Autoimmune/autoinflammatory

Alopecia areata

What is alopecia areata?

Alopecia areata is anautoimmune condition affectinghairfollicles causing hair loss. It typically presents withdiscrete bald patches on the scalp but can cause hair loss from all hair-bearing areas on the body.

Alopecia is a Latin term meaning hair loss, and areata refers to the patchy nature of the hair loss. The term alopecia areata is considered an umbrella term, which encompasses a number of variants including alopecia areata totalis or universalis, ophiasis, ophiasis inversus, anddiffuse alopecia areata.

A singlepatch of alopecia areata (AA-patient1)

Extensive patchy alopecia areata 

Alopecia totalis 

Ophiasic pattern alopecia areata (AA-patient5)

Extensive alopecia areata with retention of grey hairs 

Dermoscopic image of alopecia areata presenting with exclamation mark hairs 

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Who gets alopecia areata?

The lifetime risk of alopecia areata is approximately 2%. It affects children and adults of all skin and hair colours. Peakincidence occurs in the second and third decades and most patients experience onset before the fourth decade. Alopecia areata does not carry significantsex or ethnic predominance.

The following may increase the risk of alopecia areata:

• Chromosomal disorders such asDown syndrome
• Polyglandular autoimmunesyndrome type 1
• Other autoimmune conditions such asvitiligo andthyroid disease
• A family history of alopecia areata
• Certainsusceptibilitygenes (see below).

What causes alopecia areata?

A normal hairfollicle cycles through multiple phases:

• Anagen is the active growth phase lasting one to eight years
• Catagen is a shortinvolution phase lasting several weeks
• Telogen is the resting phase lasting several months
• Exogen is the shedding of the hair.

The exact mechanism responsible for hair loss in alopecia areata remains unclear. It is hypothesised that loss of immune privilege in anagen hair follicles plays a key role in thepathogenesis, andgenetic susceptibility is also thought to contribute.

Immune privilege hypothesis

• Normal anagen hair follicles are thought to exhibit immune privilege, rendering them exempt from immune surveillance and protected against autoimmune attack.
• Protective immune privilege may be lost in alopecia areata, allowing hair follicleautoantigens to be presented to autoreactive CD8+T cells.
• Subsequent autoimmune attack of the anagen follicle causes premature transition of the follicle into the telogen phase with ultimate loss of the hair.

This hypothesis is supported by the observation of a denseperifollicularinfiltrate of T cells onhistopathological examination of anagen follicles in alopecia areata; an area that is normally sparse ofimmune cells.

Genetic factors

• Alopecia areata has a stronghereditary component.
• At least 16 genetic risk loci have been detected.
  • Include numerous humanleukocyteantigen (HLA) class I and IIalleles, and several alleles of genes involved in immune pathways, hairpigmentation, and response to oxidative stress.
• Mode of inheritance appears to be complex, with environmental influences also at play.

What are the clinical features of alopecia areata?

Acute onset of hair loss maymanifest in a number of patterns.

Patchy alopecia areata is the most common pattern, producing:

• Focal hair loss
• Well-demarcated single or several round/oval patches of normal-appearing skin.

The scalp is most commonly affected, but may also affect the:

• Beard
• Eyebrows
• Eyelashes
• Any other hair-bearing areas.

Less common patterns include:

• Alopecia totalis – complete loss of scalp hair
  • Affects up to 5% of patients with autoimmune hair loss
• Alopecia universalis – complete loss of body hair
  • Affects less than 1%
• Ophiasis — bandlike hair loss on theoccipital andtemporal scalp margins
• Sisaipho (ophiasis inversus) — hair loss on the frontal, temporal, and parietal scalp which may mimic male pattern hair loss
• Diffuse alopecia areata (alopecia areata incognita) — rapid andwidespread hair loss.
• Sudden greying — loss ofpigmented hairs, resulting in the unmasking of existing grey hairs (“white overnight”).

Other features

Characteristic“exclamation point hairs” may be observed, particularly at the periphery of bald patches. An exclamation point hair is a broken strand with a relatively thickdistal portion and thinproximal portion as it enters the scalp. They are the result of anagen arrest andcessation of hair shaft formation, with weakening and tapering of the shaft.

Some patients may experiencelocalised tingling or itching preceding hair loss (trichodynia).

Upon regrowth, hairs may initially lackpigment and so grow back as white or blonde.

Nail changes can be seen in an estimated 10–40% of patients and tend to be associated with more severe disease.

• Nailpitting and ridging are most common.
• Other nail features includekoilonychia,trachyonychia, Beau’s lines,onychorrhexis,onychomadesis,onycholysis, and red spots in thelunula.

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How do clinical features vary in differing types of skin?

There are no differences in clinical features of alopecia in patients with skin of colour.

What are the complications of alopecia areata?

• Poor health-related quality of life due to distress.
• Higher rates of depression andgeneralised anxiety disorder; adjustment disorders are also common.
• Other autoimmune conditions may be more commonly observed in patients with alopecia areata e.g.thyroid disease,vitiligo,psoriasis,diabetes mellitus, andatopy.

How is alopecia areata diagnosed?

Alopecia areata is typically diagnosed on clinical features, however additional tests may aid diagnosis.

• Trichoscopy:
  • Examination of the hair follicle, hair shaft, and scalp with adermatoscope
  • Features of active disease include exclamation point hairs, broken ordystrophic hairs, yellow dots and black dots.
• Hair pull test:
  • Can help confirm hair loss and is often positive in alopecia areata
  • Involves grasping 40–60 closelygrouped hairs and applying gentle traction
  • Positive when more than 10% of hairs are easily pulled out.
• Skin biopsy:
  • May be required if diagnosis uncertain
  • In acute alopecia areata,histopathology reveals a “bee-swarm pattern” of denselymphocyticinfiltrates surrounding anagen hair follicles
  • Increase in catagen and telogen relative to anagen follicles, and follicle miniaturisation with progression of disease.

How is the severity of alopecia areata assessed?

Scalp alopecia areata is assessed on the basis of the percentage of the scalp that is affected - this is the SALT score.

SALT 0 means there is not hair loss due to alopecia areata.

SALT 50 means 50% of the scalp is affected by alopecia areata. SALT 40 is regarded by sufferers anddermatologists as severe alopecia areata.

Lash and brow alopecia can be difficult to disguise and adds to the burden of the condition.

The ASAMI score (Alopecia Areata Severity andMorbidity Index) has recently been devised to take into account not only sites and extent of alopecia, but sufferer centred symptoms such as difficulty in camouflage, affects on work recreation, relationships, and mental wellbeing.

What is the differential diagnosis for alopecia areata?

• Trichotillomania
• Temporal triangular alopecia
• Central centrifugal cicatricial alopecia
• Discoid lupus erythematosus affecting the scalp
• Tinea capitis
• Telogen effluvium (may mimicdiffuse alopecia areata)
• Androgenetic alopecia (may mimic sisaipho pattern)
• Secondarysyphilis (syphilitic alopecia)
• Lichen planopilaris
• Frontal fibrosing alopecia.

What is the treatment for alopecia areata?

There is no cure for alopecia areata. The hair loss in alopecia areata is associated with minimal harmful physical effects and spontaneous resolution may occur.

However, the psychological impact can be significant, therefore warranting treatment. Numerous therapies have been used with variable response and high quality evidence is lacking.

Treatments for mild alopecia areata (less than 50% scalp involvement)

Intralesional corticosteroid injections

• Injections of triamcinolone into areas of patchy alopecia of the scalp, beard, or eyebrow have an immunosuppressant effect and may speed up hair regrowth.
• Repeated four to six weekly and stopped once regrowth is complete.

Topical treatments

• Potent corticosteroidsolutions,creams, or ointments
  • Most beneficial if used withocclusive dressings
• Minoxidilsolution
  • Ideally in combination with other therapies
• Anthralin (dithranol)cream orointment
  • Limited use in fair-haired individuals due to brown staining of skin and hair.

Treatments for extensive alopecia areata (greater than 50% scalp involvement, alopecia totalis, or universalis)

Topical immunotherapy

• Chemicals such asdiphenylcyclopropenone are applied to affected areas to induce anallergic contact dermatitis, which may provoke hair regrowth.
  • T-cells are theorised to be “distracted” from attacking hair follicles due toantigenic competition.
  • Severe dermatitis,urticaria,lymphadenopathy, anddepigmentation are potential side effects and may limit use.

Systemic corticosteroids

• Generally reserved for short-term use inrefractory or severe cases.
• Limited by well-known adverse effects.

Janus kinase (JAK) inhibitors

• In June 2022, The FDA approvedbaricitinib use in severe alopecia areata.
• Clinical trials are ongoing, but preliminary results also show promise for other JAKinhibitors.
• JAK inhibitors block theT-cell-mediatedinflammatory response that is thought to be responsible for damage to the hair follicle.
• Some oral JAK inhibitors are more effective than topical preparations, and significantly more effective thanplacebos used in large clinical trials.
• Baricitinib has received FDA approval for use in the USA.
• Ritlecitinib has received FDA and NICE approval - after 24 weeks almost a quarter of patients achieved a SALT score of 20 or less. The response rate increased to over 40% after one year on therapy.
• Deuruxolitinib has recieved FDA approval for severe alopecia areata in adults.
• Brepocitinib may be slightly more effective than ritlecitinib, but in one trial it produced a serious inflammatory condition of skeletal muscles in two recipients.
• Long term follow up data, outcomes after drug discontinuation, and long term safely remain to be answered. They may be more effective in those who have not had the disease for several years, and in those who do not have alopecia totalis or universalis. Brow and lash regrowth has been documented. They are expensive medications.

Others

Improvement following numerous other less common and less studied treatments have been reported.

• Systemic examples include:
  • Dupilumab
  • Methotrexate
  • Ezetimibe-simvastatin
  • Antidepressants.
• Localised examples include:
  • Topical retinoids
  • Platelet-rich plasma
  • Micro-needling.

Education and counselling

Patients should be informed that there is no cure and response to treatments are variable.

• Alopecia areata may spontaneously resolve,persist,relapse, and/orprogress. Explaining the various possible disease courses can help manage expectations.
• Some patients may benefit from professional counselling to adjust to the appearance altering aspect of the disorder and regain self-confidence.
• Consider patient support groups.

Camouflage

Camouflaging hair loss can be helpful for patients who decide against pharmacological treatment or in those who have incomplete response.

• A prosthesis can be used to disguise scalp hair loss.

  • Options include a full wig, hairpiece (clipped or glued to existing hair), or mesh integration system (custom made unit with hair extensions in the areas of alopecia).

• Styling products such as gels, mousses, powders, and sprays help to keep hair in place, achieve scalp coverage, and add volume.

• False eyelashes or artificial eyebrows

  • Eyebrow tattooing or microblading can be helpful.
  • Waterproof eyebrow pencil or eyeliner is a less permanent option.

How do you prevent alopecia areata?

We do not yet know how to prevent alopecia areata.

What is the outcome for alopecia areata?

Alopecia areata follows an unpredictable course. Spontaneous hair regrowth and recovery may occur and is common in some reports. Relapse is also common, however, and patients may have several phases of hair loss and subsequent regrowth. The risk of progression to alopecia totalis or alopecia universalis is approximately 5–10%, from which recovery is unlikely.

Response to treatment is highly variable and hair loss mayrecur when therapy is stopped.

Poorprognostic factors include:

• Younger age at onset
• More extensive disease
• Hair loss of greater than one-year duration
• Naildystrophy
• Ophiasis pattern
• Family history of alopecia areata
• Presence of atopy or other autoimmune diseases.

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Bibliography

• ASAMI Consensus Survey Study Group, Moussa A, Bennett M, et al. The Alopecia Areata Severity and Morbidity Index (ASAMI) Study: Results From a Global Expert Consensus Exercise on Determinants of Alopecia Areata Severity. JAMA Dermatol. 2024;160(3):341–50.PubMed
• Darwin E, Hirt P, Fertig R, Doliner B, Delcanto G, Jimenez J. Alopecia areata: Review of epidemiology, clinical features, pathogenesis, and new treatment options. Int J Trichol. 2018;10(2):51. doi:10.4103/ijt.ijt_99_17. Journal
• Dillon KAL. A Comprehensive Literature Review of JAK Inhibitors in Treatment of Alopecia Areata. CCID. 2021;Volume 14:691–714. doi:10.2147/CCID.S309215.Journal
• Gilhar A, Etzioni A, Paus R. Alopecia Areata. N Engl J Med. 2012;366(16):1515–25. doi:10.1056/NEJMra1103442.Journal
• Lattouf C, Jimenez JJ, Tosti A, et al. Treatment of alopecia areata with simvastatin/ezetimibe. J Am Acad Dermatol. 2015;72(2):359–61. doi:10.1016/j.jaad.2014.11.006.Journal
• King B, Guttman-Yassky E, Peeva E, et al. A phase 2a randomized, placebo-controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24-week results. J Am Acad Dermatol. 2021;85(2):379–87.PubMed
• King B, Zhang X, Harcha WG, et al. Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial [published correction appears in Lancet. 2023 Jun 10;401(10392):1928]. Lancet. 2023;401(10387):1518–29.PubMed
• Messenger AG, McKillop J, Farrant P, et al. British Association of Dermatologists’ guidelines for the management of alopecia areata 2012. British Journal of Dermatology. 2012;166(5):916–26. doi:10.1111/j.1365-2133.2012.10955.x.Journal
• Miteva M, Villasante A. Epidemiology and burden of alopecia areata: a systematic review. CCID. Published online July 2015:397. doi:10.2147/CCID.S53985.Review
• Rajabi F, Drake LA, Senna MM, Rezaei N. Alopecia areata: a review of disease pathogenesis. Br J Dermatol. 2018;179(5):1033–48. doi:10.1111/bjd.16808.Journal
• Strazzulla LC, Wang EHC, Avila L, et al. Alopecia areata. Journal of the American Academy of Dermatology. 2018;78(1):1–12. doi:10.1016/j.jaad.2017.04.1141.Journal
• Wasserman D, Guzman-Sanchez DA, Scott K, McMichael A. Alopecia areata: Alopecia areata. International Journal of Dermatology. 2007;46(2):121–31. doi:10.1111/j.1365-4632.2007.03193.x.Journal

On DermNet

• Alopecia areata in children
• Dermatoscope
• Diffuse alopecia
• Hair loss
• Trichoscopy
• Trichoscopy of generalised noncicatricial hair loss
• Trichoscopy of localised noncicatricial hair loss

Other websites

• The National Alopecia Areata Foundation
• Alopecia New Zealand
• Australia Alopecia Areata Foundation
• Children's Alopecia Project
• Alopecia World support group

Books about skin diseases

• Books about the skin
• Dermatology Made Easy - second edition