Alopecia Areata


Article Author:
Kenia Lepe


Article Editor:
Patrick Zito


Editors In Chief:
Jasleen Jhajj
Cliff Caudill
Evan Kaufman


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes
Kavin Sugumar


Updated:
3/14/2019 4:38:51 PM

Introduction

Alopecia areata (AA) is a form of alopecia that impacts hair follicles, nails, and rarely, the retinal pigment epithelium.[1] It typically presents with round patches and is a type of non-scarring hair loss.

Etiology

Alopecia areata seems to have a genetic basis. A 55% concordance rate between identical twins has been observed.  Recent genome-wide association studies (GWAS) metanalysis have localized the HLA signal of AA mostly to the HLA-DRB1. One locus harboring the genes that encode the natural killer cell receptor D (NKG2D) was implicated in AA and not in other autoimmune diseases, which suggests a key role in pathogenesis. Therefore, CD8+ NKG2D T cells have been a subject of study and found to be the major effectors in AA.[2]

Epidemiology

The overall incidence is approximately 20.2 per 100,000 person-years.[3] The lifetime risk of presenting AA in the general population is approximately 2%.[2]

The prevalence of AA ranges from 0.1 to 0.2%, depending on the geographic location and ethnic background. The prevalence of adult patients with a family history is estimated to be between 0 and 8.6%. 

Alopecia areata incidence appears to increase almost linearly with age, but the mean age of onset appears to be between 25 and 36 years.[4] Early onset AA (between 5 to 10 years-old) predominantly presents as a more severe subtype.[2] Data shows no demonstrable sex predilection.

It carries associations with an increased overall risk of other autoimmune diseases(16%), including lupus erythematosus, vitiligo, and autoimmune thyroid disease. Additionally, an association with atopic dermatitis exists in 39% of cases.[1]

Pathophysiology

A significant feature of the hair follicle is its relative immune privilege, this mainly established by suppression of surface molecules required for presenting autoantigens to CD8+ T lymphocytes (i.e., MHC class I) and by the generation of an inhibitory local signaling environment.[3] The breakdown of the immune privilege of the hair follicle has been thought to be a significant driver of AA.[2]

Alopecia areata is a disorder of hair follicle-cycling, where inflammatory cells attack the hair follicle matrix epithelium that is undergoing early cortical differentiation (anagen hair follicles), which are then prematurely induced into the catagen phase. However, since no destruction of hair-follicle stem cells occurs, the hair follicle retains its capacity to regenerate and continue cycling. Thereby, follicles re-enter the anagen phase normally but do not develop beyond the anagen III/IV phase.

Presumably, alopecia areata develops in a previously healthy hair follicle because its immune privilege collapses. Therefore, it could occur in a genetically predisposed person only when proinflammatory signals (i.e., IFN gamma, substance P) known to upregulate MHC class Ia in human hair-follicle epithelium expose previously unrevealed follicle-associated autoantigens to preexisting autoreactive CD8+ T cells. 

Since only anagen hair follicles undergo attack, those autoantigens may generate and then be presented only during anagen.

The precise event that precipitates alopecia areata is unknown. Some triggers have been reported, most commonly emotional or physical stress, vaccines, viral infections, and drugs.[1]

Histopathology

Histologic examination demonstrates a characteristic “bee-swarm pattern” of dense lymphocytic infiltrates surrounding the bulbar region of anagen hair follicles.[1] The lymphocytic infiltrate consists of CD8+ T cells in the follicular epithelium and CD4+ T cells around the hair follicles.[5]

History and Physical

It presents as hair loss in well-circumscribed patches of normal-appearing skin. Although any hair-bearing can be affected, this occurs most commonly on the scalp and beard.  

The onset is usually fast, and it may progress and induce complete hair loss on the scalp, a condition termed alopecia areata totalis. Moreover, it may induce complete hair loss on the whole body (alopecia areata universalis) Other variants include ophiasis, in which hair loss affects the occipital region, diffuse forms of alopecia (alopecia incognito) and “sudden graying,” a variant which attacks pigmented hair follicles.[1]

Exclamation-mark hairs are a key characteristic of alopecia areata. In exclamation-mark hairs, the hair root is narrowed and suggest defective anchoring of the hair within the follicle.  Exclamation point hairs can be found at the margins of the lesions during the active phases of the disease.[3]

Alopecia areata can involve the nails, which occurs in about 10 to 15% of cases. Patients with nail involvement usually present the most severe forms of hair loss.[3] The nail manifestations consist of fine pitting of the nails, and occasionally, trachyonychia.

Alopecia areata carries associations with several comorbidities, including depression, anxiety, and several autoimmune diseases (thyroid disease, lupus erythematosus, vitiligo, psoriasis, rheumatoid arthritis, inflammatory bowel disease). These autoimmune comorbidities suggest that patients with alopecia areata are at increased risk of developing various T cell-driven inflammatory skin diseases.[2]

Evaluation

If the diagnosis is not clear after clinical evaluation, as in the diffuse variant, a skin biopsy may be helpful.[1] Despite the association with other autoimmune diseases, (i.e., thyroid disease) current evidence does not support the need to screen for these diseases without a clinical history that suggests its presence.[2] Dermoscopy can be a helpful supporting tool. The key dermoscopic findings are yellow dots, black dots, broken hairs, exclamation point hairs and short vellus hairs, which are a sign of early regrowth.

Treatment / Management

The rate of spontaneous remission makes it difficult to assess the efficacy of a therapy. Even, leaving alopecia areata untreated is a legitimate option for many patients.[6]

Despite limited evidence for the efficacy of therapeutic agents, intralesional and topical corticosteroids are considered first-line treatment for most patients with patchy AA.

Triamcinolone acetonide 5-10 mg per milliliter given every 2 – 6 weeks, stimulates localized re-growth in 60 – 67% of cases.[1]  A study comparing different concentrations of intralesional triamcinolone acetonide (2.5 mg/ml, 5 mg/ml, 10 mg/ml) for the treatment of AA on the scalp, demonstrated similar rates of hair regrowth regardless of the concentration. However, the risk of cutaneous atrophy was higher at a higher concentration (10mg/ml).[7] The use of intralesional betamethasone has been proposed, however, further studies are needed to evaluate its efficacy.[8] Side effects include localized skin atrophy, pain, and depigmentation. Local skin atrophy might resolve within a few months. Relapses are frequent after cessation of treatment.

Potent topical glucocorticoids find frequent utilization in the treatment of alopecia areata; however, evidence of effectiveness is limited.  Topical steroids can be a reasonable therapeutic option in patients unlikely to tolerate intralesional injections. Utilization of occlusive dressings confers a higher response, leading to improvement in greater than 25% of patients. Glucocorticoid-induced folliculitis is a relatively common adverse effect of this approach.[1]

Patients with extensive disease, often defined as greater than 50% scalp hair loss, may be treated with topical immunotherapy. This approach avoids the large number of injections that would be otherwise required when using intralesional corticosteroids. Moreover, one retrospective study reported superior efficacy of topical immunotherapy over intralesional corticosteroids for patients with patches of hair loss exceeding 50 cm2 in size.[9] A potent contact allergen such as diphenylcyclopropenone (DPCP) or squaric acid dibutyl ester (SADBE.) SADBE is applied weekly to the scalp to precipitate hair regrowth. Recently, a metanalysis looked at clinical outcomes of contact immunotherapy for alopecia areata.[10] The rate of hair regrowth was 74.6% in the patchy alopecia subgroup, and 54.4% in the alopecia totalis/universalis subgroups. Recurrence rates were 38.2% in patients receiving maintenance treatment vs. 49% among those not receiving maintenance treatment.

Second-line therapies include minoxidil, anthralin, and PUVA. 

Systemic therapies are generally only for patients with severe alopecia areata. Systemic glucocorticoids may induce hair growth. However, they are not widely used, mainly because of their side effects. Additionally, relapse occurs within a year in one-third of responsive patients, and the number of relapses increases with time. [1] Other systemic therapies include methotrexate, cyclosporine, azathioprine, and etanercept, all of which have shown variable clinical responses.

Current investigational treatments include platelet-rich plasma, recombinant IL-2, hydroxychloroquine, JAK inhibitors (tofacitinib), simvastatin with ezetimibe, and excimer laser.[11][12][13][14][15]

Differential Diagnosis

Traction alopecia, trichotillomania, tinea capitis, secondary syphilis, aplasia cutis, temporal triangular alopecia, are some of the conditions that may be confused with alopecia areata.

Prognosis

The potential for hair regrowth remains since the inflammatory process does not destroy hair follicles, especially stem cells. However, induction of regrowth by current treatments seems to be difficult to achieve.

Up to 34-50% of patients may recover spontaneously within one year, although most patients will experience multiple episodes of alopecia, and 14-25% of patients will progress to alopecia totalis or alopecia universalis, from which full recovery is infrequent (<10% of patients).[1]

The extent of hair loss and patient age when first diagnosed appears to be a prognostic factor, being a less favorable prognosis with childhood-onset alopecia areata and ophiasis, and a later stage of onset correlates with less extensive alopecia.[2] A family history of AA, nail dystrophy, a history of atopy, or concomitant autoimmune disease are also potential indicators of poor prognosis.[16]

Complications

Other than progressive disease, complications are inherent to the treatment of choice.

Enhancing Healthcare Team Outcomes

Alopecia areata is commonly encountered by the primary care provider and nurse practitioner. Beause there is no good treatment, it is important to educate the patient that leaving it alone is as good an option to any treatment. If the patient prefers treatment, then a referral to a dermatologist is highly recommended. The outlook for most patients is good with or without treatment. However, because of the poor cosmesis, some people may become withdrawn and depressed.[17]

 

 


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Alopecia Areata - Questions

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Which of the following is not characteristic of alopecia areata?



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Which of the following is not a typical characteristic of alopecia areata?



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A patient presents with hair loss in a well-defined area that started 3 weeks ago. The patient has no other complaints or significant medical history. On the exam, there is a 2 x 2-centimeter area without hair in the parietal area. The skin is smooth and without erythema. The hairs at the borders of the lesion come out with minimal traction. What is the most probable diagnosis?

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Which of the following would be a physical finding with alopecia areata?



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What is the best initial treatment for alopecia areata?



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A patient is noted to have well-defined areas of alopecia. There is no inflammation of the scalp in the involved areas. What laboratory test is most appropriate?



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What does Ophiasis pattern alopecia areata mean?



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What is alopecia totalis?



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What is the typical histologic picture in alopecia areata?



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To what does the term ophiasis pattern alopecia refer?



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Which of the following is often associated with alopecia areata?



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A patient presents with the findings shown. What is the classic histological feature associated with this condition?

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Which of the following is not a treatment modalities used in the treatment of alopecia areata?



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Which of the following has not been described as a potential indicator of poor prognosis in alopecia areata (AA)?



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Alopecia Areata - References

References

Gilhar A,Etzioni A,Paus R, Alopecia areata. The New England journal of medicine. 2012 Apr 19     [PubMed]
Pratt CH,King LE Jr,Messenger AG,Christiano AM,Sundberg JP, Alopecia areata. Nature reviews. Disease primers. 2017 Mar 16     [PubMed]
Safavi KH,Muller SA,Suman VJ,Moshell AN,Melton LJ 3rd, Incidence of alopecia areata in Olmsted County, Minnesota, 1975 through 1989. Mayo Clinic proceedings. 1995 Jul     [PubMed]
Mirzoyev SA,Schrum AG,Davis MDP,Torgerson RR, Lifetime incidence risk of alopecia areata estimated at 2.1% by Rochester Epidemiology Project, 1990-2009. The Journal of investigative dermatology. 2014 Apr     [PubMed]
Messenger AG,McKillop J,Farrant P,McDonagh AJ,Sladden M, British Association of Dermatologists' guidelines for the management of alopecia areata 2012. The British journal of dermatology. 2012 May     [PubMed]
Chu TW,AlJasser M,Alharbi A,Abahussein O,McElwee K,Shapiro J, Benefit of different concentrations of intralesional triamcinolone acetonide in alopecia areata: An intrasubject pilot study. Journal of the American Academy of Dermatology. 2015 Aug     [PubMed]
Melo DF,Dutra TBS,Baggieri VMAC,Tortelly VD, Intralesional betamethasone as a therapeutic option for alopecia areata. Anais brasileiros de dermatologia. 2018 Mar     [PubMed]
Ro BI, Alopecia areata in Korea (1982-1994). The Journal of dermatology. 1995 Nov     [PubMed]
Lee S,Kim BJ,Lee YB,Lee WS, Hair Regrowth Outcomes of Contact Immunotherapy for Patients With Alopecia Areata: A Systematic Review and Meta-analysis. JAMA dermatology. 2018 Oct 1     [PubMed]
Strazzulla LC,Avila L,Lo Sicco K,Shapiro J, An Overview of the Biology of Platelet-Rich Plasma and Microneedling as Potential Treatments for Alopecia Areata. The journal of investigative dermatology. Symposium proceedings. 2018 Jan     [PubMed]
Cervantes J,Jimenez JJ,DelCanto GM,Tosti A, Treatment of Alopecia Areata with Simvastatin/Ezetimibe. The journal of investigative dermatology. Symposium proceedings. 2018 Jan     [PubMed]
Iorizzo M,Tosti A, Emerging drugs for alopecia areata: JAK inhibitors. Expert opinion on emerging drugs. 2018 Mar     [PubMed]
Perper M,Aldahan AS,Fayne RA,Emerson CP,Nouri K, Efficacy of fractional lasers in treating alopecia: a literature review. Lasers in medical science. 2017 Nov     [PubMed]
Putterman E,Castelo-Soccio L, Topical 2% tofacitinib for children with alopecia areata, alopecia totalis, and alopecia universalis. Journal of the American Academy of Dermatology. 2018 Jun     [PubMed]
Madani S,Shapiro J, Alopecia areata update. Journal of the American Academy of Dermatology. 2000 Apr     [PubMed]
Rajabi F,Drake LA,Senna MM,Rezaei N, Alopecia areata: a review of disease pathogenesis. The British journal of dermatology. 2018 Nov     [PubMed]
Mulinari-Brenner F, Psychosomatic aspects of alopecia areata. Clinics in dermatology. 2018 Nov - Dec;     [PubMed]

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