A number of treatments can induce hair growth in alopecia areata but none has been shown to alter the course of the disease. The high rate of spontaneous remission makes it difficult to assess efficacy, particularly in mild forms of the disease. Some trials have been limited to patients with severe alopecia areata where spontaneous remission is unlikely. However, these patients tend to be resistant to all forms of treatment and the failure of a treatment in this setting does not exclude efficacy in mild alopecia areata. Few treatments have been subjected to randomized controlled trials and, except for contact immunotherapy, there are few published data on long-term outcomes.

No Treatment

Leaving alopecia areata untreated is a legitimate option for many patients. Spontaneous remission occurs in up to 80% of patients with limited patchy hair loss of short duration (< 1 year), although the remission rate in patients reaching secondary care is lower. Many patients may therefore be managed by reassurance alone, with advice that regrowth cannot be expected within 3 months of the development of any individual patch.

The prognosis in long-standing extensive alopecia is poor. However, all treatments have a high failure rate in this group and some patients prefer not to be treated, other than wearing a wig if appropriate.

Corticosteroids

Topical corticosteroids (Strength of recommendation C, Quality of evidence III; see Appendix 1). Potent topical corticosteroids are widely used to treat alopecia areata but there is little evidence that they promote hair regrowth. A randomized controlled trial of 0.25% desoximetasone cream in 70 patients with patchy alopecia areata failed to show a significant effect over placebo. Topical corticosteroids are ineffective in AT/AU. Folliculitis is a common side-effect of topical corticosteroid treatment.

Intralesional corticosteroids (Strength of recommendation B, Quality of evidence III). Depot corticosteroid injected intralesionally stimulates hair regrowth at the site of injection in some patients. Porter and Burton reported that tufts of hair grew in 33 of 34 sites injected with triamcinolone hexacetonide in 11 patients with alopecia areata and in 16 of 25 sites injected with triamcinolone acetonide in 17 patients. The effect lasted about 9 months. In a study from Saudi Arabia 62% of patients achieved full regrowth with monthly injections of triamcinolone acetonide, the response being better in those with fewer than five patches of < 3 cm in diameter. This method is most suitable for treating patchy hair loss of limited extent and for cosmetically sensitive sites such as the eyebrows. Hydrocortisone acetate (25 mg mL^[-1]) and triamcinolone acetonide (5-10 mg mL^[-1]) are commonly used. Corticosteroid is injected just beneath the dermis in the upper subcutis. A 0.05-0.1 mL injection will produce a tuft of hair growth about 0.5 cm in diameter. Multiple injections may be given, the main limitation being patient discomfort. Intralesional corticosteroids may also be administered by a needleless device (e.g. Dermajet^TM). The device should be sterilized between patients. Abell and Munro reported that 52 of 84 patients (62%) showed regrowth of hair at 12 weeks after three injections of triamcinolone acetonide using the Porto Jet needleless device compared with one of 15 (7%) control subjects injected with isotonic saline. The results were less favourable in AT than in localized alopecia. Skin atrophy at the site of injection is a consistent side-effect of intralesional corticosteroid therapy, particularly if triamcinolone is used, but this usually resolves after a few months. Repeated injection at the same site or the use of higher concentrations of triamcinolone should be avoided as this may cause prolonged skin atrophy. There is a risk of cataract and raised intraocular pressure if intralesional corticosteroids are used close to the eye, e.g. for treating eyebrows. There is a single case report of anaphylaxis in a patient receiving intralesional triamcinolone acetonide for treatment of alopecia areata. Intralesional corticosteroids are not appropriate in rapidly progressive alopecia nor in extensive disease.

Systemic corticosteroids (Strength of recommendation C, Quality of evidence III). Long-term daily treatment with oral corticosteroids will produce regrowth of hair in some patients. One small partly controlled study reported that 30-47% of patients treated with a 6-week tapering course of oral prednisolone (starting at 40 mg daily) showed > 25% hair regrowth. Unfortunately, in most patients continued treatment is needed to maintain hair growth and the response is usually insufficient to justify the risks. There are several reports of high-dose pulsed corticosteroid treatment employing different oral and intravenous regimens (intravenous prednisolone 2 g, intravenous methylprednisolone 250 mg twice daily for 3 days, oral prednisolone 300 mg once monthly, dexamethasone 5 mg twice weekly ). The differences in treatment protocols and patient selection make it difficult to compare these studies directly, and none was controlled. Overall, about 60% of patients with extensive patchy alopecia showed a cosmetically worthwhile response to pulsed corticosteroids, whereas fewer than 10% of those with ophiasiform disease and AT/AU responded. The oral and intravenous routes of administration appear equally effective. Significant side-effects have not yet been reported with pulsed administration of systemic corticosteroids in alopecia areata. However, short- and long-term hazards of systemic corticosteroids are well known and potentially severe, and in view of these dangers it is not possible to support their use until there is better evidence of efficacy.

Contact Immunotherapy (Strength of Recommendation B, Quality of Evidence II-ii)

Contact immunotherapy was introduced by Rosenberg and Drake in 1976. The contact allergens that have been used in the treatment of alopecia areata include 1-chloro-2,4-dinitrobenzene (DNCB), squaric acid dibutylester (SADBE) and 2,3-diphenylcyclopropenone (DPCP). DNCB is mutagenic against Salmonella typhimurium in the Ames test and is no longer used. Neither SADBE nor DPCP are mutagenic. One DPCP precursor is mutagenic and batches should be screened for contaminants by the supplier. DPCP is more stable in solution and is usually the agent of choice.

The protocol for contact immunotherapy using DPCP was described by Happle et al. The patient is sensitized using a 2% solution of DPCP applied to a small area of the scalp. Two weeks later the scalp is painted with a weak solution of DPCP, starting at 0.001%, and this is repeated at weekly intervals. The concentration is increased at each treatment until a mild dermatitis reaction is obtained. Some clinicians treat one side of the scalp initially to distinguish between a treatment response and spontaneous recovery if hair regrowth occurs. Once hair regrowth is observed, both sides of the scalp are treated. In patients with severe long-standing alopecia, in whom spontaneous recovery is unusual, this precaution is unnecessary. Opinions are divided on whether patients should be allowed to treat themselves.

Once a maximum response is achieved most practitioners reduce the frequency of treatment. In patients in whom full regrowth of hair is obtained treatment can be discontinued. Subsequent relapses will usually respond to further contact immunotherapy, although this cannot be guaranteed.

A review of all the published studies of contact immunotherapy concluded that 50-60% of patients achieve a worthwhile response but that the range of response rates was very wide (9-87%).^[29] Patients with extensive hair loss are less likely to respond.^[30,31] Other reported adverse prognostic features include the presence of nail changes, early onset and a positive family history.^[29] In most studies treatment has been discontinued after 6 months if no response is obtained. In a large case series from Canada clinically significant regrowth occurred in about 30% of patients after 6 months of treatment but this increased to 78% after 32 months of treatment, suggesting that more prolonged treatment is worthwhile. The response in patients with AT/AU was less favourable at 17% and this was not improved by treatment beyond 9 months. Relapses may occur following or during treatment. In the Canadian series relapse following successful treatment occurred in 62% of patients.

Two case report series of contact immunotherapy in children with alopecia areata reported response rates of 33% and 32%. A third study found a similar short-term response in children with severe alopecia areata, but < 10% experienced sustained benefit.

Adverse effects. Most patients will develop occipital and/or cervical lymphadenopathy during contact immunotherapy. This is usually temporary but may persist throughout the treatment period. Severe dermatitis is the most common adverse event but the risk can be minimized by careful titration of the concentration. Uncommon adverse effects include urticaria, which may be severe, and vitiligo. Cosmetically disabling pigmentary complications, both hyper- and hypopigmentation (including vitiligo), may occur if contact immunotherapy is used in patients with racially pigmented skin. Such patients should be warned of this risk before embarking on treatment. Contact immunotherapy has been in use for 20 years and no long-term side-effects have been reported.

Precautions. Contact immunotherapy is an unlicensed treatment that uses a nonpharmaceutical grade agent. Patients should be fully informed about the nature of the treatment; they should be given an information sheet and give signed consent. Great care must be taken to avoid contact with the allergen by handlers, including pharmacy, medical and nursing staff, and other members of the patient's family. Those applying the allergen should wear gloves and aprons. There are no data on the safety of contact immunotherapy during pregnancy and it should not be used in pregnant women nor in women intending to become pregnant. Owing to these concerns about sensitization and the extent of the measures required to prevent this, and also because of the possible risks in pregnancy, availability of contact immunotherapy is limited and many departments are unwilling to provide this treatment.

DPCP is degraded by light. Solutions should be stored in the dark and patients should wear a hat or wig for 24 h following application.

Phototherapy and Photochemotherapy

Ultraviolet B treatment. Although ultraviolet (UV) B erythema has been used in much the same way as other skin irritants there is little documented evidence of efficacy.

Psoralen plus ultraviolet A treatment (Strength of recommendation C, Quality of evidence III). There are several uncontrolled studies of psoralen plus UVA (PUVA) treatment for alopecia areata, using all types of PUVA (oral or topical psoralen, local or whole body UVA irradiation), claiming success rates of up to 60-65%. Two retrospective reviews have reported low response rates or suggested that the response was no better than the natural course of the disease, although these observations were also uncontrolled. The relapse rate following treatment is high and continued treatment is usually needed to maintain hair growth, which may lead to an unacceptably high cumulative UVA dose.

Minoxidil (Strength of Recommendation C, Quality of Evidence IV)

An early double-blind study reported a significantly greater frequency of hair regrowth in patchy alopecia areata in patients treated with topical 1% minoxidil compared with placebo. Subsequent controlled trials in patients with extensive alopecia areata using 1% or 3% minoxidil failed to confirm these results. Two of these studies reported a treatment response during an extended but uncontrolled part of the trial. In one study comparing 5% and 1% minoxidil in extensive alopecia areata regrowth of hair occurred more frequently in those receiving 5% minoxidil but few subjects obtained a cosmetically worthwhile result. Topical minoxidil is ineffective in AT and AU.

Dithranol (Strength of Recommendation C, Quality of Evidence IV)

There is a small number of case report series of dithranol (anthralin) or other irritants in the treatment of alopecia areata. The lack of controls makes the response rates difficult to evaluate but only a small proportion of patients seems to achieve cosmetically worthwhile results. In one open study 18% of patients with extensive alopecia areata achieved cosmetically worthwhile hair regrowth. The published data indicate that dithranol needs to be applied sufficiently frequently and in a high enough concentration to produce a brisk irritant reaction in order to be effective. Staining of hair limits its use in fair-haired individuals.

Miscellaneous

The dual properties of ciclosporin as an immunosuppressive drug and as a hypertrichotic agent make it a logical choice in treating alopecia areata and this is supported by animal studies. Although there is only a small number of published uncontrolled trials with low patient numbers the evidence that ciclosporin does stimulate hair regrowth in some patients with alopecia areata is convincin  However, as ciclosporin has to be given orally (it is not active topically) side-effects are a major consideration and, in patients with severe alopecia areata, the cosmetically worthwhile response rate is probably too low to justify the risks (Strength of recommendation D, Quality of evidence III).

Treatments which were ineffective in controlled trials include oral zinc and isoprinosine. One randomized double-blind trial showed a significant positive effect of aromatherapy.This awaits confirmation.

Wigs

For many female patients with extensive alopecia areata a wig or hairpiece is the most effective solution. Some men also request a wig although male wigs rarely appear as natural. Acrylic wigs are much cheaper than real hair wigs and are easier to look after. However, some patients prefer bespoke real hair wigs, mainly because the better fit allows a wider range of social activities. National Health Service (NHS) charges for wigs are laid out in NHS leaflet HC12 (currently £50.70 for an acrylic wig and £195.40 for a bespoke human hair wig). Information on entitlement to free wigs is given in leaflet HC11.

Summary of Recommendations