Effect of a Tranexamic Acid, Kojic Acid, and Niacinamide Containing Serum on Facial Dyschromia: A Clinical Evaluation

Background: Stubborn dyschromia such as melasma and post-inflammatory hyperpigmentation (PIH) are leading causes for cosmetic consultation. Topical treatment is challenging, using a range of modalities, to stop, hinder, and/or prevent steps in the pigment production process. Tranexamic acid (TXA), a potent plasmin inhibitor, is proposed to control pigmentation by inhibiting the release of inflammatory mediators involved in triggering melanogenesis. TXA has been recently introduced as a topical therapy aimed at reducing pigmentation in melasma. Methods: In a 12-week clinical study, a novel, topical facial serum containing 3% TXA, 1% kojic acid, and 5% niacinamide was evaluated for its effectiveness in treating melasma, PIH, and hyperpigmentation in Brazilian female subjects with Fitzpatrick skin types I-IV. Efficacy evaluations were performed at pre-treatment baseline, weeks 2, 4, 8, and 12, and included expert clinical grading, bio-instrumental measurements, and self-assessment questionnaires. Cutaneous tolerability was also evaluated by assessing subjective and objective irritation of the treatment area. Results: A significant improvement in the appearance of PIH, hyperpigmentation, melasma, skin texture, and skin tone homogeneity was observed beginning at week 2 and continued through week 12. Melanin index, as measured by Mexameter®, demonstrated a significant decrease by week 12 as compared to both pre-treatment baseline and control. Conclusions: The findings suggest that the test product is an effective and well-tolerated treatment option for addressing hyperpigmentary conditions, including melasma. Additional in vitro data suggests that TXA may act by mediating the inhibition of PGE2-stimulated human epidermal melanocytes. J Drugs Dermatol. 2019;18(5):454-459.

Gene profiling analysis of the early effects of ablative fractional carbon dioxide laser treatment on human skin.

BACKGROUND: The use of carbon dioxide (CO2) laser-mediated ablative fractional resurfacing (AFR) is currently under extensive clinical investigation, but the molecular mechanisms underlying this process are unclear. OBJECTIVES: To determine the early expressed genes that are upregulated in human skin after treatment using a CO2 fractional laser. METHODS: Whole human skin was irradiated using an AFR CO2 laser, and changes in gene expression after 2 and 24 hours were analyzed using microarray analysis. The results were validated using reverse transcriptase polymerase chain reaction (RT-PCR). Laser scanning confocal microscopy (LSCM) was used to investigate the expression of the validated proteins after AFR CO2 laser treatment of skin that had been biopsied from seven Korean patients. RESULTS: Gene expression profiling showed that the most significantly upregulated genes in these skin samples were those encoding Wnt5a, cysteine-rich angiogenic inducer 61 (CYR61), and heat shock protein (HSP) 90. These results were confirmed using real-time RT-PCR and LSCM. CONCLUSIONS: Irradiation using an AFR laser may induce the expression of Wnt5a, CYR61, and HSP90 in human skin during the early remodeling phases, suggesting that the induction of proteins may be the preceding event that is associated with the clinical effects of laser treatment.

Treatment of striae distensae with fractional photothermolysis.

BACKGROUND: Striae distensae are dermal scars characterized by flattening and atrophy of the epidermis. Although many treatment modalities have been tried with variable results, most have been disappointing. OBJECTIVE: To determine whether striae distensae might respond to fractional photothermolysis. METHODS: Twenty-two women with striae distensae were treated with two sessions each of fractional photothermolysis at a pulse energy of 30 mJ, a density level of 6, and eight passes at intervals of 4 weeks. Response to treatment was assessed by comparing pre- and post-treatment clinical photography and skin biopsy samples. RESULTS: Six of the 22 patients (27%) showed good to excellent clinical improvement from baseline, whereas the other 16 (63%) showed various degrees of improvement. Most of the lesions with excellent results were white in color and of long duration. Skin biopsy revealed that average epidermal thickness and dermal thickness were greater than at baseline. The immunoreactivity of procollagen type 1 increased after treatment. There were no significant side effects except erythema and mild pigmentation. CONCLUSION: Fractional photothermolysis may be effective in treating striae distensae, without significant side effects. Treatment outcomes were better in patients with white rather than red striae.

Increased expression of nerve growth factor receptor and neural endopeptidase in the lesional skin of melasma.

BACKGROUND: Characteristic clinical features of melasma are symmetry of hyperpigmentation and distribution related to trigeminal nerves, which suggest that the neural involvement could play a part in the pathogenic mechanisms of pigmentation. OBJECTIVE: To evaluate whether some neuropeptides and neurotrophins and their receptors were associated with the pathogenesis of melasma. METHODS: To investigate the involvement of neuronal system and neuropeptides in melasma, we examined the expression of nerve growth factor receptor (NGFR) and neural endopeptidase (NEP) in melasma lesional and nonlesional skin. Skin biopsies were obtained from lesional and nonlesional facial skin of six Korean women with melasma. Confocal laser scanning microscopic examination and western blot were performed. RESULTS: Melasma lesions showed markedly greater expression of NGFR and NEP than nonlesional skin. CONCLUSION: We suggest that neuroactive molecules, including NGF, is one of the critical factors for the pathogenesis of melasma, which may directly affect the microenvironment around melanocytes through a NGFR immunoreactivity (NGFR-IR) nerve fiber pathway, and higher levels of NEP in melasma has an important role in regulation of melanogenesis.

Baumann Skin Type in the Korean Male Population.

BACKGROUND: Research into the Baumann skin type (BST) has recently expanded, with growing interest in the development of an efficient and effective skin type classification system for better understanding of this skin condition. OBJECTIVE: We aimed to identify male-specific skin type characteristics with investigation into the distribution of BST by age and region in the Korean male population and to determine the intrinsic and extrinsic factors related to skin type. METHODS: A questionnaire was administered to collect information about age, region, working behavior, drinking behavior, smoking behavior, usual habit of sun protection, medical history, and the BST which consisted of four parameters; oily (O) or dry (D), sensitive (S) or resistant (R), pigmented (P) or non-pigmented (N), and wrinkled (W) or tight (T). RESULTS: We surveyed 1,000 Korean males aged between 20 and 60 years who were divided equally by age and region. Of the total respondents, OSNW type accounted for the largest percentage and ORPW type the lowest. In terms of Baumann parameters, O type was 53.5%, S type was 56.1%, N type was 84.4% and W type was 57.5%. Several behavioral factors were found to have various relationships with the skin type. CONCLUSION: The predominant skin type in the Korean male respondents was OSNW type, and the distribution of skin types with regards to age and region was reported to be distinct. Therefore, skin care should be customized based on detailed skin types considering the various environmental factors.

Topical immunomodulators are effective for treatment of vitiligo.

Vitiligo is a common, acquired, depigmenting disease of the skin. Although the pathogenesis of vitiligo is still unclear, it is postulated that topical immunomodulators exert therapeutic effects on treatment of vitiligo. We reviewed the treatment of vitiligo with topical immunomodulators and topical steroids to evaluate the efficacy of immunomodulators in treatment of vitiligo. We reviewed 52 patients treated with topical immunomodulators and 27 patients with topical steroids. To evaluate the efficacy, repigmentation of vitiligo was reviewed. Between the two treatments, the duration from the start of treatment to onset of repigmentation was significantly shorter in the topical immunomodulator group (P = 0.002). However, no statistically significant differences were found in sex, age, mean disease duration, sites of vitiligo lesion and ratio of patients who showed response. We may suggest topical immunomodulator as an alternative to topical steroids for treatment of vitiligo.

Liponeurofibroma: Clinicopathological features and histogenesis.

A neurofibroma is a common cutaneous benign tumor of neural origin. Various histological variants have been reported. Recently, sporadic reports of fatty variants have been reported but their clinicopathological features have not been well studied. The purpose of this study was to examine liponeurofibroma, and to report the distinctive clinicopathological features and histogenesis in comparison with the classic form. A retrospective study was performed on 130 cases. Immunohistochemical staining was performed for S100, factor VIIIa, perilipin and vascular endothelial growth factor. Masson's trichrome stain was also used. Intratumoral adipocytes were examined with transmission electron microscopy. Thirty-two (24.6%) cases were classified as liponeurofibroma on microscopic examination. This variant was more common in patients with neurofibromatosis type 1, older age and female sex. The most prevalent location was the head and neck. Intratumoral fat deposits showed differences in morphology and size compared with subcutaneous fat on light microscopy. Neurofibromatosis type 1 had the highest odds of fatty change in liponeurofibroma. In sporadic cases, fatty change can be caused by senescence, chronic injury, or tissue hypoxia secondary to internal or external stimuli. Further investigation is needed to identify the pathomechanism of fatty change in various cutaneous neoplasms, including neurofibroma.

A new classification of pattern hair loss that is universal for men and women: basic and specific (BASP) classification.

BACKGROUND: Pattern hair loss (PHL) can be classified into several patterns. Currently, the Hamilton-Norwood classification system for men and the Ludwig grade system for women are commonly used to describe patterns of hair loss. However, these pre-existing classifications have some limitations. OBJECTIVE: To establish an acceptable, universal, and accurate standard of both male and female pattern hair loss and to report its use in determining the incidence of PHL. METHODS: We developed a new classification system (BASP classification) and then applied this system to classify the types of PHL. The BASP classification was based on observed patterns of hair loss. The basic (BA) types represent the shape of the anterior hairline, and the specific types (SP) represent the density of hair on distinct areas (frontal and vertex). There are four basic types (L, M, C, and U) and two specific types (F and V). The final type is decided by the combination of the assigned basic and specific types. Between November 2004 and June 2005, 2213 Korean subjects, comprised of 1768 males and 445 females, were classified according to the BASP classification at 13 university dermatologic centers nationwide throughout South Korea, as a multicenter study of the Korean Hair Research Society. RESULTS: For both sexes, the majority of patients enrolled in the study were in the third and fourth decade of life (65.1% of males and 56.68% of females). In males, the older group as well as the younger group in the study were more likely to have little recession of the frontal hairline (classified as type M1 approximately 2) and diffuse thinning over the top of scalp (type F1 approximately 2). The women in the study developed typical female PHL. LIMITATIONS: The subjects of our study were mostly outpatients and some inpatients who complained about hair loss, not the general population of Korea. CONCLUSION: The BASP classification is a new stepwise, systematic, and universal classification system for PHL, regardless of sex.

Simultaneous effect of ursolic acid and oleanolic acid on epidermal permeability barrier function and epidermal keratinocyte differentiation via peroxisome proliferator-activated receptor-alpha.

Ursolic acid (UA) and oleanolic acid (ONA) are pentacyclic triterpenoids, which naturally occur in many medicinal herbs and plants. Recent research revealed that several pharmacological effects could be attributed to UA and ONA, such as anti-tumor, anti-inflammatory and anti-microbial activities. To evaluate the effects of UA and ONA on epidermal permeability barrier recovery and normal skin, both flanks of hairless mice were topically treated with either 0.01-0.1 mg/mL UA or 0.1-1.0 mg/mL ONA after tape stripping and transepidermal water loss (TEWL) were assessed, and then hydration and TEWL were measured for 3 weeks with application of UA and ONA (2 mg/mL). We also investigated the morphological changes using light (LM) and electron microscopic (EM) examination. Finally, we observed that UA and ONA stimulated epidermal keratinocyte differentiation via peroxisome proliferator-activated receptor (PPAR)-alpha using Western immunoblotting. The recovery rate of epidermal permeability barrier after tape stripping increased in the UA- and ONA-treated groups (0.1 mg/mL UA and 0.5 mg/mL ONA) at 6 h to more than 20% when compared to the vehicle-treated group (P < 0.05). In both groups, hydration was increased compared to the vehicle group from 1 week without TEWL alteration (P < 0.05). An LM finding showed that epidermal thickening was frequently observed (UA > ONA > vehicle). EM examination revealed an increase in secretion and in the number of lamellar bodies in treated groups and that complete formation of lipid bilayers was also prominent (ONA > UA > vehicle). Protein expression of PPAR-alpha, involucrin, loricrin and filaggrin increased twofold and threefold in HaCaT cells treated for 24 h with either ONA (10 micromol/L) or UA (10 micromol/L), respectively, reflecting that the UA and ONA can improve the recovery of skin barrier function and induce epidermal keratinocyte differentiation via PPAR-alpha. Taken together, these results suggest that UA and ONA will be pertinent candidates for the improvement of epidermal permeability barrier function.

Baumann Skin Type in the Korean Female Population.

BACKGROUND: To meet the need for a subspecialized skin type system, the Baumann skin type (BST) system was proposed. OBJECTIVE: To evaluate the distribution of BST types and influencing factors among Korean women. METHODS: BST questionnaires were administered to 1,000 Korean women. The possible responses were as follows: oily (O) or dry (D), sensitive (S) or resistant (R), pigmented (P) or non-pigmented (N), and wrinkled (W) or tight (T). The correlations of the BST with the subjects' age, location, ultraviolet (UV) ray exposure, drinking and smoking habits, and blood type were assessed. RESULTS: The OSNT, DSNT, DRNT, and OSNW skin types were the most common skin types (55.3%). The O, S, P, and W types accounted for 46.6%, 68.8%, 23.2%, and 31.9%, respectively. The proportion of the O and S type was the highest in Gyeongsangbuk-do (55.0%) and Seoul (77.2%). The proportion of the P and W type was the highest in Gyeongsangbuk-do (33.0%) and Chungcheong-do (39.0%). The O type decreased in the higher age group, whereas the P and W type showed a reversed tendency. In smokers, the proportion of W type was significantly higher than in the non-smokers (66.3% vs. 24.1%, p<0.05). CONCLUSION: The 4 most common BST types were OSNT, DSNT, DRNT, and OSNW. In the comparison across the 4 BST parameters according to the age, region, smoking and drinking habits, occupation, blood type, and UV exposure, significant differences were observed. Individualized and customized skin care is required according to the personal skin type.

An unusual case with membranous lipodystrophy in a hypertensive patient with transepidermal elimination.

Membranous lipodystrophy represents a peculiar type of fat necrosis that is present in patients with various types of skin disease. It is characterized by the presence of microcysts and macrocysts and is lined by amorphous eosinophilic material with a crenelated arabesque appearance. These findings have been associated with lupus erythematosus, diabetes mellitus, erythema nodosum, trauma, etc. We report a case of a 43-year-old woman who had a red to purple asymptomatic indurated plaque, approximately seven cm in diameter and on the left arm. She was a chronic hepatitis B antigen carrier and had hypertension for four years. Histopathology of the biopsied lesion showed transepidermal elimination of altered collagen and elastic fibers, as well as membranous lipodystrophy changes. There were hypertensive vascular changes including lymphohistiocytic infiltration around the vascular wall, swelling of endothelial cells, increased thickness of the vascular walls, and narrowing of the lumen. We report a case showing transepidermal elimination with membranous lipodystrophy. We carefully suggest that the secondary phenomenon of transepidermal elimination was associated with membranous lipodystrophy and degenerate connective tissues.

Effects of a multilamellar emulsion on glucocorticoid-induced epidermal atrophy and barrier impairment.

Skin atrophy is one of the most frequent side-effects of the topical glucocorticoid. Skin barrier impairment has also been reported as a steroid-induced side effect. Although there have been various studies on preventing or minimizing this atrophogenic effect, little has been reported about preventing barrier impairment. This study was performed to determine the effects of a multilamellar emulsion (MLE) that had a well-ordered lamellar structure on the steroid-induced barrier impairment and epidermal atrophy. To confirm these effects of MLE, 0.05% clobetasol-17-propionate (CP) and 0.05% clobetasol-17-propionate in MLE (MLE/CP) were topically applied to both flanks of hairless mice for 9 days. The topically applied CP induced a significant impairment of the epidermal permeability barrier, and MLE/CP also did not have a preventive effect on this change. However, skinfold thickness studies and histological studies showed that MLE/CP significantly reduced the steroid-induced atrophy. The topical application of MLE/CP was also shown to have a preventive effect on the steroid-induced increase of the stratum corneum (SC) surface pH. In addition, the electron microscopic findings showed relatively well-conserved lamellar bilayers in the skin treated with MLE, as compared to CP only. The results showed that the topical application of MLE immediately after CP treatment prevented the glucocorticoid-induced transepidermal water loss values increase. Light microscopy measurements showed that the skin treated with MLE immediately after CP treatment for 1 week had a slightly lower decline of skin thickness than did the CP-treated skin. These results suggest that MLE should be effective for preventing glucocorticoid-induced epidermal atrophy and for repairing the barrier impairment.

Clinical Features and Awareness of Hand Eczema in Korea.

BACKGROUND: Hand eczema is one of the most common skin disorders and negatively affects quality of life. However, a large-scale multicenter study investigating the clinical features of patients with hand eczema has not yet been conducted in Korea. OBJECTIVE: To identify the prevalence of various hand diseases, which is defined as all cutaneous disease occurring in hands, and to investigate the clinical features of patients with hand eczema and the awareness about hand eczema in the general population and to compare the prevalence of hand eczema between health care providers and non-health care providers. METHODS: To estimate the prevalence of hand diseases, we analyzed the medical records of patients from 24 medical centers. Patients were assessed by online and offline questionnaires. A 1,000 from general population and 913 hand eczema patients answered the questionnaire, for a total of 1,913 subjects. RESULTS: The most common hand disease was irritant contact dermatitis. In an online survey, the lifetime prevalence of hand eczema was 31.2%. Hand eczema was more likely to occur in females (66.0%) and younger (20~39 years, 53.9%). Health care providers and housewives were the occupations most frequently associated with hand eczema. Winter (33.6%) was the most common season which people experienced aggravation. The 63.0% and 67.0% answered that hand eczema hinders their personal relationship and negatively affects daily living activities, respectively. CONCLUSION: Hand eczema is a very common disease and hinders the quality of life. The appropriate identification of hand eczema is necessary to implement effective and efficient treatment.

Membranous lipodystrophy-like changes in two cases of traumatic lipogranuloma caused by safety belts.

A few cases of subcutaneous nodules with the histological findings of membranous lipodystrophy-like changes have been reported in the literature. However, reports of membranous lipodystrophy-like changes caused by trauma are exceedingly rare. We report two cases of traumatic lipogranuloma that had linear and multiple lesions showing membranous lipodystrophy-like changes and were induced by safety belt trauma after a car accident. These patients showed peculiar changes in their subcutaneous fat and had linear patterned, multiple, nodular lesions with membranous lipodystrophy-like changes caused by trauma.

Unilateral xanthelasma forming a kissing-like lesion.

Xanthelasma is a common cutaneous xanthomatosis which occurs usually on the medial canthus in the upper or inferior palpebra. We describe a rare case of kissing xanthelasma which was unilateral at early onset.

Trichostasis spinulosa arising within syringoma.

A forty-eight-year-old man presented with multiple pinhead to rice-sized papules on the face. Histopathologic examination showed a typical syringoma and dilated hair follicles containing several vellus hairs in the middle of a fibrotic stroma. We discuss the possible pathomechanism between these two conditions in the same lesion.