Treatments for androgenetic alopecia and alopecia areata: current options and future prospects

Androgenetic alopecia and alopecia areata are common disorders of the hair follicle which may heavily influence self esteem and self image. Androgenetic alopecia is caused by the heightened sensitivity of scalp follicles to dihydro- testosterone whereas alopecia areata is induced by an autoimmune reaction. Current drug treatment approaches include the use of regrowth stimulators such as topical minoxidil and oral finasteride for androgenetic alopecia, as well as topical minoxidil, dithranol (anthralin), corticosteroids, contact sensitisers, and psoralen plus ultraviolet A irradiation (PUVA) therapy for alopecia areata. Combination regimens are also proposed. However, extreme cases of either type of alopecia do not generally respond well to these existing treatments. For this reason, new therapeutic strategies are directed towards both improving the targeting of existing agents, as well as the development of novel hypertrichotic modalities.     

米诺地尔凝胶治疗斑秃的多中心随机双盲安慰剂对照临床试验

目的 评价2.2%米诺地尔凝胶（抗斑秃药）治疗斑秃的疗效和安全性.方法 用随机双盲安慰剂对照多中心研究,选择脱发＜40%头皮面积、病程在1年以内的患者,随机进入米诺地尔凝胶试验组（66例）或凝胶基质对照组（62例）,分别给予米诺地尔凝胶或基质,每日2次,外用,共3个月.结果 在毛发开始生长时间、生长长度、脱发面积减少和综合评价,试验组均优于对照组;2组药物不良反应发生率分别为7.58%,6.45%（P＞0.05）.结论 米诺地尔凝胶治疗斑秃安全、有效.     

2%米诺地尔酊剂外用辅治斑秃的疗效观察

目的观察2%米诺地尔酊剂外用辅治斑秃的临床疗效。方法将120例斑秃患者随机分为观察组和对照组各60例。对照组给予基础对症治疗;观察组在对照组治疗基础上加用2%米诺地尔酊剂,并用生姜汁及生蒜外擦患处,每天2次,1个月为1个疗程。治疗后比较2组疗效及不良反应。结果观察组总有效率为93.3%高于对照组的75.0%,差异有统计学意义(P<0.01)。观察组出现头晕1例,对照组出现下肢水肿1例,经调整用药后均改善。结论 2%米诺地尔酊剂外用辅治斑秃可提高治疗效果,值得临床推广应用。     

Topical minoxidil in the treatment of male pattern alopecia

Male pattern hair loss (androgenetic alopecia) is a common problem. In fact, it affects nearly all males to some degree. Expression of the disorder is variable, and while it is never life-threatening, it often becomes a major source of consternation. The biology of the process is poorly understood, and no current therapy can halt or reverse the process. Only cosmetic surgery, which is painful, time consuming, and expensive, has been effective. In the past 7 years, since it was noted that a patient taking minoxidil for hypertension had reversal of male pattern hair loss, awareness of a possible therapeutic role for topical minoxidil in the management of this disorder has grown among physicians, scientists, and the general public. It can be concluded from available data that topical application of minoxidil is effective in providing cosmetically satisfying thickening of hair in a select group of individuals with male pattern hair loss. The drug's mechanism of action remains obscure. No serious side effects have been demonstrated with its use, however, and it is therefore advised in selected patients.     

Topical minoxidil therapy for hair regrowth

The pathogenesis of hair loss, the postulated mechanisms of minoxidil action on hair growth, and clinical trials, adverse reactions, experimental formulations, and percutaneous absorption of topical minoxidil preparations are reviewed. Topical minoxidil seems to normalize hair follicles and increase blood flow to the scalp. In clinical trials of various formulations, results have varied. Improved hair growth occurred after four to six months of therapy; twice-daily application seems to be indicated. The most frequently reported adverse reactions are mild scalp dryness and irritation and, rarely, allergic contact dermatitis. Current recommendations are to reserve topical minoxidil for patients with normal cardiovascular status and to routinely monitor blood pressure, heart rate, and electrocardiographic changes. A new drug application is pending with FDA for use of topical minoxidil in androgenetic alopecia (male-pattern baldness), which is genetically determined and apparently stimulated by androgens. For alopecia areata, which involves hair loss on the body or scalp, usually patchy and of sudden onset, no reliable treatment has been found, although minoxidil may be efficacious in some patients. Minoxidil has generated new interest in hair-loss research. The etiology of hair loss must be better understood before more effective treatment regimens can be designed.     

斑秃治疗的疗效观察以及免疫功能紊乱的研究

目的：观察卡介菌多糖核酸注射液（迪苏）联合5％米诺地尔酊（蔓迪）治疗斑秃疗效进行斑秃免疫功能紊乱的研究。方法：60例斑秃患者分为两组,分别采用卡介菌多糖核酸注射液联合5％米诺地尔酊治疗（联合治疗组）、单用卡介菌多糖核酸治疗（对照组）。同时对60例患者进行自身血清皮肤试验。结果：两组临床治疗效果差异有统计学意义,X2=4.1761,P=0.041;自身血清皮肤试验的阳性率为68.33%。结论：本研究提示自身免疫功能紊乱参与斑秃的发病,联合多途径治疗斑秃的方法在临床上值得推广。     

Videocapillaroscopic pattern of alopecia areata before and after diphenylciclopropenone treatment

Alopecia areata (AA) is an inflammatory skin disease the most effective therapy for which is diphenylcyclopropenone (DPCP). Videodermatoscopy and intra-vital capillaroscopy (IVCP) are two non-invasive techniques that help in the differential diagnosis of alopecias. It is known that, after DPCP therapy, there is a histologically proven significant increase of VEGF in hair follicle keratinocytes and a consequent increase in capillary vessels in the dermis of the same follicles. The aim of our study is to emphasize any clinical and videodermatoscopic-videocapillaroscopic changes after DPCP treatment in 20 patients affected by alopecia areata. Videodermatoscopic images and an intravital videocapillaroscopic analysis were performed at T0, T12 and T24 to emphasize clinical modifications and microscopic changes in vascular pattern before and after DPCP treatment. At T0, videodermatoscopy showed the presence of exclamation point hairs, hair follicles filled with hyperkeratotic plugs (yellow dots), hair follicles containing cadaverized hairs (black dots) and broken hairs. IVCP highlighted a pale scalp, and vessels were not visible. At 24 weeks (T24), videodermatoscopy revealed the disappearance or a statistically significant reduction of AA hallmarks and an increase of number of vellus hairs. Videocapillaroscopy showed a statistically significant increase of new vessels and, where neoangiogenesis were more marked, a major hair regrowth was evident. Our study emphasizes that, after DPCP therapy, neoangiogenesis is detectable by videocapillaroscopy and these new capillaries could be considered an initial positive attempt to compensate capillary loss of T0 alopecia areata images.     

Safety concerns when using novel medications to treat alopecia

ABSTRACT

Introduction: Alopecia is often a cause of great concern to patients for cosmetic and psychologic reasons. The aim of treating non-scarring alopecias is to reduce hair loss and, to some extent, enhance hair regrowth. However, therapies for scarring alopecias are limited and aiming to halt disease progression. Nonetheless, available modalities of treatment come with numerous side effects.

Areas covered: Many new treatments for non-scarring alopecias have been introduced in recent years. This review summarizes the safety concerns when using novel therapeutic modalities such as JAK inhibitors, hair transplantation, mesotherapy, oral minoxidil, platelet-rich plasma, microneedling, and 5α-reductase inhibitors for treating hair loss. A broad literature search was performed using PubMed and Google Scholar in April 2018 to compile published articles that reported the adverse effects of new therapeutic modalities for alopecia.

Expert opinion: Although emerging therapeutic modalities for alopecia have demonstrated efficacy in hair regrowth and treating established disease, their safety profiles vary widely. When considering the new treatments for alopecia, physicians should weigh the potential benefits and risks of each treatment or combination treatment to ensure safe and successful outcomes.     

Emerging drugs for alopecia areata: JAK inhibitors

Introduction: Alopecia Areata is a common form of non-scarring hair loss that usually starts abruptly with a very high psychological impact. Due to the still not completely understood etiopathogenesis, at present there is no treatment that can induce a permanent remission and there is no drug approved for the treatment of this disorder.

Areas covered: Leading existing treatment are briefly overviewed and then ongoing research on Janus Kinases Inhibitors is discussed, reviewing trials with oral and topical formulations so as new opportunities for other forms of alopecia, such as cicatricial alopecia.

Expert opinion: JAK inhibitors represent a promise among alopecia treatments, but further studies are needed on long term safety. There is still no validated dosage for alopecia areata and the vehicles used for topical formulations seem not yet ideal in terms of skin penetration and reduced systemic absorption. Hopefully several studies are ongoing and we hope, in the near future, that JAK inhibitors will become part of the armamentarium to treat alopecia areata patients in terms of safety and costs.     

加味二至丸联合外用米诺地尔酊治疗青年型男性脱发的临床观察

目的 探讨加味二至丸联合外用米诺地尔酊对青年型男性脱发的疗效.方法 选取男性型脱发患者126例,按随机数字表法分为三组,即西药组(米诺地尔酊外用)、中药组(加味二至丸)和联合治疗组(加味二至丸加米诺地尔酊外用),每组42例.超声仪检测三组患者治疗前后血流动力学特征变化;高分辨率扫描电子显微镜-X射线能谱仪测定秃发区微量元素Ca、Fe、Zn、Cu的含量;检测各组治疗后毛发生长速度、生长长度和毛囊状况,最后进行疗效判定.结果 与治疗前相比,三组患者治疗后血流阻力指数(RI)明显下降,流速时间积分(VT1)和峰值流速(Vmax)明显升高,且联合治疗组血流动力学改善效果较西药组和中药组明显(P＜0.05);联合治疗组发中微量元素Fe、Ca、Zn、Cu含量明显升高,且升高幅度大于单纯西药和中药组(P＜0.05);联合治疗组毛发生长速度为(12.605 ±3.271) ×10-2 mm·d-1,治疗后总有效率高达92.9％,明显高于单纯中药组(76.2％)和西药组(54.8％),且联合治疗组毛囊生长期较另外两组延长(P＜0.05).结论 加味二至丸联合外用米诺地尔酊对男性型脱发患者疗效确切,值得临床推广应用.     

Nongenotoxicity of minoxidil in murine hair follicles as determined by the nuclear aberration assay

A 1-cm2 area on the back of CD1 mice was prepared for topical application of minoxidil, N-methyl-N-nitrosourea (MNU), or cyclophosphamide (CY) by clipping or plucking hair from a patch of skin. Plucking stimulates hair follicle cell division while clipping does not. Minoxidil was topically administered for 8 consecutive days. CY or MNU was administered topically once on the eighth day postplucking. The incidence of nuclear aberrations and mitotic figures were measured in hair follicles while frequency of micronuclei and the ratio of RBC/PCE were measured in the bone marrow. Results with minoxidil showed no increase in either nuclear aberrations in the hair follicle or micronuclei in the bone marrow. These results suggest that topically applied minoxidil is not genotoxic. In contrast, a dose-dependent effect of MNU on the incidence of nuclear aberrations in the hair follicle was seen. CY induced a dose-dependent increase in the incidence of micronuclei in the bone marrow and in nuclear aberrations in the hair follicle after topical application. Minoxidil applied to clipped mice significantly increased the incidence of mitotic figures above that seen in both the clipped and plucked controls. This suggests that minoxidil is a mitogenic agent in the hair follicle. These findings are consistent with the success of topically applied minoxidil in the treatment of alopecia areata.     

Treatment strategies for alopecia

Background: Hair loss is a very common complaint and dermatologists should be able to make the correct diagnosis of different types of alopecia and choose the best therapeutic strategy according to patients' and doctors' expectations. Objective: To review treatment of the most common forms of hair loss. Methods: Literature review and expert opinion. Conclusion: There is good evidence based information for the treatment of androgenetic alopecia. There are very few randomized good quality studies and no information about long-term results for most of the available treatments for alopecia areata and cicatricial alopecias. Treatment of alopecia areata and cicatricial alopecias is, therefore, selected in the absence of precise information on the expected outcome and treatment failure is common.     

Acitretin-induced alopecia areata: a case report

Alopecia areata is a common form of non-scarring hair disorder. The development of alopecia areata during anti-psoriatic treatment has been reported with the systemic therapies such as infliximab, etanercept, adalimumab, alefacept and efalizumab. Retinoid-induced alopecia areata on the eyelash and eyebrow has not been reported in the literature. We report a female patient who presented with alopecia areata of the eyebrow and eyelash one month after the initiation of acitretin therapy for psoriasis.     

梅花针结合微波治疗斑秃的疗效观察

目的:观察梅花针结合微波治疗斑秃的临床疗效。方法:将斑秃患者200例随机分为两组。治疗组100例,用梅花针叩刺,微波治疗仪照射;对照组100例,外用2%米诺地尔溶液;两组均口服胱氨酸片、维生素B6、泛酸钙。观察治疗前后脱发区的头发再生情况和不良反应。采用全分析集(fullanalysisset,FAS)进行统计分析。结果:治疗组总有效率为93.0%,对照组为84.0%,两组差异有显著性意义(P<0.05)。结论:梅花针叩刺结合微波照射是治疗斑秃的一种有效、安全的方法。     

New drugs under investigation for the treatment of alopecias

Introduction: Alopecia is a very common complaint in medical practice, which usually has a large psychological impact in patients. Treatment of alopecia is often difficult and frustrating for patients and clinicians owing to the slow growth rate of the hair, long treatment terms, limited efficacy, and possible adverse side effects.

Areas covered: This paper reviews the new and emerging treatments for two of the most common forms of alopecia, known as androgenetic alopecia and alopecia areata. A literature search of PubMed/MEDLINE and ClinicalTrial.gov was performed to gather information about active research on new treatments for alopecias. Websites of companies sponsoring clinical trials were also searched for interim result data.

Expert opinion: Many new therapies in two of the most common forms of hair loss have been developed and are currently being studied with encouraging results. In alopecia areata, JAK inhibitors are promising. The discovery of JAK inhibitors has prompted the research and identification of new molecules. In androgenetic alopecia, we are still looking for a topical treatment that is superior to topical minoxidil. However, stem-cell research is advancing and the goal to create new follicles or refresh dormant follicles may be realized in the near future.     

Preventive effects of cedrol against alopecia in cyclophosphamide-treated mice

Although numerous hypotheses have been proposed to prevent chemotherapy-induced alopecia (CIA), effective pharmaceuticals have yet to be developed. In our study, the back hairs of C57BL/6 mice were factitiously removed. These mice were then treated with cedrol or minoxidil daily. Mice with early-stage anagen VI hair follicles were treated with cyclophosphamide (CYP, 125 mg/kg) to induce alopecia. The CYP-damaged hair follicles were observed and quantified by using a digital photomicrograph. The results demonstrated that the minoxidil-treated mice suffered from complete alopecia similar to the model 6 days after CYP administration. Simultaneously, the cedrol-treated (200 mg/kg) mice manifested mild alopecia with 40% suppression. Histological observation revealed that anagen hair follicles of the cedrol-pretreated mice (82.5%) likely provided from damage compared with the sparse and dystrophic hair follicles of the model mice (37.0%). Therefore, the use of topical cedrol can prevent hair follicle dystrophy and provide local protection against CIA.     

Alopecia Associated With Zidovudine Therapy

Alopecia has been described in patients infected with the human immunodeficiency virus (HIV). Zidovudine reportedly influences hair growth in these patients, causing regrowth or thickening. A 33-year-old HIV-infected man developed alopecia areata after beginning zidovudine therapy. The alopecia reversed after the drug was discontinued.     

Preparation of topical bimatoprost with enhanced skin infiltration and in vivo hair regrowth efficacy in androgenic alopecia

To prepare a topical formulation of bimatoprost (BIM) with high skin permeability, we designed a solvent mixture system composed of ethanol, diethylene glycol monoethyl ether, cyclomethicone, and butylated hydroxyanisole, serving as a volatile solvent, nonvolatile co-solvent, spreading agent, and antioxidant, respectively. The ideal topical BIM formulation (BIM–TF#5) exhibited 4.60-fold higher human skin flux and a 529% increase in dermal drug deposition compared to BIM in ethanol. In addition, compared to the other formulations, BIM–TF#5 maximally activated human dermal papilla cell proliferation at a concentration of 5 μM BIM, equivalent to 10 μM minoxidil. Moreover, BIM–TF#5 (0.3% [w/w] BIM) significantly promoted hair regrowth in the androgenic alopecia mouse model and increased the area covered by hair at 10 days by 585% compared to the vehicle-treated mice, indicating that entire telogen area transitioned into the anagen phase. Furthermore, at day 14, the hair weight of mice treated with BIM–TF#5 (5% [w/w] BIM) was 8.45- and 1.30-fold greater than in the 5% (w/w) BIM in ethanol and 5% (w/v) minoxidil treated groups, respectively. In the histological examination, the number and diameter of hair follicles in the deep subcutis were significantly increased in the BIM–TF#5 (0.3 or 5% [w/w] BIM)-treated mice compared to the mice treated with vehicle or 5% (w/w) BIM in ethanol. Thus, our findings suggest that BIM–TF#5 is an effective formulation to treat scalp alopecia, as part of a novel therapeutic approach involving direct prostamide F2α receptor-mediated stimulation of dermal papilla cells within hair follicles.     

Male androgenetic alopecia

Importance of the field: Androgenetic alopecia affects up to 80% of males by the age of 80. The synonym ‘male-pattern hair loss’ highlights the fact that hair loss occurs in a defined and reproducible pattern. Hair loss results in reduced self esteem, loss of confidence and anxiety in affected men. An effective treatment for hair baldness would be desirable.

Areas covered in this review: In androgenetic alopecia, hair follicles undergo progressive miniaturization. Genetic factors and androgens play a major role in the pathogenesis of the disease. Polymorphism of the androgen receptor gene was first identified in association with androgenetic alopecia. Identification of new susceptibility genes on chromosomes 3q26 and 20p11 suggest that non-androgen-dependent pathways also are involved.

What the reader will gain: Topical monoxidil and oral finasteride are commonly in use and have FDA approval for the treatment of male androgenetic alopecia; dutasteride, a type I and II 5-alpha-reductase inhibitor, is on hold in Phase III trials. A combination of medical treatment and hair transplant surgery has shown superior efficacy.

Take-home message: Androgenetic alopecia is a progressive condition and although the current available treatments are effective in arresting the progression of the disease, they allow only partial regrowth of hair at its best. Early treatment achieves the best desirable outcome.     

Treatment options for alopecia: an update, looking to the future

INTRODUCTION: Hair loss is a very common complaint. The diagnosis is based on clinical, dermoscopic and pathological examination. The treatment is usually continuous and requires strong compliance. AREAS COVERED: This article aims to i) summarize current treatment options for the most common forms of hair loss; ii) update the literature on treatment options to emerge over the 3 years since the release of the first edition of this article in 2009; and iii) outline future strategies for treating alopecia. EXPERT OPINION: There is good evidence-based information for the treatment of androgenetic alopecia. There are very few good-quality randomized studies, and no information about long-term results for most of the available treatments for alopecia areata and cicatricial alopecias. Significant research success has been achieved over the past few years through i) discovering the genetic profile of alopecia areata; ii) working on follicular neogenesis in androgenetic alopecia; and iii) discovering the PPAR-γ pathway in scarring alopecia.