. Hunt N, McHale S. The psychological impact of alopecia. BMJ 2005;331:951–3. 10.1136/bmj.331.7522.951
    1. Safavi K. Prevalence of alopecia areata in the first National health and nutrition examination survey. Arch Dermatol 1992;128:702. 10.1001/archderm.1992.01680150136027
    1. Sharma VK, Dawn G, Kumar B. Profile of alopecia areata in northern India. Int J Dermatol 1996;35:22-7. 10.1111/j.1365-4362.1996.tb01610.x
    1. Tan E, Tay Y-K, Goh C-L, et al. . The pattern and profile of alopecia areata in Singapore--a study of 219 Asians. Int J Dermatol 2002;41:748–53. 10.1046/j.1365-4362.2002.01357.x
    1. Yang S, Yang J, Liu JB, et al. . The genetic epidemiology of alopecia areata in China. Br J Dermatol 2004;151:16–23. 10.1111/j.1365-2133.2004.05915.x
    1. Guzmán-Sánchez DA, Villanueva-Quintero GD, Alfaro Alfaro N, et al. . A clinical study of alopecia areata in Mexico. Int J Dermatol 2007;46:1308–10. 10.1111/j.1365-4632.2007.03320.x
    1. Furue M, Yamazaki S, Jimbow K, et al. . Prevalence of dermatological disorders in Japan: a nationwide, cross-sectional, seasonal, multicenter, hospital-based study. J Dermatol 2011;38:310–20. 10.1111/j.1346-8138.2011.01209.x
    1. Singam V, Patel KR, Lee HH, et al. . Association of alopecia areata with hospitalization for mental health disorders in US adults. J Am Acad Dermatol 2019;80:792–4. 10.1016/j.jaad.2018.07.044
    1. Sellami R, Masmoudi J, Ouali U, et al. . The relationship between alopecia areata and alexithymia, anxiety and depression: a case-control study. Indian J Dermatol 2014;59:421. 10.4103/0019-5154.135525
    1. Ruiz-Doblado S, Carrizosa A, García-Hernández MJ. Alopecia areata: psychiatric comorbidity and adjustment to illness. Int J Dermatol 2003;42:434–7. 10.1046/j.1365-4362.2003.01340.x
    1. Baghestani S, Zare S, Seddigh SH. Severity of depression and anxiety in patients with alopecia areata in Bandar Abbas, Iran. Dermatol Reports 2015;7:6063. 10.4081/dr.2015.6063
    1. Chu S-Y, Chen Y-J, Tseng W-C, et al. . Psychiatric comorbidities in patients with alopecia areata in Taiwan: a case-control study. Br J Dermatol 2012;166:525–31. 10.1111/j.1365-2133.2011.10714.x
    1. Vallerand IA, Lewinson RT, Parsons LM, et al. . Assessment of a bidirectional association between major depressive disorder and alopecia areata. JAMA Dermatol 2019;155:475. 10.1001/jamadermatol.2018.4398
    1. Paus R, Ito N, Takigawa M, et al. . The hair follicle and immune privilege. J Investig Dermatol Symp Proc 2003;8:188–94. 10.1046/j.1087-0024.2003.00807.x
    1. Barahmani N, Schabath MB, Duvic M, et al. . History of atopy or autoimmunity increases risk of alopecia areata. J Am Acad Dermatol 2009;61:581–91. 10.1016/j.jaad.2009.04.031
    1. Chen C-H, Wang K-H, Lin H-C, et al. . Follow-Up study on the relationship between alopecia areata and risk of autoimmune diseases. J Dermatol 2016;43:228–9. 10.1111/1346-8138.13165
    1. Tosti A. Practice gaps. alopecia areata and comorbid conditions. JAMA Dermatol 2013;149:794. 10.1001/jamadermatol.2013.360
    1. Tan E, Tay Y-K, Giam Y-C. A clinical study of childhood alopecia areata in Singapore. Pediatr Dermatol 2002;19:298–301. 10.1046/j.1525-1470.2002.00088.x
    1. Jagielska D, Redler S, Brockschmidt FF, 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 2012;132:2192–7. 10.1038/jid.2012.129
    1. Bhardwaj EK, Trüeb RM. Acute diffuse and total alopecia of the female scalp associated with borrelia-infection. Int J Trichology 2015;7:26–8. 10.4103/0974-7753.153454
    1. Cho M, Cohen PR, Duvic M. Vitiligo and alopecia areata in patients with human immunodeficiency virus infection. South Med J 1995;88:489–91. 10.1097/00007611-199504000-00024
    1. Gil Montoya JA, Cutando Soriano A, Jimenez Prat J. Alopecia areata of dental origin. Med Oral 2002;7:303–8.
    1. Ito T, Tokura Y. Alopecia areata triggered or exacerbated by swine flu virus infection. J Dermatol 2012;39:863–4. 10.1111/j.1346-8138.2011.01437.x
    1. Jackow C, Puffer N, Hordinsky M, et al. . Alopecia areata and cytomegalovirus infection in twins: genes versus environment? J Am Acad Dermatol 1998;38:418–25. 10.1016/s0190-9622(98)70499-2
    1. Offidani A, Amerio P, Bernardini ML, et al. . Role of cytomegalovirus replication in alopecia areata pathogenesis. J Cutan Med Surg 2000;4:63–5. 10.1177/120347540000400204
    1. Paoletti V, Mammarella A, Basili S, et al. . Prevalence and clinical features of skin diseases in chronic HCV infection. A prospective study in 96 patients. Panminerva Med 2002;44:349–52.
    1. Richardson CT, Hayden MS, Gilmore ES, et al. . Evaluation of the relationship between alopecia areata and viral antigen exposure. Am J Clin Dermatol 2018;19:119–26. 10.1007/s40257-017-0312-y
    1. Kartal ED, Alpat SN, Ozgunes I, et al. . Reversible alopecia universalis secondary to PEG-interferon alpha-2b and ribavirin combination therapy in a patient with chronic hepatitis C virus infection. Eur J Gastroenterol Hepatol 2007;19:817–20. 10.1097/MEG.0b013e32818b27e5
    1. Abdel Hafez HZ, Mahran AM, Hofny EM, et al. . Alopecia areata is not associated with Helicobacter pylori. Indian J Dermatol 2009;54:17–19. 10.4103/0019-5154.48979
    1. Domínguez-Andrés J, Netea MG. Impact of historic migrations and evolutionary processes on human immunity. Trends Immunol 2019;40:1105–19. 10.1016/j.it.2019.10.001
    1. Dubois PCA, Trynka G, Franke L, et al. . Multiple common variants for celiac disease influencing immune gene expression. Nat Genet 2010;42:295–302. 10.1038/ng.543
    1. Hung S-C, Hou T, Jiang W, et al. . Epitope selection for HLA-DQ2 presentation: implications for celiac disease and viral defense. J Immunol 2019;202:2558–69. 10.4049/jimmunol.1801454
    1. Zhernakova A, Elbers CC, Ferwerda B, et al. . Evolutionary and functional analysis of celiac risk loci reveals SH2B3 as a protective factor against bacterial infection. Am J Hum Genet 2010;86:970–7. 10.1016/j.ajhg.2010.05.004
    1. Kucharzik T, Maaser C. Infections and chronic inflammatory bowel disease. Viszeralmedizin 2014;30:326–32. 10.1159/000366463
    1. Toruner M, Loftus EV, Harmsen WS, et al. . Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology 2008;134:929–36. 10.1053/j.gastro.2008.01.012
    1. Brassard P, Bitton A, Suissa A, et al. . Oral corticosteroids and the risk of serious infections in patients with elderly-onset inflammatory bowel diseases. Am J Gastroenterol 2014;109:109. 10.1038/ajg.2014.313
    1. Lichtenstein GR, Feagan BG, Cohen RD, et al. . Serious infections and mortality in association with therapies for Crohn's disease: treat registry. Clin Gastroenterol Hepatol 2006;4:621–30. 10.1016/j.cgh.2006.03.002
    1. Lichtenstein GR, Feagan BG, Cohen RD, et al. . Serious infection and mortality in patients with Crohn's disease: more than 5 years of follow-up in the TREAT™ registry. Am J Gastroenterol 2012;107:1409–22. 10.1038/ajg.2012.218
    1. Fardet L, Petersen I, Nazareth I. Common infections in patients prescribed systemic glucocorticoids in primary care: a population-based cohort study. PLoS Med 2016;13:e1002024. 10.1371/journal.pmed.1002024
    1. Nikiphorou E, de Lusignan S, Mallen C. Haematological abnormalities in new-onset rheumatoid arthritis and risk of common infections: a population-based study. Rheumatology 2019;59. 10.1093/rheumatology/kez344
    1. Gilhar A, Keren A, Paus R. Jak inhibitors and alopecia areata. Lancet 2019;393:318–9. 10.1016/S0140-6736(18)32987-8
    1. Correa A, Hinton W, McGovern A, et al. . Royal College of general practitioners research and surveillance centre (RCGP RSC) sentinel network: a cohort profile. BMJ Open 2016;6:e011092. 10.1136/bmjopen-2016-011092
    1. de Lusignan S, van Weel C. The use of routinely collected computer data for research in primary care: opportunities and challenges. Fam Pract 2006;23:253–63. 10.1093/fampra/cmi106
    1. de Lusignan S, Metsemakers JF, Houwink P, et al. . Routinely collected general practice data: goldmines for research? A report of the European Federation for medical informatics primary care informatics Working Group (EFMI PCIWG) from MIE2006, Maastricht, the Netherlands. Inform Prim Care 2006;14:203–9. 10.14236/jhi.v14i3.632
    1. Woodmansey C, McGovern AP, McCullough KA, et al. . Incidence, demographics, and clinical characteristics of diabetes of the exocrine pancreas (type 3C): a retrospective cohort study. Diabetes Care 2017;40:1486–93. 10.2337/dc17-0542
    1. Nikiphorou E, de Lusignan S, Mallen C, et al. . Prognostic value of comorbidity indices and lung diseases in early rheumatoid arthritis: a UK population-based study. Rheumatology 2020;59:1296–305. 10.1093/rheumatology/kez409
    1. de Lusignan S, Alexander H, Broderick C, et al. . Epidemiology and management of atopic dermatitis in England: an observational cohort study protocol. BMJ Open 2020;10:e037518. 10.1136/bmjopen-2020-037518
    1. Galloway J, Barrett K, Irving P, et al. . Risk of venous thromboembolism in immune-mediated inflammatory diseases: a UK matched cohort study. RMD Open 2020;6:e001392. 10.1136/rmdopen-2020-001392
    1. Pathirannehelage S, Kumarapeli P, Byford R, et al. . Uptake of a Dashboard designed to give RealTime feedback to a sentinel network about key data required for influenza vaccine effectiveness studies. Stud Health Technol Inform 2018;247:161–5.
    1. Office for National Statistics . Ethnicity, 2018. Available: [Accessed 2 Jan 2020].
    1. Ministry of Housing CLG . English indices of deprivation 2015: technical report, 2015. Available: [Accessed 2 Jan 2020].
    1. Kessler RC, Chiu WT, Demler O, et al. . Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National comorbidity survey replication. Arch Gen Psychiatry 2005;62:617–27. 10.1001/archpsyc.62.6.617
    1. Hayter SM, Cook MC. Updated assessment of the prevalence, spectrum and case definition of autoimmune disease. Autoimmun Rev 2012;11:754–65. 10.1016/j.autrev.2012.02.001
    1. Cooper GS, Bynum MLK, Somers EC. Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J Autoimmun 2009;33:197–207. 10.1016/j.jaut.2009.09.008
    1. Dean LE, Jones GT, MacDonald AG, et al. . Global prevalence of ankylosing spondylitis. Rheumatology 2014;53:650–7. 10.1093/rheumatology/ket387
    1. Gladman DD, Antoni C, Mease P, et al. . Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis 2005;64 Suppl 2:ii14-7. 10.1136/ard.2004.032482
    1. Prickitt J, McMichael AJ, Gallagher L, et al. . Helping patients cope with chronic alopecia areata. Dermatol Nurs 2004;16:237–41.
    1. Rayner L, Sherlock J, Creagh-Brown B, et al. . The prevalence of COPD in England: an ontological approach to case detection in primary care. Respir Med 2017;132:217–25. 10.1016/j.rmed.2017.10.024
    1. De Lusignan S. In this issue: ontologies a key concept in informatics and key for open definitions of cases, exposures, and outcome measures. J Innov Health Inform 2015;22. 10.14236/jhi.v22i2.170
    1. Mathur R, Bhaskaran K, Chaturvedi N, et al. . Completeness and usability of ethnicity data in UK-based primary care and hospital databases. J Public Health 2014;36:684–92. 10.1093/pubmed/fdt116
    1. Rayner LH, Mcgovern A, Sherlock J, et al. . The impact of therapy on the risk of asthma in type 2 diabetes. Clin Respir J 2019;13:299–305. 10.1111/crj.13011
    1. Kumar S, de Lusignan S, McGovern A, et al. . Ischaemic stroke, haemorrhage, and mortality in older patients with chronic kidney disease newly started on anticoagulation for atrial fibrillation: a population based study from UK primary care. BMJ 2018;360:k342. 10.1136/bmj.k342
    1. Behr MA, Divangahi M, Lalande J-D. What's in a name? The (mis)labelling of Crohn's as an autoimmune disease. Lancet 2010;376:202–3. 10.1016/S0140-6736(10)60282-6

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere