Clinical presentations of alopecia areata

Alopecia areata (AA) may can occur on any hair-bearing region. Patients can develop patchy nonscarring hair loss or extensive loss of all body hair. Hair loss may fluctuate. Some patients experience recurrent hair loss followed by hair regrowth, whereas others may only develop a single patch of hair loss, never to see the disease again. Still others experience extensive loss of body hair. The heterogeneity of clinical presentations has led investigators conducting clinical therapeutic trials to typically group patients into three major groups, those with extensive scalp hair loss [alopecia totalis (AT)], extensive body hair loss [alopecia universalis (AU)], or patchy disease (AA). Treatment outcomes have been correlated with disease duration and extent. Recently, guidelines were established for selecting and assessing subjects for both clinical and laboratory studies of AA, thereby facilitating collaboration, comparison of data, and the sharing of patient-derived tissue. For reporting purposes the terms AT and AU, though still used are defined very narrowly. AT is 100% terminal scalp hair loss without any body hair loss and AU is 100% terminal scalp hair and body loss. AT/AU is the term now recommended to define the presence of AT with variable amounts of body hair loss. In this report the term AA will be used broadly to encompass the many presentations of this disease. Development of AA may occur with changes in other ectodermal-derived structures such as fingernails and toenails. Some investigators have also suggested that other ectodermal-derived appendages as sebaceous glands and sweat glands may be affected in patients experiencing AA. Whether or not function of these glands is truly impaired remains to be confirmed. Many patients who develop patchy or extensive AA complain of changes in cutaneous sensation, that is, burning, itching, tingling, with the development of their disease. Similar symptoms may occur with hair regrowth. The potential involvement of the nervous system in AA has led to morphologic investigations of the peripheral nervous system as well as analysis of circulating neuropeptide levels. In this article the clinical presentations of AA are reviewed. The guidelines for conducting treatment studies of AA are presented and observations on changes in cutaneous innervation are introduced. Throughout the text, unless otherwise noted, AA will be used in a general way to denote the spectrum of this disease.     

Alopecia areata treatment with a phototoxic dose of UVA and topical 8-methoxypsoralen

Twenty-five patients with alopecia totalis (AT) or alopecia universalis and 124 patients with alopecia areata (AA) were treated with photochemotherapy, combining topical 8-methoxypsoralen (8-MOP) with UV irradiation of the scalp at a phototoxic dose. The mean energy required was 15 J/cm2 for AA and 42 J/cm2 for AT. Ninety-four patients had multiple bald patches and 12 with AT had complete or > 50% hair regrowth. Positive treatment results did not seem to depend on the age of onset or the duration of the disease. Few side-effects of topical psoralens plus UVA (PUVA) treatment were noted, except a for few days of slight erythema caused by the high dose of UV.     

Alopecia areata: autoimmune basis of hair loss

Alopecia areata (AA) is a heterogeneous disease characterized by nonscarring hair loss on the scalp or any hair-bearing surface. A wide range of clinical presentations can occur -- from a single patch of hair loss to complete loss of hair on the scalp (alopecia totalis) or the entire body (alopecia universalis). Particularly in severe or chronic cases, AA may cause considerable psychological and emotional distress for affected individuals. The estimated lifetime risk of developing AA is 1.7%. While the precise etiology of this common disorder has not been elucidated, a substantial body of evidence suggests that AA is an organ-specific, autoimmune disease, targeted to hair follicles. However, the antigenic target(s), mechanisms, and consequences of autoimmune attack in AA have yet to be determined. Here, we critically explore the evidence supporting the hypothesis that AA is an autoimmune disease and propose specific pathways by which self-directed immune responses are generated.     

Multiple courses of pulse corticosteroid therapy for alopecia areata

Various systemic corticosteroid therapies are used for alopecia areata (AA). Pulse therapy using methylprednisolone is a treatment approach for AA. The efficacy of multiple courses of pulse therapy for various severities of AA was evaluated. AA patients with less than 50% hair loss, less than or equal to 6 months after AA onset, needed 1.9 courses of pulse therapy for vellus hair to develop. On the other hand, AA patients with more than 50% hair loss, less than 6 months after AA onset, needed more courses of pulse therapy for vellus hair to develop. Regardless of the disease duration, AA patients with less than 50% hair loss showed a good response rate (100%) after both a short period and a long period after therapy. After receiving multiple courses of pulse therapy, the AA patients with more than 50% hair loss also showed improvement with limited adverse reactions.     

Treatment of chemotherapy-induced alopecia

Chemotherapy-induced alopecia has been well documented as a cause of distress to patients undergoing cancer treatment. Despite the importance of hair loss to patients, however, patients often receive little more counseling than the advice to purchase a wig or other head covering for the duration of their treatment. Research into non-camouflage (wigs, turbans, and head scarves) treatment methods has been complicated both by a lack of a standardized methodology for evaluating hair loss and hair regrowth and by a lack of human trials. Nevertheless, scalp cooling as a method of preventing hair loss during chemotherapy and 2% topical minoxidil as a therapy for accelerating regrowth after chemotherapy are both effective non-camouflage options for treatment. Other proposed treatments for prevention of hair loss during chemotherapy have demonstrated promise in early trials, but these findings will need validation from rigorous further studies. The increasing number of reports of permanent alopecia not just with pre-bone marrow transplant, high-dose busulfan, and cyclophosphamide regimens but also with standard breast cancer chemotherapy regimens illustrates the importance of further research into treatment methods for chemotherapy-induced alopecia.     

The role of the National Alopecia Areata Foundation in the management of alopecia areata

Like a mysterious thief in the night, alopecia areata (AA) suddenly appears without warning—seemingly without rhyme or reason—randomly robbing the hair and subsequently the self-esteem of those affected. Very persuasive scientific evidence now suggests that AA is a T-lymphocyte-mediated autoimmune disease directed against an as yet unidentified hair follicle autoantigen in genetically susceptible individuals. The severity of the clinical phenotypes seen in AA run the gamut from patchy hair loss localized in one or more areas, to total scalp hair loss [alopecia totalis (AT)], to complete body hair loss [alopecia universalis (AU)]. Although not life threatening, AA is most certainly life altering, and its sudden onset, recurrent episodes, and highly unpredictable course have a profound psychological impact on the lives of those with the disease. There are a limited number of therapeutic agents available to treat AA. Responses vary widely and the hard fact remains that any treatment, no matter how successful, does not alter the ultimate course of this capricious and recalcitrant disease. Founded in 1981 to meet the challenges of AA and mollify the deep emotional pain inflicted by this disease, the National Alopecia Areata Foundation (NAAF) now serves as the world center of information and hope for those with AA. The foundation plays a crucial role in the management of AA by encouraging and funding medical research for better treatment and an ultimate cure, by providing support and resources for those with the condition, and by raising public awareness of the disease.     

Hair restoration approaches for early onset male androgenetic alopecia

Society places great emphasis on the presence of hair. Some degree of hair loss is accepted as a normal part of the aging process, in line with the observation that more than 50% of men will develop androgenetic alopecia by the age of 50 years. However, it is possible to understand the psychosocial isolation and distress felt by men with a strong familial predisposition to androgenetic alopecia, who tend to display hair loss in their late teens or twenties. There are currently two drugs which have been licensed for the treatment of male androgenetic alopecia: oral finasteride and topical minoxidil solution which are effective to some extent. Furthermore, upon discontinuing treatment, any gain that has been achieved is quickly lost. Added to which there is an entire market of unproven over the counter products: advertised in the electronic media, local hair salons, and various departmental stores. In this review, we highlight the important advances in the management of male androgenetic alopecia with emphasis on approaches that can lead to more successful and long‐term hair restoration for young adults. In particular, we discuss the evidence supporting the use of the follicular unit grafting technique in conjunction with medical treatment before and after the procedure. Moreover, some other alterations of this most popular state of the art hair restoration technique have been mentioned briefly. As a result, patients and physicians seem equally satisfied from this procedure for its naturally looking results which are cosmetically more acceptable and esthetically pleasing for longer period of time.     

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.     

CD8+ mycosis fungoides clinically masquerading as alopecia areata

A 33‐year‐old female with a 7‐year history of CD8‐positive hypopigmented mycosis fungoides (MF) involving the trunk and extremities presented with a large well‐defined alopecic patch on her frontal scalp. Clinically, this area resembled alopecia areata (AA) and was without hypopigmentation or erythema. A scalp biopsy revealed a non‐scarring inflammatory alopecia and a superficial band‐like atypical lymphoid infiltrate with prominent epidermotropism. Atypical, predominately CD8‐positive lymphocytes were seen surrounding and infiltrating the bulb portion of several hair follicles. Treatments for her MF lesions have included topical bexarotene, topical corticosteroids and phototherapy. Her alopecia has been treated with high potency topical corticosteroids and multiple intralesional triamcinolone injections with very minimal hair regrowth to date. Alopecia due to cutaneous lymphoma is an uncommon phenomenon but can occur in erythrodermic MF or Sezary syndrome. AA‐like changes have most often been reported in conventional patch/plaque stage MF and folliculotropic MF. In these cases, the atypical lymphoid infiltrate is comprised predominately of CD4‐positive lymphocytes. This is a rare report of a CD8‐positive MF causing AA‐like changes. This case highlights the importance of a scalp biopsy in patients with a history of cutaneous lymphoma presenting with alopecia in order to evaluate the nature of their hair loss.     

Higher concentrations of dithranol appear to induce hair growth even in severe alopecia areata

Alopecia areata (AA) is the commonest autoimmune cause of non‐scarring alopecia. Topical treatments including corticosteroids and irritants maybe beneficial. Studies report variable hair regrowth with dithranol (anthralin) but all used low concentrations (0.1–1.25%) and inconsistent measurements of AA severity. We report retrospective data (2005–2014) of 102 patients who had failed ultra‐potent topical steroids and were referred to a specialist hair clinic for treatment with dithranol up to 3%. The severity of alopecia areata tool was used and participants graded as mild (<25%), moderate (>25 to 75%), and severe (>75%) hair loss. Compared with baseline any and at‐least 50% hair regrowth [72%, 68%, 50% and 61.5%, 48.4%, 37.5%, in mild, moderate and severe AA respectively] occurred in all groups (median treatment duration 12 months). Twenty‐nine patients (28.4%) were discharged with complete regrowth; with no difference in proportions in severity groups (33.3%, 29%, and 21.9%) but in the period to discharge [7.9, 6.3, and 29.4 months (p‐values <.05)] for mild, moderate, and severe AA. Treatment trials of 12 months with dithranol at higher concentrations may be an option in patients who failed potent topical or intra‐lesional steroids) regardless of AA severity. Randomized trials (of less staining formulations) of dithranol are warranted.     

Management of alopecia areata: Updates and algorithmic approach

Alopecia areata is a chronic, recurrent and non‐scarring alopecia. The prognoses of patients are very diverse. The larger the area of hair loss, the poorer the treatment response and greater the probability of chronic disease progression. Numerous treatments have been introduced, but curative treatments have yet to be established. The long‐term efficacy of the current treatments is minimal, and the therapeutic response varies widely. Recent clinical trials have attempted to apply therapeutic metrics, such as the Severity of Alopecia Tool, and many have been designed as randomized controlled studies, enabling a more precise evaluation of existing treatments. There have been updates in practice, efficacy or indications of therapeutics that have been previously used. Moreover, the use of novel treatments such as biologics has recently been introduced. Commonly, the most important factor in determining the treatment modality for alopecia areata has been the extent of hair loss. However, if the disease activity is high and likely to progress, combination therapy with adjuvant modalities will be more desirable. This review will discuss the therapeutic effects of existing and newly‐introduced treatments based on their quantity, quality of evidence and expected complications. In addition, an algorithmic approach to management of alopecia areata is proposed according to clinical subtype, severity, onset and activity of the disease.     

Clinical characteristics,trichoscopy, histopathology and treatment outcomes of frontal fibrosing alopecia in an Asian population: A retro-prospective cohort study

Frontal fibrosing alopecia (FFA) is a distinctive lymphocytic scarring alopecia with rapid increase in prevalence. Most FFA series are retrospectively reported from Caucasians with only few from Asians. The objective of this study was to characterize the clinical, trichoscopic and histopathological findings as well as treatment outcomes. This was a retro-prospective cohort study of patients diagnosed with FFA from 1 January 2010 to 1 November 2019. All patients were asked to present for re-examination. Clinical, trichoscopic, histopathological and laboratory data were recorded. A questionnaire was used to investigate hair care, hairstyle and facial skin care compared with age-matched normal controls. Multivariate analysis was performed in order to clarify factors associated with severity. All 58 FFA patients were female, of whom 27.6% were premenopausal, 37.7% had a history of surgical menopause, 13.8% had thyroid diseases, 69% had eyebrow loss and 32.8% facial papules. On physical examination, 10.3% showed linear pattern, 46.6% diffuse pattern and 43.1% pseudo-fringe sign. Concomitant lichen planopilaris was found in 25.9%, lichen planus pigmentosus in 24.1% and female pattern hair loss in 48.3%. The most common trichoscopic characteristics in the frontal hairline were lack of follicular ostia (91.4%), perifollicular scales (79.3%) and perifollicular erythema (63.8%). Up to 90% of patients reported FFA as improved or stable after receiving antiandrogen (finasteride or dutasteride) or antimalarial with topical treatment. Multivariate analyses revealed that facial lentiginous macules and trichoscopic perifollicular erythema at the frontal area were FFA severity-associated factors. “Front puff” Thai hairstyle was associated with FFA, while sunscreens and other cosmetic products were not. In conclusion, diffuse and pseudo-fringe sign pattern are common in Asian FFA. The most common autoimmune systemic comorbidity is thyroid disease, while common concomitant dermatological diseases are female pattern hair loss, lichen planopilaris and lichen planus pigmentosus. Antiandrogens or antimalarial plus topical treatment are the most useful therapy.     

Narrowband ultraviolet B phototherapy for alopecia areata

Although narrowband ultraviolet B (NB UVB) phototherapy is a well-established treatment in many dermatosis, there is little evidence of efficacy of this method for alopecia areata (AA) treatment in the literature. We undertook a retrospective review of the 25 AA patients treated with NB UVB. Intramuscular triamcinolone acetonide injections per month were used as concomitant treatment in some patients who did not have any contraindication. Eight patients (32%) received monthly intramuscular corticosteroid injections. Four (22.2%) and two (20%) patients achieved excellent response in extensive patchy hair loss patients and entire scalp hair loss patients, respectively. Four of six patients who achieved excellent response also received monthly intramuscular corticosteroid injections. When patients receiving systemic corticosteroid injections were compared with patients given only NB UVB with respect to the treatment responses, a statistically significant difference was seen in patients who achieved excellent response. NB UVB is not an effective treatment with only 20% excellent treatment responses in patients with severe AA, most of whom were also treated with systemic corticosteroids.     

Prognostic factors in methylprednisolone pulse therapy for alopecia areata

Many treatments induce remission in patients with alopecia areata. Systemic steroids, for example, are effective in the treatment of severe alopecia areata but have many side-effects. To avoid these side-effects, high-dose bolus infusions of methylprednisolone have been used to treat severe alopecia areata. The purpose of this study was to evaluate the prognostic factors associated with pulse therapy and to establish proper indications for methylprednisolone pulse therapy. Seventy patients with severe alopecia areata were treated i.v. with methylprednisolone on 3 consecutive days. All of the patients had rapid and extensive hair loss with the bald area exceeding 50% of the scalp. Seventy percent of the patients showed terminal hair growth and 41.4% showed complete responses with acceptable cosmetic outcomes. The prognostic factors that influenced successful outcome were the disease duration before treatment and the type of alopecia areata. Based on these two factors, a good response was obtained for all types of alopecia areata with a duration of 3months or less before treatment and for the plurifocal type of alopecia areata with a duration of 4-6months. Methylprednisolone pulse therapy is indicated for those alopecia areata patients who fall within our good response group.     

Adalimumab‐induced scalp psoriasis with severe alopecia

In recent years, with the increase usage of tumor necrosis factor (TNF) inhibitors, more side effects have revealed. The incidence of paradoxical psoriasis (psoriasis vulgaris, palmoplantar pustulosis, scalp psoriasis, or their combinations) ranges from 1 to 5%; however alopecia due to anti‐TNF‐α‐induced scalp psoriasis, rarely reported in the literature. We report a 37‐year‐old woman who developed palmoplantar pustulosis and scalp psoriasis with severe alopecia after 2 months of treatment with adalimumab for chronic plaque psoriasis. Biopsies from the palmar and scalp lesions showed psoriasiform changes. Adalimumab treatment was discontinued, and methotrexate was started (15 mg/weekly, subcutaneously) with topical adjuvant agents. A dramatic improvement was seen in both the skin and scalp with complete hair regrowth in 1 month. We conclude that, in anti‐TNF‐α‐induced scalp psoriasis, suspension of anti‐TNF‐α agent and systemic and topical treatments should be considered to avoid scarring alopecia.     

Maternal IL‐6 can cause T‐cell‐mediated juvenile alopecia by non‐scarring follicular dystrophy in mice

Aiming to decipher immunological mechanisms of the autoimmune disorder alopecia areata (AA), we hypothesized that interleukin‐6 (IL‐6) might be associated with juvenile‐onset AA, for which there is currently no experimental model. Upon intramuscular transgenesis to overexpress IL‐6 in pregnant female C57BL/6 (B6) mice, we found that the offspring displayed an initial normal and complete juvenile hair growth cycle, but developed alopecia around postnatal day 18. This alopecia was patchy and reversible (non‐scarring) and was associated with upregulation of Ulbp1 expression, the only mouse homolog of the human AA‐associated ULBP3 gene. Alopecia was also associated with inflammatory infiltration of hair follicles by lymphocytes, including alpha‐beta T cells, which contributed to surface hair loss. Despite these apparently shared traits with AA, lesions were dominated by follicular dystrophy that was atypical of human AA disease, sharing some traits consistent with B6 alopecia and dermatitis. Additionally, juvenile‐onset alopecia was followed by complete, spontaneous recovery of surface hair, without recurrence of hair loss. Prolonging exposure to IL‐6 prolonged the time to recovery, but once recovered, repeating high‐dose IL‐6 exposure de novo did not re‐induce alopecia. These data suggest that although substantial molecular and cellular pathways may be shared, functionally similar alopecia disorders can occur via distinct pathological mechanisms.     

Intramuscular triamcinolone acetonide: An undervalued option for refractory alopecia areata

Severe alopecia areata (AA ) can have an unpredictable clinical course and become refractory to contact immunotherapy. Novel treatment options include low‐dose interleukin‐2 and Janus kinase inhibitors; however, these treatments are still under investigation. Therefore, we evaluated the efficacy and safety of intramuscular (i.m.) triamcinolone acetonide (TAC ) as a rescue therapy for refractory AA . We retrospectively analysed efficacy, adverse effects and relapse rate of i.m. TAC monthly in 27 patients with refractory AA . We defined AA as refractory if the patient showed an unsatisfactory response to both systemic treatment (not i.m. TAC ) and the consecutive diphenylcyclopropenone immunotherapy. The initial systemic treatment of other forms of corticosteroids and/or cyclosporin was used to control extensive AA involving more than 25% of the scalp. Administration of i.m. TAC for 3–6 months resulted in a 63.0% response rate, and all patients showed inactive disease after treatment. Final hair regrowth negatively correlated with initial scalp involvement (Spearman r = ?0.595, P = 0.001). All patients showed complete recovery of adrenocortical reserve within 3 months after the last injection. Adverse effects of systemic steroid therapy were observed only in female patients (dysmenorrhea and osteoporosis). i.m. TAC may provide a valuable therapeutic option to manage active hair loss and facilitate hair regrowth in refractory AA , especially in male patients.     

Alopecia areata: Clinical presentation, diagnosis, and unusual cases

Alopecia areata (AA) is a nonscarring hair loss disorder with a 2% lifetime risk. Most patients are below 30 years old. Clinical types include patchy AA, AA reticularis, diffuse AA, AA ophiasis, AA sisiapho, and perinevoid AA. Besides scalp and body hair, the eyebrows, eyelashes, and nails can be affected. The disorder may be circumscribed, total (scalp hair loss), and universal (loss of all hairs). Atopy, autoimmune thyroid disease, and vitiligo are more commonly associated. The course of the disease is unpredictable. However, early, long‐lasting, and severe cases have a less favorable prognosis. The clinical diagnosis is made by the aspect of hairless patches with a normal skin and preserved follicular ostia. Exclamations mark hairs and a positive pull test signal activity. Dermoscopy may reveal yellow dots. White hairs may be spared; initial regrowth may also be nonpigmented. The differential diagnosis includes trichotillomania, scarring alopecia, and other nonscarring hair loss disorders such as tinea capitis and syphilis.     

Guidelines for the diagnosis and treatment of male‐pattern and female‐pattern hair loss, 2017 version

Male‐pattern hair loss (MPHL, androgenetic alopecia) is a slowly progressive form of alopecia which begins after puberty. In 2010, we published the first Japanese edition of guidelines for the diagnosis and treatment of MPHL. It achieved the original goal of providing physicians and patients in Japan with evidence‐based information for choosing efficacious and safe therapy for MPHL. Subsequently, new therapeutic drugs and treatment methods have been developed, and women's perception of MPHL has undergone change and the term “female‐pattern hair loss (FPHL)” is becoming more common internationally. Thus, here we report a revised version of the 2010 guidelines aimed at both MPHL and FPHL. In these guidelines, finasteride 1 mg daily, dutasteride 0.5 mg daily and topical 5% minoxidil twice daily for MPHL, and topical 1% minoxidil twice daily for FPHL, are recommended as the first‐line treatments. Self‐hair transplantation, irradiation by light‐emitting diodes and low‐level lasers, and topical application of adenosine for MPHL are recommended, whereas prosthetic hair transplantation and oral administration of minoxidil should not be performed. Oral administration of finasteride or dutasteride are contraindicated for FPHL. In addition, we have evaluated the effectiveness of topical application of carpronium chloride, t‐flavanone, cytopurine, pentadecane and ketoconazole, and wearing a wig. Unapproved topical application of bimatoprost and latanoprost, and emerging hair regeneration treatments have also been addressed. We believe that the revised guidelines will improve further the diagnostic and treatment standards for MPHL add FPHL in Japan.     

Multi‐therapies in androgenetic alopecia: review and clinical experiences

Androgenetic alopecia (AGA) is a genetically determined progressive hair‐loss condition which represents the most common cause of hair loss in men. The use of the medical term androgenetic alopecia reflects current knowledge about the important role of androgens and genetic factors in its etiology. In addition to androgen‐dependent changes in the hair cycle, sustained microscopic follicular inflammation contributes to its onset. Furthermore, Prostaglandins have been demonstrated to have the ability in modulating hair follicle cycle; in particular, PGD2 inhibits hair growth while PGE2/F2a promote growth. Due to the progressive nature of AGA, the treatment should be started early and continued indefinitely, since the benefit will not be maintained upon ceasing therapy. To date, only two therapeutic agents have been approved by the Food and Drug Administration and European Medicines Agency for the treatment of AGA: topical minoxidil and oral finasteride. Considering the many pathogenetic mechanisms involved in AGA, various treatment options are available: topical and systemic drugs may be used and the choice depends on various factors including grading of AGA, patients' pathological conditions, practicability, costs and risks. So, the treatment for AGA should be based on personalized therapy and targeted at the different pathophysiological aspects of AGA.