Early Intervention with High-Dose Steroid Pulse Therapy Prolongs Disease-Free Interval of Severe Alopecia Areata: A Retrospective Study

Background

Spontaneous recovery of severe alopecia areata is rare and the condition is difficult to treat.

Objective

The aim of this study is to investigate and compare the effects and safety of steroid pulse therapy between oral and intravenous administrations between 1999 and 2010 at the Department of Dermatology, National Cheng Kung University Hospital.

Methods

Data were retrospectively retrieved. A satisfactory response was defined as more than 75% hair regrowth in the balding area.

Results

A total of 85 patients with more than 50% hair loss were identified and treated, with an overall satisfactory response rate of 51.8%. The mean follow-up time was 37.6 months, with a relapse rate of 22.7%. Patients with alopecia areata (hereafter, AA) of recent onset within one year showed higher response rates (p<0.001) and lower relapse rates compared to patients with AA persisting for more than 1 year. Further, even in patients with alopecia totalis, alopecia universalis or ophiasis type, early treatment resulted in a satisfactory response rate of 47% among the treated patients. In general, oral therapy was as effective and well-tolerated as intravenous therapy.

Conclusion

The response rate is determined by disease severity and time of intervention, not by the administration form of steroid pulse therapy. Oral steroid pulse therapy can be considered as the first-line treatment for patients with severe AA of recent onset within one year.     

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.     

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.     

Interleukin-17 and Interleukin-22 Induced Proinflammatory Cytokine Production in Keratinocytes via Inhibitor of Nuclear Factor ��B Kinase-�� Expression

Background

The pathogenesis of psoriasis may involve the interleukin (IL)-23 and Th17-mediated immune responses. Th17 cells secret IL-17 and IL-22, which mediates dermal inflammation and acanthosis.

Objective

As inhibitor of nuclear factor κB kinase-α (IKKα) has been previously identified as a primary regulator of keratinocyte differentiation and proliferation, we proposed that IL-17 and IL-22 might affect keratinocyte differentiation by changing the expression of IKKα.

Methods

We employed HaCaT cells maintained culture medium at a low calcium concentration (0.06 mM) and induced differentiation by switching to the high concentration (2.8 mM) media with IL-17 or IL-22, then compared the IKKα expression and the cell cycle. We employed reconstituted human epidermal skin (Neoderm) and mice ears for the in vivo studies.

Results

Elevated calcium concentration induced IKKα expression and terminal differentiation with cell cycle arrest in HaCaT cell cultures. Moreover, IL-17 and IL-22 treatment also induced IKKα in HaCaT cells and reconstituted human epidermis. IKKα induction was also noted, following the injection of IL-17 and IL-22 into mice ears.

Conclusion

Although the induction of IKKα was accompanied by keratinocyte differentiation, IL-17 and IL-22 did not affect calcium-mediated differentiation or the cell cycle. Rather, IL-17 and IL-22 appear to contribute to the inflammation occurring via the induction of IKKα from keratinocytes or skin layers.     

Detection of a Novel Missense Mutations in Atrichia with Papular Lesions

Background

Atrichia with papular lesions (APL) is a rare inherited disease characterized by early onset of total hair loss, followed by papular lesions over the extensor areas of the body. Recently, mutations in the human hairless (HR) gene have been implicated in its pathogenesis. The identification of mutations in the HR gene is important for differentiating between APL and alopecia universalis (AU).

Objective

We compared the HR genes of patients with presumed AU who showed minimal or no response to treatment with the HR genes of healthy controls.

Methods

The subjects were 11 patients with presumed AU who had not responded to treatments. Fifty healthy people were included as controls for molecular analysis. To screen for mutations, polymerase chain reaction was performed.

Results

DNA analysis identified a novel heterozygous G-to-A transition at nucleotide position 191 in exon 5. The mutation was not found in the controls, other AU patients, or any unaffected family members except for the patients'' mother and maternal grandfather, who were heterozygous HR gene carriers.

Conclusion

Our study identifies a novel missense mutation in exon 5 of the HR gene in a Korean APL patient previously diagnosed as AU.     

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.     

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.     

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.     

The Efficacy and Safety of 17α-Estradiol (Ell-Cranell? alpha 0.025%) Solution on Female Pattern Hair Loss: Single Center,Open-Label,Non-Comparative,Phase IV Study

Background

There are several commercially available agents to treat female pattern hair loss (FPHL), including minoxidil solution, anti-androgen agents and mineral supplements. However, these treatments are not always satisfactory. We report the results of a clinical trial of 17α-estradiol (Ell-Cranell® alpha 0.025%) solution to Korean female patients with FPHL.

Objective

This study was designed to examine the efficacy and safety of Ell-Cranell® alpha 0.025% solution in Korean female patients with FPHL.

Methods

A total of 53 women, 18 to 55 years old, applied topical Ell-Cranell® alpha 0.025% solution once daily for 8 months. Efficacy was evaluated by the change of hair counts and diameter, subjective assessment, and photographic assessment by investigators.

Results

Hair counts and diameter from baseline to 4 and 8 months after treatment increased in treated patients and these changes were statistically significant (p<0.0001). 17α-estradiol (Ell-Cranell® alpha 0.025%) solution showed significant improvement by subjective self-assessment and by investigator photographic assessment. Ell-Cranell® alpha 0.025% solution was well tolerated over 8-months period.

Conclusion

This study showed that Ell-Cranell® alpha 0.025% solution is a safe and effective agent for Korean women with FPHL.     

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.     

The Annual Changes of Clinical Manifestation of Androgenetic Alopecia Clinic in Korean Males and Females: A Outpatient-Based Study

Background

Androgenetic alopecia (AGA) is characterized by the local and gradual transformation of terminal scalp hair into vellus hair, which has a shorter and thinner shaft. There are no studies that analyze annual changes in age, patterns, family history, and associated disease.

Objective

We investigated the severity of hair loss, age of onset, the frequency of family history, and past medical histories in Korean patients with AGA.

Methods

A retrospective chart review was performed to identify all patients with AGA referred to the Dermatology Clinic at Chung-Ang University Hospital from January 2006 to December 2010.

Results

The age of onset was also gradually decreased from 34.1±10.1 years to 31.6±10.9 years between 2006 and 2010. In female patients, specific annual changes were not observed. Hamilton-Norwood Type IIIv AGA was most common in male patients and Ludwig Type I AGA was most common in female patients at all times between 2006 and 2010. The majority of patients with AGA had a family history of baldness and was most commonly associated with a paternal pattern of inheritance. Seborrheic dermatitis was the most common associated disease in male and female patients.

Conclusion

Our results show the possibilities that the average age of onset is decreasing. The period of the present study was only 5 years, which is not sufficient for the precise determination of onset age for AGA. Clearly, a long-term study is needed.     

The Pattern of Hair Dyeing in Koreans with Gray Hair

Background

Hair graying is considered as a part of normal ageing process. Nonetheless, this process raises a significant cosmetic concern, especially among ethnic Korean elderly whose baseline hair color is black. For this reason, Korean elderly dye their hair with frequency despite the risk of dermatologic problems such as allergic contact dermatitis.

Objective

In this study, the authors investigate the prevalence and pattern of hair dyeing and its relation with scalp diseases in Korea.

Methods

Six hundred twenty subjects (330 men and 290 women) with graying hair were given a questionnaire survery and underwent a physical examination.

Results

Of the 620 total, 272 subjects (43.9%) dyed their hair. Hair dyeing was significantly more frequent among women than among men (p<0.001). Subjects from 50 to 69 years of age showed higher prevalence of hair dyeing when compared to either younger or older groups. Subjective self-assessment of the extent of hair graying was associated with increased prevalence of hair dyeing, that is, individuals who feel graying has advanced by more than 20% of the overall hair were much more likely to dye their hair (p<0.001). Hair dyeing did not correlate with either alopecia or scalp disease.

Conclusion

Our survey has found that the prevalence of hair dyeing is higher among Korean women than men. People in their fifties and sixties and people with more than 20% extent of grayness were more likely to dye their hair than otherwise. Hair dyeing was not associated with any increase in the prevalence of scalp diseases.     

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.     

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.     

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.     

mRNA Expression Level of Interleukin Genes in the Determining Phases of Beh?et's Disease

Background

Behçet''s disease (BD), first described in 1937 as a triadic complex of symptoms (oral aphthae, genital ulcers, and hypopyon uveitis), is a chronic, relapsing, multisystemic idiopathic inflammatory disease.

Objective

The objective of this study was to investigate the usability of messenger RNA (mRNA) expression of cytokine genes for following up patients with BD and also assess polymorphisms in these genes as to how they influence mRNA expression.

Methods

This study investigated the role of the IL1A -889(C/T), IL1B -511(C/T), and IL2 -330(T/G) polymorphisms by polymerase chain reaction (PCR)-restriction fragment length polymorphisms and the expression levels of the genes by real-time PCR in BD.

Results

The frequency of the IL2 -330 G allele was found to be significantly higher in patients with BD. A decreased level of IL1A gene expression was found in the patient group with clinically active BD compared to controls. Increased IL1B gene expression levels werefound in patient groups with active, inactive, or ocular BD (p<0.001). IL2 gene expression level manifested no significant change compared to controls in the patient group with clinically active BD; it increased in the groups with clinically inactive BD or ocular involvement.

Conclusion

IL1A, IL1B, and IL2 gene expression, and IL2 promoter polymorphisms, may be valuable markers for predicting risk in the development of BD. We believe that the results reveal the importance of achieving a better understanding of BD and the prospects of developing future therapeutic strategies.     

Sox9 Increases the Proliferation and Colony-forming Activity of Outer Root Sheath Cells Cultured In Vitro

Background

β-catenin plays a pivotal role in hair follicle development and hair growth cycle.

Objective

The aim of this study was to identify β-catenin-regulated genes in cultured human hair outer root sheath (ORS) cells.

Methods

Primary cultured ORS cells were transduced with recombinant adenovirus expressing N-terminal truncated β-catenin (constitutive active form), and β-catenin-regulated genes were identified.

Results

Overexpression of the constitutively active form of β-catenin led to induction of Sox9 expression at both mRNA and protein levels. To investigate the potential role of Sox9, we made the recombinant adenovirus expressing green fluorescent protein-tagged Sox9, and then transduced into cultured ORS cells. Interestingly, Sox9 induced the expression of keratin 15, increased the proliferation of ORS cells in vitro, and enhanced colony-forming activity.

Conclusion

Our results suggest that Sox9 is a β-catenin-regulated gene in ORS cells, and has potential importance in the regulation of hair follicle homeostasis.     

Genetic Polymorphism of FLG in Korean Ichthyosis Vulgaris Patients

Background

Filaggrin is a key protein that facilitates the formation of skin barrier by forming a stratum corneum. Mutations in the gene encoding filaggrin (FLG) have recently been reported in patients with ichthyosis vulgaris (IV). Interestingly, there are ethnic differences between FLG mutations identified in Asians and Europeans, and few FLG mutations are overlapping between Chinese and Japanese IV patients.

Objective

The aim of this study was to investigative the genetic polymorphism of FLG in Korean IV patients.

Methods

Genomic DNA was extracted from whole venous blood specimen of Korean patients with IV and a control group, and the full sequence of FLG was determined via overlapping long-range polymerase chain reaction method.

Results

Analysis of base sequence previously unreported reveal new nonsense mutation p.Y1767X in a Korean IV patient, and additional new single nucleotide polymorphisms.

Conclusion

On the basis of this study, it is anticipated that analysis of FLG gene sequence be extended to other dermatoses associated with FLG, such as atopic dermatitis.     

Lack of Association between PTPN22 Gene +1858 C>T Polymorphism and Susceptibility to Generalized Vitiligo in a Turkish Population

Background

Vitiligo is an autoimmune polygenic disorder characterized by loss of pigmentation due to melanocyte destruction. The PTPN22 gene +1858 C>T single nucleotide polymorphism (rs2476601) has been shown to be associated with various autoimmune disorders.

Objective

The aim of this study was to investigate whether the PTPN22 gene +1858 C>T single nucleotide polymorphism is associated with susceptibility to generalized vitiligo in a Turkish population.

Methods

One hundred and seven patients with generalized vitiligo, and one hundred and twelve gender-, age-, and ethnic-matched controls were enrolled in the study. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism.

Results

The PTPN22 +1858 C>T genotype and allele frequencies of the generalized vitiligo patients did not differ significantly from those of healthy controls.

Conclusion

We found no association between the PTPN22 +1858 C>T gene polymorphism and vitiligo susceptibility in Turkish generalized-vitiligo patients.