Pilot study of fractional microneedling radiofrequency for hidradenitis suppurativa assessed by clinical response and histology.

BACKGROUND: Hidradenitis suppurativa (HS) is a devastating chronic inflammatory skin disease with frequent recurrences. Various systemic treatments and procedures have been used but the efficacy of fractional microneedling radiofrequency (FMR) has not been reported. AIM: To evaluate the clinical and histological efficacy of FMR in the treatment of HS lesions. METHODS: An 8-week, prospective, split-body, unblinded study was conducted, which enrolled 10 adult patients with mild to moderate HS to receive 3 sessions of FMR treatment biweekly. HS severity was assessed using the number and type of lesions, HS Physician Global Assessment (HS-PGA) and the modified Sartorius score (mSS). Skin biopsies were performed on participants to assess change in inflammation before and after FMR. RESULTS: Severity of HS was significantly reduced on the FMR-treated side of the body, but not on the control side. Inflammatory HS lesions were significantly reduced after 4 weeks, while HS-PGA and mSS were significantly decreased after 6 weeks. Immunohistochemistry staining showed decreased expression of inflammatory markers including neutrophil elastases, interleukin (IL)-8 and IL-17, tumour necrosis factor-α, transforming growth factor-ß1 and matrix metalloproteinases. CONCLUSION: FMR may be a viable treatment option for mild to moderate HS.

Atrophic acne scar: a process from altered metabolism of elastic fibres and collagen fibres based on transforming growth factor-ß1 signalling.

BACKGROUND: Atrophic acne scar, a persistent sequela from acne, is undesirably troubling to many patients due to its cosmetic and psychosocial aspects. Although there have been some reports emphasizing the role of early inflammatory responses in atrophic acne scarring, evolving perspectives on the detailed pathogenic processes are promptly needed. OBJECTIVES: Examining the histological, immunological and molecular changes in early acne lesions susceptible to atrophic scarring can provide new insights to understand the pathophysiology of atrophic acne scar. METHODS: We experimentally validated several early fundamental hallmarks accounting for the transition of early acne lesions to atrophic scars by comparing molecular profiles of skin and acne lesions between patients who were prone to scar (APS) or not (ANS). RESULTS: In APS, compared with ANS, devastating degradation of elastic fibres and collagen fibres occurred in the dermis, followed by their incomplete recovery. Abnormally excessive inflammation mediated by innate immunity with T helper 17 and T helper 1 cells was observed. Epidermal proliferation was significantly diminished. Transforming growth factor (TGF)-ß1 was drastically elevated in APS, suggesting that aberrant TGF-ß1 signalling is an underlying modulator of all of these pathological processes. CONCLUSIONS: These results may provide a basis for understanding the pathogenesis of atrophic acne scarring. Reduction of excessive inflammation and TGF-ß1 signalling in early acne lesions is expected to facilitate the protection of normal extracellular matrix metabolism and ultimately the prevention of atrophic scar formation. What's already known about this topic? The dermis of atrophic acne scars shows alteration of extracellular matrix components such as collagen fibres. Inflammation in acne lesions is associated with the development of acne scars. What does this study add? Abnormalities in the metabolism of collagen fibres and elastic fibres were observed in the early developmental stages of acne lesions that were progressing into atrophic scars. Exacerbated inflammation and aberrant epidermal proliferation by increased transforming growth factor (TGF)-ß1 signalling may affect the abnormal extracellular matrix metabolism. What is the translational message? Abnormal changes in elastic fibres and collagen fibres are found in the early developmental process of acne in patients who are prone to atrophic scarring. An early treatment regimen strongly inhibiting inflammation and TGF-ß1 signalling to help the normal recovery of the extracellular matrix components is required to prevent atrophic scarring.

Autophagy mechanisms in sputum and peripheral blood cells of patients with severe asthma: a new therapeutic target.

BACKGROUND: Autophagy and genetic predisposition have been suggested to potentially play roles in the development of asthma. However, little is known about the role of autophagy in the pathogenesis of severe asthma. OBJECTIVE: We compared autophagy in the sputum granulocytes, peripheral blood cells (PBCs) and peripheral blood eosinophils (PBEs) between patients with severe asthma and those with non-severe asthma and investigated the functional effects of autophagy. METHODS: We enrolled 36 patients with severe asthma, 14 with non-severe asthma and 23 normal healthy controls in this study. Sputum granulocytes, PBCs and PBEs were isolated from each subject. Autophagy was evaluated based on the expression of microtubule-associated protein light chain 3 (LC3) by Western blot, confocal microscopy, transmission electron microscopy and flow cytometry. IL-8 levels were measured by ELISA. To induce autophagy, HL-60 cells, human primary small airway epithelial cells (SAECs) and A549 cells were treated with IL-5, IL-1ß and TNF-α. To inhibit autophagy, PI3K inhibitors (LY29400 and 3-methyladenine [3-MA]) and hydroxychloroquine (HCQ) were used. Knockdown of ATG5 and Beclin-1 was performed in A549 cells, and the therapeutic effects of dexamethasone were evaluated. RESULTS: Higher autophagy levels were noted in sputum granulocytes, PBCs and PBEs from patients with severe asthma than from patients with non-severe asthma and healthy controls (P < 0.05 for all). IL-5 increased autophagy levels in both PBCs and PBEs (P < 0.05). 3-MA attenuated the increased expression of LC3-II and eosinophil cationic protein in HL-60 cells induced by IL-5 (P = 0.034 for both). Dexamethasone did not affect autophagy levels in PBEs. IL-1ß increased LC3-II expression and IL-8 production (P < 0.01) in SAECs, and this was attenuated by LY294002, 3-MA, HCQ and knockdown of ATG5 and Beclin-1 (in A549 cells) (P < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Autophagy could play a role in the pathogenesis of severe asthma. Autophagy modulation may be a novel therapeutic target for conventional therapy-resistant severe asthma.

Body composition is more closely related to the development of knee osteoarthritis in women than men: a cross-sectional study using the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1, 2).

OBJECTIVE: To evaluate the association between knee osteoarthritis (OA) and body composition parameters, and to analyze the correlations of both obesity and lower extremity muscle mass with radiographic knee OA in relation to sex. METHODS: This was a cross-sectional study using data on body composition parameters measured using dual energy X-ray absorptiometry in 4246 participants in the Fifth Korea National Health and Nutrition Examination Survey. The relationships between knee OA and body composition parameters were evaluated. The associations between knee OA and the four subgroups corresponding to obesity and muscle mass percentage in both lower extremities were analyzed separately for each sex. RESULTS: The lower extremity muscle mass showed a decreasing trend, while fat parameters showed an increasing linear trend (P for trend <0.05) with increasing severity of knee OA in women. The odds ratio of each quarter percentile group (25 percentile) for fat parameters showed an increasing trend, while that of the lower extremity muscle mass showed a decreasing linear trend in relation to knee OA in women (P for trend < 0.05). In women, low percentage of lower extremity muscle mass was more associated with knee OA regardless of obesity (P < 0.05). However, there were no associations between all body composition parameters and knee OA in men. CONCLUSION: In women, high fat mass and low lower extremity muscle mass were associated with presence and severity of knee OA. Lower extremity muscle mass was more closely correlated with knee OA than obesity in women.

What's new in the physiopathology of acne?

There are four central factors that contribute to acne physiopathology: the inflammatory response, colonization with Propionibacterium acnes, increased sebum production and hypercornification of the pilosebaceous duct. In addition, research in the areas of diet and nutrition, genetics and oxidative stress is also yielding some interesting insights into the development of acne. In this paper we review some of the most recent research and novel concepts revealed in this work, which has been published by researchers from diverse academic disciplines including dermatology, immunology, microbiology and endocrinology. We discuss the implications of their findings (particularly in terms of opportunities to develop new therapies), highlight interrelationships between these novel factors that could contribute to the pathology of acne, and indicate where gaps in our understanding still exist.

Epidemiology and risk factors of childhood acne in Korea: a cross-sectional community based study.

BACKGROUND: The epidemiology of acne vulgaris appears to be evolving, with an increasingly earlier onset seen in childhood. Relevant studies have been rarely performed in Asia. AIM: We sought to estimate the prevalence and clinical characteristics of acne among schoolchildren, and its association with treatment-seeking behaviour, body mass index (BMI), nutritional habits and other lifestyle elements. METHODS: A cross-sectional study was conducted with elementary schoolchildren aged 7-12 years. Children were interviewed by self-administered questionnaires, and were subsequently evaluated by dermatologists. RESULTS: Of 693 children enrolled, 36.2% were diagnosed with acne, and the prevalence increased with age. Additionally, clinical characteristics including severity, duration of disease and lesion distribution were significantly different between the lower (aged 7-9 years) and the higher (aged 10-12 years) grades. Subjective features including recognition about acne and treatment-seeking behaviours were also different between the two groups. Overweight or obesity (BMI ≥ 25 kg/m(2) at 18 years of age; OR = 2.7) and consumption of chocolates/sweets (OR = 1.6) were significant risk factors for acne. CONCLUSIONS: In the current study, the prevalence of acne among elementary schoolchildren was high, but only a few children had received treatment. Physicians should be attentive to childhood acne, and educate patients and their parents about the need to treat it.

Cutaneous manifestations of the subtypes of polycystic ovary syndrome in Korean patients.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in women of childbearing-age. Although PCOS has common dermatological manifestations, including hirsutism, acne and androgenetic alopecia, little is known about the dermatological characteristics of PCOS patients in Asia. OBJECTIVE: The goal of this study is to elucidate the dermatological characteristics and metabolic and hormonal parameters of Korean PCOS patients classified by the three ASRM/ESHERE criteria. METHODS: We investigated 40 untreated PCOS patients who were newly diagnosed in the Department of Obstetrics & Gynecology of Seoul National University Hospital. Patients were classified according to the presence of irregular menstruation (IM), polycystic ovary morphology (PCOM) and hyperandrogenism (HA). Acne specific questionnaire, physical examination, and blood sampling were thoroughly conducted. RESULTS: Twenty four patients (60.0%) met the criteria for the IM/HA/PCOM group and sixteen (40.0%) belonged to the IM/PCOM group. Acne was the most commonly observed dermatological manifestation (95.0%) followed by hirsutism (60.0%), seoborrhea (47.5%), acanthosis nigricans (20.0%) and androgenetic alopecia (12.5%). Hirsutism was more frequently observed in the IM/HA/PCOM group; the prevalence of other cutaneous manifestations did not differ significantly. Acne was most often observed on the face and most acne lesions were distributed on the forehead and cheek. Serum dehydroepiandrosterone sulphate level was higher in IM/HA/PCOM group, while serum cholesterol and high density lipoprotein concentrations were higher in the IM/PCOM group. CONCLUSION: We described several dermatological manifestations and serum hormonal and metabolic parameters in Korean PCOS patients. Cutaneous manifestations might be the first signs of PCOS; therefore, dermatologists should be more aware of cutaneous manifestations of various ethnicities.

Double-blind, randomized non-inferiority trial of a novel botulinum toxin A processed from the strain CBFC26, compared with onabotulinumtoxin A in the treatment of glabellar lines.

BACKGROUND: Botulinum toxins have been widely used in cosmetic dermatology. Neurotoxin from the CBFC26 strain (NTC) is a recently developed botulinum toxin type A product manufactured through refined procedures. OBJECTIVE: A double-blinded, randomized, multicentre-designed, phase III trial to investigate the non-inferiority of NTC to existing botulinum toxin A, onabotulinumtoxin A in the treatment of moderate to severe glabellar lines. METHODS: A total of 272 subjects were randomized in a 1 : 1 ratio to receive 20 U of NTC or onabotulinumtoxin A. The primary endpoint was the response rate of physicians' assessment (PA) using the Facial Wrinkle Scale at week 4. The secondary endpoints included the response rate of PA at weeks 8, 12 and 16, and photographic assessment at weeks 4, 8, 12 and 16. Subjects' improvement assessment and subjective self-satisfaction levels were also investigated. RESULTS: Response rates for maximum frown were 89.3% in the NTC group and 81.9% in the onabotulinumtoxin A group at week 4. NTC also resulted in comparable results for both the response rates of the other evaluation points and incidence of adverse events compared to those of onabotulinumtoxin A. In subjects' improvement assessment and photographic evaluations, NTC even demonstrated better results compared with onabotulinumtoxin A in the early phase after treatment. Analysis of these results strongly supports the non-inferiority of NTC to onabotulinumtoxin A in the efficacy and safety. CONCLUSION: NTC is as effective as onabotulinumtoxin A in the treatment of glabellar lines, and both products were well tolerated.

Analysis of distribution patterns of Propionibacterium acnes phylotypes and Peptostreptococcus species from acne lesions.

BACKGROUND: The precise roles of Propionibacterium acnes and other anaerobic bacteria in the pathogenesis of acne are still unclear. Recent studies have shown that P. acnes can be further classified into several phylotypes with distinct phenotypes and virulence. Their distribution patterns in acne lesions have rarely been demonstrated. OBJECTIVES: To analyse distribution patterns of P. acnes phylotypes and Peptostreptococcus species on the skin surface of patients with acne and healthy controls, and in comedones, papules and pustules from patients. METHODS: A total of 370 samples from 95 patients with acne and 65 samples from 65 healthy controls were investigated. Three P. acnes phylotypes and three Peptostreptococcus species were identified by polymerase chain reaction primarily using type-specific primers. RESULTS: There was no significant difference in the microflora of the skin surface samples between patients with acne and healthy controls. In acne lesions, distribution patterns between skin surface and comedonal lesions were similar, but they were significantly different from those of both papules and pustules. In the inflammatory acne lesions, the proportion of type IA P. acnes was increased, while those of type IB and II were decreased. The proportion of Peptostreptococcus species was also increased significantly in the inflammatory lesions. CONCLUSIONS: At the precision of this qualitative study, our results do not provide any evidence that different phylotypes in the surface microflora might be important in triggering acne. However, type IA P. acnes and Peptostreptococcus species might be more closely associated with inflammatory acne lesions.

The clinical and histological effect of home-use, combination blue-red LED phototherapy for mild-to-moderate acne vulgaris in Korean patients: a double-blind, randomized controlled trial.

BACKGROUND: Blue and red light have been reported to have beneficial effects on acne. However, there has been no double-blind, randomized study of acne treatment for combined blue and red light-emitting diode (LED) devices, and the associated molecular mechanisms have rarely been investigated. OBJECTIVES: To evaluate the efficacy, safety and histological changes of combined blue and red LED phototherapy for acne vulgaris. METHODS: Thirty-five patients with mild-to-moderate acne were randomly assigned to either a home-use irradiation group using an LED device, or a control group using a sham device. The treatment group was instructed to serially irradiate their forehead and cheeks with 420-nm blue light and 660-nm red light for 2.5 min twice daily for 4 weeks. RESULTS: At the final visit at 12 weeks, both inflammatory and noninflammatory acne lesions had decreased significantly, by 77% and 54%, respectively, in the treatment group. No significant difference was observed in the control group. In the treatment group, sebum output reduction, attenuated inflammatory cell infiltrations and a decreased size of the sebaceous gland were found. The immunostaining intensities for interleukin (IL)-8, IL-1α, matrix metalloproteinase-9, toll-like receptor-2, nuclear factor-κB, insulin-like growth factor-1 receptor and sterol response element binding protein (SREBP)-1 were reduced concomitantly. Messenger RNA expression of SREBP-1c was also decreased. No severe adverse reactions were reported. CONCLUSIONS: This LED phototherapy was safe and effective for treating not only inflammatory but also noninflammatory acne lesions, with good compliance. The experimental results correlated well with clinical results, partly elucidating the related molecular mechanisms.

Intense pulsed light vs. pulsed-dye laser in the treatment of facial acne: a randomized split-face trial.

BACKGROUND: Various laser and light therapy have been increasingly used for the treatment of acne vulgaris. PATIENTS AND METHODS: Twenty patients with facial acne were treated using intense pulsed light (IPL) on one side of the face and pulsed dye laser (PDL) on the other to compare the efficacy and safety of IPL and PDL. Treatment was performed 4 times at 2-week intervals. Treatment effectiveness was determined using lesion counts, acne severity, patient subjective self-assessments of improvement, and histopathological examinations, which included immunohistochemical staining for transforming growth factor-beta (TGF-beta). RESULTS: Numbers of total acne lesions decreased following both treatments. For inflammatory lesions such as papules, pustules and nodules, IPL-treated sides showed an earlier and more profound improvement than PDL-treated sides. However, at 8 weeks after the 4th treatment, a rebound aggravation of acne was observed on IPL-treated sides. On the contrary, PDL produced gradual improvements during the treatment sessions and these improvements lasted 8 weeks after the 4th treatment. Non-inflammatory lesions as open and closed comedones also showed improvement following both treatments and PDL-treated sides showed better improvement as the study proceeded. Histopathological examinations showed amelioration in inflammatory reactions and an increase in TGF-beta expression after both treatments, which were more prominent for PDL-treated sides. CONCLUSION: Both PDL and IPL were found to treat acne effectively, but PDL showed a more sustained effect. TGF-beta might play a key role in the resolution of inflammatory acne lesions.

Impact of guideline adherence on patient outcomes in early-stage epithelial ovarian cancer.

AIM: The aim of this study was to evaluate the effects of adherence to National Comprehensive Cancer Network (NCCN) guidelines on survival outcomes in patients with early-stage epithelial ovarian cancer. METHODS: Our institutional cancer registry data on 266 patients with Stage I epithelial ovarian cancer was reviewed retrospectively and compliance with treatment guidelines for surgery and adjuvant treatment was determined. Patients were categorized according to adherence or non-adherence. The primary endpoints were recurrence-free survival and disease-specific survival. Hazard ratios (HRs) for survival were estimated with a Cox proportional hazards model. RESULTS: Of the 266 patients, 71 (26.7%) underwent adequate surgical staging in accordance with the guidelines. The guidelines for adjuvant chemotherapy were followed adequately in all 71 patients that were adherent to surgical staging and in 163 of the 195 patients with non-adherence to surgical staging (83.6%). Multivariate analysis, adjusted for prognostic factors, identified higher recurrence-free survival (HR, 0.36; 95% CI, 0.15-0.88) and disease-specific survival (HR, 0.42; 95% CI, 0.16-1.12) among patients whose treatment adhered to both surgical and chemotherapy guidelines, although disease-specific survival was not statistically significant. When excluding clear cell histology from the cohort, the guideline-adherent group had significantly better disease-specific survival than the non-adherent group (HR, 0.13; 95% CI, 0.02-0.94). CONCLUSION: The results of this study suggest that adherence to NCCN guidelines may improve survival outcomes in patients with early-stage epithelial ovarian cancer, particularly in cases other than clear cell histology.

Effects of 12-O-tetradecanoyl-phorbol-13-acetate [corrected] and sodium lauryl sulfate on the production and expression of cytokines and proto-oncogenes in photoaged and intrinsically aged human keratinocytes.

Skin aging may be divided into photoaging and intrinsic aging. The purpose of this study was to investigate the effects of 12-O-tetradecanoyl-phorbol-13-acetate and sodium lauryl sulfate on the production and expression of cytokines and proto-oncogenes in photoaged and intrinsically aged skin, compared with young skin. Keratinocytes were taken from newborns, young adults in their twenties, and from the forearm and thigh of volunteers in their fifties and seventies. Interleukin-1alpha and -6, and interleukin-1 receptor antagonist, c-fos and c-myc were measured after cultured keratinocytes had been treated with 12-O-tetradecanoyl-phorbol-13-acetate and sodium lauryl sulfate. There has been no report concerning the dependence of cytokine production by sodium lauryl sulfate upon photoaging and intrinsic aging. This study also involves the first investigation of the effects of aging on c-myc expression by 12-O-tetradecanoyl-phorbol-13-acetate treatment. Cytokine production decreased markedly with age. These results suggest the progressive decline of cellular function with age. The ratio of cytokine production in the irritant-treated group compared with that in the control group showed a different pattern in photoaging and intrinsic aging. With the significant difference between photoaging and intrinsic aging, T/C ratio decreased in interleukin-1alpha and interleukin-1 receptor antagonist upon aging, whereas it increased in interleukin-6. S/C ratio was uniquely elevated on photoaged skin in the 50 y age group. It is suggested that photoaged skin shows an exaggerated reaction to surfactant. Compared with the control, c-fos expression in 12-O-tetradecanoyl-phorbol-13-acetate-treated keratinocytes decreased with age in the thigh, but increased in the photoaged skin of forearm. The increased c-fos expression in 12-O-tetradecanoyl-phorbol-13-acetate-treated keratinocytes could be relevant for the predisposition of photoaged keratinocytes to malignant transformation.

Comprehensive outlook of in vitro tests for assessing skin irritancy as alternatives to Draize tests.

In vitro alternative methods have been verified for the possibility to assess cutaneous irritancy because humans cannot be direct initial experimental subjects and animal experimentation could be forbidden in the near future. Many kinds of cell cytotoxicity assays have been tried, revealing their own advantages and limitations. Cell function-based tests have been used less frequently than cytotoxicity assays. Three-dimensional culture systems are promising because they are closer to the actual in vivo skin, and some of them are commercialized nowadays. The ultimate objective of in vitro irritancy tests, which is the high degree of correlation with human in vivo test results, has been accomplished in many experimental settings. Before applying these in vitro methods we must consider several points, including cell sources, irritant characteristics, exposure time, endpoint of experiment, extrinsic factors affecting irritation, etc. In vitro skin irritancy tests have been developed continuously, and in the future they could assume a heavy responsibility of estimating the irritancy in human skin in vivo.

The use of Q-switched Nd:YAG laser in the treatment of superficial pigmented lesions in Koreans.

AIM: There are still insufficient clinical reports concerning quality-switched Nd:YAG laser (QSNYL) in the treatment of superficial pigmented lesions in Asians. The purpose of this study was to analyse the efficacy and side effect profiles of QSNYL-assisted pigment removal in brown skin. METHODS: A total of 71 patients, presenting a wide gamut of superficial epidermal lesions, were treated with QSNYL. Clinical responses were assessed by comparing photographs that were taken serially in every treatment. RESULTS: Treatment using the QSNYL is reported individually for the various superficial pigmented lesions in the skin of Korean patients. CONCLUSION: QSNYL may be a beneficial alternative tool for the treatment of a number of benign pigmented lesions including freckles, lentigines and unilateral lentiginosis.

Clinical use of the Q-switched Nd:YAG laser for the treatment of acquired bilateral nevus of Ota-like macules (ABNOMs) in Koreans.

BACKGROUND: There are still insufficient clinical reports about quality-switched Nd:YAG laser (QSNYL) in the treatment of acquired bilateral nevus of Otalike macules (ABNOMs) in Asians. OBJECTIVE: To analyze the efficacy and side-effect profiles of QSNYL treatment of ABNOMs in Korean skin. METHODS: A prospective study was designed to follow 10 Korean patients with ABNOMs through laser treatment until maximal eradication of the lesions had been achieved. RESULTS: Five patients (50%) with ABNOMs were treated with excellent or good results. The more treatments a patient underwent, the greater the possibility of improvement. There were no cases of persistent skin textural change or persistent erythema. CONCLUSION: The clinical data support QSNYL being a beneficial alternative tool for treating ABNOMs in brown skin. This is, to the best of the authors' knowledge, the first report about laser treatment of ABNOMs using QSNNL.