Efficacy and safety of methotrexate in alopecia areata

BACKGROUND

Alopecia areata is a chronic disorder of the hair follicles and nails, of unknown etiology, with clear autoimmune components and genetic factors. Several therapeutic options have been suggested; however, no treatment is able to modify the disease course. Methotrexate is an immunosuppressant used in various dermatoses and recently introduced as a therapeutic option for alopecia areata.

OBJECTIVES

To evaluate the efficacy and safety of methotrexate in alopecia areata.

METHODS

In a retrospective, non-controlled study, we evaluated 31 patients with alopecia areata in current or prior treatment with methotrexate to assess the therapeutic response according to sex, age, pattern of alopecia areata, disease duration, cumulative dose of methotrexate, use of systemic corticosteroids or other treatments, and drug safety.

RESULTS

Regrowth greater than 50% was observed in 67.7% of patients, with the best responses observed in those with <5 years of disease progression (79%), age over 40 years (73.3%), male patients (72.8%), cumulative dose of methotrexate 1000-1500 mg, and multifocal alopecia areata (93%). Among patients receiving systemic corticosteroids in combination with methotrexate, 77.3% had greater than 50% regrowth, compared with 44.4% in those who used methotrexate alone. The therapeutic dose ranged from 10-25 mg/week. No patient had serious adverse effects. Relapse was observed in 33.3% of patients with more than 50% regrowth.

CONCLUSION

Methotrexate appears to be a promising and safe medication for the treatment of severe alopecia areata when used alone or in combination with corticosteroids.     

Combination Therapy with Cyclosporine and Psoralen Plus Ultraviolet A in the Patients with Severe Alopecia Areata: A Retrospective Study with a Self-Controlled Design

Background

Alopecia areata (AA) is believed to be an organ-specific autoimmune disease in which a mononuclear cell infiltrate develops in and around anagen hair follicles. There is no definitive therapy for AA.

Objective

We sought to determine whether the combination therapy of cyclosporine and psoralen plus ultraviolet A (PUVA) could be an effective treatment for severe AA.

Methods

A total of 41 patients with severe AA were treated with oral cyclosporine and topical PUVA. Cyclosporine was given at an initial daily dose of 200 mg for adult and 100 mg for children for periods of up to 16 weeks. Eight-methoxypsoralen (Methoxsalen) was applied topically 20 minutes prior to ultraviolet A (UVA) exposure, and the patients were irradiated with UVA twice a week for 16 weeks.

Results

Of the total 41 patients, 2 (7.3%) patients were lost to follow-up, and 1 (2.4%) patient discontinued the treatment due to abdominal discomfort. Six (14.6%) patients were treated for less than 12 weeks. Of remaining 32 patients, 3 (9.4%) showed excellent response, 3 (9.4%) showed good response, 12 (37.5%) showed fair response, and 14 (43.7%) showed poor response.

Conclusion

Although limited by its uncontrolled character, this study shows that the combination therapy with cyclosporine and PUVA may be an additional choice for severe and recalcitrant AA.     

ALOPECIA AREATA IS NOT ASSOCIATED WITH HELICOBACTER PYLORI

Background:

Alopecia areata (AA) is an immune-mediated form of hair loss that occurs in all ethnic groups, ages, and both sexes. Helicobacter pylori has been associated with many extra-digestive dermatological conditions. The causal relation between alopecia areata and Helicobacter pylori is discussed in this study.

Materials and Methods:

We have screened for the presence of H. pylori in patients with AA, in order to determine any potential role in its patho-physiology. We have prospectively studied 31 patients with alopecia areata and 24 healthy volunteers of similar gender, for the presence of H. pylori stool antigen (HpSAg).

Results:

Optical density values for H. pylori infection was positive in 18 of the 31 patients evaluated (58.1%), while in 13 patients, the values did not support H. pylori infection (41.9%). In the control group, 10 of the 24 (41.7%) had positive results. Within the group of alopecia areata, there was no significant difference between HpSAg positive and negative patients.

Conclusions:

The results have shown that a relation between Helicobacter pylori and alopecia areata is not supported. We advise that H. pylori detection need not to be included in the laboratory work up of alopecia areata.     

Alopecia Areata in the Elderly: A 10-Year Retrospective Study

Background

Alopecia areata (AA) is an organ-specific autoimmune disease that typically occurs in young adults. AA in the elderly is relatively rare, thus little data have been reported.

Objective

This study aimed to understand the clinical characteristics of AA in the elderly.

Methods

We performed a 10-year retrospective study of AA in the elderly who visited our dermatologic clinic from January 2002 to December 2011. A clinical review of medical records and telephone interviews were performed by two dermatologists.

Results

Among 1,761 patients with newly diagnosed AA, 61 (3.5%) were older than 60 years at the first visit. Among those who completed a telephone interview, 74.3% (26/35) had less than 50% of scalp-localized hair loss. There was no association between the extent of AA and hair graying (p=0.679). Favorable therapeutic response was observed in 62.9% (22/35) of cases.

Conclusion

AA in the elderly shows mild disease severity and favorable treatment response. There is no association between graying and the extent of AA. However, the influence of aging on the pathogenesis of AA in the elderly deserves further investigation.     

Utility of dermoscopy in alopecia areata

Background:

Alopecia areata (AA) shows several well-defined dermoscopic features which may help in confirming diagnosis in AA.

Aims:

We carried out a study to examine the dermoscopic features of AA and develop a protocol for diagnosis of AA by dermoscopy.

Materials and Methods:

Dermoscopy was performed in 66 patients with AA. Hanse HVS-500NP dermoscope (magnification of ×32 and ×140) was used.

Results:

The mean age of the patients (46 males and 20 females) was 26.85 years. The mean age of onset was 25.15 years. The mean duration of alopecia was 10.3 months. Most common AA in our study was patchy type (57/66, 87.7%). Single patch was seen in 24 patients and multiple patches in 33 patients. Diffuse AA was seen in five patients. Ophiasis and alopecia universalis were seen in two patients each. Nail changes were fine pitting (4), ridging (2), thinning of nail plate (2). Twenty nail dystrophy, distal onycholysis, striate leukonychia and coarse pitting were seen in one patient each. Intralesional triamcinolone acetonide was the most common therapy offered. Others were oral betamethasone minipulse therapy, dexamethasone pulse, minoxidil, anthralin and corticosteroids. The most common dermoscopic finding was yellow dots seen in 54 patients (81.8%), followed by black dots (44 patients, 66.6%), broken hairs (36 patients, 55.4%), short vellus hair (27 patients, 40.9%) and tapering hairs (8 patients, 12.1%).

Conclusions:

The most common dermoscopic finding of AA in our study was yellow dots, followed by black dots, broken hairs, short vellus hair and tapering hairs. Dermoscopic findings were not affected by the type of AA or the severity of the disease.     

Association between IL17A/IL17RA Gene Polymorphisms and Susceptibility to Alopecia Areata in the Korean Population

Background

Alopecia areata is marked by autoimmune assault on the hair follicle resulting in hair loss. T helper 17 cell subset has important roles in protecting the host against extracellular pathogens, however, also promotes inflammatory pathology in autoimmune disease, and it expresses both interleukin (IL)-17A and IL-17F, which can signal via the IL-17 receptor A.

Objective

To investigate the significance of IL17A and IL17RA gene polymorphisms in the susceptibility to alopecia areata.

Methods

We conducted case-control association study of 238 alopecia areata patients and 270 matched healthy controls. Allele frequency of total 2 single nucleotide polymorphims in the IL17A gene and 4 single nucleotide polymorphims in the IL17RA gene were studied. The statistical analyses were performed according to onset age, the presence of familyhistory, clinical subtypes, and presence of nail involvement or body hair involvement.

Results

One single nucleotide polymorphim (rs879577) of IL17RA gene showed significant difference between alopecia areata patients group and controls group (p= 0.0288). One single nucleotide polymorphim (rs4819554) of IL17RA gene showed significant difference between the early onset and late onset alopecia areata (p=0.0421).

Conclusion

IL17RA gene polymorphism might contribute to the increased susceptibility to alopecia areata in Korean population, and IL17RA gene polymorphism may be associated with onset age.     

Preferential Recognition of Hydroxyl Radical-Modified Superoxide Dismutase by Circulating Autoantibodies in Patients with Alopecia Areata

Background

Alopecia areata (AA) is a common form of localized, non-scarring hair loss. The cause of AA is unknown but reports suggest an autoimmune etiology, where oxygen free radicals play an important role.

Objective

The aim of this study was to investigate the role of a hydroxyl radicals (·OH)-modified antioxidant enzyme, superoxide dismutase (SOD), in AA autoimmunity.

Methods

SOD was modified by ·OH radicals. Binding characteristics of autoantibodies in AA patients (n=26) against ·OH-modified SOD (·OH-SOD) were evaluated by immunoassays and the results were compared with those of healthy, age-matched controls (n=30). The effects of ·OH radicals on immunoglobulin G (IgG) isolated from AA patients were studied.

Results

Highly specific binding to ·OH-SOD was observed in 32% of the samples of patient sera, whereas normal human sera showed negligible binding with either antigen. Competitive inhibition immunoassays reiterated the results from direct binding. Protein-A-purified IgG from AA patients (AA-IgG) also showed strong binding to ·OH-SOD as compared to IgG from normal human controls (p<0.001). In addition, AA-IgG from patients with alopecia universalis recognized ·OH-SOD to a greater extent than did AA-IgG from patients with the patchy, persistent type of alopecia. Furthermore, sera from AA patients had lower levels of SOD activity as compared to control sera.

Conclusion

This is the first report showing an association between ·OH-modified SOD and AA. These novel results demonstrate that ·OH radical-mediated changes in SOD present unique neo-epitopes that might contribute to antigen-driven antibody induction in AA.     

Dermoscopic Approach to a Small Round to Oval Hairless Patch on the Scalp

Background

Various kinds of alopecia can show small round or oval hairless patch. Dermoscopy could be a simple, useful tool for making a correct diagnosis.

Objective

The aim of this study is to investigate clinical usefulness of dermoscopy for diseases with small round or oval hairless patch on the scalp.

Methods

Dermoscopic examination was performed for 148 patients with small round or oval hairless patch using DermLite® II pro. The type and its patient number of alopecia investigated in the study were as below: alopecia areata (n=81), trichotillomania (n=24), tinea captis (n=13), traction alopecia (n=12), lichen planopilaris (n=8), discoid lupus erythematosus (n=7), congenital triangular alopecia (n=2) and pseudopelade of Brocq (n=1). The significance of dermoscopic findings for each disease were evaluated.

Results

Characteristic dermoscopic findings of alopecia areata were tapering hairs and yellow dots. Those of trichotillomania and traction alopecia were broken hairs. Dermoscopic findings of tinea capitis included bent hairs, perifollicular white macules and greasy scales. Discoid lupus erythematosus and lichen planopilaris were characterized by dermoscopic findings of lack of follicular ostia. Furthermore, keratin plugs were frequently seen in discoid lupus erythematosus whereas perifollicular hyperkeratosis and erythema were frequently seen in lichen planopilaris.

Conclusion

Dermoscopic examination for small round or oval hairless patch showed characteristic findings for each disease. Based on these results, we propose dermoscopic algorithm for small round or oval hairless patch on the scalp.     

Differences in Comorbidity Profiles between Early-Onset and Late-Onset Alopecia Areata Patients: A Retrospective Study of 871 Korean Patients

Background

Alopecia areata (AA) is a common dermatologic condition with a broad spectrum of clinical features and age of onset, classically characterized by nonscarring patches of hair loss. In the past, early-onset (before adolescence) AA has been associated with various autoimmune diseases, especially atopic diseases and lupus erythematosus and demonstrates a worse prognosis compared with late onset AA.

Objective

To evaluate the differences in the comorbidity profile of AA with regard to age at onset.

Methods

We completed a retrospective study of 871 Korean AA patients seen at our department within the last 10 years. After these patients were subdivided according to onset before or after age 13 years, the two groups were compared on the basis of their comorbid disorders, family history of AA, and hematologic test results.

Results

Our results demonstrate that significantly more patients in the early-onset group had a personal history of atopic dermatitis or family history of AA. These findings are consistent with previous reports associating early-onset AA with autoimmune diseases and a family history of AA in different ethnic populations. Most of the serologic test values showed no significant differences between the groups and the results were considerably affected by age.

Conclusion

This study is significant because it is a large group study in Korean AA patients, and Korean AA patients with an onset age before adolescence show similar clinical manifestations to other ethnic populations.     

Trichoscopic Findings of Hair Loss in Koreans

Background

Trichoscopic findings of hair loss have been well described for the differential diagnosis of alopecia; however, critical findings were not thoroughly investigated or compared among all ethnic groups, including Asians.

Objective

We aimed to find any characteristic trichoscopic findings in Korean alopecia patients and to verify whether those findings are closely related to previously reported observations.

Methods

Three hundred and twenty-seven patients with hair loss of various causes and 160 normal scalps were analyzed. Trichoscopic examination was performed with a polarized-light handheld dermoscope.

Results

A total of 35 patterns of trichoscopic features were represented, and certain features were significantly common or observed exclusively in a particular type of alopecia as follows: yellow dots, exclamation mark hairs, and proximal tapering hairs (alopecia areata), trichoptilosis and pointed hairs (trichotillomania), corkscrew hairs, septate hyphae hairs, and comma hairs (tinea capitis), diffuse white area, fibrotic white dots, and tufting hairs (primary cicatricial alopecia), hair diameter diversity and peripilar sign (androgenetic alopecia), and short nonvellus hairs (telogen effluvium).

Conclusion

The characteristic trichoscopic features for the differential diagnosis of alopecia in Koreans, shown as follicular, perifollicular, and hair shaft patterns, are similar to those of Caucasians; however, the frequencies of the pigment patterns are different between Koreans and Caucasians because of the contrast effect of the skin and hair color. Therefore, racial difference should be considered in the trichoscopic evaluation for differential diagnosis.     

COMPARATIVE ASSESSMENT OF TOPICAL STEROIDS, TOPICAL TRETENOIN (0.05%) AND DITHRANOL PASTE IN ALOPECIA AREATA

Background:

There have been various controversial reports regarding the efficacy of topical agents in topical therapy of alopecia areata.

Aim:

The study aims to find out the effective ones among the readily available ones for a dermatologist.

Materials and Methods:

Eighty patients were chosen from the skin OPD of Bankura Sammilani Medical College, Bankura, West Bengal, after evaluating the exclusion criterions. Treatments were continued for 3 month period and a follow up after further 3 months. After dividing them into four groups–group-I (topical steroids), group-II (topical tretinoin 0.05%) group-III (dithranol paste 0.25%), and group-IV (white soft petrolatum jelly)–patients were evaluated.

Results:

Seventy percent of group-I, 55% of group-II, 35% of group-III, and 20% of the control group (white soft petrolatum jelly) responded favorably. Side effects in the form of dermatitis and hyperpigmentation were seen in group-III. However, no patient discontinued from the study.

Conclusion:

We conclude that both topical steroids and tretinoin were fairly effective in limited variant of alopecia areata.     

Analysis of Serum Zinc and Copper Concentrations in Hair Loss

Background

It is well known that some trace elements such as zinc and copper play a significant role in many forms of hair loss. However, the effect of zinc and copper in the pathogenesis of hair loss is still unknown.

Objective

The purpose of this study is to evaluate the zinc and copper status in each of four types of hair loss.

Methods

A study was carried out with 30 health controls and 312 patients who were diagnosed with alopecia areata (AA), male pattern hair loss, female pattern hair loss and telogen effluvium (TE) (2008 to 2011; Hallym University Kangdong Sacred Heart Hospital). Zinc and copper serum concentrations were evaluated between controls and each of four types of hair loss patients.

Results

In all of the hair loss patients, the mean serum zinc was 84.33±22.88, significantly lower than the control group (97.94±21.05 µg/dl) (p=0.002), whereas the serum copper was 96.44±22.62, which was not significantly different (p=0.975). The analysis of each group showed that all groups of hair loss had statistically lower zinc concentration, but not copper concentrations. However, the ratio of the patients with serum zinc concentration lower than 70 µg/dl was significantly high in only the AA group (odds ratio, OR 4.02; confidence interval, CI 1.13 to 14.31) and the TE group (OR 1.12; CI 1.12 to 17.68).

Conclusion

The data led to the hypothesis of zinc metabolism disturbances playing a key role in hair loss, especially AA and TE, whereas the effect of copper on hair growth and shedding cycles still needs more study.     

Tumor necrosis factor-alpha in patients with alopecia areata

Background:

Alopecia areata (AA) is a common form of localized, nonscarring hair loss. It is characterized by the loss of hair in patches, total loss of scalp hair (alopecia totalis, AT), or total loss of body hair (alopecia universalis, AU). The cause of AA is unknown, although most evidence supports the hypothesis that AA is a T-cell-mediated autoimmune disease of the hair follicle and that cytokines play an important role.

Aims:

The aim of the study was to compare the serum levels of tumor necrosis factor-alpha (TNF-α) in patients with AA and the healthy subjects and also to investigate the difference between the localized form of the disease with the extensive forms like AT and AU.

Materials and Methods:

Sixty patients with AA and 20 healthy controls were enrolled in the study. Forty-six patients had localized AA (LAA), and 14 patients had AT, AU, or AT/AU. The serum levels of TNF-α were measured using enzyme-linked immunoassay techniques.

Results:

Serum levels of TNF-α were significantly higher in AA patients than in controls (10.31 ± 1.20 pg ml vs 9.59 ± 0.75 pg/ml, respectively). There was no significant difference in serum levels of TNF-α between patients with LAA and those with extensive forms of the disease.

Conclusion:

Our findings support the evidence that elevation of serum TNF-α is associated with AA. The exact role of serum TNF-α in AA should be additionally investigated in future studies.     

Scalp Dermatoscopic Findings in Androgenetic Alopecia and Their Relations with Disease Severity

Background

Clinicians are searching for new methods to diagnose and predict the course of androgenetic alopecia noninvasively.

Objective

Our aim is to evaluate trichoscopic findings and their relations with disease severity in androgenetic alopecia.

Methods

The videodermatoscopic findings of 143 female and 63 male patients with androgenetic alopecia were compared with each other, with those of healthy subjects (n=100), and with those of patients with other nonscarring alopecias (n=208). Mann-Whitney U-test, χ² analyses, and logistic regression analysis were used for statistical analysis.

Results

No statistically significant relation was found between trichoscopic findings and severity in male androgenetic alopecia (MAGA) on the basis of the modified Hamilton Norwood scale (among 7 degrees); however, multihair follicular unit and perifollicular pigmentation were related to low severity whereas white dots, honeycomb pattern pigmentation, and brown dots were related to high severity. On the other hand, according to the Ludwig classification, arborizing red lines were related to low severity and brown dots were related to high severity, whereas there was no difference in stages between the Ebling and Olsen classifications in female androgenetic alopecia (FAGA). In the characteristic trichoscopic findings in this study, perifollicular pigmentation was found as a normal feature of the scalp, whereas multihair follicular unit and honeycomb pigment pattern, which were previously considered as normal features, were observed to be related to androgenetic alopecia.

Conclusion

No relation was found between MAGA severity and trichoscopic findings, as well as between FAGA severity according to different disease severity classifications and trichoscopic findings.     

Quality of Life Assessment in Male Patients with Androgenetic Alopecia: Result of a Prospective, Multicenter Study

Background

Androgenetic alopecia (AGA) is a common hair loss disease with genetic predisposition among men and women, and it may commence at any age after puberty. It may significantly affect a variety of psychological and social aspects of one''s life and the individual''s overall quality of life (QoL).

Objective

This study aimed to investigate the QoL of AGA patients and discover the factors that can influence the QoL of AGA patients, including previous experience in non-medical hair care, reasons for hospital visits, age, duration, and the severity of AGA.

Methods

A total of 998 male patients with AGA were interviewed, using the Hair Specific Skindex-29 to evaluate the QoL of AGA patients.

Results

The results of the Hair Specific Skindex-29 on patients with AGA were as follows: symptom scale: 26.3±19.5, function scale: 24.0±20.1, emotion scale: 32.1±21.8, and global score: 27.3±19.1. According to this assessment, QoL was more damaged if the patient had severe alopecia, a longer duration of AGA, younger age, had received previous non-medical hair care, and visited the hospital for AGA treatment.

Conclusion

This study showed that AGA could harmfully affect the patients'' QoL. These findings indicate that dermatologists should address these QoL issues when treating patients with alopecia.     

The Relationship Between Alopecia Areata and Alexithymia,Anxiety and Depression: A Case-Control Study

Background:

Alopecia areata (AA) is a skin disease characterized by the sudden appearance of areas of hair loss on the scalp and other hair-bearing areas, but its aesthetic repercussions can lead to profound changes in patient''s psychological status and relationships.

Aim:

The goal was to investigate a possible relationship between AA and alexithymia as well as two other emotional dimensions, anxiety and depression.

Materials and Methods:

Fifty patients with AA seen in the Department of Dermatology of Hedi Chaker University Hospital, Sfax were included in this study. Anxiety and depression were evaluated by Hospital Anxiety and Depression scale questionnaire, alexithymia was assessed by Toronto Alexithymia scale 20, and severity of AA was measured by Severity of Alopecia Tool.

Results:

Patient''s mean age was 32.92 years. 52% of patients were females. Depression and anxiety were detected respectively in 38% and 62% of patients. There was statistically significant difference between patients and control group in terms of depression (P = 0.047) and anxiety (P = 0.005). Forty-two percent of patients scored positive for alexithymia. No significant difference was found between patient and control groups (P = 0.683) in terms of alexithymia. Anxiety was responsible for 14.7% of variation in alexithymia (P = 0.047).

Conclusions:

Our study shows a high prevalence of anxiety and depressive symptoms in AA patients. Dermatologists should be aware of the psychological impact of AA, especially as current treatments have limited effectiveness.     

Topical Corticosteroid Phobia among Parents of Children with Atopic Eczema in Korea

Background

Topical corticosteroids (TCS) are the first-line agents for the treatment of atopic dermatitis (AD). However, a vague phobia concerning the use of TCS exists among parents of children with AD because of misinformation, and studies on the subject are insufficient.

Objective

To assess the current state of steroid phobia among parents of atopic children in Korea and to investigate the importance of education in its reduction.

Methods

By using a structured questionnaire, 126 parents of children with AD (22.2% fathers, 77.8% mothers) were interviewed. After the questionnaire administration, all participants were educated about TCS use.

Results

Overall, 67.5% of the parents showed steroid phobia. A statistical correlation was found between steroid phobia and knowledge of potential adverse events, experience of TCS use, and adherence to treatment (p<0.05). Adherence to treatment tended to be lower among parents with steroid phobia. The most recognized adverse effects of TCS were skin atrophy and thinning (71.9%). The most prevalent information source leading to steroid phobia was the Internet (49.2%). The risk factors for steroid phobia were AD severity (odds ratio [OR]=5.332 [moderate], 9.040 [severe] vs. mild; p=0.001) and the knowledge of potential adverse events (OR=2.658; p=0.021).

Conclusion

We found a high prevalence of steroid phobia among parents of patients with AD, and here show the impact of this phobia on treatment adherence. We emphasize the important role of dermatologists as providers of accurate information and appropriate education about the use of TCS.     

Comorbid autoimmune diseases in patients with pemphigus: a nationwide case-control study in Taiwan

Background

Previous studies have proposed the association between pemphigus and several autoimmune diseases, but no large-scale study has been reported.

Objectives

To delineate the association between pemphigus and autoimmune diseases including psoriasis.

Materials & Methods

A total of 1,998 patients with pemphigus and 7,992 control subjects were enrolled from the National Health Insurance Research Database in Taiwan from 1997 to 2010. The odds of comorbidities between these two groups were analysed by multivariate logistic regression.

Results

Compared with control subjects, patients with pemphigus were much more likely to have Sjögren’s syndrome (odds ratio [OR]: 15.0; 95% confidence interval [CI]: 3.16-71.5), psoriasis (OR: 7.18; 95% CI: 5.55-9.29), systemic lupus erythematosus (OR: 4.46; 95% CI: 1.88-10.6), and alopecia areata (OR: 2.68; 95% CI: 1.26-5.67). According to gender-stratified analyses, however, the association between pemphigus and Sjögren’s syndrome or alopecia areata was found to be significant only in the female patients.

Conclusion

We confirm the association between pemphigus and some autoimmune diseases, including Sjögren’s syndrome, systemic lupus erythematosus, and alopecia areata. In addition, we present the novel finding that patients with pemphigus have an increased risk of psoriasis.