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).     

重症斑秃治疗进展

重症斑秃是指脱发面积大于头皮面积的30%，治疗方法包括系统用药及外用药物，本文就近年来有关重症斑秃治疗的进展进行综述。     

HLA class II alleles in patients with alopecia areata

Our purpose was to determine which HLA class II alleles are associated with Turkish alopecia areata patients. Also we investigated whether there was a relationship between the age of onset and severity of disease and HLA alleles or not. Sixty-five patients with alopecia areata were included in this study, and 50 healthy transplant donors were used as a control group. The total group of alopecia areata patients as well as various subgroups according to scalp hair loss were compared to the control group. HLA DNA typing was performed by polymerase chain reaction/sequence specific primer method. The frequency of DQB1*03 allele was 86.1% in all patients compared to 62.0% in controls (P = 0.005). While the frequency of DQB1*03 was significantly increased, the frequency of DRB1*03 was decreased in the all patients group (4.6% versus 22.0%, P = 0.01). In the group of scalp hair loss less than 25%; the frequency of DRB1*03 was decreased (3.2%, P = 0.02). The group of patients with 25-75% scalp hair loss was compared to control group; the frequencies of DRB1*04 (66.7% versus 28.0%, P = 0.02) was increased. When the alopecia totalis, alopecia universalis or alopecia totalis/alopecia universalis group was compared to control group; DQB1*03 was associated with an increased frequency in this group versus control group (90.9%, P = 0.03). There were no significant differences for the other DQ alleles and the DR alleles tested in the patients and in the controls. When patients with early onset were compared to patients with late onset; no significant allele differences were found. Our findings suggested that DQB1*03 allele is a marker for general susceptibility to alopecia areata and may also serve as special genetic marker for susceptibility for the severe form of alopecia areata in our population. However, this association is not related to age at onset of the disease.     

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.     

未累及皮损内白发的斑秃

报告1例未累及皮损内白发的斑秃.患者男,45岁.头顶部片状脱发1周,皮损中白发未累及.患者否认有外伤或情绪低落等诱发因素.患者家族成员中无白癜风和斑秃病史.皮肤科检查:头顶部可见直径约5 cm圆形脱发区,其中散在分布白发,其发干直径和头发的长度与其他尚未脱落的黑发相同.笔者认为斑秃仅累及黑发可能是一种新的斑秃亚型.     

Antibodies against hair follicles are associated with alopecia totalis in autoimmune polyendocrine syndrome type I

In the autosomal recessively inherited autoimmune polyendocrine syndrome type I (APS I) patients have autoantibodies directed against several endocrine and nonendocrine organs. Alopecia areata is present in about one-third of the patients and usually in the more severe forms, alopecia universalis or totalis. Sera from 39 patients with APS I, diluted 1:150, were used in indirect immunofluorescence staining of cryo-sections from normal human scalp. Two hair follicle staining patterns were observed. A cytoplasmic staining of the differentiating matrix, cuticle, and cortex keratinocytes in the anagen hair follicle was seen in five (13%) APS I sera. All these five patients had alopecia totalis, representing 63% of the eight patients with alopecia totalis (p < 0.0001). Furthermore, four (10%) of the APS I sera stained the nuclei of the melanocytes in the hair follicle. Two of these patients had vitiligo. None of 20 healthy control sera stained the keratinocyte cells or the melanocyte nuclei. These data show that many patients with APS I have high-titer autoantibodies directed against the anagen matrix, cuticle, and cortex keratinocytes and a melanocyte nuclear antigen, and also that the hair follicle keratinocyte staining is associated with alopecia, especially alopecia totalis. This study emphasizes the role of the differentiating anagen keratinocytes as an important structure in the autoimmune etiology of alopecia, both in APS I and at least in a subgroup of patients with alopecia areata unrelated to APS I.     

Treatment of alopecia totalis with a combination of inosine pranobex and diphencyprone compared to each treatment alone

Recent developments in alopecia areata have included the use of oral inosine pranobex and the introduction of diphencyprone as a contact sensitizer. Good results have been claimed for these treatments even in severe forms of the disease. We performed a study to investigate the efficacy of a combination of these treatments in the most severe form of alopecia areata. Thirty-three patients suffering from alopecia totalis were enrolled. Subjects were divided into three groups matched for age and sex. One group received treatment with inosine pranobex (50 mg/kg/day) for 6 months. The second was sensitized to diphencyprone and treated for 6 months by maintenance of contact allergic dermatitis on the scalp. The third received both treatments. There was no evidence of response to inosine pranobex in any of the 22 subjects who received this treatment. Only two of 22 patients responded to diphencyprone. Patients with long-standing alopecia totalis contemplating diphencyprone therapy should be advised that the chances of success are only around 10%. Inosine pranobex does not appear to improve the response rate.     

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.     

Intravenous pulse methylprednisolone therapy for severe alopecia areata: an open study of 66 patients

INTRODUCTION: Treatment of alopecia areata is a difficult challenge. Some European publications have shown encouraging results with high dose pulse corticosteroid therapy in extensive plurifocal alopecia areata. We undertook a prospective open study between January 2000 and December 2001 using repeated pulse each month, with the aim of identifying the effects of this repetition and underlining the best indications. PATIENTS AND METHODS: Sixty-six patients aged 9 to 60 years old presenting an extensive alopecia areata exceeding 30% of the scalp surface (n=47), alopecia totalis (n=8), alopecia universalis (n=8), ophiasic alopecia (n=3), for less than 12 months entered this study. The administered treatment was methylprednisolone 500 mg/d during 3 days or 5 mg/kg twice per day during 3 days in children. These pulses were repeated after 4 and 8 weeks, then a second series was carried out or not according to cases. The main evaluation criterion was the percentage of new terminal hair appearing on the bald areas, appreciated by clinical and photographic evaluation at 3 and 6 months. RESULTS: Ophiasic alopecia areata did not respond to treatment. A quarter of patients presenting universal alopecia had a good response (higher than 80 p. 100) followed by a relapse in half the cases. Half of the patients presenting alopecia totalis had a good response, which was maintained three times out of four. Multifocal alopecia areata seems the best indication since the patients under study presented a good response in 63.8 p. 100 of cases (78 p. 100 when it was a first episode and 90.5 p. 100 if the treatment had been started in less than 3 months before). The repetition of the pulses did not appear to increase the number of responders. CONCLUSION: This study provides the best indication of pulse methylprednisolone therapy: first recent episode of extensive plurifocal alopecia areata. These results are less convincing in long term history or other forms of alopecia areata.     

Treatment of alopecia areata with diphencyprone

26 patients with alopecia areata were treated topically with diphencyprone. 10 had alopecia universalis, 7 alopecia totalis and 9 had alopecia areata. The treatment lasted from 4 to 14 months. In 13 patients a little response was obtained; only in 1 case it was satisfactory. Factors that appear to influence these results are discussed.     

A new contact sensitizer, diphencyprone, in the treatment of alopecia areata

Producing an allergic contact dermatitis on the scalp is a recognized treatment for alopecia areata (AA), alopecia totalis (AT) and alopecia universals (AU).¹ We report our experience with diphencyprone which, in contrast to dinitrochlorobenzene, is non-mutagenic in the Ames test.
Thirty-five patients commenced treatment: two were unable to tolerate the allergic reaction, and six withdrew (after a mean of 14 weeks) because hair was not growing. Of the remaining 27 (six male, 21 female), nine (33%) had AA (mean duration 16 years) and 18 (67%) had AU/AT (mean duration 17 years); eight (30%) had a family history of alopecia; three (11%) had thyroid disease and 11 (41%) had circulating autoantibodies.
Treatment was restricted to one half of the scalp and applied weekly in the department for 6 months; haematological and biochemical parameters remained normal during this time.
When hair growth began (mean 10 weeks, range 6–20 weeks), treatment was extended to the whole scalp. Eight of the nine patients with AA regrew hair (89%), and three had a cosmetically acceptable result (33%); eight of the 18 patients with AT/AU also regrew (44%), with seven having a good cosmetic result (39%). Four patients were able to discard their wigs. There was no correlation between the patients'age, or duration of alopecia, and hair regrowth.     

Induction of hair growth in alopecia totalis with diphencyprone sensitization

The therapeutic use of the induction of an allergic contact sensitivity to diphencyprone in alopecia areata has been studied. Fourteen subjects had alopecia totalis and four had extensive and long-standing alopecia areata. Topical diphencyprone was capable of inducing an allergic contact sensitivity in 16 subjects (89%), and 13 of these agreed to proceed to repeated intermittent applications to the left side of the scalp, the right side acting as an untreated control; six subjects achieved cosmetically useful regrowth of normally pigmented terminal hair. No clinical features seemed to distinguish those who showed a favourable response from those who did not.     

Circumscribed alopecia areata incognita

The characteristic lesion of alopecia areata is a smooth bald patch on the scalp. When there is no bald surface it is called alopecia areata incognita. To date, all cases of alopecia areata reported as so‐called ‘incognito’ have shown a diffuse involvement of the scalp as in acute telogen effluvium. Recently, we have observed two patients who showed localised hair thinning of the scalp without bald spots. Histopathologically, the lesions were typical of alopecia areata with peribulbar lymphocytic infiltrates. The response to corticosteroid treatment and its clinical course were also compatible with alopecia areata.     

Acute alopecia totalis

From a group of 1,189 AA patients seen in our dermatology unit, thirteen (3 males, 10 females) experienced hair shedding that started profusely and diffusely over the entire scalp. They were under observation for about 5 years, histopathology and trichograms being performed in all instances. The mean age of the patients was 26.7 years. It took only 2.3 months on average from the onset of hair shedding to total denudation of the scalp. The trichogram at the time of diffuse shedding showed that about 80% had dystrophic roots and the remaining 20% had telogen roots. Histopathological findings and exclamation mark hairs were compatible with alopecia areata. Regrowth of hair was noted 3.2 month after the onset of hair shedding and recovery observed in 4.8 months. All patients were treated by methylprednisolone pulse therapy. During the follow-up period, 53 months on average after recovery, 8 of the 13 patients (61.5%) showed normal scalp hair without recurrence, in 4 patients the recovery was cosmetically acceptable in spite of focal recurrences and only 1 patient showed a severe relapse after recovery. Considering all of the above findings, this group of the patients should be delineated by the term acute alopecia totalis.     

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.     

Systemic treatment for alopecia areata

Of the world population, 1.7% is suffering from alopecia areata at some point in their lives. The exact etiology of this disease is still unknown, and the course of the disease is unpredictable. Effective treatments, especially for severe multifocal alopecia areata, alopecia areata totalis, and alopecia areata universalis, are lacking. The present article will discuss side effects and relapse rates of different systemic agents for treatment of severe and rapid progressive alopecia areata.     

Alopecia Areata

Alopecia areata is a common form of non-scarring alopecia that appears equally in males and females of any age, although children and adolescents are more commonly affected. The disorder is usually characterized by limited alopecic patches on the scalp, but more severe forms may affect the entire scalp (alopecia totalis) or body (alopecia universalis). Characteristic nail changes may also accompany hair loss. Alopecia areata has been linked with certain human leukocyte antigen (HLA) class II alleles, indicating a probable autoimmune etiology. Current research implicates T lymphocytes in the pathogenetic mechanism of disease. Other autoimmune diseases are also linked with alopecia areata. The diagnosis of alopecia areata is usually made clinically, although a biopsy is diagnostic for this condition. Treatment is challenging and aims at the regrowth of hair in affected individuals. Intralesional corticosteroid injections are widely used in mild disease. Topical anthralin and minoxidil may also be clinically efficacious. Topical sensitizers, such as squaric acid dibutlyester and diphenylcyclopropenone, are sometimes employed. Various therapies for the disease may have efficacy in different patients, making a universal treatment algorithm difficult to implement. Patients should be handled on an individual basis, with the final outcome based on the cosmetic regrowth of hair. Maintenance therapy is also important in patients that do achieve acceptable regrowth, necessitating a highly motivated patient and good rapport with the treating physician.     

Alopecia totalis incognito

We report an 11-year-old boy with a strong family history of alopecia areata who initially developed alopecia areata with a single circular patch of hair loss on the scalp with exclamation mark hairs at the periphery, which evolved over time into alopecia totalis and then into a novel pattern of hair growth with fine depigmented hair, uniformly 5 mm in length. The hair has not grown any longer over a 48-month follow-up period. Scalp biopsies from the occipital scalp demonstrate dense peribulbar lymphocytic infiltrate and uniform miniaturized secondary vellus hairs. This previously undescribed pattern of alopecia areata is remarkable for total lack of alopecia.     

Five‐year experience in the treatment of alopecia areata with DPC

Background The effectiveness of Diphencyprone (DPC) in alopecia areata (AA) was demonstrated in several studies with highly variable response rates ranging from 5% to 85%. Objective The response rate and variable factors affecting the prognosis were studied focusing on long‐term follow‐up with or without maintenance therapy. Methods A total of 135 cases of AA were treated with DPC. Patients were divided into five groups according to the area of scalp affected: Grade 1 AA: 25–49% scalp affection; Grade 2 AA: 50–74% scalp affection; Grade 3 AA: 75–99% scalp affection; alopecia totalis and alopecia universalis. An initial response was defined as appearance of new terminal hair within treated sites. Excellent response was defined as terminal hair covering >75% of the scalp. Relapse meant >25% hair loss. Maintenance therapy meant ongoing therapy once every 1–4 weeks after excellent response. Follow‐up was performed to detect any relapse of AA. Results Ninety‐seven patients continued therapy for ≥3 months. After an initial 3 month lag, cumulative excellent response was seen in 15 patients (15.4%), 47 patients (48.5%), 51 patients (52.6%) and 55 patients (55.7%) after 6, 12, 18 and 24 months respectively in a mean median time of 12 months. The only patient variable affecting the prognosis was baseline extent of AA. Excellent response was seen in 100%, 77%, 54%, 50% and 41% in Grade 1, Grade 2, Grade 3, AA totalis and AA universalis patients respectively. Side‐effects were few and tolerable. Hair fall >25% occurred in 17.9% of patients on maintenance and 57.1% of patients without maintenance therapy (P‐value = 0.025). Conclusion Diphencyprone is an effective and safe treatment of extensive AA. A long period of therapy is needed and will increase the percentage of responders especially in alopecia totalis and universalis. Maintenance therapy is recommended to reduce the risk of relapse.