Metformin: A Potential Treatment for Acne, Hidradenitis Suppurativa and Rosacea.

Metformin is a widely used drug for treatment of diabetes mellitus, due to its safety and efficacy. In addition to its role as an antidiabetic drug, numerous beneficial effects of metformin have enabled its use in various diseases. Considering the anti-androgenic, anti-angiogenic, anti-fibrotic and antioxidant properties of metformin, it may have the potential to improve chronic inflammatory skin diseases. However, further evidence is needed to confirm the efficacy of metformin in dermatological conditions, This review focuses on exploring the therapeutic targets of metformin in acne vulgaris, hidradenitis suppurativa and rosacea, by studying their pathogeneses.

Itch and Janus Kinase Inhibitors.

Itch is a common skin symptom, with complex aetiology and pathogenesis. It is mediated by 2 pathways, the histaminergic and non-histaminergic pathways. Chronic itch is understood to be processed by the latter and is difficult to treat with traditional pruritus therapies. The Janus kinase and signal transducer and activator of transcription pathway is a signalling mechanism that regulates gene expression through various cytokines. Janus kinase inhibitors, which have been tested and used for several autoimmune diseases, have also been shown to be effective for itch through clinical trials and case reports. Janus kinase inhibitors could be a good choice for pruritus in atopic dermatitis, psoriasis, and other diseases, such as prurigo nodularis and lichen planus, with rapid itch relief compared with conventional treatments. The most common adverse effects reported include nasopharyngitis, acne, and elevated blood creatine phosphokinase levels. Janus kinase inhibitors are currently prescribed with warnings about a potential increase in malignancies and cardiovascular diseases and usage in people of older ages. This review aims to provide knowledge about itch and the Janus kinase and signal transducer and activator of transcription pathway and to analyse the current evidence for itch relief by Janus kinase inhibitors.

The Human Microbiota and Skin Cancer.

Skin cancer is the most common type of cancer in the US with an increasing prevalence worldwide. While ultraviolet (UV) radiation is a well-known risk factor, there is emerging evidence that the microbiota may also contribute. In recent years, the human microbiota has become a topic of great interest, and its association with inflammatory skin diseases (i.e., atopic dermatitis, acne, rosacea) has been explored. Little is known of the role of microbiota in skin cancer, but with the recognized link between microbial dysbiosis and inflammation, and knowledge that microbiota modulates the effect of UV-induced immunosuppression, theories connecting the two have surfaced. In this paper, we provide a comprehensive review of the key literature on human microbiota, especially the skin microbiota, and skin cancer (i.e., non-melanoma skin cancer, melanoma, cutaneous T cell lymphoma). Also, mechanistic perspectives as to how our microbiota influence skin cancer development and treatment are offered.

Updates on the Risk of Neuropsychiatric and Gastrointestinal Comorbidities in Rosacea and Its Possible Relationship with the Gut-Brain-Skin Axis.

Rosacea is a common chronic cutaneous inflammatory disorder. Recently, patients with rosacea were identified as having a higher risk of developing various comorbidities such as cardiovascular disease, psychiatric disorders, neurologic disorders, and gastrointestinal disorders. However, the risks of some comorbidities in patients with rosacea are somewhat contradictory, depending upon the study design. Moreover, pathomechanisms associated with the comorbidities of patients with rosacea remain poorly elucidated. The purpose of this review was to provide the most up-to-date evidence on the risks of neuropsychiatric and gastrointestinal comorbidities in patients with rosacea. Moreover, the molecular pathomechanisms associated with neuropsychiatric and gastrointestinal comorbidities in patients with rosacea were evaluated based on recent studies. This review was also intended to focus more on the role of the gut-brain-skin axis in the association of neuropsychiatric and gastrointestinal comorbidities in rosacea.

Fractional Carbon Dioxide Laser as an "Add-on" Treatment for Vitiligo: A Meta-analysis with Systematic Review.

Treatment of vitiligo is challenging and requires a multidisciplinary approach. Fractional carbon dioxide (CO2) laser as an add-on to conventional treatment has been reported to be effective, but there is no consensus on its use. A systematic review was performed by searching major databases for relevant publications to February 2017. Six studies with 85 participants were included. For those with refractory vitiligo, the addition of fractional CO2 laser to routine treatment modalities was superior to conventional treatment alone in terms of > 50% re-pigmentation (risk ratio (RR) 4.90, 95% confidence interval (95% CI), 1.15-20.93; p = 0.03), physician improvement score (mean difference (MD) 0.81, 95% CI 0.33-1.29; p < 0.001), < 25% re-pigmentation (RR 0.64, 95% CI, 0.49-0.85; p=0.002) and patient satisfaction (MD 1.61, 95% CI 0.73-2.49; p< 0.001). Side-effects were minor. These results provide evidence supporting that fractional CO2 laser is a valuable treatment modality for patients with vitiligo, especially for those with refractory vitiligo.

Autophagy in Human Skin Fibroblasts: Impact of Age.

Autophagy is an intracellular stress response that is enhanced under starvation conditions, and also when the cellular components are damaged. Aging accompanies an increase in intracellular stress and has significant impact on the skin. Since dermal fibroblasts are a powerful indicator of skin aging, we compared the autophagic activity of human skin fibroblasts between the young and old. According to TEM analyses, the number of autophagosomes per 1 µm² cytoplasmic area was similar between young and aged fibroblasts. The amount of LC3 (microtubule-associated protein 1 light chain 3)-II, a form associated with autophagic vacuolar membranes, was also similar between the groups from Western blot analysis. Although residual bodies were more common in aged dermal fibroblasts, LC3 turnover and p62 assay showed little difference in the rate of lysosomal proteolysis between the young and old. RNA-seq analysis revealed that the major autophagy-modulating genes (BECN1, MAP1LC3B, ATG5, ATG7, ULK1, PIK3C3, mTOR) were not differentially expressed with age. Our results suggest that the basal autophagic flux in aged dermal fibroblasts is largely comparable to that of young fibroblasts. However, with a higher speed and amount of waste production in aged cells, we postulate that such autophagic flux may not be sufficient in keeping the old cells "clean", resulting in skin aging. Aging is a complex process and, as such, the relationship between autophagy and aging is not straightforward. That is to say, autophagy does not simply decline with age. Regardless of the controversies on autophagic activity with age, autophagy plays a crucial role in counteracting aging, and strategies aimed at its modulation should hold promise for the prevention of skin aging.

Air Pollution, Autophagy, and Skin Aging: Impact of Particulate Matter (PM10) on Human Dermal Fibroblasts.

A World Health Organization (WHO) report from 2016 states that over 3 million people die annually from air pollution, which places air pollution as the world's largest single environmental health risk factor. Particulate matter (PM) is one of the main components of air pollution, and there is increasing evidence that PM exposure exerts negative effects on the human skin. To see the impact of air pollution on skin aging, we analyzed the effect of PM exposure on human dermal fibroblasts (HDFs) with Western blot, enzyme-linked immunosorbent assay (ELISA), and gene analysis. Cultured HDFs were exposed to PM10 at a concentration of 30 µg/cm² for 24 h, and their gene/protein expression of inflammatory cytokines, fibroblast chemical mediators, and autophagy were assessed. A total of 1977 genes were found to be differentially expressed following PM exposure. We observed a significantly increased expression of pro-inflammatory genes interleukin (IL)-1ß, IL-6, IL-8 and IL-33 in dermal fibroblasts exposed to PM10. Protein expression of IL-6 and IL-8 also significantly increased, which complemented our gene analysis results. In addition, there was a significant increase in cytochrome P450 (CYP1A1, CYP1B1), matrix metalloproteinase (MMP-1, MMP-3) mRNA expression, and significant decrease in transforming growth factor (TGF)-ß, collagen type I alpha chain (COL1A1, COL1A2), and elastin (ELN) mRNA expression in PM-exposed dermal fibroblasts. Protein expression of MMP-1 was significantly increased and that of TGF-ß and procollagen profoundly decreased, similar to the gene analysis results. Autophagy, an integrated cellular stress response, was also increased while transmission electron microscopy (TEM) analysis provided evidence of PM internalization in the autolysosomes. Taken together, our results demonstrate that PM10 contributes to skin inflammation and skin aging via impaired collagen synthesis. Increased autophagy in our study suggests a reparative role of autophagy in HDFs stressed with PM, but its biological significance requires further research.

Delayed onset filler complication: Two case reports and literature review.

Soft tissue augmentation by fillers has become a popular cosmetic tool to offer rejuvenation and aesthetic improvement. Its results are comparable to those previously achieved only by plastic surgery. However, marked increase of filler procedures is associated with a great number of complications. Complications associated with filler injection might have early onset (within days) or late onset (after weeks to years). Delayed complications include infections, foreign body granulomatous reaction, migration of filler material, persistent discoloration, and scarring. Here we report two cases of delayed complications: one case of foreign body granuloma with migration and one case of acute inflammation involving a quiescent granuloma.

Efficacy and Safety of Tranexamic Acid in Melasma: A Meta-analysis and Systematic Review.

Tranexamic acid is a novel treatment option for melasma; however, there is no consensus on its use. This systematic review searched major databases for relevant publications to March 2016. Eleven studies with 667 participants were included. Pooled data from tranexamic acid-only observational studies with pre- and post-treatment Melasma Area and Severity Index (MASI) showed a decrease of 1.60 in MASI (95% confidence interval (CI), 1.20-2.00; p<0.001) after treat-ment with tranexamic acid. The addition of tranexamic acid to routine treatment modalities resulted in a further decrease in MASI of 0.94 (95% CI 0.10-1.79; p = 0.03). Side-effects were minor, with a few cases reporting hypo-menorrhoea, mild abdominal discomfort, and transient skin irritation. These results support the efficacy and safety of tranexamic acid, either alone or as an adjuvant to routine treatment modalities for melasma.

Transient Receptor Potential Vanilloid-1 in Epidermal Keratinocytes May Contribute to Acute Pain in Herpes Zoster.

The role of transient receptor potential vanilloid-1 (TRPV1) in the initiation of neurogenic inflammation and transduction of pain is well established. In this study 33 patients with herpes zoster (HZ) were recruited from a single centre and underwent a questionnaire interview at their first visit. Punch biopsies from the HZ lesions and the contralateral unaffected skin were performed to localize and quantify the expression of TRPV1. Immunofluorescent staining for TRPV1 was most prominent in the epidermal keratinocytes. Both TRPV1 mRNA and protein levels were significantly higher in the HZ epidermis than in control epidermis (relative ratio 1.62 ± 0.27, p = 0.033 and 2.55 ± 0.51, p = 0.005, respectively). Protein TRPV1 ratio (HZ lesion/control) correlated with the degree of pain (measured on a visual analogue scale; VAS) (p = 0.017) and was significantly lower in patients who had taken either HZ medication or painkillers prior to their visit. These results suggest that non-neuronal TRPV1 may contribute to acute pain in herpes zoster.

Adverse reactions to injectable soft tissue fillers: memorable cases and their clinico-pathological overview.

BACKGROUND: Filler injection is a minimally invasive procedure widely used for soft tissue augmentation. Although the safety profile is favorable, adverse events can occur, especially after illegal filler injection. OBJECTIVES: The authors present memorable cases of filler complications and review their clinico-pathological features and treatment strategies. PATIENTS AND METHODS: This is a retrospective, single-center case series. The authors identified eight patients with significant complications following filler injection. A medical record review was performed for clinical history, histopathological studies, and treatment. RESULTS: Six female and two male subjects presented with significant filler complications. The time interval between filler injection and the development of a complication varied greatly among cases (immediately afterwards to 14 years following filler injection). Four of the patients received illegal filler injection where the injected material was either unknown (25%) or was told as paraffin (12.5%) or Vaseline(®) (12.5%). Hyaluronic acid fillers were used in two patients (25%) and the rest were injected with porcine atelocollagen (12.5%) and polyacrylamide hydrogel (12.5%). The complications were classified as an allergic reaction (25%), filler material migration (12.5%), injection necrosis + embolism (25%), and foreign body granuloma (37.5%), based on their clinico-pathological features and were treated accordingly. CONCLUSION: Adverse effects are not uncommon following filler injection. Physicians should be aware of the potential side effects, recognize their presentations, and understand how to manage them.

Early postoperative treatment of thyroidectomy scars using botulinum toxin: a split-scar, double-blind randomized controlled trial.

Operational scars, especially those located on the exposed parts of the body, can be distressing. Despite high demand for an early intervention to minimize surgical scars, there is yet no universal consensus on optimal treatment. A split-scar, double-blind randomized controlled trial was held to assess the safety and efficacy of early postoperative botulinum toxin type A (BTA) injection in surgical scars. A single session of treatment was performed where BTA was allocated to one half of the scar and 0.9% saline to the control half. Scars were assessed using the modified Stony Brook Scar Evaluation Scale (SBSES) with standardized photographs. Fifteen patients completed the study, and their data were analyzed. At 6 months' follow-up, a significant improvement in SBSES score was noted for the BTA-treated halves of the scars (p < 0.001), with minimal change on the saline-treated side (p = 0.785). The mean calculated difference in SBSES scores (final/initial) between the BTA-treated side and the saline-treated side was also significant (p < 0.001). Early postoperative BTA injection was safe and effective in modulating thyroidectomy scars and may be a promising option for scar prevention.

A woman with a nose like an "Elephant's Trunk".

For more than a century, exogenous lipids and injectable silicone have been used by nonmedical personnel or even licensed physicians to correct body defects and augment parts of the human body. Any skin-implanted exogenous substances can trigger an inflammatory response in individuals. Notably, oily substances have commonly been reported to produce a foreign body granulomatous reaction known as "sclerosing lipogranuloma". Despite local and systemic complications, injections of illegal materials by unlicensed practitioners are widespread and are still a problem throughout East Asian Countries. We herein present a unique case of sclerosing lipogranuloma following illegal filler injection.

A patient with cupping-related post-inflammatory hyperpigmentation successfully treated with a 1,927 nm thulium fiber fractional laser.

Post-inflammatory hyperpigmentation is a rare complication following cupping therapy. We report a case of a 26-year-old woman who presented with hyper-pigmented skin lesions on her lower back which was persistent for 6 months following cupping therapy. The 1,927 nm thulium fiber laser (Fraxel re:store Dual, Solta Medical Inc., Hayward, CA) was tested leading to near complete resolution within four sessions.

The safety and efficacy of poly-L-lactic acid on sunken cheeks in Asians.

BACKGROUND: Poly-L-lactic acid (PLLA) is a biocompatible and biodegradable polymer device used for correction of facial contour deficiencies, with a gradual onset of effect that is maintained for up to 25 months. PLLA is currently widely used to correct age-related facial volume deficits in Asians. OBJECTIVES: We sought to evaluate the safety and long-term efficacy of PLLA on treating age-related sunken cheeks in Asians. PATIENTS AND METHODS: This was a retrospective, single-center study of 11 subjects with age-related sunken cheeks who were treated with three sessions of PLLA, and then followed-up for 24 months. A questionnaire was used to evaluate patient satisfaction and the incidence of adverse reactions. RESULTS: Seven female and four male subjects with mild-to-moderate age-related sunken cheeks were included in the study. The mean age of the subjects was 41.5 (range: 25-50). Overall, 90.9% of patients replied that they were either satisfied or very satisfied with the results at 24 months follow-up; 91% of patients rated the volume correction to be good or excellent. Despite the high incidence of bruising (63.7%) and post-treatment nodules (27.3%), all subjects (100%) were willing to undergo the procedure again. CONCLUSION: PLLA has shown long-lasting effects in reversing age-related sunken cheeks in Asians, with high patient satisfaction. Special consideration should be made to minimize the side effects.

A split-face, evaluator-blind randomized study on the early effects of Q-switched Nd:YAG laser versus Er:YAG micropeel in light solar lentigines in Asians.

BACKGROUND: Asians are prone to develop epidermal pigmentary lesions as a result of photoaging. Solar lentigines, especially those which are light in color, show somewhat limited response to pigment lasers and intense pulsed light sources. OBJECTIVES: We sought to compare the early effects as well as side effects of Q-switched Nd:YAG and Er:YAG micropeel in treating light solar lentigines in Asians. PATIENT AND METHODS: This was a split-face, evaluator-blind, randomized controlled study. A single session of treatment was performed on Asian patients with light facial lentigines. Q-switched Nd:YAG laser was allocated to one half of the face, and Er:YAG micropeel to the other half. The response to therapy was evaluated by two independent dermatologists with standardized photographs taken 2 weeks and 1 month after the laser treatment. Patients' satisfaction and preference in treatment were also assessed. RESULTS: Fifteen patients completed the study and were analyzed. A reduction in pigment was observed with both lasers during the study period. The degree of pigment reduction in the Q-switched Nd:YAG treated side of the face was significantly higher than that of the Er:YAG micropeel treated side at 2-week follow-up (p < 0.001). The degree of pigment reduction between the Q-switched Nd:YAG-treated side and the Er:YAG micropeel-treated side was similar at 1-month follow-up (p = 0.110). CONCLUSION: While there is no perfect therapy for light solar lentigines, a single session of Q-switched Nd:YAG laser and Er:YAG micropeel was shown to reduce pigmentation. The immediate effects (2-week follow-up) were better with the Q-switched Nd:YAG laser but there was no great difference between the two laser types at 1-month follow-up due to the greater degree of post-inflammatory hyperpigmentation following Q-switched Nd:YAG. Both laser types could be applied either singly in turns, or in combination for maximal efficacy in future.

Varicella-zoster virus as a possible cause of pityriasis lichenoides et varioliformis acuta.

The etiologic agents for pityriasis lichenoides et varioliformis acuta (PLEVA) are largely unknown, although it has been suggested that foreign antigens such as infectious agents are the pathogenic mechanism. We present a case suggesting a possible relationship between varicella-zoster virus and PLEVA.

A split-face, evaluator-blind randomized study on the early effects of Q-switched Nd:YAG laser plus Er:YAG micropeel (combined therapy) versus Q-switched Nd:YAG alone in light solar lentigines in Asians.

Solar lentigines are a common sign of aging in Asians, who often asked for treatment. Various lasers, including Q-switched Nd:YAG and Er:YAG, have been adopted, but the results are not always satisfactory, especially for those who are relatively light in color. Our objective was to compare the early effects as well as side effects of Q-switched Nd:YAG laser plus Er:YAG micropeel (combined therapy) with those of Q-switched Nd:YAG laser (QSNY) alone in light solar lentigines in Asians. This was a split-face, evaluator-blind, randomized controlled study. A single session of treatment was performed on Asian patients with light facial lentigines. A combined treatment with QSNY and Er:YAG micropeel was allocated to one half of the face, and QSNY alone to the other half. The response to therapy was evaluated by two independent dermatologists, with standardized photographs taken 2 weeks and 1 month after the laser treatment. Patients' satisfaction and preference in treatment were also assessed. Fifteen patients completed the study and were analyzed. Overall, a reduction in pigment was observed with both treatment arms during the study period. The degree of pigment reduction following combined therapy and QSNY alone was similar at 2 weeks' follow-up ( = 0.433). However, due to the higher incidence of postinflammatory hyperpigmentation (PIH) with combined therapy (73.3 vs 40%), the degree of pigment reduction in the combined side of the face was found significantly lower than that of the QSNY-alone side at 1-month follow-up (P = 0.014). Although our study results show that both combined therapy and QSNY alone are capable of reducing pigmentation, QSNY alone is considered to have more favorable qualities than combined treatment for light solar lentigines in Asians.

Clinical Efficacy of 5-Fluorouracil and Bleomycin in Dermatology.

Bleomycin and 5-fluorouracil (5-FU) are widely used in various dermatological disorders. Both drugs are well-recognized as antineoplastic drugs and exert their effect by blocking the cell cycle. Topical and intralesional formulations are available and have been studied in both non-neoplastic and cancerous lesions. However, data comparing the effect of bleomycin and 5-FU in the dermatological disorders are limited. This review outlines the action mechanisms of both drugs and compares their clinical efficacies in a wide range of dermatologic diseases including hypertrophic scar, wart, skin cancer, vascular malformation, hemangioma, and vitiligo, and discusses the overall safety of the drugs. Intralesional bleomycin treatment is effective in hypertrophic scars and warts, but intralesional 5-FU may also be considered since it is cheaper and less painful. Moreover, intralesional 5-FU and bleomycin injection is a viable option for premalignant lesions (i.e., actinic keratosis) and inoperable skin cancers. Both bleomycin and 5-FU have been applied as treatment adjuncts for vitiligo, with 5-FU showing a slightly better outcome. Both agents have a good safety profile, and no serious side effects have been reported following their use in the field of dermatology.