今日の臨床サポート

円形脱毛症

著者: 伊藤泰介 浜松医科大学 皮膚科学教室

監修: 戸倉新樹 掛川市・袋井市病院企業団立 中東遠総合医療センター 参与/浜松医科大学 名誉教授

著者校正/監修レビュー済:2022/04/27
参考ガイドライン:
  1. 日本皮膚科学会:円形脱毛症診療ガイドライン2017
患者向け説明資料

概要・推奨   

  1. 円形脱毛症は代表的な後天性脱毛症で典型的には円形から斑状の脱毛斑が主として頭部に生じるものである。
  1. 円形脱毛症は毛包の下端、毛球部を主な標的とする自己免疫疾患と捉えられている。
  1. 円形脱毛症とアトピー素因には関連があり既往を問診することが勧められる(推奨度2
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
伊藤泰介 : 研究費・助成金など(マルホ株式会社)[2022年]
監修:戸倉新樹 : 講演料(マルホ,サノフィ,協和キリン),原稿料(医学書院)[2022年]

改訂のポイント:
  1. 診断におけるダーモスコピー所見、ならびに治療に関する最新の報告を追記した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 円形脱毛症は代表的な後天性脱毛症で典型的には円形から斑状の脱毛斑が主として頭部に生じるものである<図表><図表>。眉毛、髭、体毛など全身の毛髪も影響を受けることがある。
  1. 広く精神的ストレスと発症の関連がいわれているが、円形脱毛症発症と精神的ストレスとの直接的な関連は科学的には証明されていない。一方的に、本人のストレスのせいであるという説明は避けたほうがよい。
  1. 人口の0.1~0.2%に生じるとする統計もあり頻度は比較的高い。性差はなく全年齢に発症する。
  1. 家族内の発症率は一般より高く、HLA遺伝子との関連や、最近のゲノムワイド関連解析にて相関する遺伝子が同定されていることから何らかの遺伝的背景をもとに発症している可能性が示唆されている。
  1. 活動期の脱毛斑およびその周囲では易抜毛性を認め、抜けた毛は毛球部が傷害され、根元にいくほど細い“感嘆符毛” や、"漸減毛"となる。病変部では断裂した毛、毛包内黒点などもみられる。
  1. 毛包組織に対する自己免疫疾患と捉えられており、病理組織学的には成長期毛の毛球部(根元)周囲の密なリンパ球主体の細胞浸潤が特徴である。
 
円形脱毛症の病理組織像

毛球部から毛球上部にかけて、毛包周囲性に密なリンパ球主体の炎症性細胞浸潤を認める。

出典

img1:  著者提供
 
 
 
  1. 関連する疾患として甲状腺機能異常、膠原病、アトピー素因などが知られている。
  1. 脱毛斑が単発、または数個多発するのが典型的であるが全頭、全身の脱毛を生じる場合<図表>があり患者の生活の質が大きくそこなわれる可能性がある。
  1. 良質なエビデンスにもとづく治療法が少ないが、診療の指針として日本皮膚科学会円形脱毛症診療ガイドライン2017がある。
問診・診察のポイント  
  1. 円形脱毛症は毛包の下端、毛球部を主な標的とする自己免疫疾患と捉えられている。

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文献 

W V Shellow, J E Edwards, J Y Koo
Profile of alopecia areata: a questionnaire analysis of patient and family.
Int J Dermatol. 1992 Mar;31(3):186-9.
Abstract/Text Eight hundred patients with alopecia areata (AA) responded to a detailed questionnaire that was compiled, distributed, and analyzed by Help Alopecia International Research, Inc. (HAIR). Among those responding, 28% were men and 72% were women. Fifty percent had localized alopecia, 30% had alopecia totalis, and 20% had alopecia universalis. Forty-eight percent developed their initial onset before the age of 20. A very strong family history of 42% was found. There were 333 additional family members with AA. Many patients and relatives had concurrent atopic diseases (seasonal rhinitis, bronchial asthma, and atopic dermatitis). Associated autoimmune diseases including vitiligo, thyroid disease, and collagen vascular disease in patients and relatives appeared consistent with previous reports. Insulin dependent diabetes mellitus (IDDM) was not increased in patients but greatly increased in relatives. Additional analysis suggests a genetic association between the two diseases where expression of AA may prevent the development of IDDM.

PMID 1568816
Kazumoto Katagiri, Shoko Arakawa, Yutaka Hatano
In vivo levels of IL-4, IL-10, TGF-beta1 and IFN-gamma mRNA of the peripheral blood mononuclear cells in patients with alopecia areata in comparison to those in patients with atopic dermatitis.
Arch Dermatol Res. 2007 Jan;298(8):397-401. doi: 10.1007/s00403-006-0700-2. Epub 2006 Sep 22.
Abstract/Text Alopecia areata (AA) has been considered to be supported by an aberrant expression of IFN-gamma as a result of antigen dependent immune response. On the other hand, AA sometimes concurs with atopic diseases, although the mechanism of the concurrence is not clear. This study was designed to elucidate the immune status of AA and the similarity between AA and atopic dermatitis (AD) by analysis of in vivo levels of mRNA of Th1, Th2, and suppressive cytokines of peripheral blood mononuclear cells (PBMC). Using semiquantitative RT-PCR, the levels of cytokine mRNA were measured in freshly isolated PBMC of 47 patients with AA, 15 patients with AD, and 12 healthy controls (HC). The levels of IL-4, IFN-gamma, and TGF-beta1 mRNA were lower in patients with AA than those in HC. The levels of IL-10 mRNA in AA were comparable with those in HC. Decreased levels of IFN-gamma and TGF-beta1 were also shown in patients with AD. These results indicated a similarity (decreased levels of IFN-gamma and TGF-beta1) between AD and AA based on the cytokine profile. In addition, decreased levels of IL-4 mRNA in AA might also explain the experience that the severity of atopic disease coincident with AA is mild in the most of cases. Next, we compared the levels of these cytokine mRNA among the three subgroups of AA that were categorized based on the severity of the symptoms: mild, severe and totalis. Although there was no significant difference between any combinations of the subgroups, there was a tendency to increase the levels of IFN-gamma mRNA and to decrease the levels of IL-4 mRNA according to the severity of alopecia. However, the levels of IFN-gamma mRNA in any subgroups were less than those of HC. These results suggest that IFN-gamma is therefore involved in the pathogenesis of AA, although the information from PBMC is limited. In conclusion, AA might be induced by an aberrant expression of IFN-gamma in individuals whose PBMC produce low amounts of IFN-gamma and TGF-beta1. Further analysis is therefore required to investigate the phenotypes of the population in PBMC with or without reference to regulatory T cells.

PMID 17021766
Girish C Mohan, Jonathan I Silverberg
Association of Vitiligo and Alopecia Areata With Atopic Dermatitis: A Systematic Review and Meta-analysis.
JAMA Dermatol. 2015 May;151(5):522-8. doi: 10.1001/jamadermatol.2014.3324.
Abstract/Text IMPORTANCE: Previous studies found conflicting results as to whether atopic dermatitis (AD) is increased in patients with vitiligo and alopecia areata (AA).
OBJECTIVE: To compare the prevalence of AD between patients with either vitiligo or AA and those without these disorders by performing a meta-analysis of observational studies.
DATA SOURCES: MEDLINE, EMBASE, Cochrane Library, Google Scholar, and a manual search of 12 additional journals between 1946 and April 5, 2014.
STUDY SELECTION: Observational studies published in any language that compared the prevalence of AD among patients with and without either vitiligo or AA.
DATA EXTRACTION AND SYNTHESIS: Data were extracted by 2 independent investigators. Quality of evidence was assessed using the Newcastle-Ottawa Scale and Methodological Evaluation of Observational Research checklist. A meta-analysis of studies assessing AD, vitiligo, and/or AA was performed using a fixed-effects model to estimate pooled odds ratios (ORs). Subset analyses were performed for childhood vs adult-onset vitiligo and alopecia totalis or alopecia universalis vs patchy alopecia.
MAIN OUTCOMES AND MEASURES: Self-reported and/or physician-diagnosed AD, vitiligo, and AA.
RESULTS: In total, 16 studies of vitiligo and 17 studies of AA were included in the review. In the pooled analysis of the studies that included control patients without vitiligo (n = 2) and control patients without AA (n = 3), patients with vitiligo (Cochran-Mantel-Haenszel OR, 7.82; 95% CI, 3.06-20.00, P < .001) or AA (OR, 2.57; 95% CI, 2.25-2.94, P < .001) had significantly higher odds of AD than did control patients without these disorders. Pooled analysis of 3 studies found higher odds of AD in patients with early-onset vitiligo (<12 years) compared with those with late-onset vitiligo (OR, 3.54; 95% CI, 2.24-5.63, P < .001). Pooled analysis of 4 studies found higher odds of AD in patients with alopecia totalis or alopecia universalis compared with those with patchy alopecia (OR, 1.22; 95% CI, 1.01-1.48, P = .04).
CONCLUSIONS AND RELEVANCE: Patients with either vitiligo, especially early-onset disease, or AA, especially alopecia totalis or alopecia universalis, have significantly increased risk for AD.

PMID 25471826
J De Weert, L Temmerman, A Kint
Alopecia areata: a clinical study.
Dermatologica. 1984;168(5):224-9.
Abstract/Text 100 cases of alopecia areata are examined and the possible relationship with the presumed etiological factors (atopy, autoimmunity and psychosomatics) are looked for. When atopy or autoantibodies are present alopecia areata always runs a serve course. It is, however, impossible to establish a definite etiological relation between atopy or autoimmunity and alopecia areata.

PMID 6724078
Regina C Betz, Jana Pforr, Antonia Flaquer, Silke Redler, Sandra Hanneken, Sibylle Eigelshoven, Anne-Katrin Kortüm, Thomas Tüting, Julien Lambert, Jozef De Weert, Axel M Hillmer, Christine Schmael, Thomas F Wienker, Roland Kruse, Gerhard Lutz, Bettina Blaumeiser, Markus M Nöthen
Loss-of-function mutations in the filaggrin gene and alopecia areata: strong risk factor for a severe course of disease in patients comorbid for atopic disease.
J Invest Dermatol. 2007 Nov;127(11):2539-43. doi: 10.1038/sj.jid.5700915. Epub 2007 Jun 21.
Abstract/Text Alopecia areata (AA) is a common dermatological disease, which affects nearly 2% of the general population. Association of AA with atopic disease has been repeatedly reported. Loss-of-function mutations in the filaggrin gene (FLG) may be considered as promising candidates in AA, as they have been observed to be a strong risk factor in atopic dermatitis. The FLG mutations R501X and 2282del4 were genotyped in a large sample of AA patients (n=449) and controls (n=473). Although no significant association was observed in the patient sample overall, FLG mutations were significantly associated with the presence of atopic dermatitis among AA patients. Furthermore, the presence of FLG mutations had a strong impact on the clinical course of AA in comorbid patients. For example, 19 of the 22 mutation carriers among AA patients with atopic dermatitis showed a severe form of the disease (P=0.003; odds ratio (OR)=5.47 (95% confidence interval (CI): 1.59-18.76)). In conclusion, our data suggest that when AA occurs in conjunction with FLG-associated atopic disorder, the clinical presentation of AA may be more severe.

PMID 17581619
P van der Steen, H Traupe, R Happle, J Boezeman, R Sträter, H Hamm
The genetic risk for alopecia areata in first degree relatives of severely affected patients. An estimate.
Acta Derm Venereol. 1992 Sep;72(5):373-5.
Abstract/Text Substantial evidence indicates that genetic factors may have a role in the etiology of alopecia areata (AA). Most studies, however, provide only general information on the familial incidence but fail to specify family relationships. We therefore obtained information on the incidence of AA in first degree relatives of 348 severely affected patients. In 7% one of the parents was affected. Among the siblings of the patients 3% had developed AA, while AA was present in 2% of the children. Taking into account the age of the children, their lifetime risk was calculated to approach 6%. However, a severe type of AA is to be expected only in about 2% of the children. The degree of involvement observed in the patients did not influence the frequency and type of AA present in their first degree relatives.

PMID 1361288
S Yang, J Yang, J B Liu, H Y Wang, Q Yang, M Gao, Y H Liang, G S Lin, D Lin, X L Hu, L Fan, X J Zhang
The genetic epidemiology of alopecia areata in China.
Br J Dermatol. 2004 Jul;151(1):16-23. doi: 10.1111/j.1365-2133.2004.05915.x.
Abstract/Text BACKGROUND: Alopecia areata (AA) is hypothesized to be an organ-specific autoimmune disease with genetic predisposition and an environmental trigger. There are few clinical data in Asians.
OBJECTIVES: To describe the genetic epidemiological features of AA patients in China and to determine the possible genetic model for AA.
METHODS: Data for 1032 patients with AA were obtained by questionnaire in the Institute of Dermatology of Anhui Medical University in China from 2001 to 2003. Complex segregation analysis and heritability analysis were performed using Falconer's method, EPI INFO 6.0 and SAGE-REGTL programs.
RESULTS: In total, 1032 AA patients (male/female ratio 1.1 : 1) were enrolled, representing 0.94% of the total number of cases seen in our outpatient clinic during that time. The mean +/- SD age of onset was 28.98 +/- 13.43 years. The difference between the mean age of onset in males and females was not significant. Most patients (82.6%) experienced their first episode of AA within the first four decades of life. A positive family history of AA was obtained in 87 patients (8.4%). The prevalence of AA in first-, second- and third-degree relatives of the proband with AA was 1.6%, 0.19% and 0.03%, respectively. These figures were higher than those in controls. A greater severity and longer duration of AA were seen in the early onset group than in the late-onset group. The early onset group also had more affected first- and second-degree relatives. The heritability of AA in first-, second- and third-degree relatives was 47.16%, 42.53% and 22.29%, respectively. Based on the REGTL results, the best model was a polygenic additive model for AA.
CONCLUSIONS: The effect of genetic factors is strong in AA, but environmental factors such as infection and psychological stress may still play an important role. Our findings on the genetics of AA are consistent with a polygenic additive mode of inheritance.

PMID 15270868
C Jackow, N Puffer, M Hordinsky, J Nelson, J Tarrand, M Duvic
Alopecia areata and cytomegalovirus infection in twins: genes versus environment?
J Am Acad Dermatol. 1998 Mar;38(3):418-25.
Abstract/Text BACKGROUND: Alopecia areata (AA) is hypothesized to be an organ-specific autoimmune disease mediated by T cells directed to the hair follicle. Genetic susceptibility may be conferred by HLA, and an environmental trigger, such as a viral infection, is suspected. The incidence of AA in the population is estimated to be 1.7%, with an average of one in four patients having a positive family history.
OBJECTIVE: Our purpose was to examine the concordance rate of AA among identical versus fraternal twins and the correlation between stress, cytomegalovirus (CMV) infection, and disease.
METHODS: Families with AA were solicited from dermatologists in the United States and through a Website on the Internet. HLA class 2 typing and identification of CMV early and late genes were performed by polymerase chain reaction (PCR) on genomic peripheral blood DNA. Serum antibodies for CMV were determined by enzyme-linked immunosorbent assay.
RESULTS: From 114 families, we identified 11 sets of monozygotic twins and 3 sets of dizygotic twins. The concordance rate was 55% for monozygotic twins and 0% for fraternal twins. Most identical twins were male. The severity of the AA phenotype varied and appeared most severe in the first affected twin. Five of 24 twins were CMV seropositive but CMV DNA was not detected in blood lymphocytes of any of the subjects when studied after the onset of AA. The presence of AA in twins was not correlated with evidence of CMV.
CONCLUSION: A 55% concordance rate in identical twins and AA occurring in families support a genetic component as well as possible environmental triggers that remain unknown.

PMID 9520023
Lynn Petukhova, Madeleine Duvic, Maria Hordinsky, David Norris, Vera Price, Yutaka Shimomura, Hyunmi Kim, Pallavi Singh, Annette Lee, Wei V Chen, Katja C Meyer, Ralf Paus, Colin A B Jahoda, Christopher I Amos, Peter K Gregersen, Angela M Christiano
Genome-wide association study in alopecia areata implicates both innate and adaptive immunity.
Nature. 2010 Jul 1;466(7302):113-7. doi: 10.1038/nature09114.
Abstract/Text Alopecia areata (AA) is among the most highly prevalent human autoimmune diseases, leading to disfiguring hair loss due to the collapse of immune privilege of the hair follicle and subsequent autoimmune attack. The genetic basis of AA is largely unknown. We undertook a genome-wide association study (GWAS) in a sample of 1,054 cases and 3,278 controls and identified 139 single nucleotide polymorphisms that are significantly associated with AA (P
PMID 20596022
Abdullah Alkhalifah, Adel Alsantali, Eddy Wang, Kevin J McElwee, Jerry Shapiro
Alopecia areata update: part I. Clinical picture, histopathology, and pathogenesis.
J Am Acad Dermatol. 2010 Feb;62(2):177-88, quiz 189-90. doi: 10.1016/j.jaad.2009.10.032.
Abstract/Text Alopecia areata (AA) is an autoimmune disease that presents as nonscarring hair loss, although the exact pathogenesis of the disease remains to be clarified. Disease prevalence rates from 0.1% to 0.2% have been estimated for the United States. AA can affect any hair-bearing area. It often presents as well demarcated patches of nonscarring alopecia on skin of overtly normal appearance. Recently, newer clinical variants have been described. The presence of AA is associated with a higher frequency of other autoimmune diseases. Controversially, there may also be increased psychiatric morbidity in patients with AA. Although some AA features are known poor prognostic signs, the course of the disease is unpredictable and the response to treatment can be variable. Part one of this two-part series on AA describes the clinical presentation and the associated histopathologic picture. It also proposes a hypothesis for AA development based on the most recent knowledge of disease pathogenesis. LEARNING OBJECTIVES: After completing this learning activity, participants should be familiar with the most recent advances in AA pathogenesis, recognize the rare and recently described variants of AA, and be able to distinguish between different histopathologic stages of AA.

Copyright (c) 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
PMID 20115945
S A MULLER, R K WINKELMANN
ALOPECIA AREATA. AN EVALUATION OF 736 PATIENTS.
Arch Dermatol. 1963 Sep;88:290-7.
Abstract/Text
PMID 14043621
Elise A Olsen, Maria K Hordinsky, Vera H Price, Janet L Roberts, Jerry Shapiro, Doug Canfield, Madeleine Duvic, Lloyd E King, Amy J McMichael, Valerie A Randall, Maria L Turner, Leonard Sperling, David A Whiting, David Norris, National Alopecia Areata Foundation
Alopecia areata investigational assessment guidelines--Part II. National Alopecia Areata Foundation.
J Am Acad Dermatol. 2004 Sep;51(3):440-7. doi: 10.1016/j.jaad.2003.09.032.
Abstract/Text
PMID 15337988
Brett King, Justin Ko, Seth Forman, Manabu Ohyama, Natasha Mesinkovska, Guanglei Yu, Jill McCollam, Margaret Gamalo, Jonathan Janes, Emily Edson-Heredia, Katrin Holzwarth, Yves Dutronc
Efficacy and safety of the oral Janus kinase inhibitor baricitinib in the treatment of adults with alopecia areata: Phase 2 results from a randomized controlled study.
J Am Acad Dermatol. 2021 Oct;85(4):847-853. doi: 10.1016/j.jaad.2021.05.050. Epub 2021 Jun 16.
Abstract/Text BACKGROUND: There are no treatments approved by the Food and Drug Administration for alopecia areata.
OBJECTIVE: To evaluate the efficacy and safety of baricitinib in patients with ≥50% scalp hair loss in a phase 2 study of adults with alopecia areata (BRAVE-AA1).
METHODS: Patients were randomized 1:1:1:1 to receive placebo or baricitinib 1 mg, 2 mg, or 4 mg once daily. Two consecutive interim analyses were performed after all patients completed weeks 12 and 36 or had discontinued treatment prior to these time points. The primary endpoint was the proportion of patients achieving a Severity of Alopecia Tool (SALT) score ≤20 at week 36. Logistic regression was used with nonresponder imputation for missing data.
RESULTS: A total of 110 patients were randomized (placebo, 28; baricitinib 1-mg, 28; 2-mg, 27; 4-mg, 27). The baricitinib 1-mg dose was dropped after the first interim analysis based on lower SALT30 response rate. At week 36, the proportion of patients achieving a SALT score of ≤20 was significantly greater in baricitinib 2-mg (33.3%, P = .016) and 4-mg (51.9%, P = .001) groups versus placebo (3.6%). Baricitinib was well tolerated with no new safety findings.
LIMITATIONS: Small sample size limits generalizability of results.
CONCLUSION: These results support the efficacy and safety of baricitinib in patients with ≥50% scalp hair loss.

Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
PMID 34090959
S Charuwichitratana, P Wattanakrai, S Tanrattanakorn
Randomized double-blind placebo-controlled trial in the treatment of alopecia areata with 0.25% desoximetasone cream.
Arch Dermatol. 2000 Oct;136(10):1276-7.
Abstract/Text
PMID 11030789
Antonella Tosti, Matilde Iorizzo, Gian Luca Botta, Massimo Milani
Efficacy and safety of a new clobetasol propionate 0.05% foam in alopecia areata: a randomized, double-blind placebo-controlled trial.
J Eur Acad Dermatol Venereol. 2006 Nov;20(10):1243-7. doi: 10.1111/j.1468-3083.2006.01781.x.
Abstract/Text BACKGROUND: Clinical efficacy of topical corticosteroids in alopecia areata (AA) is still controversial. Positive clinical results have been obtained using ointments with occlusive dressing but this approach has a low patient compliance. Recently, a new topical formulation (thermophobic foam: Versafoam) of clobetasol propionate 0.05% has been introduced on the market (Olux, Mipharm, Milan, Italy) (CF). This formulation is easy to apply. After application to the skin the foam quickly evaporates without residues and it has a good patient compliance. In vitro studies have also shown that this formulation enhances the delivery of the active compound through the skin.
AIM: To evaluate the efficacy, safety and tolerability of CF in the treatment of moderate to severe AA.
SUBJECTS AND METHODS: Thirty-four patients with moderate to severe AA (eight men, mean age 40+/-13 years) were enrolled in a randomized, double-blind, right-to-left, placebo-controlled, 24-week trial. Alopecia grading score (AGS) was calculated at baseline and after 12 and 24 weeks of treatment using a 0-5 score (0=no alopecia; 5=alopecia totalis). Clobetasol foam and the corresponding placebo foam (PF) were applied twice a day for 5 days/week for 12 weeks (phase 1) using an intrapatient design (right vs. left). From weeks 13 to 24 each enrolled patient continued only with the treatment (both on the right and left site) that was judged to have a greater efficacy than that on the contralateral side (phase 2). The primary outcome of the trial, evaluated on an intention-to-treat basis, was the hair regrowth rate, which was evaluated using a semiquantitative score (RGS) (from 0: no regrowth, to 4: regrowth of 75%).
RESULTS: At baseline the AGS was 4.1 (range: 2-5). Nine (26%) patients prematurely concluded the trial. At the end of phase 1, a greater hair regrowth was observed in 89% of the head sites treated with CF vs. 11% in the sites treated with PF. The RGS was 1.2+/-1.6 in the CF-treated sites and 0.4+/-0.8 in the PF-treated sites (P=0.001). A RGS of 2 (hair regrowth of more than 25%) was observed in 42% CF-treated sites and in 13% of PF-treated sites (P=0.027). In seven subjects (20%) a RGS of 3 to 4 (hair regrowth of 50%) was observed in CF-treated sites. In three subjects (9%) a RGS of 4 (hair regrowth of 75%) was observed in CF-treated sites. In one patient only, in a PF-treated region, a RGS of 3 was observed. The AS was reduced to 3.8 by CF treatment at the end of phase 1 and to 3.3 at the end of phase 2 (P=0.01). From weeks 12 to 24 the treatment with CF induced a further increase in the RGS (from 1.2 to 1.5+/-1.4). Forty-seven per cent of CF-treated patients had a RGS of 2 at the end of the trial. A total of eight patients (25%) at the end of the treatment with CF showed a RGS of 3. Folliculitis occurred in two patients. No significant modifications in cortisol and ACTH blood levels were observed during the trial.
CONCLUSION: This new formulation of clobetasol propionate foam is an effective, safe and well-tolerated topical treatment for AA. This formulation has a good cosmetic acceptance and patient compliance profile.

PMID 17062039
Antonella Tosti, Bianca Maria Piraccini, Massimiliano Pazzaglia, Colombina Vincenzi
Clobetasol propionate 0.05% under occlusion in the treatment of alopecia totalis/universalis.
J Am Acad Dermatol. 2003 Jul;49(1):96-8. doi: 10.1067/mjd.2003.423.
Abstract/Text BACKGROUND: Efficacy of topical steroids in alopecia areata is still discussed.
OBJECTIVE: The purpose of this study was to evaluate the efficacy of clobetasol propionate 0.05% ointment under occlusion in 28 patients with alopecia areata totalis (AT) or AT/alopecia universalis.
METHODS: A total of 28 patients were instructed to apply 2.5 g of clobetasol propionate to the right side of the scalp every night under occlusion with a plastic film. Treatment was performed 6 days a week for 6 months. When regrowth of terminal hair occurred, treatment was extended over the entire scalp. All patients were followed up for another 6 months.
RESULTS: Of the 28 patients included in the study, 8 were treated successfully (28.5%). Regrowth of terminal hair began on the treated side 6 to 14 weeks after the start of treatment. Of these 8 patients, 3 had a relapse and were not able to maintain hair regrowth.
CONCLUSION: Our study shows that clobetasol propionate 0.05% under occlusion is effective in inducing hair regrowth in patients with AT or AT/alopecia universalis. Occurrence of hair regrowth only on the treated half of the scalp clearly shows that efficacy of treatment is a result of a local and not systemic effect of the drug. Although only 17.8% of patients had long-term benefit by treatment, our results were obtained in a population of patients with severe and refractory forms of the disease.

PMID 12833016
A G Messenger, J McKillop, P Farrant, A J McDonagh, M Sladden
British Association of Dermatologists' guidelines for the management of alopecia areata 2012.
Br J Dermatol. 2012 May;166(5):916-26. doi: 10.1111/j.1365-2133.2012.10955.x.
Abstract/Text
PMID 22524397
Eileen Tan, Yong-Kwang Tay, Chee-Leok Goh, Yoke Chin Giam
The pattern and profile of alopecia areata in Singapore--a study of 219 Asians.
Int J Dermatol. 2002 Nov;41(11):748-53.
Abstract/Text 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.

PMID 12452996
E P Kubeyinje
Intralesional triamcinolone acetonide in alopecia areata amongst 62 Saudi Arabs.
East Afr Med J. 1994 Oct;71(10):674-5.
Abstract/Text Evaluation of 62 Saudi Arabs with alopecia areata on monthly intralesional injection of triamcinolone acetonide, showed complete regrowth in 40 (63%) patients at 4 months. Regrowth was likely in young adults with few lesions (less than 5 patches), lesions of short durations (less than 1 month) patches less than 3 cm in diameter. Regrowth was poor when associated with atopy (2 patients) and mongolism (1 patient). Side effects of treatment were minimal and the drug was well tolerated.

PMID 7821250
C K Rokhsar, J L Shupack, J J Vafai, K Washenik
Efficacy of topical sensitizers in the treatment of alopecia areata.
J Am Acad Dermatol. 1998 Nov;39(5 Pt 1):751-61. doi: 10.1016/s0190-9622(98)70048-9.
Abstract/Text It has been more than 2 decades since the first report of the use of dinitrochlorobenzene to induce hair growth in 2 patients with alopecia areata. Other topical sensitizers, namely squaric acid dibutylester and diphenylcyclopropenone, have been used with variable success. This article reviews the efficacy and safety of the use of topical sensitizers in the treatment of alopecia areata.

PMID 9810892
S H Chua, C L Goh, C B Ang
Topical squaric acid dibutylester therapy for alopecia areata: a double-sided patient-controlled study.
Ann Acad Med Singapore. 1996 Nov;25(6):842-7.
Abstract/Text In this prospective, double-sided patient-controlled therapeutical trial involving 20 patients with alopecia areata, we investigated the efficacy of topical acid dibutylester (SADBE) in the treatment of alopecia areata. Sensitisation was achieved with 2% SADBE in acetone followed by weekly application of topical SADBE to designated alopecia sites for 20 weeks. Untreated alopecia sites on the same patient acted as controls. Nineteen of the twenty patients completed 20 weeks of treatment. On the SADBE treated sites, excellent response (> 75% hair regrowth) was observed in 68% (13/19) of patients at the end of 20 weeks of treatment. On the untreated control sites, the corresponding figure was 11% (2/19). The difference in response between SADBE treated and untreated sites was statistically significant (P < 0.001). Mean onset of hair regrowth was 6 weeks after starting treatment. Patients with duration of alopecia 12 months or longer fared poorer compared with patients with a shorter duration of the disease. The extent of involvement did not appear to influence treatment outcome. Side effects were mainly local and were mainly local and were well tolerated. At 6 months follow-up, 33% (2/6) of responders with alopecia totalis relapsed compared to 11% (19) of those with patchy alopecia areata. We conclude that topical immunotherapy with SADBE is effective in inducing hair regrowth in alopecia areata.

PMID 9055014
Abstract/Text BACKGROUND: Immunotherapy with sqauric acid dibutyl ester (SADBE) is a well-accepted therapy for alopecia areata.
OBJECTIVE: To study efficacy, safety, and factors influencing the outcome in the treatment of alopecia areata.
METHOD: During a 4-year period, 70 patients of alopecia areata, unresponsive to conventional therapies, were treated with SADBE for a period of 4 months and thereafter depending on the response with initial therapy. The percent scalp hair loss was calculated using "Severity of Alopecia Tool" (SALT) score before and after the therapy.
RESULTS: Out of 70 patients, 6 were lost to follow-up and 4 could not develop sensitization; therefore, data of 60 patients was available for analysis. The overall success rate was 43%. In patients with <50% scalp involvement; the success rate was better (68%) than in those with >50% involvement (29%). The response was better in patients with late onset and shorter duration of disease. Family history of alopecia areata or other autoimmune diseases, personal or family history of atopy, presence of auto antibodies in serum, and presence of nail changes were associated with poorer prognosis. Out of 26 patients who responded, relapse occurred in 21 (81%) patients.
CONCLUSION: In conclusion, SADBE is an effective and well-tolerated mode of therapy in Indian patients of AA, although the long-term results of SADBE were not encouraging.

PMID 16573260
Manabu Ohyama, Atsushi Shimizu, Kyoko Tanaka, Masayuki Amagai
Experimental evaluation of ebastine, a second-generation anti-histamine, as a supportive medication for alopecia areata.
J Dermatol Sci. 2010 May;58(2):154-7. doi: 10.1016/j.jdermsci.2010.03.009. Epub 2010 Mar 23.
Abstract/Text
PMID 20388588
Shigeki Inui, Takeshi Nakajima, Naoyuki Toda, Satoshi Itami
Fexofenadine hydrochloride enhances the efficacy of contact immunotherapy for extensive alopecia areata: Retrospective analysis of 121 cases.
J Dermatol. 2009 Jun;36(6):323-7. doi: 10.1111/j.1346-8138.2009.00647.x. Epub 2009 Apr 28.
Abstract/Text To study the effect of fexofenadine on extensive alopecia areata (AA), we evaluated retrospectively 121 patients with AA having alopecia in more than 50% of the scalp and followed them for at least 6 months. Patients were treated by immunotherapy using diphenylcyclopropenone or squaric acid dibutylester with or without oral fexofenadine. The regrowth score was estimated as decrease of Severity of Alopecia Tool (SALT) score. In AA with atopic background (atopic AA), the mean regrowth score of the fexofenadine group was 1.333 (n = 33) and that of the control 0.471 (n = 34). The fexofenadine group showed significantly better regrowth than control by Mann-Whitney's U-test (P = 0.00213). In non-atopic AA, the mean regrowth score of the fexofenadine group was 1.303 (n = 33) and that of the control 1.048 (n = 21). There was no significant difference by Mann-Whitney's U-test (P = 0.872). Together, fexofenadine is a helpful reagent in the treatment extensive atopic AA with contact immunotherapy.

PMID 19500180
Shigeki Inui, Takenobu Inoue, Satoshi Itami
Psychosocial impact of wigs or hairpieces on perceived quality of life level in female patients with alopecia areata.
J Dermatol. 2013 Mar;40(3):225-6. doi: 10.1111/1346-8138.12040. Epub 2012 Dec 17.
Abstract/Text
PMID 23252418
C J DILLAHA, S ROTHMAN
Therapeutic experiments in alopecia areata with orally administered cortisone.
J Am Med Assoc. 1952 Oct 11;150(6):546-50.
Abstract/Text
PMID 12980788
F Kern, W H Hoffman, G W Hambrick, R M Blizzard
Alopecia areata. Immunologic studies and treatment with prednisone.
Arch Dermatol. 1973 Mar;107(3):407-12.
Abstract/Text
PMID 4571041
E A Olsen, S C Carson, E A Turney
Systemic steroids with or without 2% topical minoxidil in the treatment of alopecia areata.
Arch Dermatol. 1992 Nov;128(11):1467-73.
Abstract/Text 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.

PMID 1444500
Masahiro Kurosawa, Satoshi Nakagawa, Masato Mizuashi, Yoshinori Sasaki, Maki Kawamura, Makiko Saito, Setsuya Aiba
A comparison of the efficacy, relapse rate and side effects among three modalities of systemic corticosteroid therapy for alopecia areata.
Dermatology. 2006;212(4):361-5. doi: 10.1159/000092287.
Abstract/Text BACKGROUND: Systemic corticosteroids are one of the most commonly used therapeutic modalities for patients with extensive alopecia areata (AA), although they entail several drawbacks.
OBJECTIVE: To determine the best modality for systemic corticosteroid use in terms of their efficacy, relapse rate, and side effects.
METHODS: Fifty-one patients with single or multiple AA (AA/multiplex) and 38 patients with alopecia totalis or AA universalis (AA totalis/universalis) were enrolled in this open study. They were randomly divided into three groups depending on the time of their initial visit. They were administered (1) oral dexamethasone (Dex) 0.5 mg/day for 6 months (Dex group), (2) intramuscular triamcinolone acetonide (imTA) 40 mg once a month for 6 months followed by 40 mg once every 1.5 months for 1 year (imTA group), and (3) pulse therapy (PT) using oral predonine 80 mg for 3 consecutive days once every 3 months (PT group). After the treatment, each treatment modality was evaluated by the response rate, relapse rate, and side effect profile.
RESULTS: The response rate of AA/multiplex was significantly better in the imTA group than in the Dex group. The overall relapse rate and that of AA totalis/universalis were significantly better in the PT group than in the Dex group. Dysmenorrhea was the most common and problematic side effect. Impairment of the adrenocortical reserve was seen in 7% of the PT group and 23% of the imTA group, which was recovered without any further medical treatment.
CONCLUSION: imTA or pulse therapy is effective for AA and has an acceptable level of side effects. The development of a new strategy to reduce the relapse rate is needed.

2006 S. Karger AG, Basel
PMID 16707886
Bikash Ranjan Kar, Sanjeev Handa, Sunil Dogra, Bhushan Kumar
Placebo-controlled oral pulse prednisolone therapy in alopecia areata.
J Am Acad Dermatol. 2005 Feb;52(2):287-90. doi: 10.1016/j.jaad.2004.10.873.
Abstract/Text BACKGROUND: Systemic corticosteroids administered as pulse therapy have been found helpful in a wide array of diseases including alopecia areata (AA). None of the studies published so far regarding their use in AA have been randomized or placebo-controlled.
OBJECTIVE: We sought to compare the efficacy of weekly oral prednisolone pulse therapy in a placebo-controlled trial for patients with extensive AA.
METHODS: A total of 43 patients were randomly divided into two groups. Patients in group A (23 patients) were treated with oral prednisolone (200 mg once weekly, 5 40-mg tablets) and patients in group B (20 patients) were given placebo tablets on an identical schedule. The total study period was 6 months, consisting of 3 months of active therapy followed by another 3 months of observation.
RESULTS: Significant hair regrowth was obtained in 8 patients in the prednisolone-treated group. Two of the responders experienced a relapse during the observation period of 3 months. In the placebo group, none of the patients had significant hair regrowth at the end of the study.
CONCLUSION: Oral prednisolone pulse therapy is useful in AA. Placebo-controlled studies with varying dosage schedules are required to standardize the dose of prednisolone used in pulse therapy, optimize the therapeutic efficacy, and minimize side effects.

PMID 15692475
Takeshi Nakajima, Shigeki Inui, Satoshi Itami
Pulse corticosteroid therapy for alopecia areata: study of 139 patients.
Dermatology. 2007;215(4):320-4. doi: 10.1159/000107626.
Abstract/Text BACKGROUND/AIM: Recent reports of pulse corticosteroid therapy for alopecia areata (AA) show its efficacy for patients with a history of < or = 1 year but not for recalcitrant cases or alopecia totalis/universalis. The purpose of this study was to evaluate the efficacy and safety of pulse corticosteroid therapy for recent-onset AA patients.
METHOD: A total of 139 severe AA patients aged >15 years were included in this study. The duration from the onset of active hair loss was within 12 months for 125 (89.9%) of those patients.
RESULTS: Of the patients, 72.7% had hair loss on > 50% of their scalp area. Among the recent-onset group (duration of AA < or = 6 months), 59.4% were good responders (> 75% regrowth of alopecia lesions), while 15.8% with > 6 months duration showed a good response. Recent-onset AA patients with less severe disease (< or = 50% hair loss) responded at a rate of 88.0%, but only 21.4% of recent-onset patients with 100% hair loss responded. No serious adverse effects were observed.

2007 S. Karger AG, Basel
PMID 17911990
P Assouly, P Reygagne, C Jouanique, B Matard, E Marechal, P Reynert, H Bachelez, L Dubertret
[Intravenous pulse methylprednisolone therapy for severe alopecia areata: an open study of 66 patients].
Ann Dermatol Venereol. 2003 Mar;130(3):326-30.
Abstract/Text 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.

PMID 12746668
A Friedli, M P Labarthe, E Engelhardt, R Feldmann, D Salomon, J H Saurat
Pulse methylprednisolone therapy for severe alopecia areata: an open prospective study of 45 patients.
J Am Acad Dermatol. 1998 Oct;39(4 Pt 1):597-602.
Abstract/Text BACKGROUND: Oral corticosteroids may be effective in the treatment of severe alopecia areata (AA), but the side effects of prolonged therapy limit their use. The benefit of a single intravenous pulse of methylprednisolone has not been evaluated in patients with ongoing hair loss of less than 12 months' duration.
OBJECTIVE: Our purpose was to determine the effectiveness of an intravenous pulse of methylprednisolone at 1, 3, 6, and 12 months in patients with active severe AA of less than 12 months' duration.
METHODS: Forty-five patients were included in this open study. All had rapid and extensive hair loss for less than 1 year (first occurrence or relapse), with the bald area exceeding 30% of the scalp. There were 20 multifocal, 10 ophiasic, 9 universalis, and 6 totalis cases. Intravenous methylprednisolone, 250 mg, was administered twice a day on 3 successive days. Follow-up for at least 12 months (up to 29 months) was performed. The percentage of pretreatment bald area covered by hair regrowth at 1,3,6, and 12 months was measured.
RESULTS: No major side effects were observed. Patients with multifocal AA (n = 20) showed the best response rate, with 9, 12, 13, and 12 showing 100% or 50% to 100% regrowth at 1, 3, 6, and 12 months, respectively. Relapse occurred at 3 months in 1 patient, at 6 months in 2, and at 12 months in 4. A second pulse was tried in 2 patients with relapse with 100% regrowth that was stable at 12 and 28 months. In patients with ophiasic AA (n = 10), no total regrowth was observed; 6 had no response, 4 showed 20% to 70% regrowth at 1 month with relapse at 3 and 6 months. A second series of pulses was given to the 4 initial responders 3 to 13 months after the first series; the response rate to this second treatment was better than the first. In patients with universalis and totalis AA (n = 15), no total regrowth was observed initially; 8 patients had no response, and 3 showed 50% to 90% regrowth at I month, with subsequent improvement at 3 and 6 months. In 4 patients who did not show an initial response, a significant (90% to 100%) delayed regrowth was observed between 9 and 16 months after the pulse therapy.
CONCLUSION: A single series of intravenous pulse of methylprednisolone appears to be well tolerated and effective in patients with rapidly progressing extensive multifocal AA, but not those with ophiasic and universalis AA.

PMID 9777767

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