Skin atrophy caused by topical glucocorticoids is less common in patients with atopic dermatitis than in those with psoriasis.

Although the long-term use of topical glucocorticoids (TGC) may induce skin atrophy including striae distensae (SD), patients with atopic dermatitis (AD) appear to have lesser degree of skin atrophy than those with psoriasis (PSO). Periostin, encoded by POSTN, is involved in tissue remodelling processes of chronic AD lesions. This study was designed to investigate the difference in the occurrence of skin atrophy in patients with AD or PSO when treated with TGC and to elucidate the association between skin atrophy and periostin. Big data analysis using Korean Health Claims Database was performed to determine the prevalence of SD in AD and PSO patients. Blood and skin eosinophils count and dermal fibrosis between AD and PSO patients were compared, and immunohistochemistry for periostin and mRNA sequencing in the dermis were performed. Animal experiments using AD and PSO murine model were conducted. Big data analysis revealed that patients with AD have significantly lesser degree of SD than patients with PSO. The ratio of the dermal fibrous tissues and eosinophil counts were significantly higher in AD patients. In AD skin, periostin was more widely distributed in the entire dermis and POSTN mRNAs were significantly upregulated. Dermal thickness and fibrosis were significantly higher in AD mice even after TGC treatment. A significant positive correlation was observed between dermal fibrosis and tissue eosinophil counts. Lesser skin atrophy in AD patients even after long-term TGC application could be resulted from skin fibrosis caused by increased tissue eosinophils and periostin deposition.

Increased Expression of 11ß-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged Skin.

Inactive cortisone is converted into active cortisol by 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1). Excessive levels of active glucocorticoids could deteriorate skin barrier function; barrier impairment is also observed in aged skin. In this study, we aimed to determine whether permeability barrier impairment in the aged skin could be related to increased 11ß-HSD1 expression. Aged humans (n = 10) showed increased cortisol in the stratum corneum (SC) and oral epithelium, compared to young subjects (n = 10). 11ß-HSD1 expression (as assessed via immunohistochemical staining) was higher in the aged murine skin. Aged hairless mice (56-week-old, n = 5) manifested greater transepidermal water loss, lower SC hydration, and higher levels of serum inflammatory cytokines than the young mice (8-week-old, n = 5). Aged 11ß-HSD1 knockout mice (n = 11), 11ß-HSD1 inhibitor (INHI)-treated aged wild type (WT) mice (n = 5) and young WT mice (n = 10) exhibited reduced SC corticosterone level. Corneodesmosome density was low in WT aged mice (n = 5), but high in aged 11ß-HSD1 knockout and aged INHI-treated WT mice. Aged mice exhibited lower SC lipid levels; this effect was reversed by INHI treatment. Therefore, upregulation of 11ß-HSD1 in the aged skin increases the active-glucocorticoid levels; this suppresses SC lipid biosynthesis, leading to impaired epidermal permeability barrier.

Adverse Sexual Effects of Treatment with Finasteride or Dutasteride for Male Androgenetic Alopecia: A Systematic Review and Meta-analysis.

Treatment of male androgenetic alopecia with 5α-reductase inhibitors is efficacious. However, the risk of adverse sexual effects remains controversial. This systematic review and meta-analysis investigated the risk of adverse sexual effects due to treatment of androgenetic alopecia in male patients with finasteride, 1 mg/day, or dutasteride, 0.5 mg/day. Fifteen randomized double-blinded placebo-controlled trials (4,495 subjects) were meta-analysed. Use of 5α-reductase inhibitors carried a 1.57-fold risk of sexual dysfunction (95% confidence interval (95% CI) 1.19-2.08). The relative risk was 1.66 (95% CI 1.20-2.30) for finasteride and 1.37 (95% CI 0.81-2.32) for dutasteride. Both drugs were associated with an increased risk, although the increase was not statistically significant for dutasteride. As studies into dutasteride were limited, further trials are required. It is important that physicians are aware of, and assess, the possibility of sexual dysfunction in patients treated with 5α-reductase inhibitors.

Subclinical sensitization with diphenylcyclopropenone is sufficient for the treatment of alopecia areata: Retrospective analysis of 159 cases.

BACKGROUND: Contact immunotherapy with diphenylcyclopropenone (DPCP) is presently considered the treatment of choice for extensive alopecia areata. However, a major concern with contact immunotherapy is that it causes various adverse effects (AEs) that contribute to discontinuation of treatment. OBJECTIVE: We investigated whether a modified DPCP treatment protocol can promote hair regrowth with fewer AEs. METHODS: All patients were sensitized with 0.1% DPCP and began treatment with 0.01% DPCP. Thereafter, the DPCP concentration was slowly increased according to the treatment response and AEs. This was a retrospective review of DPCP treatment with modified protocols in 159 patients with alopecia areata. RESULTS: Of the 159 patients, 46 (28.9%) showed a complete response and 59 (37.1%) showed a partial response. No patients had AEs after sensitization. During the treatment, only 3 patients (1.9%) showed severe AEs, and 55 showed moderate AEs; however, all were well controlled with antihistamines alone or antihistamines and medium-potency topical steroids. There was no association between treatment response and AEs. LIMITATIONS: Sample size, subject composition, and the retrospective study design represent potential limitations. CONCLUSION: A modified DPCP treatment protocol with subclinical sensitization could induce a favorable therapeutic response and result in fewer AEs.

Microimplant-assisted rapid palatal expansion appliance to orthopedically correct transverse maxillary deficiency in an adult.

This case report describes the use of a microimplant-assisted rapid palatal expansion (MARPE) appliance to orthopedically correct a transverse maxillary deficiency in an adult patient. Expansion forces transmitted through the teeth in traditional rapid palatal expansion appliances create unwanted dental effects rather than true skeletal expansion, particularly in older patients with more rigid interdigitation of the midpalatal suture. This 19-year-old patient had maxillary constriction with a unilateral posterior crossbite. A MARPE appliance secured to the palatal bones with 4 microimplants was expanded by 10 mm. Pre-MARPE and post-MARPE cone-beam computed tomography cross sections demonstrated 4 to 6 mm of expansion of the maxillofacial structures, including the zygoma and nasal bone area, and widening of the circummaxillary sutures. Minor buccal tipping of the dentition was observed, but the integrity of the alveolar bone was preserved. This report demonstrates that careful design and application of the MARPE appliance can achieve successful transverse expansion of the maxilla and the surrounding structures in a patient beyond the age typically considered acceptable for traditional rapid palatal expansion.

Long-term risk of autoimmune diseases after mRNA-based SARS-CoV2 vaccination in a Korean, nationwide, population-based cohort study.

The long-term association between mRNA-based coronavirus disease 2019 (COVID-19) vaccination and the development of autoimmune connective tissue diseases (AI-CTDs) remains unclear. In this nationwide, population-based cohort study involving 9,258,803 individuals, we aim to determine whether the incidence of AI-CTDs is associated with mRNA vaccination. The study spans over 1 year of observation and further analyses the risk of AI-CTDs by stratifying demographics and vaccination profiles and treating booster vaccination as time-varying covariate. We report that the risk of developing most AI-CTDs did not increase following mRNA vaccination, except for systemic lupus erythematosus with a 1.16-fold risk in vaccinated individuals relative to controls. Comparable results were reported in the stratified analyses for age, sex, mRNA vaccine type, and prior history of non-mRNA vaccination. However, a booster vaccination was associated with an increased risk of some AI-CTDs including alopecia areata, psoriasis, and rheumatoid arthritis. Overall, we conclude that mRNA-based vaccinations are not associated with an increased risk of most AI-CTDs, although further research is needed regarding its potential association with certain conditions.

Modified basic and specific (BASP) classification for pattern hair loss.

BACKGROUND: In 2007, Lee et al. introduced a basic and specific (BASP) classification for pattern hair loss that was comprehensive and applicable regardless of race or gender. However, this BASP classification has several limitations. Frontal type hair loss classification is relatively crude, and a specific hair loss pattern cannot be ascertained when hair loss is associated with the temporal and occipital areas. METHODS: In our modified BASP classification, frontal type classification was subdivided into five instead of three grades. Basic type classification remained the same as in the previous method. In addition, information regarding the involvement of the temporal or occipital scalp was recorded. Accuracy and ease of use were evaluated and compared with the existing BASP classification in 138 patients with pattern hair loss. RESULTS: Temporal or occipital involvement was observed in 14 patients, accounting for 11.1% of subjects. Final type accuracy was 82.5% in the existing BASP classification and 71.4% in the modified classification. Ease of use for two practitioners was 70.2 and 72.1% for the existing BASP classification, and 48.9 and 52.2% for the modified method. CONCLUSION: We expect that the modified BASP classification will overcome the limitations of the existing BASP classification. We believe this modified classification will be a valuable tool for pattern hair loss classification because of its classification of previously unclassified types.

Oxidation of catechin and rutin by pentaammineruthenium(III) complexes.

The reaction of catechin and rutin with Ru(NH(3))(5)L(3+) (L = N-methylpyrazinium (pzCH(3)(+)), pyrazine (pz), and isonicotinamide (isn)) complexes underwent a two-electron oxidation on the catechol ring (B ring) with the formation of quinone products. The kinetics of the oxidation, carried out at [H(+)] = 0.01-1.0 M and pH = 4.0-7.6, suggested that the reaction process involves the rate determining one-electron oxidation of the flavonoids in the form of H(2)X (k(0)), HX(-) (k(1)), and X(2-) (k(2)) by Ru(NH(3))(5)L(3+) complexes to form the corresponding semiquinone radicals, followed by the rapid scavenge of the radicals by the Ru(III) complexes. The specific rate constants (k(0), k(1), and k(2)) were measured and the results together with the application of the Marcus theory were used to estimate the self-exchange parameters for the one-electron couples of the flavonoids, H(2)X/H(2)X(+*), HX(-)/HX(*), and X(2-)/X(-*).

Ginsenoside Rb1 Enhances Keratinocyte Migration by a Sphingosine-1-Phosphate-Dependent Mechanism.

The cutaneous wound healing process is tightly regulated by a range of cellular responses, including migration. Sphingosine-1-phosphate (S1P) is a signaling lipid produced in keratinocytes (KC) and it is known to stimulate skin wound repair through increased KC migration. Of the multifunctional triterpene ginsenosides, Rb1 enhances cutaneous wound healing process by increasing KC migration, but cellular mechanisms responsible for the Rb1-mediated increase in KC migration are largely unknown. Therefore, we hypothesized that, and assessed whether, Rb1 could stimulate KC migration through S1P-dependent mechanisms. Rb1 significantly increases S1P production by regulating the activity of metabolic conversion enzymes associated with S1P generation and degradation, sphingosine kinase 1 (SPHK1) and S1P lyase, respectively, in parallel with enhanced KC migration. However, blockade of ceramide to S1P metabolic conversion using a specific inhibitor of SPHK1 attenuated the expected Rb1-mediated increase in KC migration. Furthermore, a pan-S1P receptor inhibitor pertussis toxin significantly attenuated Rb1-induced stimulation of KC migration. Moreover, the Rb1-induced increases in KC migration required S1P receptor(s)-mediated activation of ERK1/2 and NF-κB, leading to production of key cutaneous migrating proteins, matrix metalloproteinase (MMP)-2 and MMP-9. Taken together, the results show that Rb1 stimulates KC migration through an S1P→S1P receptor(s)→ERK1/2→NF-κB→MMP-2/-9 pathway. This research revealed a previously unidentified cellular mechanism for Rb1 in enhancing KC migration and pointing to a new therapeutic approach to stimulate the cutaneous wound healing process.

Intensely Pruritic Papules and Plaques in Waldenstrom's Macroglobulinemia.

Waldenstrom's macroglobulinemia (WM) is lymphoplasmacytoid malignancy that affects B lymphocytes. Cutaneous involvement of WM is rare, but various cutaneous manifestations have been reported. These findings are due to various pathological processes including direct invasion of tumor cells into the skin, deposition of paraproteins, hyperviscosity syndrome, and cryoglobulinemia. A 64-year-old man presented with a 10-day history of pruritic erythematous papules and plaques on his trunk and elbows. The clinical features were suspicious for eczematous dermatitis. However, treatments such as oral antihistamines, topical steroids, ultraviolet light therapy and immunomodulators (dapsone and cyclosporine) were minimally effective. The patient's hemoglobin decreased gradually, and he was referred to the department of hematology. Serum electrophoresis exhibited a monoclonal peak in the ß1 region. The diagnosis of WM was established based on a bone marrow biopsy that revealed 80% lymphoplasma cellularity, staining positive for CD20 and CD79a. However, there was no direct infiltration of tumor cells or immunoglobulin deposition on the skin biopsy. After the patient started rituximab, cyclophosphamide and dexamethasone therapy, anemia and neutropenia gradually improved. His pruritus also markedly subsided. Although there was no evidence of infiltration of WM in the skin lesions, they were thought to be strongly associated with monoclonal gammopathy. This dermatologic feature has not been documented as a nonspecific cutaneous manifestation of WM or monoclonal gammopathy. To clarify the association between intensely pruritic papules/plaques and WM, more reports and further studies could be needed.

Gender-specific risk factors for androgenetic alopecia in the Korean general population: Associations with medical comorbidities and general health behaviors.

BACKGROUND: The relationships between androgenetic alopecia (AGA) and various factors related to metabolic syndrome have been demonstrated in previous studies. However, it remains unclear because of inconsistent results. We investigated the associations between AGA and various risk factors related to metabolic syndrome according to gender. METHODS: We conducted a population-based cross-sectional survey of 2028 Koreans (1050 men, 978 women). The basic and specific (BASP) classification was used for diagnosis of AGA. We collected information on risk factors though questionnaires and medical records. RESULTS: AGA was significantly associated with age, family history of AGA, hypertension, diabetes mellitus, and waist circumference in both genders. Female subjects with AGA were more likely to have cerebrovascular disease, dyslipidemia, and obesity; however, these associations were not observed in the male subjects. When multiple regression analysis was applied, there was a significant relationship between hypertension and AGA in male subjects. However, there was no statistically significant association in female subjects. CONCLUSION: The different results according to gender might arise from different mechanisms of AGA. There was a significant relationship between hypertension and AGA in male subjects. Evaluation of blood pressure in male patients with AGA might facilitate interventions for hypertension.

Psychological Stress Deteriorates Skin Barrier Function by Activating 11ß-Hydroxysteroid Dehydrogenase 1 and the HPA Axis.

Psychological stress (PS) increases endogenous glucocorticoids (GC) by activating the hypothalamic-pituitary-adrenal axis. The negative effects of GC on skin barrier function under PS have been well-established. However, endogenous GC can also be active when cortisone (inactive form) is converted to cortisol (active form) by 11ß-hydroxysteroid dehydrogenase type I (11ß-HSD1) in the peripheral tissue. Here, we evaluated the changes in 11ß-HSD1 and barrier function under PS. Elevated 11ß-HSD1 in oral mucosa correlated with increased cortisol in the stratum corneum and deteriorated barrier function. Expression of 11ß-HSD1 in the oral mucosa correlated with that in the epidermal keratinocytes. We further investigated whether barrier function improved when PS was relieved using a selective serotonin reuptake inhibitor (SSRI) in patients with anxiety. Decreased 11ß-HSD1 and improved barrier function were observed after SSRI treatment. The collective findings suggest that elevated 11ß-HSD1 under PS increases the level of cutaneous GC and eventually impairs barrier function. PS-alleviating drugs, such as SSRI, may help to treat PS-aggravated skin diseases.

Effects of picosecond laser on the multi-colored tattoo removal using Hartley guinea pig: A preliminary study.

Picosecond lasers have emerged as the leading technology for tattoo removal due to their shorter pulse lengths. To clarify the features of picosecond lasers, we compared picosecond and nanosecond lasers in their ability to remove multi-colored tattoo in an animal model. We first compared a nanosecond quality-switched Nd:YAG laser with picosecond Alexandrite and quality-switched Nd:YAG lasers and then the picosecond quality-switched Nd:YAG laser with the picosecond Alexandrite laser, using a guinea pig model. The colors in the tattoos included red, orange, yellow, green, blue, and black. Guinea pigs were treated for one session with each type of laser. The clearance of pigmentation and local reactions were evaluated based on clinical photographic assessment, quantitative assessment using a colorimeter, histopathology, and electron microscopic examination before laser treatment, immediately after, and at 3 weeks after the treatment. Regardless of pulse duration, a 532-nm laser was the most effective in clearing red, orange, and yellow pigments, although the overall effect and safety was better with the picosecond 532 nm laser. A picosecond 755 nm laser demonstrated excellent efficacy in removing only green and blue pigments. a picosecond 1064 nm laser demonstrated some effects on non-black colored tattoos. In terms of safety, picosecond lasers produced less tissue injury than nanosecond lasers. Conclusively, picosecond lasers are more effective and safer than nanosecond lasers.

Efficacy of superficial cryotherapy on the eyebrows of patients with alopecia universalis also treated with contact immunotherapy on the scalp: a prospective, split-face comparative study.

BACKGROUND: Few treatment modalities are available for treating alopecia areata (AA) of the eyebrow. Due to the anatomical proximity of the eyebrows to the eyes, safety issues and side effects should always be taken into consideration when choosing the treatment modality. This study was designed to examine the efficacy of superficial cryotherapy on patients with AA of the eyebrow. METHODS: Superficial cryotherapy was performed every other week on the right eyebrow (SC-treated) in a total of 20 patients who had been previously treated with diphenylcyclopropenone (DPCP) immunotherapy on the scalp. No specific treatment was performed on the left eyebrows as a control. The degree of eyebrow recovery was compared in 15 patients who continued to receive more than 10 superficial cryotherapy treatments (5 months of treatment) on their right eyebrow. RESULTS: Hair density was significantly increased on both treated and control eyebrows after 5 months of treatment compared with the pretreatment density; moreover, the SC-treated eyebrows exhibited a significantly greater increase in density than the control eyebrows. Although hair thickness in the control eyebrows did not change significantly over the treatment period, hair thickness of the SC-treated eyebrows showed a statistically significant increase at months 3 and 5. CONCLUSIONS: Superficial cryotherapy is associated with minimal to no adverse events and exhibits high compliance and relatively good efficacy. Thus, this treatment is an important additional option for patients with AA of the eyebrow.

Almost Unilateral Focal Dermal Hypoplasia.

Focal dermal hypoplasia, caused by mutations in PORCN, is an X-linked ectodermal dysplasia, also known as Goltz syndrome. Only seven cases of unilateral or almost unilateral focal dermal hypoplasia have been reported in the English literature and there have been no previously reported cases in the Republic of Korea. A 19-year-old female presented with scalp defects, skin lesions on the right leg and the right trunk, and syndactyly of the right fourth and fifth toes. Cutaneous examination revealed multiple atrophic plaques and a brown and yellow mass with fat herniation and telangiectasia that was mostly located on the lower right leg. She had syndactyly on the right foot and the scalp lesion appeared to be an atrophic, membranous, fibrotic alopecic scar. A biopsy of the calf revealed upper dermal extension of fat cells, dermal atrophy, and loss of dermal collagen. A diagnosis of almost unilateral focal dermal hypoplasia was made on the basis of physical and histologic findings. Henceforth, the patient was referred to a plastic surgeon and an orthopedics department to repair her syndactyly.

Therapeutic Efficacy of a Combination Therapy of Topical 17α-Estradiol and Topical Minoxidil on Female Pattern Hair Loss: A Noncomparative, Retrospective Evaluation.

BACKGROUND: A variety of agents have been used to treat female pattern hair loss (FPHL), including topical minoxidil, topical 17α-estradiol, oral anti-androgen agents, and mineral supplements. Compared with these single agent regimens, combination therapies could be a better therapeutic option in expectation of superior treatment outcome. OBJECTIVE: This study was designed to determine the efficacy of a combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil in Korean patients with FPHL. METHODS: Therapeutic efficacy was evaluated in 34 women who applied topical 0.025% 17α-estradiol and 3% minoxidil once daily for more than 6 months. Phototrichogram analysis was performed before and after therapy. The efficacy was evaluated with respect to total hair count, hair caliber (as assessed by phototrichogram analysis), and photographic assessment. RESULTS: Total hair count and hair caliber both increased from baseline to 6 months in patients treated with the combination therapy of topical 0.025% 17α-estradiol and 3% minoxidil (p<0.001). Photographic assessment also revealed significant disease improvement, thus supporting the therapeutic efficacy. CONCLUSION: A combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil can be tried as an effective treatment for FPHL.

The Effect of Rhus verniciflua Stokes Extracts on Photo-Aged Mouse Skin.

BACKGROUND: Rhus verniciflua Stokes (RV) has traditionally been used in Korea as an indigenous food (Rhus chicken soup) and as an herbal medicinal plant. While the anticancer, antimicrobial, and anti-inflammatory properties of RV have been actively studied in the medical field, its antioxidant effects in the skin that resist the reactive oxygen species in keratinocytes and fibroblasts is less understood. OBJECTIVE: We designed to evaluate the effects of R. verniciflua Stokes extract (RVE) on the photo-aged skin by an in vitro experiment using human fibroblasts and an in vivo experiment using a photo-aged murine model. METHODS: For the in vitro experiments, human fibroblasts irradiated with ultraviolet (UV) B were treated with RVE or vehicle, and the growth levels and the expression level of type 1 procollagen were compared. For the in vivo experiment, photo-aged mice irradiated with UVB and UVA were administered drinking water with or without RVE, and histological changes and the expression level of type 1 procollagen and matrix metalloprotease (MMP)-13 were compared. RESULTS: In vitro experiments using fibroblasts irradiated with UVB showed that RVE promoted growth and significantly increased the expression of type 1 procollagen as compared to the control group. In the photo-aged mice, RVE increased collagen content in the dermis and promoted the synthesis of type 1 procollagen without any visible decrease in MMP-13 as compared to control group. CONCLUSION: In addition to the previously reported antioxidant effects of RVE, oral intake of RVE effectively inhibited photo-aging in hairless mice by enhancing collagen synthesis.