Alopecia areata (AA) is a common nonscarring alopecia. It affects 1.7% of the population at some point in their lives. AA is an autoimmune condition characterized by dense peribulbar lymphocytic infiltrate. The exact cause and triggering factors are still unknown. The scalp is the most commonly affected area but any hair-bearing area can be involved. All available treatment options are neither curative nor preventive. This article will discuss updates in AA with focus on etiopathogenesis, clinical presentation, and treatment options and suggest treatment plans based on the age of the patient and extent of the disease.
Key Points
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Alopecia areata (AA) is a common nonscarring autoimmune condition that has no race or gender predilection.
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Although most AA patches are asymptomatic, few patients may complain of itching or burning sensation.
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Diagnosis is usually straightforward and routine blood testing is not generally indicated.
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Treatment is tailored according to the age of the patient and the extent of the disease.
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The most important poor prognostic factor is extensive disease presentation.
Epidemiology
Alopecia areata (AA) is a common nonscarring hair condition responsible for 0.7% to 3.8% of dermatology clinics visits. The lifetime risk in the United States was estimated at 1.7%. The 2 sexes are equally affected. When it comes to age distribution, children constitute approximately 20% of patients with AA, and as many as 60% present with their first patch before the age of 20. Only 20% of patients are older than 40.
Epidemiology
Alopecia areata (AA) is a common nonscarring hair condition responsible for 0.7% to 3.8% of dermatology clinics visits. The lifetime risk in the United States was estimated at 1.7%. The 2 sexes are equally affected. When it comes to age distribution, children constitute approximately 20% of patients with AA, and as many as 60% present with their first patch before the age of 20. Only 20% of patients are older than 40.
Clinical picture
AA is most commonly noticed incidentally by the patient, a family member, or hairdresser. The disease is asymptomatic although some patients may report pruritus, burning sensation, or pain.
Typical lesions are sharply demarcated, round to oval, skin-colored patches of nonscarring alopecia ( Fig. 1 ). Less commonly, the color of the lesions can be peachy or reddened ( Fig. 2 ). Hairs that are tapered proximally and wider distally (“exclamation mark hairs”) are characteristic findings within or at the periphery of the lesions ( Fig. 3 A, B). The hair pull test can be positive at the periphery of active lesions. Although any hair-bearing area can be affected, the scalp is involved in 90% of the cases. In patients with graying hair, AA initially spares the white hairs. Eventually, these hairs will be involved as the disease progresses. Initial hair regrowth can also be hypopigmented, but it usually restores the color with time.
AA can be classified according to the extent or the pattern of hair loss ( Table 1 ). Based on the extent of hair loss, the disease is clinically classified as follows: patchy AA (see Fig. 1 ), in which there is a partial loss of scalp hair; alopecia totalis (AT) ( Fig. 4 ), in which 100% of scalp hair is lost; or alopecia universalis (AU) ( Fig. 5 ), in which there is a 100% loss of all scalp and body hair. Patchy AA is seen in up to 75% of patients and is the most common pattern. Other patterns include reticular pattern; ophiasis type ( Fig. 6 ), bandlike hair loss in parieto-temporo-occipital area; ophiasis inversus (sisapho), very rare bandlike hair loss in the fronto-parieto-temporal area; and a diffuse thinning over part of or the entire scalp.
| Classification by Extent | Classification by Pattern |
|---|---|
| Patchy AA | Patchy AA |
| AT | Ophiasis |
| AU | Ophiasis inversus |
| Reticular | |
| Diffuse |
A recently described, distinct clinical variant is acute diffuse and total alopecia. This new variant is characterized by its rapid progression and extensive involvement, along with a favorable prognosis.
Dermoscopic features that are seen in AA include yellow dots, black dots, broken hairs, short vellus hairs, and tapered hairs (see Fig. 3 B). These findings are not specific for AA but can be very helpful when the diagnosis is uncertain.
Nail pitting is the most common nail abnormality observed in AA. Other reported nail abnormalities include trachyonychia, beau lines, onychorhexis, thinning or thickening, onychomadesis, koilonychia, punctuate or transverse leukonychia, and red spotted lunulae. The reported frequency of nail abnormalities ranges from 7% to 66%.
Associated abnormalities
Autoimmune thyroid disease is the most common abnormality associated with AA with an incidence between 8% and 28%. The presence of thyroid autoantibodies has no clinical correlation with AA severity. Vitiligo occurs in 3% to 8% of AA patients compared with 1% in the general US population. Atopy is twice as common in AA patients as it is in the general population.
Other diseases and genetic disorders reported to be associated with AA include Down syndrome, Addison disease, autosomal recessive autoimmune polyglandular syndrome (APS-1) (chronic hypoparathyroidism-mucocutaneous candidiasis-autoimmune adrenal insufficiency), pernicious anemia, psoriasis, lupus, Sjögren syndrome, intermediate uveitis, rheumatoid arthritis, celiac disease, ulcerative colitis, myasthenia gravis, and multiple sclerosis. These less common autoimmune diseases are more likely to be associated with AT/AU.
There may be an increased risk of type 1 diabetes in family members of AA patients; in contrast, the patients themselves may have a reduced incidence compared with the general population. There may be a high psychiatric morbidity in AA, especially anxiety and mood disturbance. Ophthalmologic findings such as asymptomatic lens opacities and fundus changes occurred in 51% and 41% of patients with AA, respectively.
Differential diagnosis
In children, AA should be differentiated from tineacapitis and trichotillomania. Tineacapitis can be associated with inflammation and scaling, which are typically not seen in AA. Trichotillomania is usually bizarre shaped and has broken hairs with varying length. In children with a single congenital patch of hair loss on the temporal area, temporal triangular alopecia should be considered in the differential diagnosis. If AA involves the frontal and temporal hair line, frontal fibrosing alopecia (FFA) should be ruled out. FFA is a scarring hair condition primarily affecting postmenopausal women. FFA may have perifollicular erythema and scales, which are not present in AA. Diffuse AA can be challenging and may require a biopsy to differentiate it from telogen effluvium. If the clinical context is suspicious for syphilis or lupus, serologic examination is indicated to rule out this possibility.
Etiopathogenesis
Many etiologic factors have been suggested to contribute to the development of AA. These include stress, infectious agents, vaccinations, hormonal factors, and genetics. The exact cause is still unknown. The disease onset and severity are probably determined by multiple factors.
Most of the recent literature supports autoimmunity as the major pathogenic process in AA. Several observations support this hypothesis. These include the presence of lesional inflammatory cells, hair follicle–specific autoantibodies in the blood of patients with AA, the response to treatment with immunosuppressive medications, and the association of AA with other autoimmune diseases.
The follicular infiltrate is mainly composed of CD4 + and CD8 + T cells. This leads to disruption of the normal hair cycle. Inflammation can maintain hair follicles in dystrophic anagen state, force them into premature telogen, or –in chronic cases–keep them in prolonged telogen state.
Recently, genomewide association study in AA has identified at least 8 regions in the genome with evidence for association with AA. This may have significant implications on the way this common disease is treated.
Prognosis
The most important factors indicating a poor prognosis are the extent of hair loss presentation (extensive AA/AT/AU) or an ophiasis pattern of hair loss. Other factors associated with a poor prognosis include a long duration of hair loss, atopy, a positive family history, the presence of other autoimmune diseases, nail involvement, and young age at first onset.
The course of AA is unpredictable. Up to 50% of patients will recover within 1 year even without treatment. However, 85% of patients will have more than 1 episode of hair loss. In patients with AA before puberty, the chance of AT is 50%. In AT/AU, the chance of full recovery is less than 10%.
Investigations
Routine blood testing in AA is not generally indicated because of insufficient clinical evidence. Potassium hydroxide, fungal culture, lupus serology, syphilitic screening, and a scalp biopsy may be necessary if the diagnosis is in question. However, most AA cases are straight forward and don’t require investigations.
Histopathology
The histologic picture of AA varies according to the duration of the disease. In acute stage, anagen follicles are targeted by lymphocytic infiltrate “swarm of bees” composed of CD4 + and CD8 + T cells. Other cells that can be found include Langerhans cells, eosinophils, mast cells, and plasma cells. Edema, microvesiculation, apoptosis, necrosis, macrophages, and foreign body giant cells can be seen in and around the affected hair follicles.
In the subacute stage, there is marked increase in the catagen, followed by telogen hair. Some inflammation may still present around fibrous streamers as the follicles ascend higher in the dermis. Significant hair follicle miniaturization with little or no inflammation characterizes chronic AA.
Treatment
There are no Food and Drug Administration–approved treatments for AA. Many therapeutic options exist, but none are curative or preventive. For many reasons, it is difficult to assess treatment options for AA. There is high rate of spontaneous remission in patchy AA. There is also paucity of randomized-controlled trials investigating treatment efficacy. Long-term follow-up is not addressed in many of the published reports. Another important drawback is the great variation in treatment outcome evaluation. To overcome this issue in particular, the Severity of Alopecia Tool score seems to be ideal.
In this section, localized and systemic agents used in the treatment of AA will be discussed. At the end, approach to treatment is suggested based on age of the patient and extent of the disease.
Localized therapies
Intralesional Corticosteroids
Since 1958, intralesional corticosteroids (ILCS) have been used widely for the treatment of AA. Despite their common use, there are no randomized controlled trials. The most commonly used drug is triamcinolone acetonide. Hair regrowth has been reported in 71% of patients with subtotal AA treated by triamcinolone acetonide injections 3 times every 2 weeks and in 7% of control subjects injected with isotonic saline. Porter and Burton showed that hair regrowth was possible in 64% and 97% of AA sites treated by intralesional injections of triamcinolone acetonide and its less soluble derivative, triamicinolone hexacetonide, respectively. Using monthly intralesional triamcinolone acetonide, 40 of 62 patients with AA (63%) showed complete regrowth in 4 months. In this uncontrolled trial, response was better in patients with fewer patches (<5), shorter duration of disease (<1 month), and smaller patches diameter (<3 cm). In another report, 6 of 10 patients with extensive AA responded to intralesional triamcinolone acetonide.
For adult patients with limited involvement, ILCS (preferably triamicinolone acetonide) are considered first-line therapy. Triamicinolone acetonide is injected in the deep dermal/upper subcutaneous plane using a ½-inch-long 30-gauge needle ( Fig. 7 ); 0.1 mL is injected at 0.5- to 1-cm intervals every 4 to 6 weeks. Various concentrations (2.5–10 mg/mL) are used but 5 mg/mL and 2.5 mg/mL are the preferred concentrations used by the author for the scalp and face, respectively. The maximum dose per session was suggested to be 20 mg of triamcinolone acetonide. Topical anesthetic cream can be applied before treatment to minimize pain, especially if treating younger patients. Treatment should be stopped if there is no improvement after 6 months. The decreased expression of thioredoxin reductase 1 in the outer root sheath may be the cause for glucocorticoid resistance in some patients with AA.
Side effects include transient atrophy and telangiectasia, which can be prevented by the use of smaller concentrations and volumes, minimizing the number of injections per site, and avoiding injecting too superficially.
Topical Corticosteroids
Midpotent and potent topical corticosteroids are widely used in the treatment of AA. The evidence for their efficacy is limited. A double-blind half-head placebo-controlled study compared 0.2% fluocinolone acetonide cream twice a day with base vehicle and showed unilateral regrowth in 54% in the treatment arm compared with 0% in the vehicle group. A multicenter prospective, randomized, controlled, investigator-blinded trial in patients with less than 26% hair loss showed a greater than 75% hair regrowth rate in 61% of patients using 0.1% betamethasone valerate foam in comparison with 27% in the 0.05% betamethasone dipropionate lotion group. In a study of unilateral application of 0.05% clobetasol propionate ointment under occlusion in patients with AT/AU, Tosti and colleagues showed that 28.5% of patients had almost complete hair regrowth and 17.8% of patient had long-term benefit on the treated side. In another randomized, double-blind, placebo-controlled trial, 47% of 0.05% clobetasol propionate foam–treated patients had greater than 25% hair regrowth, and 25% of participants had hair regrowth greater than 50%. No significant modifications in cortisol and adrenocorticotropic hormone blood levels were observed during this trial. On the other hand, in another randomized, double-blinded, placebo-controlled trial using desoximetasone cream 0.25%, the complete regrowth rates in the active and control groups were 57.6% and 39.2%, respectively. These results were not statistically significant compared with placebo.
Side effects include folliculitis (more with ointment compared with foam formulations) and rarely skin atrophy and telangiectasia. The relapse rate varies from 37% to 63% after topical corticosteroid treatment has stopped and even with continuation of therapy.
Minoxidil
Minoxidil was initially used as antihypertensive therapy. Although it has been used to promote hair growth for more than 20 years, its mechanism of action is not fully understood. Vasodilatation, angiogenesis, enhanced cell proliferation, and potassium channel opening have been all proposed.
In a double-blind placebo-controlled trial on extensive AA, 3% minoxidil under occlusion with petrolatum resulted in hair regrowth in 63.6% compared with 35.7% in the placebo arm. Only 27.3% of minoxidil-treated patients had cosmetically acceptable hair growth. A dose-response efficacy was shown in a study comparing 1% and 5% topical minoxidil in the treatment of patients with extensive AA. The response rates were 38% and 81% with 1% and 5% topical minoxidil, respectively.
Minoxidil 5% solution twice daily is used as adjuvant treatment to conventional AA therapy (mainly topical corticosteroids or ILCS). Contact dermatitis and hypertrichosis are the most common side effects. Contact dermatitis can be minimized by using minoxidil foam, which does not contain propylene glycol.
Anthralin
There are a few uncontrolled case series assessing anthralin efficacy in the treatment of AA. Response rates of 75% in patients with patchy AA and 25% in patients with AT have been reported ( Fig. 8 ). Anthralin cream 0.5% to 1.0% was used to treat 68 patients with severe AA. Cosmetic response was seen in 25% of the patients.
In mice, anthralin has been shown to decrease the expression of tumor necrosis factor (TNF)-α and -β in the treated area in comparison to vehicle-treated sites. Its mechanism of action in AA treatment is unknown.
Anthralin 1% cream can be used as short-contact therapy. It is applied daily for 15 to 20 minutes initially then washed. The contact time is increased by 5 minutes weekly up to 1 hour or until low-grade dermatitis develops. The contact time is then fixed and continued daily for at least 3 months before judging the response to treatment. Anthralin should produce a mild irritant reaction to be effective. Side effects include severe irritation, folliculitis, regional lymphadenopathy, and staining of skin ( Fig. 9 ), clothes, and fair hair. Patients should avoid eye contact with this chemical and the treated area should be protected from the sun.
Topical Immunotherapy
The mechanism of action of topical sensitizers is poorly understood. Many theories have been suggested including antigenic competition, perifollicular lymphocytes apoptosis, changes in the peribular CD4/CD8 lymphocyte ratio, and interleukin (IL)-10 secretion after diphenylcyclopropenone (DPCP) application.
Dinitrochlorobenzene was the first topical sensitizer to be used in the treatment of extensive AA since 1976, but it has been discontinued because it has been shown to be mutagenic in the Ames test. Squaric acid dibutylester (SADBE) and DPCP are the 2 compounds still in use today. DPCP is preferred because it is cheaper and is more stable in acetone.
Although no randomized controlled trials have evaluated the effectiveness of topical immunotherapy in AA, observational studies have used the half-head method to control for spontaneous regrowth of hair. A comprehensive review of published topical immunotherapy studies (SABDE = 13 trials; DPCP = 17 trials) found little difference between the 2 agents. The success rate of DPCP and SADBE is about 50% to 60% with a wide range of 9% to 87%. The largest reported series of DPCP treatment found that cosmetically acceptable regrowth was achieved in 17.4% of patients with AT/AU, 60.3% with 75% to 99% AA, 88.1% with 50% to 74% AA, and 100% with 25% to 49% AA. A lag of 3 months was present between initiation of therapy and development of significant hair regrowth in the first responders. Relapse after achieving significant regrowth developed in 62.6% of patients with median time to relapse being 2½ years. Although contact immunotherapy has been used mainly for adults, there are reports of success in the pediatric population.
In a recent study of 20 patients treated with DPCP, neoangiogenesis seen with videocapillaroscopy was significantly correlated with a better clinical response. The most important negative prognostic factors in the treatment of AA with DPCP are disease severity, duration of AA before therapy, and presence of nail changes. Other factors include age at onset, atopy, and a family history of AA. It was also suggested that if patients with AT or AU are suffering with hyperpigmentation from the sensitizer, these patients will show poor response to contact immunotherapy.
Because DPCP is very light sensitive, it should be stored in amber bottles to protect it from exposure to ultraviolet light ( Fig. 10 ). DPCP 2% is applied using a cotton swab to a 4-cm circular area on the scalp to sensitize the patient. Two weeks later, a 0.001% DPCP solution is applied to the same half of the scalp ( Fig. 11 ). The concentration of DPCP is increased gradually each week until a mild dermatitis reaction is obtained. The goal is to achieve a low-grade erythema and mild pruritus on the treated area for 24 to 36 hours after application.
After establishing the appropriate concentration for the patient, therapy should be continued on a weekly basis. DPCP should be left on the scalp for 48 hours and then washed off. Patients should not expose the treated area to the sun during this time. Treatment of both sides is recommended only after achieving a trichogenic response on the treated side ( Fig. 12 ). If there is no improvement at 6 months, DPCP is less likely to be successful. If the patient does not develop an allergic reaction to 2% DPCP, SADBE can be tried.
A vesicular or bullous reaction is one of the undesired adverse effects of topical sensitizers. If this reaction develops, the patient should wash off the contact sensitizer and a topical corticosteroid should be applied to the affected area. Other adverse effects include cervical and occipital lymphadenopathy, facial and scalp edema, contact urticaria, flulike symptoms, erythema multiforme-like reactions, and pigmentary disturbances (hyperpigmentation, hypopigmentation, dyschromia in confetti, and even vitiligo) ( Fig. 13 ).
Prostaglandin Analogs
Latanoprost, a prostaglandin F2α analog, and bimatoprost, a synthetic prostamide F2α analog, are used in the treatment of open angle glaucoma patients. Hypertrichosis of the eyelashes and vellus hair on the malar area is one of the reported side effects. Prostaglandin F2α and its analogs showed stimulatory effects on murine hair follicles and follicular melanocytes in both the telogen and anagen stages and stimulated conversion from the telogen to the anagen phase. Bimatoprost (Lattisse; Allergan, Inc, Irvine, CA) received approval from the Food and Drug Administration for the treatment of hypotrichosis of the eyelashes.
Latanoprost and bimatoprost failed to induce regrowth in a blinded randomized controlled trial on 11 patients with extensive (>50%) eyelash AA. Another 16-week randomized, right-left, investigator-blinded study of 8 patients with severe eyebrow AA showed the same result. In a larger trial, 26 patients with symmetric eyelash and eyebrow AA were treated during 4 months with topical latanoprost for one side. This trial also failed to show a difference between the treated and the untreated sides. On the other hand, a recent nonblinded, nonrandomized trial showed a cosmetically acceptable response in 45% of the latanoprost-treated group compared with none of the control group. Complete eyelashes regrowth was noted in 24% of 37 patients of AU using 0.03% bimatoprost to the eyelid margin once a day during the course of 1 year. Patients with less extensive eyelash loss caused by AA may benefit from treatment with instilled bimatoprost. This attractive area of AA therapy needs further evaluation with blinded prospective right-left controlled trials to confirm either of the conflicting evidence available so far. The treatment is usually well tolerated. Side effects include transient mild eye irritation or hyperemia.
Phototherapy
Randomized controlled trials for phototherapy with oral or topical psoralen plus ultraviolet A light are lacking. Two large retrospective studies showed that the response rate is no better than the spontaneous remission rate. Insufficient evidence and the risk of cutaneous malignancies with psoralen plus ultraviolet A make it a less-favored treatment option. Narrow band ultraviolet B was not effective in a retrospective analysis of 25 patients with AA. A few case series have shown successful results with 308-nm excimer laser in treating patchy AA. The initial fluences were 50 mJ/cm 2 less than the minimal erythema dose. Fluences were then increased by 50 mJ/cm 2 every 2 sessions. Each patch was treated twice a week for a maximum of 24 sessions. Hair regrowth has been shown in 41.5% of patches.
Potential Topical and Localized Treatments
There are several treatment modalities that can be administered locally and have shown some efficacy. Indeed, these require further testing and evaluation. Bexarotene 1% gel treatment on half head was evaluated in a single blinded study involving 42 patients with AA. Five patients (12%) had 50% or more partial regrowth on the treated side, and 6 patients (14%) had a response on both sides. 73% of the subjects had some degree of dermal irritation. Capsaicin ointment was comparable to clobetasol 0.05% ointment in a nonblinded study of 50 subjects with patchy AA. This finding should be supported with blinded randomized controlled trials with large number of subjects. There is a single case report of refractory AA that responded to fractional Er:glass laser. One animal study demonstrated the efficacy of 655-nm laser comb in a C3H/HeJ mouse model for AA.
Systemic therapies
Corticosteroids
Systemic corticosteroids have been used for decades in patients with extensive AA. Several regimens have been used with varying success. The only randomized placebo-controlled study on oral prednisolone was published in 2005. Forty-three patients with extensive AA were randomized to receive prednisolone 200 mg weekly or placebo. The treatment period was 3 months followed by 3 months of observation time. Significant hair regrowth was noted in 35% of patients in the treatment group compared with none in the placebo group. The relapse rate was 25% during the observation period. Significant hair regrowth was noted in 28 of 34 patients (82%) with extensive AA treated with prednisolone 300 mg once monthly for 3 to 6 months. Poor response was associated with presence of other autoimmune abnormality, nail involvement, and universalis form. Only 15% of the patients had side effects in that report.
Other systemic corticosteroids regimens include prednisolone 40 mg daily tapered over 6 weeks, dexamethasone 5 mg on 2 consecutive days weekly, intravenous methylprednisolone 250 mg twice daily on 3 consecutive days monthly, dexamethasone 0.5 mg daily for 6 months, intramuscular triamcinolone acetonide 40 mg monthly, and prednisolone 80 mg daily on 3 consecutive days every 3 months.
The side effects of systemic steroids include hyperglycemia, osteoporosis, cataracts, immunosuppression, mood changes, obesity, dysmenorrhea, acne, and Cushing syndrome. The reported relapse rate is 14% to 100%. The addition of 2% topical minoxidil 3 times daily may alleviate poststeroid relapse. Systemic steroids used in AA is less-favored option because of the side effect profile and high relapse rate.
Cyclosporine
Cyclosporine is an immunosuppressant agent that inhibits helper T-cell activation and suppresses interferon-γ production. Cyclosporine alone or in conjunction with systemic steroids was tried with variable results. The success rate ranges from 25% to 76.7%. Notably, however, AA has been reported in several organ transplant patients who were taking cyclosporine. One report suggested that increased serum soluble IL-2 receptor level and lower IL-18 level at baseline was associated with a poor response to a combination of cyclosporine and methylprednisolone.
Cyclosporine is not a preferred option in AA because of high side effect profile and relapse rate. Side effects include nephrotoxicity, immune suppression, hypertension, and hypertrichosis of body hair.
Although no beneficial response has been observed by using topical cyclosporine in humans, Verma and colleagues showed good hair regrowth and reduced inflammation in the Dundee experimental bald rat model using cyclosporine specially formulated in lipid vesicles. No response was noted in the Dundee experimental bald rat group treated with cyclosporine in ethanol, but further studies in humans are needed to assess the efficacy and safety of this specific formulation.
Sulfasalazine
Sulfasalazine has both immunomodulatory and immunosuppressive actions, including inhibition of T-cell proliferation, natural killer cell activity, and antibody production. Sulfasalazine also inhibits the T-cell cytokines IL-2 and interferon-γ and the monocyte/macrophage cytokines IL-1, TNF- α, and IL-6.
In a retrospective study, cosmetically acceptable hair regrowth was noted in 23% of patients with severe AA. In another open-label study done on patients with severe AA, complete hair regrowth was achieved in 27.3% of patients. Sulfasalazine was started at 0.5 g twice daily for 1 month, 1 g twice daily for 1 month, and then 1.5 g twice daily for 4 months. The relapse rate was 45.5%. Thirty-two percent of patients suffered from adverse effects, which included gastrointestinal distress, rash, headache, and laboratory abnormalities. A similar response rate (25.6%) was shown in another uncontrolled trial of 39 patients with AA.
Methotrexate
Methotrexate (15–25 mg/wk) alone or in conjunction with 10 to 20 mg/d of prednisone resulted in complete regrowth in 57% and 63% of patients, respectively. The onset of hair regrowth was noted after a median delay of 3 months. Relapsed rate was 80% (16 of 20 responders). Seven patients (21%) experienced adverse events consisting of transient elevated transaminases, persistent nausea, and lymphocytopenia. Using the same regimens, complete hair regrowth was achieved in 64% of 22 patients with AT/AU. In a retrospective study including 14 children with severe AA treated with methotrexate (mean dose of 18.9 mg/wk), the response rate was 38%.
Azathioprine
Azathioprine is a cytotoxic and immunosuppressive drug that has been used in the treatment of autoimmune diseases for more than 50 years. It seems to impair T-cell function and IL-2; it seems to be more selective for T lymphocyte than for B lymphocytes. Azathioprine was used on 20 patients with extensive AA in an open-label uncontrolled study. With use of azathioprine 2 mg/kg/d for 6 months, the mean hair regrowth was 52%. Azathioprine had its onset of action after 3 months of therapy. Side effects included gastrointestinal symptoms, mild leukopenia, and elevated liver enzymes.
Psychosocial Support
AA is associated with high psychiatric comorbidities (mainly adjustment disorder, generalized anxiety disorder, and depressive disorders). The efficacy of antidepressants in AA treatment has not been evaluated by large-scale randomized controlled trials. In a small trial of 8 patients with AA treated with 20 mg paroxetine, a selective serotonin reuptake inhibitor, and 5 patients with placebo for 3 months, complete hair regrowth was observed in 2 patients in the paroxetine group versus 1 patient in the placebo arm. Four patients in the paroxetine group showed partial hair regrowth. Willemsen and colleagues showed 75% to 100% hair regrowth in 12 of 21 patients with extensive AA after 3 to 8 sessions of hypnotherapy. In the follow-up period (ranging from 4 months to 4 years), the relapse rate was 42%. The small sample size and less than optimum hair regrowth assessment make the evaluation of some trials of antidepressants difficult.
Support groups that involve regular meetings of patients with AA and family members can be an invaluable resource for them. Patients can derive emotional support and information that can help them develop positive coping strategies, overall improved quality of life, and increased treatment compliance. The National Alopecia Areata Foundation ( www.naaf.org ) provides patients and physicians with brochures, research updates, bimonthly newsletters, a pen pal program, sources for scalp prostheses, and many patient conferences. Also, the National Alopecia Areata Foundation supports research and research workshops that add to the scientific knowledge about AA.
Treatment Failures
Topical tacrolimus and pimecrolimus have been tried in several case series in the treatment of AA, but the results have not been encouraging. Imiquimod was tried on patchy and extensive AA but failed to show positive results. Photodynamic therapy was shown to be ineffective in the treatment of patients with AA. There are a few reported cases that have shown either development of AA or complete failure to respond to different TNF-α antibodies, including adalimumab, infliximab, and etanercept.
Management Plan
At the patient’s first visit, a careful medical history and a good physical examination should be conducted, including an examination of all hair-bearing areas and nails. Full information about his or her disease including the relapsing nature of AA, prognosis, and risk/benefit ratio of treatment options should be provided. No routine testing is required for patients with AA. Because of the possibility of spontaneous remission in 34% to 50% of patients within 1 year, some patchy AA patients can just be followed without active intervention. If the patient opted for active treatment, options would be offered according to the patient’s age and extent of the disease ( Fig. 14 ).
