Seung Hwan Paik

Pretreatment of epidermal growth factor promotes primary hair recovery via the dystrophic anagen pathway after chemotherapy-induced alopecia.

Epidermal growth factor (EGF) is not only a cell growth stimulant but also has a catagen‐inducing effect. Because chemotherapeutic agents primarily damage anagen hair follicles, it would be important to investigate whether catagen inducers have beneficial effects in chemotherapy‐induced alopecia (CIA). We pretreated hair follicles with topical EGF‐liposomal solution in the C57BL/6 mouse model of cyclophosphamide‐induced alopecia and observed the catagen‐inducing property and damage response pathway after CIA. We confirmed that topical EGF application induced a catagen‐like stage and found that these catagen‐like hairs were protected from chemotherapy‐mediated damage. Moreover, our results showed that EGF treatment favoured primary hair recovery via the dystrophic anagen pathway after CIA. Given that hair follicles subjected to less severe chemotherapeutic insult enter the dystrophic anagen pathway followed by primary recovery, the results of this study suggest that catagen inducers could be useful as a new alopecia‐protection strategy, especially in the context of CIA.

Clinical characteristics and prognostic factors in early-onset alopecia totalis and alopecia universalis.

Alopecia totalis (AT) and alopecia universalis (AU), severe forms of alopecia areata (AA), show distinguishable clinical characteristics from those of patch AA. In this study, we investigated the clinical characteristics of AT/AU according to the onset age. Based on the onset age around adolescence (< or ≥ 13 yr), 108 patients were classified in an early-onset group and the other 179 patients in a late-onset group. We found that more patients in the early-onset group had a family history of AA, nail dystrophy, and history of atopic dermatitis than those in the late-onset group. These clinical differences were more prominent in patients with AU than in those with AT. In addition, significantly more patients with concomitant medical disorders, especially allergic diseases were found in the early-onset group (45.8%) than in the late-onset group (31.2%). All treatment modalities failed to show any association with the present hair condition of patients. In the early-onset group, patients with AU or a family history of AA showed worse prognosis, whereas this trend was not observed in the late-onset group. Systemic evaluations might be needed in early-onset patients due to the higher incidence of comorbid diseases. It is suggested that patients with AU or family history of AA make worse progress in the early-onset group than in the late-onset group.

Treatment of Keratoacanthoma with 5% Imiquimod Cream and Review of the Previous Report

Keratoacanthoma (KA) is a benign epidermal tumor, characterized by rapid and abundant growth, a tendency toward spontaneous regression and histopathologic similarity to squamous cell carcinoma (SCC). Because KA can be easily misdiagnosed as SCC, surgery is considered the treatment of choice. Recently, regression of KAs following application of 5% imiquimod cream (Aldara®) has been reported. We present 4 cases of KA treated with topical imiquimod, applied 3 to 4 times a week. Obvious improvement was observed after 4 to 6 weeks of application and the lesions were almost cleared leaving scars after 9 to 11 weeks. These results show that topical imiquimod can be an effective option for the conservative management of KA as previously reported. We also suggest that lesions treated with imiquimod cream should be considered for biopsy to judge histopathological remission after 5 to 8 weeks of application to shorten the duration of the treatment.

Exomic Sequencing of Immune-Related Genes Reveals Novel Candidate Variants Associated with Alopecia Universalis

Alopecia areata (AA) is a common autoimmune disorder mostly presented as round patches of hair loss and subclassified into alopecia totalis/alopecia universalis (AT/AU) based on the area of alopecia. Although AA is relatively common, only 5% of AA patients progress to AT/AU, which affect the whole scalp and whole body respectively. To determine genetic determinants of this orphan disease, we undertook whole-exome sequencing of 6 samples from AU patients, and 26 variants in immune-related genes were selected as candidates. When an additional 14 AU samples were genotyped for these candidates, 6 of them remained at the level of significance in comparison with 155 Asian controls (p<1.92×10−3). Linkage disequilibrium was observed between some of the most significant SNPs, including rs41559420 of HLA-DRB5 (p<0.001, OR 44.57) and rs28362679 of BTNL2 (p<0.001, OR 30.21). While BTNL2 was reported as a general susceptibility gene of AA previously, HLA-DRB5 has not been implicated in AA. In addition, we found several genetic variants in novel genes (HLA-DMB, TLR1, and PMS2) and discovered an additional locus on HLA-A, a known susceptibility gene of AA. This study provides further evidence for the association of previously reported genes with AA and novel findings such as HLA-DRB5, which might represent a hidden culprit gene for AU.

Gene mapping study for constitutive skin color in an isolated Mongolian population

To elucidate the genes responsible for constitutive human skin color, we measured the extent of skin pigmentation in the buttock, representative of lifelong non-sun-exposed skin, and conducted a gene mapping study on skin color in an isolated Mongolian population composed of 344 individuals from 59 families who lived in Dashbalbar, Mongolia. The heritability of constitutive skin color was 0.82, indicating significant genetic association on this trait. Through the linkage analysis using 1,039 short tandem repeat (STR) microsatellite markers, we identified a novel genomic region regulating constitutive skin color on 11q24.2 with an logarithm of odds (LOD) score of 3.39. In addition, we also found other candidate regions on 17q23.2, 6q25.1, and 13q33.2 (LOD ≥ 2). Family-based association tests on these regions with suggestive linkage peaks revealed ten and two significant single nucleotide polymorphisms (SNPs) on the linkage regions of chromosome 11 and 17, respectively. We were able to discover four possible candidate genes that would be implicated to regulate human skin color: ETS1, UBASH3B, ASAM, and CLTC.

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.

Efficacy and Safety of Pueraria lobata Extract in Gray Hair Prevention: A Randomized, Double-Blind, Placebo-Controlled Study

Background Graying of hair-a sign of aging-raises cosmetic concerns. Individuals with gray hair often look older than others their age; therefore, some dye their hair for aesthetic purposes. However, hair colorants can induce many problems including skin irritation, allergic reaction and hair-breakage. Objective This randomized, double-blind clinical trial was performed in order to examine the effects of APHG-1001, a compound including an extract from Pueraria lobata, on graying hair. Methods A total of 44 female subjects were randomly treated with either APHG-1001 or placebo twice daily for 24 weeks. Using the phototrichogram analysis, a count of newly developed gray hair was estimated. Investigator assessment and subject self-assessment were also performed in order to evaluate the efficacy of the compound. Results The mean number of newly developed gray hair at 24 weeks was 6.3/cm2 in the APHG-1001 group and 11.4/cm2 in the placebo group; the difference was statistically significant (p<0.05). However, the investigator assessment and subject self-assessment did not show any significant change in the gross appearance of hair grayness by the end of the study. No severe adverse events in either group were observed. Moreover, the incidence of adverse events did not differ between the groups. Conclusion This clinical trial revealed that APHG-1001, which contains an extract of P. lobata, could prevent the development of new gray hair without any remarkable adverse effects. Thus, it can be considered as a viable treatment option for the prevention of gray hair.

A Case of Assisted Reproductive Therapy-induced Erythema Nodosum

Erythema nodosum is a common variant of panniculitis. It is characterized by tender erythematous nodule and plaque on the anterior aspect of the leg. The etiology is not fully understood. It may be associated with a variety of disorders, including infection, medication, autoimmune disorders, pregnancy, and malignancy. A 33-year-old Korean woman presented with 1 week history of painful erythematous plaques on both knees. She was 7 weeks pregnant with assisted reproductive therapy, and had been maintained on daily intramuscular progesterone injection for 4 weeks. Histological examination of the lesions revealed septal panniculitis without vasculitis. Two days after discontinuing progesterone injection, the symptoms and lesions started to resolve. Herein we present a case of erythema nodosum caused by progesterone injection for endometrial preparation.

Development of a Model for Chemotherapy-Induced Alopecia: Profiling of Histological Changes in Human Hair Follicles After Chemotherapy.

Optimized research models are required to further understand the pathogenesis and prophylaxis of chemotherapy-induced alopecia. Our aim was to develop a mouse model for chemotherapy-induced alopecia by follicular unit transplantation of human hair follicles onto immunodeficient mice. Twenty-two weeks after transplantation, a single dose of cyclophosphamide (Cph) was administered to mice in the Cph100 (100 mg/kg) and Cph150 (150 mg/kg) groups. On day 6, hair follicles showed dystrophic changes, with swollen dermal papilla and ectopic melanin clumping in the hair bulb. In addition, upregulated expression of apoptotic regulators [P53, Fas/Fas-ligand, tumor necrosis factor-related apoptosis-inducing ligand/tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAIL/TRAIL receptor), and Bax], increased apoptotic matrix keratinocytes, downregulated Ki67 expression, and decreased melanogenic protein in the hair bulb were noted in both groups. After 12 treatment days, hair follicles in Cph100 mice appeared to diminish dystrophic changes. In contrast, hair follicles of Cph150 mice prematurely entered a dystrophic catagen phase after 9 treatment days, and immunofluorescence staining for Ki67 and melanogenic protein expressions was barely visible. Two hair follicle damage response pathways were observed in this model, namely dystrophic anagen (Cph100) and catagen (Cph150) pathways. Our model might be useful for further understanding the impact of chemotherapy on human hair follicles.

Long-Term Utility and Durability of the Therapeutic Effects of Bimatoprost 0.03% for Eyelash Augmentation in Healthy Asian Subjects

Background: Eyelashes of Asians differ from those of Caucasians in morphology and growth characteristics. Ethnic differences also exist for the tolerability profile of prostaglandin analogues. Objective: To evaluate the long-term utility and durability of bimatoprost 0.03% in eyelash augmentation in Asian females. Methods: One cohort received bimatoprost 0.03% for 36 weeks and another for 20 weeks, with the latter cohort followed for 16 weeks after treatment cessation. The primary endpoint was the percent change in eyelash length at week 20. Secondary measures included percent change in eyelash thickness and darkness, physicians Global Eyelash Assessment and patient satisfaction. Results: At week 20, eyelash length was enhanced in a time-dependent manner, with maximum improvement achieved (19.3%; p < 0.0001). Significant improvements in thickness and darkness were also achieved (22.9%, 6.0%; p < 0.0001). 77.8% of subjects improved by ≥1 grade on Global Eyelash Assessment, with 83.1% satisfied/very satisfied. Improvements were maintained with ongoing treatment to 36 weeks, while these effects were progressively lost with discontinuation. Conclusion: Bimatoprost 0.03% safely enhanced eyelashes in Asian females, maintained with ongoing treatment. Cessation of treatment was associated with progressive loss of effects.