A Practical Approach to the Treatment of Alopecia Areata : Indian Dermatology Online Journal

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Trichology Symposium - Review Article

A Practical Approach to the Treatment of Alopecia Areata

Dhurat, Rachita; Sharma, Richa

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Indian Dermatology Online Journal: Nov–Dec 2022 - Volume 13 - Issue 6 - p 725-728
doi: 10.4103/idoj.idoj_176_22
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Abstract

Introduction

Alopecia areata (AA) is an autoimmune condition characterized by non-scarring patchy alopecia. It may present as circumscribed patchy alopecia or diffuse hair loss and sometimes may progress to involve the entire scalp or body. It has significant impact on quality of life including emotional, mental health, and social functioning.

Pathogenesis of AA includes IFN-gamma-mediated collapse of immune privilege which can be triggered by stress, infections, and so on.[1] IFN-gamma is an activator of the Janus kinase- signal transducers and activators of transcription (JAK_STAT) pathway which ultimately results in transcription of genes which promote a CD8 response. Thus, immunosuppressants are the main modality of treatment.

The disease has varied clinical presentations ranging in severity from patchy circumscribed alopecia, reticular pattern, ophiasis, sisaipho, diffuse, or incognito type to alopecia totalis (AT) and alopecia universalis (AU). The various available treatment options include topical/intralesional steroids, topical immunotherapy/contact irritants, systemic steroids, and steroid-sparing agents like cyclosporine, azathioprine, methotrexate, and the JAK-STAT inhibitors.

None of the available treatment modalities are FDA approved or supported by enough randomized controlled trials.

Majority of clinicians follow the British Association of Dermatologists guidelines which focuses on various therapeutic options rather than focusing on which treatment to choose depending on severity of disease. However, this guideline states that “It may be necessary or even desirable to depart from the guidelines in the interests of specific patients or special circumstances. Just as adherence to these guidelines may not constitute a defence against a claim of negligence, so deviation from them should not necessarily be deemed negligent.”[2] Thus, clinicians in various circumstances do not adhere to published guidelines in the interest of patient.

This article aims at providing practical tips to the clinicians based on published data and author’s clinical experience which can help them in deciding what and when to choose in a given clinical scenario of AA.

Treatment of AA based on Clinical Presentation

It is important to know the duration of the solitary patch of AA in children as the risk of developing chronic AA and AT/AU increases with duration of AA. Chronic AA has been defined as the AA that continues beyond 1 year, tends to develop additional areas of AA, and has persistent hair loss for many years.[3]

It is said that spontaneous remission is seen in up to 80% of patients when duration of alopecia is less than 1 year—so giving no treatment may be a preferred option by many clinicians.[4] However if the patch is left untreated, chances of progression to chronic AA or AT/AU are more. A study done by Ikeda on prognosis of AA showed that in patients with solitary stable patch of AA of less than 6 months duration, the risk of developing chronic AA is 13% and risk of developing totalis/universalis is 6%; this risk increases to 65% and 30%, respectively, when duration is more than 6 months but less than 12 months.[4] When duration is more than 12 months, the risk of developing chronic AA is 100% and risk of developing AT/AU is as high as 45%.[4]

Patients showing signs of disease activity like history of enlargement of patch, multifocal hair pull test positive, must be treated irrespective of duration as these are likely to progress.

Thus in the author’s opinion, giving no treatment may not be a legitimate option in all cases of AA.

Treatment Options

Treatment options and practical tips in the management of AA are mentioned in [Table 1].

T1
Table 1:
Practical tips on management of alopecia areata

Solitary Patch of AA in Children

High-potency topical steroids are considered as first-line therapy in children as intralesional steroid injections are painful and not tolerated. Topical steroids can be applied under occlusion (such as covering with plastic wrap) to improve their penetration.[56] In majority of cases, initial signs of improvement can take anywhere from 6 weeks to 3 months (up to 6 months in some) and that relapse rates can be as high as 63%.[56] In patients undergoing treatment with corticosteroids, clinicians should monitor for side effects such as folliculitis, telangiectasia, local atrophy, and the rare possibility of hypothalamic–pituitary–adrenal axis suppression.[5678] Steroid abuse is a common problem in Indian patients. In warm and humid conditions, cases of folliculitis after application of topical steroids are not uncommon.

Solitary patch of AA in children can also be managed by topical contact irritants. They are different from topical immunotherapy as they act by disrupting the normal cell growth and differentiation instead of causing direct stimulation of immunity.[9] This physical damage then stimulates the immune system. Anthralin 0.5–1% short contact therapy is a commonly used irritant. Small studies have shown adequate results in 25–75% of patients depending on the severity of involvement.[1011] The application can be started with short contact of 5 min twice or thrice a week; depending upon the reaction, the duration and frequency can be increased up to 30 min to 8 h per day.[910] Regimen is tailor-made for each patient with titration of duration and frequency with aim to achieve mild-to-moderate dermatitis. Topical retinoids can act as contact irritants; 0.1% tazarotene and 1% bexarotene have shown some response in few studies.[12] Other irritants used include phenol, salicylic acid, azelaic acid, tretinoin, and tincture iodine.[13141516]

Topical calcineurin inhibitors like tacrolimus though used by many clinicians may not be effective in AA. Studies have failed to show response. The reason could be poor penetration into deeper tissues.[17] Tacrolimus may be used for facial AA patches.

Solitary Patch of AA in Adults

Intralesional or topical corticosteroids are the first line of treatment irrespective of disease activity.

Intralesional corticosteroids: Triamcinolone acetonide in a dose of 2.5–10 mg/ml is used. A study conducted by Chu et al.[18] showed that 2.5 mg/ml concentration of triamcinolone acetonide was as beneficial as 5 or 10 mg/ml for patchy AA. The advantage of using this low concentration is that it minimizes local side effects of skin atrophy and telangiectasia and decreases the possibility of systemic adrenal suppression. Using lower concentrations also allows injection of a greater volume, increasing the maximal treatment area.[18] A volume of 0.1 ml is injected at a distance of 1 cm in the periphery into the dermis or subcutaneous. Maximum dose in one session for an adult is 10–20 mg.[19] For getting the concentration of 2.5 mg/ml triamcinolone, 10 mg/ml vial should be diluted at ratio of 1:3, that is, one part of triamcinolone and three parts of normal saline. A practical tip for dilution is to inject the saline directly into triamcinolone vial which ensures proper mixing and uniform dosage of triamcinolone injection. The vial of triamcinolone can accommodate up to 2.6 ml of saline.

Betamethasone is a more potent and longer acting corticosteroid as compared to triamcinolone acetonide. Liu et al.[20] found better efficacy of intralesional betamethasone as compared to intralesional triamcinolone in oral erosive lichen planus. Injection betamethasone sodium phosphate 4 mg/ml is available in India and can be diluted to 1:9 to get a concentration equivalent to 2.5 mg/ml of triamcinolone acetonide for the use in AA.

Patients not willing for intralesional injections can be managed on topical steroids but the efficacy is less.[9] Other options include topical contact irritants which have been mentioned earlier.

Multiple Patches with Mild Disease

Mild AA has been described as AA with scalp involvement of less than 20%.[21] The first-line treatment of multiple patches with mild disease is similar to that of solitary patch as mentioned earlier (topical steroid/intralesional steroid).

Topical immunotherapy can also be considered, especially in patients not responding to topical/intralesional steroids. The topical immunotherapy agents of choice are DPCP (diphenylcyclopropenone) and SADBE (squaric acid dibutyl ester). SADBE is expensive and less stable as compared to DPCP. Dinitrochlorobenzene is no longer preferred due to its mutagenic property. DPCP is more stable but has to be stored in amber-colored bottles as it is photolabile. Acetone is used as a diluent for storage. During the application of DPCP, acetone can get evaporated changing the concentration of DPCP. The practical tip to avoid this problem is to store DPCP in empty lignocaine injection crimp vials. Storage in a vial with a rubber stopper and metal cap will prevent evaporation of the acetone.[22]

Topical minoxidil can be used alone or in combination with other modalities. It helps in accelerating regrowth of hair within alopecia patch. It has also been found to decrease perifollicular lymphocytic infiltration in cases of AA which reduces the disease activity.[23] Caution should be exercised while using topical minoxidil in children as hypertrichosis is a common side effect and thus 2% minoxidil solution is advocated on alternate days.

Prostaglandin F2 alpha analogues like latanoprost and bimatoprost are known to stimulate hair growth by prolonging the anagen phase of hair.[24] These can be used for eyebrow and eyelash AA.

There are several uncontrolled studies showing benefits of psoralen with UVA in AA. Psoralen can be used systemically or applied topically as in turban psoralen ultraviolet A. However, the relapse rate following stopping of treatment is high and usually continuous treatment may be necessary to maintain hair growth. This may lead to an unacceptably high cumulative UVA dose.[2]

Multiple Patches with Moderate to Severe Disease

Patients with scalp involvement of 21–49% are considered to have moderate disease while severe involvement is considered when scalp involvement is more than 50%.[21] All patients with scalp involvement of more than 20% can be considered for immunotherapy like DPCP or systemic therapy.

Systemic therapy can also be offered to patients with mild disease who are not responding to topical therapy for more than 6 months or have body hair involvement, diffuse multifocal hair pull test positivity, or severe psychosocial impairment.

Few clinicians prefer to use oral prednisolone and oral minipulse (betamethasone 0.1 mg/kg/day two consecutive days a week) as a first-line systemic therapy for children. Various doses of prednisolone have been used in treatment of AA varying from 0.1 mg/kg/day to 1 mg/kg/day.[3] Due to the risk of stunted growth, its use in pediatric population should be deferred. There is no international consensus to guide systemic steroid therapy.[25] Most patients require continued treatment to maintain hair growth and the response is usually insufficient to justify the risks associated with therapy.[26]

Steroid-sparing agents like cyclosporine (2.5–5 mg/kg/day), azathioprine (2–2.5 mg/kg/day), and methotrexate (5–15 mg/week) can be used in combination with systemic steroids or as standalone therapy. Regular monitoring for each drug as per standard guidelines should be followed. These agents appear to be more effective when used as steroid-sparing agents to prevent relapses rather than as monotherapy to initiate regrowth in AA.[3] There is no expert consensus regarding which steroid-sparing agent to choose over another.[3]

JAK-STAT inhibitors: JAK-STAT inhibitors have shown to be promising over conventional systemic therapy. In pathogenesis of AA, there is a positive feedback loop in which skin infiltrating CD8 + NKG2D + T cells produce IFN-gamma, which induces IL-15 and 1L-15 R alpha production by follicular epithelial cells, which in turn activates and sustains the CD8 + NKG2D + T cells’ response and autoimmunity.[27] JAK-STAT inhibitors like tofacitinib (JAK 1 and 3 inhibitor) inhibit this positive feedback loop, thus inhibiting the autoimmune process. Numerous case series have shown regrowth of hair during treatment with tofacitinib.[28293031] It is used at a dose of 5 mg BD in adults, while in younger children, 5 mg OD or 5 mg alternate days can be used. Baricitinib (JAK 1 and 2 inhibitor) at a dose of 2–4 mg daily in a case report of long-standing AA has also shown result.[32] Before starting JAK inhibitors, baseline investigations like complete blood count, liver function tests, serum lipids, chest X-ray, and interferon-gamma release assay should be done. Side effects can include increased susceptibility to infections, pancytopenia, raised transaminases levels, hyperlipidemia, and increased risk for thromboembolic events. A regular monitoring of blood parameters like complete blood count, liver function tests, and serum lipids is advocated.[33]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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Keywords:

Alopecia areata; practical tips; treatment

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