THERE IS SOME EVIDENCE THAT IT COULD BE AUTOIMMUNE ALSO IN SOME CASES.
Medical Care: Treatment is not mandatory because the condition is benign, and spontaneous remissions and recurrences are common. Treatments used are believed to stimulate hair growth, but no evidence exists that they influence the ultimate natural course of the disease. Treatment modalities usually are considered first according to the extent of hair loss and the patient's age.
Assessment of the efficacy of a treatment must be considered with care, since 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. The high spontaneous remission rate makes it difficult to assess clearly the true efficacy of a therapy unless appropriate controls with placebo treatment are studied.
For patients with extensive AA (>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 Savin reviewed 50 patients with extensive AA. 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 AA.
Patients with AT/AU usually have a poorer prognosis, and treatment failure is seen in most patients with any therapy.
Since AA is believed to be an autoimmune condition, different immunomodulators have been used to treat this condition. Additional treatment options for AA include minoxidil and other treatment modalities.
Corticosteroids
Intralesional steroids: Few studies are available regarding the efficacy of intralesional steroids, but they are used widely in the treatment of AA.
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 AA and 61% of patients with AT. Regrowth persisted 3 months after treatment in 71% of patients with patchy AA and 28% of patients with AT. Regrowth usually is seen within 4-6 weeks in responsive patients. Patients with rapidly progressive, extensive, or long-standing AA responded poorly.
Another study showed regrowth in most patients (480) treated with intralesional steroids, except in 2 patients with AU.
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 mL.
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 Image 8).
Adverse effects mostly include pain during injection and minimal transient atrophy (10%). The atrophy rarely can be severe and permanent.
Injections are administered every 4-6 weeks.
Avoid reinjecting areas of denting, which usually is sufficient to allow atrophy to revert.
Topical steroids: Few studies have been performed regarding the efficacy of topical steroids in the treatment of AA, and their usefulness remains under debate.
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 al in patients with AT/AU 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.
Prednisone: The use of systemic steroids for the treatment of AA is under much debate. Some authors support a beneficial role of systemic steroids in halting the progression of AA, but many others have had poor results with this form of therapy.
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 AA because of the adverse effects associated with both short-term and long-term treatment.
Topical immunotherapy: Topical immunotherapy 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). 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 on humans exist with the use of these agents.
Although DPCP and SADBE have not been found mutagenic in the Ames assay, neither is approved by the 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 AA (>50% involvement) varies from 22-68%. Most studies have a success rate of 30-50%. Wiseman et al retrospectively reported the results of a large cohort of 148 consecutive patients treated with diphencyprone.
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 AT/AU, 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 AA before treatment, duration of the disease, and 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 has 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 and occurred in 1.6% of 243 patients treated. Less common adverse effects include erythema multiformeโlike eruptions and urticaria, which were reported in 3 patients treated with DPCP.
The mechanism of action of topical immunotherapy is unknown. Antigenic competition was hypothesized, ie, 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.
Since 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 effective equally. 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 one 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, since 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 al showed no benefit in using anthralin. Other studies showed a response rate of 20-75%, respectively, for patchy AA and a 25% response rate for AT. 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 AA. 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.
Psoralen plus UV-A: Many studies have been performed regarding the efficacy of psoralen plus UV-A (PUVA) in the treatment of AA, 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 AT or AU appear to indicate a poorer outcome.
Taylor and Hawk published 10 years of experience with PUVA. The initial response rate (>90% regrowth) was comparable to other studies and was 43.8% for partial AA and 50% for AT and AU. However, after excluding patients with of 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 AA and 12.5% for AT and AU. They concluded that PUVA generally is not an effective long-term treatment for AA.
PUVA is a relatively safe treatment modality; adverse effects include burning and, possibly, an increased risk of skin cancer.
Cyclosporine: Cyclosporine has been used both topically and systemically in the treatment of AA.
Topical cyclosporine has not proven to be effective in severe AA, since 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 resulted in vellus growth in 3 of 14 patients and normal hair growth in 3 patients with patchy AA. No regrowth was seen in 8 of the patients.
Neither study showed systemic absorption of CsA, and routine blood examination showed only transient increase of hepatic enzymes in 1 patient.
Oral cyclosporine was effective in the DEBR model for AA. All rats had a full pelage by 5 weeks of treatment with 10 mg/kg/day, 5 days per week for 7 weeks. Studies in humans also have proven efficacy with doses of 6 mg/kg daily 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 exists that CsA can prevent hair loss during an active episode, since reports exist of patients on CsA who developed AA while they were under treatment for unrelated conditions.
The mechanism of action of cyclosporine remains unclear. It may act through its immunosuppressive effect, since 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 AA, 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 AA.
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 AA in a small 2005 study by Price et al that included 11 patients.
Interferon: A study of 11 patients with AA ranging from patchy AA to AU showed no benefit using intralesional interferon alfa-2 (1.5 million IU, 3 times per wk for 3 wk).
Dapsone: Dapsone 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 to 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.
Minoxidil: Minoxidil appears to be effective in the treatment of AA 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 AT/AU.
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 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 was 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.
Other treatment modalities: Many other modalities have been reported to have variable response rates in small studies. These include latanoprost (Ross, 2005), 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.
Nonpharmacologic methods: Cosmetic treatments for patients with AA include the following:
Dermatography has been used to camouflage the eyebrows of patients with AA. 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.