Topical and intralesional therapies for alopecia areata

Alopecia areata is a common form of nonscarring alopecia. It affects males and females equally and has no racial predilection. It usually affects the scalp, but any hair-bearing area can be involved. It presents as patchy hair loss, loss of hair on the entire scalp (alopecia totalis), or the whole body (alopecia universalis). The histopathology varies according to the disease stage, but usually a perifollicular lymphocytic infiltrate is seen. The course of the disease and response to treatment are unpredictable. Various therapeutic modalities are used including topical, intralesional, and systemic agents, although none are curative or preventive. This article will review the available topical and intralesional agents that are used in the treatment of alopecia areata and suggest a management approach based on the age of the patient and extent of the disease.     

Hair transplantation for therapy‐resistant alopecia areata of the eyebrows: Is it the right choice?

Alopecia areata is a common skin disorder of presumed autoimmune etiology and it usually shows an unpredictable course. Treatment of alopecia areata is challenging. There is very little information on the use of surgical therapies for the treatment of alopecia areata in the medical published work. A 24-year-old male patient was referred to a private hair transplantation clinic owned by one of the authors for the treatment of therapy-resistant alopecia areata affecting both eyebrows. He had quickly lost all body hair 4 years prior beginning from the scalp. He received psoralen and ultraviolet A (PUVA) therapy for alopecia universalis and all body hair re-grew except his eyebrows. Alopecia areata was stable for the 18 months following the last medical treatment he received. Because there was no response to various medical therapeutic agents, we decided to transplant occipital hairs to the eyebrow area. After the patient understood and accepted all risks, occipital hairs were transplanted to the eyebrows by using the follicular unit extraction technique. Postoperatively, the patient did not receive any topical or systemic therapies for alopecia areata. Although 40% hair re-growth was detected in his eyebrows at 1 year postoperation, this rate was 80% by 2 years postoperation. However, there was resistance to re-growth in the medial eyebrow regions. New eyebrows grew as occipital hairs and required trimming. His satisfaction from the surgical procedure was 90% at the end of the 24th postoperative month. Surgical treatment of diseases like alopecia areata is still controversial. Our case report offers an additional contribution to the published work on the surgical methods used in the treatment of stable alopecia areata.     

Twice weekly 5 mg dexamethasone oral pulse in the treatment of extensive alopecia areata.

Thirty patients (20 males, 10 females) with widespread alopecia areata (25 extensive alopecia areata, 5 alopecia areata) for a mean period of 4.2 years were included in the study. All patients above 12 years were administered 5 mg dexamethasone oral pulse on two consecutive days every week. Three children (< 12 years) received 2.5 mg to 3.5 mg dexamethasone oral biweekly pulse. Patients who had received treatment for a minimum period of 12 weeks were evaluated for terminal hair growth. Complete to excellent (75-95%) hair growth was observed in 16 (63.3%) patients. Growth was good (50-74%) in 2 cases and poor (< 50%) in 3 (10%) cases. Six (20%) patients has no growth of terminal hair. Complete to excellent growth of hair was obtained after a mean period of 5.35 months (range 3-10 months). Relapse occurred in one case each after three and six months but hair regrew with re-treatment. Side effects of corticosteriods were frequent, seen in 8 (26.6%) patients, but were mild. In only one case, treatment had to be discontinued. We propose that twice weekly 5 mg dexamethasone oral pulse for six months may be considered as one of the modalities in the treatment of extensive long standing alopecia areata.     

Hair regrowth with topical triiodothyronine ointment in patients with alopecia areata: a double‐blind,randomized pilot clinical trial of efficacy

Background Thyroid hormone receptors are expressed in hair follicles and it is known that thyroid hormones can have a positive effect on hair growth, i.e. process which is disrupted in alopecia areata. Objectives The aim of this study was to determine the efficacy of topical triiodothyronine in patients with patchy alopecia areata. Methods Ten patients with patchy alopecia areata were treated with triiodothyronine and placebo applied twice daily to either of two bilaterally symmetrical patches for 12 weeks. The two sides were randomly assigned following simple randomization procedure to one of the two treatment groups. The patients and the investigator were blinded to the content of the tubes. Hair regrowth was evaluated every 4 weeks. Blood samples for measurements of complete blood count along with thyroid function (T3, T4 and TSH) and liver function tests were taken at the baseline and at the end of study. Results After 12 weeks of treatment, there was no statistically significant difference between the outcome in terms of reduction of the patch size and hair regrowth. No adverse effects were noted. Conclusion Triiodothyronine in the studied dosage and formulation was safe but not more effective than placebo. However, newer thyroid hormone analogues might be more effective and evaluating their effects probably warrants further consideration.     

Topical minoxidil in alopecia areata: a double-blind trial

Early reports of the success of topical minoxidil in alopecia areata have been followed by a mixture of enthusiasm and disappointment. Our double-blind trial was prompted by remaining doubts about its effectiveness and safety.
Fifty adult patients (22 male, 28 females) with longstanding alopecia areata (mean age at onset 20 years, mean duration 16 years) took part in the trial. The severity of their disease was categorised as universalis (23 patients), totalis (10), ophiasiform (6) and severe patchy alopecia (11). Thirty-eight per cent had a personal history of atopy and 14% had circulating thyroid antibodies.
For the first 2 months patients were randomly allocated to treatment wjth i % minoxidil in Unguentum Merck® or Unguentum Merck® alone. At the end of this period the same treatment was continued if hair growth was observed; if not, the alternative treatment was used. After 4 months, if no hair growth had occurred, 1% minoxidil was prescribed. Forty-eight patients were treated for at least 6 months, 46 for 10 months and 13 for longer periods.
Equal proportions of the patients treated with minoxidil or with placebo experienced regrowth, but this was substantial only in seven patients and cosmetically acceptable in only two. No patient felt able to stop wearing a wig. Many patients disliked the greasy nature of the preparation. Patients with alopecia universalis had the highest prevalence of nail changes, and the worst response to treatment.     

斑秃的外用药物治疗

外用药物在斑秃治疗中具有重要作用,本文就外用糖皮质激素、致敏剂二苯基环丙烯酮和斯夸酸二丁酯、蒽林、米诺地尔、比马前列素、维A酸、贝沙罗汀、卡泊三醇、辣椒碱、壬二酸、大蒜凝胶和洋葱汁治疗斑秃的在斑秃中的应用进行综述。     

308-nm Excimer Laser for the Treatment of Alopecia Areata in Children

Abstract:  Alopecia areata (AA) is a common skin disease which is characterized by nonscarring localized or diffused hair loss. In this study we assessed the efficacy of 308-nm Excimer laser in the treatment of alopecia areata in children. A total of 9 children with 30 recalcitrant patches alopecia areata and two children with alopecia areata totalis were enrolled in this study which included seven male and four female patients, aged between 4 and 14 years and the durations of their disease were between 7 and 25 months. All of these patients had more than one lesion of alopecia areata and at least one of them was left as a control for comparison. The lesions were treated with the 308-nm Excimer laser twice a week for a period of 12 weeks. Regrowth of hair was observed in 18 (60%) alopecia patches in the scalp, while there was no response in the control patches and over the extremities. Only four patients with scalp lesions showed a recurrence of alopecia after 6 months post laser therapy. So, 308-nm Excimer laser is considered an effective safe therapeutic option for patchy alopecia areata in children.     

Treatment of alopecia areata with squaric acid dibutylester

Fourteen of 18 patients with extensive alopecia areata completed a course of weekly treatments with the topical allergen squaric acid dibutylester in acetone. The concentration of squaric acid was varied as needed to maintain a moderate dermatitis. Only one area of alopecia was treated in each patient until marked hair growth occurred. The remainder of the scalp was then treated. Four patients (28.5%) had complete regrowth of hair during treatment; one of these patients had recurrent alopecia after stopping treatment. Ten patients (71.4%) were treatment failures. Of these ten failures, seven developed a moderate dermatitis and hair regrowth but experienced recurrent alopecia with continued treatment. One patient failed to maintain an adequate persistent dermatitis, and two failed to grow any hair despite the presence of dermatitis. Successful results in these patients correlated with (1) a duration of alopecia of less than two years, (2) the development of a moderate dermatitis within three weeks of starting treatment, (3) persistent hair growth within two months of developing dermatitis, and (4) an age of 16 years or older.     

Topical minoxidil dose-response effect in alopecia areata

Topical 5% minoxidil solution was used to treat 47 patients with severe alopecia areata. Forty patients (85%) had terminal hair regrowth after 48 to 60 weeks of treatment. In the majority of patients, hair regrowth was not cosmetically acceptable. Data were compared with those from a previous study with topical 1% minoxidil solution. Both the percentage of responders and the quality of their hair regrowth were significantly greater with 5% than with 1% topical minoxidil solution. One patient developed an allergic contact dermatitis to minoxidil, but no systemic side effects were detected. The results strongly suggest a dose-response effect for topical minoxidil treatment of alopecia areata and the importance of exploring modifications in dosing and delivery systems to enhance therapeutic efficacy.     

Use of the pulsed infrared diode laser (904 nm) in the treatment of alopecia areata.

BACKGROUND: Alopecia areata is a rapid and complete loss of hair in one or several patches, usually on the scalp, affecting both males and females equally. It is thought to be an autoimmune disease which is treated with different modalities with variable success. Laser treatment of different wavelengths has been used in the management of this problem. OBJECTIVE: To study the effect of the pulsed infrared diode laser (904 nm) in the treatment of alopecia areata.Methods. Sixteen patients with 34 resistant patches that had not responded to different treatment modalities for alopecia areata were enrolled in this study. In patients with multiple patches, one patch was left as a control for comparison. Patients were treated on a four-session basis, once a week, with a pulsed diode laser (904 nm) at a pulse rate of 40/s. A photograph was taken of each patient before and after treatment. RESULTS: The treated patients were 11 males (68.75%) and five females (31.25%). Their ages ranged between 4 and 50 years with a mean of 26.6+/-SD of +/-13.8, and the durations of their disease were between 12 months and 6 years with a mean of 13.43+/-SD of +/-18.34. Regrowth of hair was observed in 32 patches (94%), while only two patches (6%) failed to show any response. No regrowth of hair was observed in the control patches. The regrowth of hair appeared as terminal hair with its original color in 29 patches (90.6%), while three patches (9.4%) appeared as a white villous hair. In patients who showed response, the response was detected as early as 1 week after the first session in 24 patches (75%), while eight patients (25%) started to show response from the second session. CONCLUSION: The pulsed infrared diode laser is an effective mode of therapy with a high success rate for resistant patches of alopecia areata.     

Platelets rich plasma versus minoxidil 5% in treatment of alopecia areata: A trichoscopic evaluation

Alopecia areata is a common cause of nonscarring alopecia that occurs in a patchy, confluent, or diffuse pattern. Dermoscopy is a noninvasive technique for the clinical diagnosis of many skin diseases. Topical minoxidil solution 5% and platelet rich plasma are important modalities used in treatment of alopecia areata. We aimed to evaluate the efficacy of PRP versus topical minoxidil 5% in the treatment of AA by clinical evaluation and trichoscopic examination. Ninety patients were allocated into three groups; the first was treated with topical minoxidil 5% solution, the second with platelets rich plasma injections, and the third with placebo. Diagnosis and follow up were done by serial digital camera photography of lesions and dermoscopic scan before and every 1 month after treatment for 3 months. Patients treated with minoxidil 5% and platelets rich plasma both have significant hair growth than placebo (p < .05). Patients treated with platelets rich plasma had an earlier response in the form of hair regrowth, reduction in short vellus hair and dystrophic hair unlike patients treated with minoxidil and control (p < .05). In conclusion, platelets rich plasma is more effective in the treatment of alopecia areata than topical minoxidil 5% as evaluated by clinical and trichoscopic examination.     

Linear polarized infrared irradiation using Super Lizer is an effective treatment for multiple-type alopecia areata

BACKGROUND: Super Lizer trade mark is a linear polarized light instrument, which has been used with good effect in orthopedics and anesthesiology to treat arthralgia and neuralgia with a high output of infrared radiation. AIM: To test Super Lizer trade mark 's efficacy for the treatment of alopecia areata. METHODS: Fifteen patients over 18 years of age, diagnosed with alopecia areata and displaying symptoms of patchy hair loss, were topically irradiated with infrared radiation using the Super Lizer trade mark. The patients were irradiated intermittently for an interval of 3 min once every week or every 2 weeks. RESULTS: Seven of 15 (46.7%) of the irradiated areas showed hair regrowth 1.6 months earlier than the nonirradiated areas (chi2 official approval, P = 0.003). With regard to adverse effects caused by Super Lizer trade mark treatment, only one patient complained of a sensation of heat in the irradiated area. CONCLUSIONS: These findings suggest that Super Lizer trade mark, with its noninvasive properties, is a useful apparatus for the treatment of mild forms of alopecia areata.     

Interleukin-1 receptor antagonist allele 2 and familial alopecia areata

Alopecia areata affects 1%-2% of the population and is hypothesized to be an autoimmune, organ specific T-cell mediated reaction directed against the human hair follicle. It is characterized by loss of hair in patches (alopecia areata) with progression in some individuals to total loss of scalp hair (alopecia totalis) or to loss of all scalp and body hair (alopecia universalis). The interleukin-1 receptor antagonist (IL-1RN) gene was found to be associated with more severe clinical outcome in several chronic inflammatory diseases, including alopecia areata. The IL-1RN*2 allele was found to be associated with alopecia areata severity in a British case-control study. In this paper, we analyzed alopecia areata probands in a family-based sample (n = 131 parent-offspring trios) to study the association between alleles of the IL-1RN and various phenotypes of alopecia areata. In considering all patients with any form of alopecia areata, no association was found with IL-1RN. IL-1RN*2 allele was not associated with alopecia totalis and alopecia universalis. A borderline association was observed between IL-1RN and patchy alopecia areata but it was not statistically significant (p =0.06). We also observed an association between IL1-RN*1 allele and patchy alopecia areata (p =0.045).     

Topical 5-fluorouracil is ineffective in the treatment of extensive alopecia areata

We report the results of a pilot study of topical 5% 5-fluorouracil (FU) cream for the treatment of alopecia areata, an immunologically modulated disorder of hair growth. Patients with extensive (>50% scalp surface area involvement) alopecia areata that was refractory to previous treatments applied 5-FU to one side of their scalp twice daily for 3 to 6 months. In all, 9 patients enrolled, and 8 completed the study. No patient experienced measurable hair growth on the treated side. Only mild irritation was observed in a subset of patients with application of 5-FU to the nonphotodamaged scalp skin. Based on these results, we cannot recommend the use of topical 5-FU for treatment of alopecia areata without further evidence of therapeutic benefit.     

The pattern and profile of alopecia areata in Singapore--a study of 219 Asians

BACKGROUND: Alopecia areata is believed to be an autoimmune condition with a worldwide occurrence. It usually presents as patchy, nonscarring hair loss. There is a paucity of clinical data in Asians. OBJECTIVE: To study the epidemiology, clinical aspects, associations, and treatment of alopecia areata in an Asian population over a 1-year period. METHODS: Records of all newly diagnosed alopecia areata cases seen from May 1998 to April 1999 at the National Skin Center were collated with regard to the epidemiology, pattern of alopecia, and associations according to the investigational guidelines published by Oslen et al. The treatment and psychologic impact of alopecia areata were also assessed. RESULTS: Two hundred and nineteen new case referrals of alopecia areata were seen from May 1998 to April 1999. The incidence of alopecia areata was 3.8%. There were 173 Chinese (79%), 35 Indians (16%), and 11 Malays (5.0%). The male to female ratio was 1 : 1.3. The median age at presentation was 25.2 years. The majority of patients (85.5%) had their first episode of alopecia areata before the age of 40 years. Of the patients with onset of alopecia areata before the age of 40 years, 36.5% presented with extensive alopecia, compared with 5.5% above the age of 40 years (P < 0.05). Nail changes, consisting of pitting, trachyonychia, and longitudinal ridging, were reported in 23 patients (10.5%). A significant percentage of patients had an associated personal and family history of atopy (60.7%). There was no significant association between a personal history of atopy and the extent of alopecia areata. The frequencies reported for the following associated diseases were: thyroid disease, 2.3%; vitiligo, 4.1%; diabetes mellitus, 3.2%; Down's syndrome, 1.4%; and rheumatic arthritis, 0.9%. A family history of alopecia areata was reported in 4.6%. Intralesional triamcinolone acetonide was the first-line treatment for limited alopecia areata, while squaric acid dibutyl ester was used for extensive involvement. The majority of patients with limited alopecia areata (82.1%) had more than 50% improvement with intralesional triamcinolone acetonide after 3 months. The majority of patients who received squaric acid dibutyl ester (87.5%) achieved more than 50% regrowth at the end of 6 months. Poor prognostic factors for alopecia areata were extensive involvement, early age of onset, and Down's syndrome. Thirteen out of 132 respondents (9.8%) recalled stressful events preceding hair loss. Patients with extensive alopecia areata experienced more psychologic adverse effects than those with limited alopecia areata (P < 0.05). Males with extensive alopecia areata experienced more severe psychologic ill-effects, such as depression and feelings of inability to improve hair loss. CONCLUSIONS: Our findings are similar to those reported in the Western literature where alopecia areata is predominantly a disease of the young. A holistic approach is important in the management of alopecia areata as the disease can have a severe psychologic impact on an individual's well-being.     

Severe alopecia areata treated with systemic corticosteroids

Background Treatment of severe alopecia areata is difficult, and most efforts to successfully treat this condition have been disappointing. Systemic corticosteroids have been demonstrated as an effective treatment of severe alopecia areata. Methods Eighteen patients with alopecia areata (extensive patchy and totalis universalis types) were treated with systemic corticosteroids. Results Satisfactory hair regrowth was achieved in seven patients (38.9%). Hair fall subsequently occurred in all of these patients on discontinuation or tapering of corticosteroid therapy. Conclusions Systemic corticosteroid therapy does not prevent the spread or relapse of severe alopecia areata and, when complete regrowth is obtained, it is rarely maintained off therapy.     

3 percent topical minoxidil compared with placebo for the treatment of chronic severe alopecia areata

The efficacy of a 3 percent topical minoxidil solution (2,4-diamino-6-piperidinopyrimidine-3-oxide) in a propylene glycol-water-ethanol base applied twice daily for one year to half the scalp was evaluated in patients with severe chronic alopecia areata. A randomized, double-blind, bilateral comparison-controlled study design was used. Of the twenty-one patients, thirteen were women and eight were men; their ages ranged from nineteen to fifty-five years. All the patients had alopecia totalis or alopecia universalis, except for two who had lost two-thirds of their scalp hair. The mean disease duration was 11.5 years (range, one to forty years). Transient regrowth of sparse vellus hair occurred in twelve patients, bilaterally in eight, but it was not significant in any. No cosmetically acceptable results were achieved. No significant side effects were noted, except for a moderately severe bilateral dermatitis in one patient. The results indicate that 3 percent topical minoxidil solution is ineffective as treatment for severe chronic alopecia areata.     

Systemic steroids with or without 2% topical minoxidil in the treatment of alopecia areata.

BACKGROUND AND DESIGN--Thirty-two patients with mild to extensive alopecia areata, including 16 patients with alopecia totalis or universalis, entered a randomized, controlled trial of a 6-week taper of prednisone followed by either 2% topical minoxidil or vehicle applied three times daily for an additional 14 weeks. The results of this study were compared with an open trial of 48 patients with alopecia areata treated with a similar taper of prednisone with concomitant 2% topical minoxidil applied twice daily. Only terminal hair growth was considered and was quantitated as 1% to 24%, 25% to 49%, 50% to 74%, and 75% to 100%: only those with more than 25% terminal hair regrowth were considered to have had an objective response. RESULTS--At the end of 6 weeks of prednisone, 47% (15/32) of patients had more than 25% regrowth, including nine of 20 patients who had had at least 75% hair loss at baseline. Side effects of prednisone were primarily weight gain and mood changes/emotional lability. At 3 months, six of seven minoxidil-treated patients vs one of six vehicle-treated patients who had an objective response to prednisone maintained or augmented this hair growth: at the 20-week visit, these numbers were three of seven and zero of four patients, respectively. In the open trial, objective hair growth with prednisone was 30%, related to the extent of hair loss at baseline, and this growth persisted in more than 50% of patients at 6 months with the use of 2% topical minoxidil. CONCLUSIONS--A 6-week taper of prednisone offers potential for more than 25% regrowth in 30% to 47% of patients with alopecia areata with predictable and transient side effects. Two percent topical minoxidil three times daily appears to help limit poststeroid hair loss.     

The therapeutic use of topical minoxidil

Topical minoxidil is a trichogenic agent that stimulates the hair follicle via the vasoactive metabolite minoxidil sulfate without any evidence of antiandrogen activity or an effect on the immune system. Less than 5% of the applied dose is absorbed. The therapeutic effect on hair regrowth is demonstrated for androgenetic alopecia in males and females, by a computer-assisted image analysis counting technique of nonvellus hairs from a photographic print. Patients with severe alopecia areata respond poorly to topical minoxidil treatment. The most common adverse reactions are limited to irritant and allergic contact dermatitis on the scalp. The use of retinoic acid with topical minoxidil has been disappointing relative to the increase in systemic exposure. The value of topical minoxidil as an adjunct for the hair transplant procedure and its effect on hair loss from chemotherapy are being evaluated.     

PUVA treatment of alopecia areata

Twenty-three patients with alopecia areata were treated with photochemotherapy combining oral or topical methoxsalen and UV-A irradiation of the scalp or of the whole body. Eleven of 17 patients with multiple plaques of alopecia areata, alopecia totalis, and alopecia universalis, who were treated with oral methoxsalen and total body irradiation, had complete or more than 90% hair regrowth. Three patients had a relapse. The mean energy required was 505 joules/sq cm. In six cases, topical applications of methoxsalen or oral methoxsalen combined with local irradiation of the scalp were treatment failures. In the patients responding to treatment, the result did not seem to depend on the age of onset or the extent or duration of disease. However, patients with long-lasting alopecia had a higher risk of recurrence notwithstanding a good initial regrowth of hair. Few side effects of psoralens and UV-A (PUVA) treatment were noted. The mean follow-up period was 18.6 months after the completion of treatment. We discuss the possible mechanisms of action of PUVA in the treatment of alopecia areata.