eMedicine Specialties > Dermatology > Diseases of the Adnexa

Alopecia Areata: Treatment & Medication

Author: Chantal Bolduc, MD, FRCP(C), Assistant Professor, Department of Dermatology, University of Montreal
Coauthor(s): Harvey Lui, MD, FRCPC, Professor and Head, Department of Dermatology and Skin Science, Vancouver General Hospital, University of British Columbia; Medical Director, The Skin Centre, Lions Laser Skin Centre and Psoriasis and Phototherapy Clinic, Vancouver General Hospital; Jerry Shapiro, MD, FRCP(C), Clinical Associate Professor, Department of Medicine, Division of Dermatology, University of British Columbia, Canada
Contributor Information and Disclosures

Updated: Apr 13, 2009

Treatment

Medical Care

A treatment algorithm is available in Media File 9.

Assessment of the efficacy of a treatment must be considered with care because the condition is highly unpredictable in presentation, evolution, and response to treatment. Little data exist regarding the natural evolution of the condition. For example, in patients with less than 40% scalp involvement, a study showed no benefit with treatment (minoxidil 1% and topical immunotherapy) over placebo.¹⁵ The high spontaneous remission rate makes clearly assessing the true efficacy of a therapy difficult unless appropriate controls with placebo treatment are studied.

For patients with extensive alopecia areata (>40% hair loss), little data exist on the natural evolution. The rate of spontaneous remission appears to be less than in patients with less than 40% involvement. Vestey and Savin¹⁶ reviewed 50 patients with extensive alopecia areata. Of the 50 patients, 24% experienced spontaneous complete or nearly complete regrowth at some stage during the observation period of 3-3.5 years. The relapse rate is high in patients with severe forms of alopecia areata.

Patients with alopecia totalis or alopecia universalis usually have a poorer prognosis, and treatment failure is seen in most patients with any therapy.

Because alopecia areata is believed to be an autoimmune condition, different immunomodulators have been used to treat this condition. Additional treatment options for alopecia areata include minoxidil and other treatment modalities.

Topical treatments

Corticosteroids

Corticosteroid therapies can include intralesional injections or topical application.

• For intralesional steroids, few studies are available regarding efficacy; however, they are used widely in the treatment of alopecia areata.
• Intralesional steroids are the first-line treatment in localized conditions.
• In a study including 84 patients, regrowth on treated areas was present in 92% of patients with patchy alopecia areata and 61% of patients with alopecia totalis. Regrowth persisted 3 months after treatment in 71% of patients with patchy alopecia areata and 28% of patients with alopecia totalis. Regrowth usually is seen within 4-6 weeks in responsive patients. Patients with rapidly progressive, extensive, or longstanding alopecia areata respond poorly.
• Another study showed regrowth in most patients (480) treated with intralesional steroids, except in 2 patients with alopecia universalis.
• Hair growth may persist for 6-9 months after a single injection.
• Injections are administered intradermally using a 3-mL syringe and a 30-gauge needle.
• Triamcinolone acetonide (Kenalog) is used most commonly; concentrations vary from 2.5-10 mg/mL. The lowest concentration is used on the face. A concentration of 5 mg/mL is usually sufficient on the scalp.
• Less than 0.1 mL is injected per site, and injections are spread out to cover the affected areas (approximately 1 cm between injection sites; see Media File 8).

• Adverse effects mostly include pain during injection and minimal transient atrophy (10%). Rarely, the atrophy can be severe and permanent. The presence of atrophy should not lead to treatment discontinuation. Avoidance of the atrophic site is usually sufficient. Alternatively, the concentration can be reduced.
• Injections are administered every 4-6 weeks.
• Avoid reinjecting areas of denting, which usually is sufficient to allow atrophy to revert.
• For topical steroids, again, few studies have been performed regarding efficacy in the treatment of alopecia areata; however, they can be useful, especially in children who cannot tolerate injections. 
• Fluocinolone acetonide cream 0.2% (Synalar HP) twice per day induced a satisfactory-to-excellent response in 61% of patients, which was maintained in 71% of patients. Children younger than 10 years responded better, as did patients with a duration of hair loss of less than 1 year.
• Betamethasone dipropionate cream 0.05% (Diprosone) showed similar efficacy.
• A 2005 study by Tosti et al¹⁷ in patients with alopecia totalis or alopecia universalis showed that the use of 2.5 g of clobetasol propionate under occlusion with a plastic film 6 d/wk for 6 months induced regrowth in 8 (28.5%) of 28 patients. Regrowth was seen 6-14 weeks after the onset of therapy. Regrowth was maintained for at least 6 months after cessation of therapy in 5 (62.5%) of 8 patients. Even though only 17.8% of patients showed long-term benefits from that treatment, keep in mind that the study was performed in a subgroup of patients that is usually refractory to treatment.
• Treatment must be continued for a minimum of 3 months before regrowth can be expected, and maintenance therapy often is necessary.
• Despite these data, the authors do not believe that monotherapy with a topical steroid has been of great benefit in the authors' practice.
• The most common adverse effect is local folliculitis, which appears after a few weeks of treatment. Telangiectasias and local atrophy also have been reported. No systemic adverse effects have been reported.

Immunotherapy

Topical immunotherapy¹⁸ is defined as the induction and periodic elicitation of an allergic contact dermatitis by topical application of potent contact allergens.

• Commonly used agents for immunotherapy include squaric acid dibutylester (SADBE) and diphencyprone (DPCP).¹⁹ These 2 sensitizers are not present in the natural or industrial environment. Dinitrochlorobenzene (DNCB) has become less popular as a result of reports that it is mutagenic in the Ames assay (a bacterial assay).
• No rigorous toxicologic and pharmacologic studies have been performed on the use of these agents in humans.
• Although DPCP and SADBE have not been found mutagenic in the Ames assay, neither is approved by the US Food and Drug Administration, and unknowns still exist concerning their safety profiles.
• No contaminants have been found in SADBE. Acetone solutions and alcohol solutions of SADBE are equally stable for 2 months under storage conditions.
• DPCP occasionally can contain mutagenic contaminants; therefore, it should be screened periodically to ensure purity. No formal data are available on DPCP regarding its longevity in solution.
• Cosmetically acceptable regrowth with topical immunotherapy rates in patients with severe alopecia areata (>50% involvement) varies from 22-68%. Most studies have a success rate of 30-50%. Wiseman et al²⁰ retrospectively reported the results of a large cohort of 148 consecutive patients treated with DPCP. 
• Their analysis showed that the cumulative patient response at 32 months was 77.9%.
• The response rate varied with the extent of the alopecia. Cosmetically acceptable regrowth was seen in 17.4% of patients with alopecia totalis or alopecia universalis, 60.3% in patients with 75-99% hair loss, 88.1% in patients with 50-74% hair loss, and 100% regrowth in those with 25-49% hair loss.
• Age at onset was also a significant variable, with older age at onset leading to a better prognosis. A lag period of 3 months was usually present between the onset of therapy and the presence of regrowth.
• The median time to achieve significant regrowth was 12.2 months. Some patients showed regrowth on the treated side after 18 months of therapy.
• No benefit is achieved with continuing therapy after 24 months in the absence of regrowth.
• The relapse rate after reaching significant regrowth was 62.6%.
• The type of alopecia areata before treatment, duration of the disease, and the presence of nail changes were found to predict a lower response to treatment. Age at onset and sex of the patient do not appear to influence the prognosis. Controversy exists concerning whether atopy is an adverse prognosis factor.
• Topical immunotherapy has been used for almost 20 years; no serious adverse effects have been reported.
• The most common side effect, which is desired, is a mild contact dermatitis (redness, scaling, itching). 
• Adverse effects include cervical lymphadenopathy and pigment changes. Vitiligo developed on the application site in 6.7-7.5% of patients. Transient leucoderma on a distant untreated area has been reported. Of patients who develop vitiligo, 31% (4 of 13) had a history of vitiligo. Only 0.75% of patients developed hyperpigmentation. Confetti-type dyschromia (ie, hyperpigmentation, hypopigmentation) has been described as an adverse effect of DPCP treatment and occurred in 1.6% of 243 patients treated. Less common adverse effects include erythema multiforme–like eruptions and urticaria, which were reported in 3 patients treated with DPCP.
• The mechanism of action of topical immunotherapy is unknown. Antigenic competition has been hypothesized. That is, the introduction of a second antigen can initiate a new infiltrate containing T-suppressor cells and suppressor macrophages that may modify the preexisting infiltrate and allow regrowth.
• Because topical immunotherapy involves the production of contact sensitivity in a previously naive patient, it is best to seek approval for the treatment by the ethics review board and to have the patient sign an informed consent.
• Both SADBE and DPCP appear to be equally effective. Acetone-based solutions usually are preferred because they evaporate quickly, allowing patients to wear a hat or wig immediately after treatment. Quick drying also decreases the chances of dissemination to other body parts by contact. 
• Treatment is provided weekly.
• The patient first is sensitized directly on the scalp with a 2% concentration on a small area (2 cm). 
• The following week, a low concentration (0.0001%) is applied.
• The concentration is increased slowly every week as needed until a mild tolerable allergic contact dermatitis is elicited. Many concentrations are available that achieve this goal.
• Treating only half of the head allows the physician to use the untreated half as a control. Once regrowth occurs on the treated half, treatment can be applied to the entire scalp. If regrowth initially occurs on both sides, spontaneous remission is likely, although treatment cannot be excluded as the cause.
• Avoid severe contact dermatitis. Patients are advised to avoid light exposure on the scalp for 48 hours because light degrades the chemical. Patients also are advised not to wash the scalp for 48 hours.
• Initial regrowth may be seen at weeks 12-24. Once cosmetically acceptable regrowth is achieved, the treatment can be tapered gradually. Almost all patients relapse if the treatment is discontinued, and maintenance treatment is needed.

Anthralin

The efficacy of anthralin was assessed in 3 studies, which unfortunately were uncontrolled.

• Both short-contact and overnight treatments have been used. Anthralin concentrations varied from 0.2-1%.
• A 2004 study by Tang et al²¹ showed no benefit in using anthralin. Other studies showed a response rate of 20-75%, respectively, for patchy alopecia areata and a 25% response rate for alopecia totalis. The mean time to response was 11 weeks, and the mean time to cosmetic response was 23 weeks. Anthralin was used by Tang et al in balding C3H/HeJ mice, which is one animal model for alopecia areata. Half the body was treated with anthralin 0.2%, while the other side was treated with the vehicle ointment. Regrowth was seen on the treated side in 64% of mice after 10 weeks. Four mice had almost complete regrowth. The untreated side showed either no regrowth or continued hair loss. Cytokine studies performed with an RNase protection assay showed that tumor necrosis factor-alpha and -beta were inhibited in mice that responded to treatment.
• Most patients experienced irritant contact dermatitis. Whether the dermatitis is necessary for efficacy remains under debate.
• Cosmetically acceptable regrowth was maintained during therapy in 71% of responders. No correlation exists between duration of the current episode and response to treatment.
• Adverse effects include pruritus, erythema, scaling folliculitis, local pyoderma, and regional lymphadenopathy. Withholding treatment for a few days results in rapid disappearance of adverse effects. Treatment then can be reinstituted, but anthralin should be left on for shorter periods. Staining of clothes and skin can be a concern.
• The mechanism of action of anthralin is unknown. Most likely, it creates inflammation by generating free radicals, which have antiproliferative and immunosuppressive actions.

Minoxidil

Minoxidil appears to be effective in the treatment of alopecia areata in patients with extensive disease (50-99% hair loss). Response rates in that group vary from 8-45%. Minoxidil was of little benefit in patients with alopecia totalis or alopecia universalis.  

• The 5% solution appears to be more effective.
• No more than 25 drops are applied twice per day regardless of the extent of the affected area.
• Initial regrowth can be seen within 12 weeks, but continued application is needed to achieve cosmetically acceptable regrowth.
• Minoxidil usually is well tolerated. Adverse effects include distant hypertrichosis (5%) and irritation (7%).
• The exact mechanism of action of minoxidil remains unclear. Minoxidil does not appear to have either a hormonal or an immunosuppressant effect. Minoxidil most likely has a direct mitogenic effect on epidermal cells, both in vitro and in vivo. Anagen-phase hair bulbs plucked from men applying minoxidil showed a significant increase in proliferation index as measured by DNA flow cytometry. Minoxidil also has been shown to prolong the survival time of keratinocytes in vitro. Finally, minoxidil may oppose intracellular calcium entry. Calcium influx normally enhances epidermal growth factors to inhibit hair growth. Minoxidil is converted to minoxidil sulfate, which is a potassium channel agonist and enhances potassium ion permeability, thus opposing the entry of calcium into cells. Local vasodilatation does not appear to play a primary role in hair growth associated with minoxidil.

Systemic treatments

Psoralen plus UV-A

Many studies have been performed regarding the efficacy of psoralen plus UV-A (PUVA) in the treatment of alopecia areata, and the initial response rate varies from 20-73%. The relapse rate, unfortunately, is high (50-88%). Most patients relapse within a few months (mean 4-8 mo) after treatment is stopped.  

• Both systemic and topical PUVA therapies have been used.
• The number of treatments required for regrowth varies, but 20-40 treatments usually are sufficient in most cases.
• A younger age at onset, a longer duration of disease, and the presence of alopecia totalis or alopecia universalis appear to indicate a poorer outcome.
• Taylor and Hawk²² published 10 years of experience with PUVA. The initial response rate (>90% regrowth) was comparable to other studies and was 43.8% for partial alopecia areata and 50% for alopecia totalis and alopecia universalis. However, after excluding patients with vellus hair regrowth and patients who relapsed rapidly in the follow-up period (approximately 4 mo), they found the success rate to be, at best, 6.3% for partial alopecia areata and 12.5% for alopecia totalis and alopecia universalis. They concluded that PUVA generally is not an effective long-term treatment for alopecia areata.
• PUVA is a relatively safe treatment modality; adverse effects include burning and, possibly, an increased risk of skin cancer.

Prednisone

The use of systemic steroids for the treatment of alopecia areata is sometimes justifiable, but hair loss frequently follows discontinuation of the medication and benefits must be carefully weighed against long-term risks. Some authors support a beneficial role of systemic steroids in halting the progression of alopecia areata,²³ but many others have had poor results with this form of therapy.  

• The rate of regrowth varies greatly (27-89%), and many dose regimens have been used in these studies.
• Although the initial regrowth appears promising, the prednisone dose necessary to maintain cosmetic growth usually must be high enough that adverse effects are inevitable, and most patients relapse after therapy is discontinued.
• Some benefit was shown using minoxidil 2% solution applied twice per day following a 6-week taper of prednisone, but the relapse rate remained at a minimum of 50% at 4 months in the treated group.
• Adverse effects from systemic therapy were common in these reports and included diabetes, weight gain, hypertension, psychological changes, osteoporosis, suppression of the adrenocorticotropic axes, striae, acne, hypertrichosis, and purpura.
• Systemic steroids most likely are effective via their immunosuppressive effects.
• An initial benefit may occur by using systemic prednisone in some patients, but the relapse rate is high, and it does not appear to alter the course of the condition.
• Systemic prednisone is not an agent of choice for alopecia areata because of the adverse effects associated with both short- and long-term treatment.

Cyclosporine

Cyclosporine has been used both topically and systemically in the treatment of alopecia areata.  

• Topical cyclosporine has not proven to be effective in severe alopecia areata because no patient (0 of 10) showed benefit with application of a 10% cyclosporin A (CsA) solution twice per day for 12 months.
• Another study of 14 patients using a 5% solution of cyclosporine twice per day for 4-6 months reported vellus growth in 3 of 14 patients and normal hair growth in 3 patients with patchy alopecia areata. No regrowth was seen in 8 of the patients.
• Neither study showed systemic absorption of CsA, and routine blood examination showed only a transient increase of hepatic enzymes in 1 patient.
• Oral cyclosporine was effective in the DEBR model for alopecia areata. All rats had a full pelage by 5 weeks of treatment with 10 mg/kg/d, 5 d/wk for 7 weeks. Studies in humans also have proven efficacy with doses of 6 mg/kg/d for 3 months in 6 patients. All patients experienced regrowth, and cosmetically acceptable regrowth was seen in 3 of 6 patients. Unfortunately, all patients relapsed within 3 months of discontinuation of cyclosporine. No evidence indicates that CsA can prevent hair loss during an active episode because reports have described patients taking CsA who developed alopecia areata while they were under treatment for unrelated conditions.
• The mechanism of action of cyclosporine remains unclear. It may act through its immunosuppressive effect, because, in patients who regrew hair, clearance of immune cells from the hair follicles and alteration in the balance of regulatory lymphocytes occurred (ie, decrease of the CD4/CD8 ratio). Cyclosporine causes hypertrichosis in patients treated for conditions unrelated to hair loss. The mechanism by which cyclosporine stimulates hair growth remains unknown.
• In conclusion, topical cyclosporine has shown limited efficacy. Although systemic CsA appears to be effective in alopecia areata, the adverse effect profile, the recurrence rate after treatment discontinuation, and thus, the inability to produce long-term remissions, make CsA unattractive for the treatment of alopecia areata.

Tacrolimus

Regrowth was shown on the application site of topical tacrolimus in 2 studies using the DEBR model. Oral tacrolimus was ineffective. No benefit was shown in the use of topical tacrolimus for alopecia areata in a small 2005 study by Price et al that included 11 patients.²⁴

Interferon

A study of 11 patients with alopecia areata ranging from patchy alopecia areata to alopecia universalis showed no benefit using intralesional interferon alfa-2 (1.5 million IU, 3 times per wk for 3 wk).

Dapsone

Dapsone at 50 mg twice per day was used in a 6-month, double-blind, placebo-controlled study. Of patients in the study, 54% (7 of 13) withdrew from the dapsone group because of adverse effects such as malaise. Of the remaining 6 patients, 3 experienced generalized growth of terminal hair, compared with 4 (4 of 13) patients in the placebo group, who experienced only sparse patchy regrowth of vellus hair. The authors concluded that although dapsone showed some efficacy, the high incidence of adverse effects rendered it unacceptable. Another study showed a rate of success comparable to the occurrence of spontaneous regrowth reported in the literature.

Methotrexate

Joly²⁵ reported 22 patients with longstanding, severe alopecia areata who responded well to methotrexate, with or without systemic corticosteroids. Although the results from that study are surprisingly good, a more standardized study involving more patients is needed because other dermatologists have not had such good efficacy with methotrexate. 

Other treatment modalities

Many other modalities have been reported to have variable response rates in small studies. These include latanoprost,²⁶ nitrogen mustard, massage and relaxation, isoprinosine, acupuncture, and aromatherapy, among others. The efficacy of these treatments needs to be demonstrated in larger, placebo-controlled trials before they can be recommended.

Biological agents

The majority of studies^27,28 and case reports published in the last few years regarding the use of biologic agents (including adalimumab, alefacept, etanercept and infliximab) in the treatment of alopecia areata did not show efficacy, and some patients developed alopecia areata while under treatment with biologic agents for other conditions.

Nonpharmacologic methods

Cosmetic treatments for patients with alopecia areata include dermatography and hairpieces.

• Dermatography has been used to camouflage the eyebrows of patients with alopecia areata. Follow-up visits at 4 years showed that 30 of 39 of patients demonstrated excellent cosmetic results and 3 had good results. On average, 2-3 sessions lasting 1 hour each were required for each patient. No adverse effects were reported.
• Hairpieces are useful for patients with extensive disease and allow them to carry on their usual social life. Reassure patients about the natural look provided by hairpieces.

Surgical Care

Surgical intervention has no role in the treatment of alopecia areata.

Medication

Therapies most commonly include corticosteroid injections, corticosteroid creams, minoxidil, anthralin, topical immunotherapy, and phototherapy. The choice of one agent over the others depends on patient age (children do not always tolerate adverse effects), extent of condition (localized vs extensive), and the patient's personal preference. The University of California (San Francisco) and University of British Columbia have devised a treatment algorithm that can guide the physician in the treatment of alopecia areata (see Media File 9).

Immunomodulators

Because alopecia areata is believed to be an autoimmune condition, different immunomodulators have been used to treat the condition. Exact mechanism of action of topical immunotherapy is unknown. Antigenic competition was hypothesized (ie, introduction of a second antigen can initiate a new infiltrate containing T-suppressor cells and suppressor macrophages that may modify preexisting infiltrate and allow regrowth).

Commonly used agents for immunotherapy include SADBE and DPCP.

Squaric acid dibutylester and diphencyprone

May modulate key factors of the immune system.

Cyclosporine (Sandimmune, Neoral)

Used both topically and systemically for the treatment of alopecia areata. Topical cyclosporine has shown limited efficacy. Although systemic CsA appears to be effective in alopecia areata, the adverse effect profile, recurrence rate after treatment discontinuation, and inability to produce long-term remissions make CsA unattractive for the treatment of alopecia areata.
Mechanism by which cyclosporine stimulates hair growth remains unknown. May act through its immunosuppressive effect because patients who regrew hair had clearance of immune cells from the hair follicles and alteration in the balance of regulatory lymphocytes (ie, decreased CD4/CD8 ratio). Causes hypertrichosis in patients treated for conditions unrelated to hair loss.

Methoxsalen (8-MOP, Oxsoralen)

Inhibits mitosis by binding covalently to pyrimidine bases in DNA when photoactivated by UV-A.

Anthralin (Dritho-Scalp 0.5% cream, Anthra-Derm 1% cream, Drithocreme 1%, Micanol 1% cream)

Synthetic derivative of a tree bark extract. Mechanism of action in alopecia areata is unknown. Most likely creates inflammation by generating free radicals, which have antiproliferative and immunosuppressive actions. Both short-contact and overnight treatments have been used. High concentration (1-3%) is used for short-contact treatments. Lower concentrations (0.1-0.4%) are used for overnight treatments. Applications in excessive amounts may stain clothing.

Glucocorticoids

Have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Topical corticosteroids (including intralesional corticosteroids) are safe and easy to use. They are acceptable cosmetically and allow patients to wear hats or wigs shortly after application. They also are relatively inexpensive. While the usefulness of high-potency topical corticosteroids is under debate, they remain a good (painless) option in children.

Intralesional steroids are first-line treatment in localized conditions.

Oral prednisone usually is reserved for patients with rapidly progressive alopecia areata. The relapse rate is high, and the potential for multiple severe adverse effects when used long term limits its usefulness.

Clobetasol propionate (Temovate)

Class I superpotent topical steroid. Suppresses mitosis and increases synthesis of proteins that decrease inflammation and cause vasoconstriction. Treatment should continue until cosmetically acceptable regrowth is achieved or for a minimum of 3-4 mo.

Prednisone (Deltasone, Meticorten, Sterapred)

Immunosuppressant occasionally used in rapidly progressive alopecia areata in an attempt to halt condition, but relapse rate is high. Use of systemic steroids for treatment of alopecia areata is under much debate. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.
Many drug doses and regimens have been used in treatment of alopecia areata, but no formal recommendation exists.

Triamcinolone acetonide suspension (Kenalog 10 mg/mL or 40 mg/mL)

In alopecia areata, intralesional triamcinolone is believed to suppress the immune system locally and thereby allow hair to regrow. Injections are administered with 3-mL syringe and 30-gauge needle intralesionally.
Pediatric patients generally are less tolerant of intralesional injections because of local discomfort.

Betamethasone dipropionate cream 0.05% (Diprosone)

For inflammatory dermatosis responsive to steroids. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability.

Vasodilators

Relax arteriolar smooth muscle, causing vasodilation; hair growth effects are secondary to vasodilation.

Minoxidil 5% solution (Rogaine Extra Strength)

Stimulates hair growth in general and is effective in many types of hair loss. Exact mechanism of action remains unclear, but does not appear to have either hormonal or immunosuppressant effects. The 5% solution appears to be more effective.

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