A prospective, split-face, randomized study of the efficacy and safety of a novel fractionated intense pulsed light treatment for melasma in Asians.

BACKGROUND: Intense pulsed light (IPL) has been reported to effectively treat melasma in previous studies, but an aggravation of pigmentation was noted. Fractionated IPL is a novel technique in which microsecond-domain fractionated pulses are delivered to the target area. OBJECTIVE: To compare the safety and efficacy of low-fluency, frequently scheduled fractionated IPL and conventional IPL for melasma treatment. MATERIALS AND METHODS: This was a 14-week, split-face study in which 30 Asian women were treated with weekly fractionated IPL on one side of the face and biweekly conventional IPL on the other side. RESULTS: The non-inferiority of a weekly fractionated IPL regimen to a biweekly conventional IPL regimen was verified by a lower margin of the 95% confidence interval for the difference in the Melasma Area and Severity Index (MASI) change from baseline of 2.61 for each side. This value was greater than the previously determined non-inferiority margin of -2.68 (P < 0.025). On the fractionated IPL side, the modified MASI score decreased continuously, but in the conventional IPL group, the MASI score rebounded during the treatment course. CONCLUSION: Fractionated IPL shows moderate efficacy as a melasma treatment and is therefore a good alternative to conventional IPL as there is no indication of melasma exacerbation. Fractionated IPL can also be used as a maintenance treatment for melasma.

Activation of autophagic pathways is related to growth inhibition and senescence in cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (SCC) is a very common resectable cancer; however, cutaneous SCC is highly resistant to chemotherapy if metastasis develops. Activating transcription factor 3 (ATF3) has been suggested as a marker of advanced or metastatic cutaneous SCC. Autophagy is one of the most important mechanisms in cancer biology and commonly induced by in vitro serum starvation. To investigate the role of autophagy activation in cutaneous SCC, we activated autophagic pathways by serum starvation in SCC13 and ATF3-overexpressing SCC13 (ATF3-SCC13) cell lines. ATF3-SCC13 cells demonstrated high proliferative capacity and low p53 and autophagy levels in comparison with control SCC13 cells under basal conditions. Intriguingly, autophagic stimulation via serum starvation resulted in growth inhibition and senescence in both cells, while ATF3-SCC13 cells further demonstrated growth inhibition and senescence. Apoptosis was not significantly induced by autophagy activation. Taken together, autophagy activation may be a promising antitumor approach for advanced cutaneous SCC.

Combination treatment of low-fluence 1,064-nm Q-switched Nd: YAG laser with novel intense pulse light in Korean melasma patients: a prospective, randomized, controlled trial.

BACKGROUND: Recently, intense pulsed light (IPL) and low-fluence Q-switched neodymium-doped yttrium aluminum (LF-QS-Nd:YAG) laser have been successfully used to treat melasma. OBJECTIVE: To evaluate the effectiveness and safety of combined novel fractionated IPL (IPL-F) with LF-QS-Nd:YAG laser in patients with melasma. METHODS: Twelve patients underwent 6 treatment sessions of concomitant IPL-F and LF-QS-Nd:YAG laser (combination group), and 12 patients underwent 6 treatment session of IPL-F alone (IPL only group). Partial melasma area and severity index (MASI) scores were evaluated by 2 dermatologists using digital photography. RESULTS: In the combination group, the partial MASI score has significantly decreased by 47% at 1 month after the treatment (p < .05) and 50% at 2 months after the last treatment (p < .01). At 1 month and 2 months after the treatment, the decrease in the partial MASI score of the combination group was significantly larger than that of the IPL only group (p < .05). In both groups, treatment with IPL-F and LF-QS-Nd:YAG laser was well tolerated. CONCLUSION: Our results suggest that the combination of the IPL-F with LF-QS-Nd:YAG laser may be an effective and safe modality for melasma patients.

Epidermal growth factor and epidermal growth factor signaling attenuate laser-induced melanogenesis.

BACKGROUND: Epidermal growth factor (EGF) is a peptide that promotes cell growth by binding to its receptor (EGFR) on the cell surface. EGF has been used in cosmetics to whiten the skin and for the prevention of postinflammatory hyperpigmentation (PIH), presumably by accelerating wound healing, but the effects of EGF on melanogenesis are not known, and the presence of EGFR on melanocytes has not been confirmed. METHODS: To establish a role of EGF in melanogenesis, we first investigated expression of EGFR on melanocytes. Second, in the search for an effect of EGF on PIH, we investigated the effect of EGF on melanin production by melanocytes with or without laser-treated keratinocyte-conditioned culture media (LCM). RESULTS: Treatment with EGF did not affect proliferation of melan-A, mouse-derived immortalized melanocytes. Melanocytes treated with LCM had greater prostaglandin-E2 (PGE2) expression and tyrosinase enzyme activity than melanocytes treated with control media. Treatment with EGF lowered melanin production of LCM-treated melanocytes but not of melanocytes treated with control media. CONCLUSION: Our results support EGF as a candidate target for development of antimelanogenic agents in PIH.

The first documented case of true botulinum toxin granuloma.

We report a unique case of foreign-body granuloma following botulinum neurotoxin type A (BoNTA) injection. A 44-year-old woman was injected with BoNTA by a dermatologist. Within 2 months of treatment, palpable nodules developed on injection site and biopsy revealed foreign-body granuloma.

Clinical efficacy of the dual-pulsed Q-switched neodymium:yttrium-aluminum-garnet laser: Comparison with conservative mode.

The quality (Q)-switched neodymium:yttrium-aluminum-garnet (Nd:YAG) laser is one of the first non-ablative lasers to be used for facial resurfacing and photorejuvenation. Recently, the method of low-fluence Q-switched Nd:YAG lasers known as 'laser toning' has been used for non-ablative skin rejuvenation and for the treatment of melasma in Asian countries. We report our experience of using a novel Q-switched Nd:YAG laser that was operated as a dual pulse at half fluence and 140-µs intervals compared with conservative mode laser.

Pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica: comparison of lesional T-cell subsets and investigation of viral associations.

BACKGROUND: Pityriasis lichenoides (PL) exhibits a broad clinical spectrum that includes both acute and chronic forms. The precise biologic mechanisms underlying PL remain unclear. OBJECTIVES: To evaluate the immunohistochemical characteristics of PL and to investigate lesional T-cell subsets and the possible role of viral infection in its pathogenesis. PATIENTS AND METHODS: Samples from 10 patients with PL et varioliformis acuta (PLEVA) and 13 with PL chronica (PLC) were analyzed immunohistochemically. Epstein-Barr virus early regions were assayed by in situ hybridization and T-cell receptor-γ (TCR-γ) gene rearrangements were assayed by polymerase chain reaction (PCR). We also utilized PCR to assay for human herpesvirus-8 (HHV-8) DNA in 51 patients with PL and in 25 controls. RESULTS: Lymphocytes expressing CD8 and T-cell intracellular antigen-1 were more abundant in patients with PLEVA than with PLC, whereas CD4+ lymphocytes and FOXP3-positive regulatory T-cells were more abundant in PLC. HHV-8 DNA was present in 11 of 51 (21.6%) PL patients and 0 of 25 controls. A clonal TCR-γ gene rearrangement was observed in only one patient with PLEVA. CONCLUSIONS: Our data suggests that PL may represent an inflammatory condition induced by various triggering agents, such as HHV-8, rather than a lymphoproliferative disorder. PLEVA, characterized by an acute course with severe symptoms, may indicate a relative lack of regulatory T-cells in comparison with PLC.

Microtubule-associated protein light chain 3 is involved in melanogenesis via regulation of MITF expression in melanocytes.

Although autophagy plays a role in melanogenesis by regulating melanosome degradation and biogenesis in melanocytes, a detailed understanding of the regulatory functions of autophagy factors is lacking. Here, we report a mechanistic link between microtubule-associated protein light chain 3 (LC3) activation and melanogenesis. We observed high expression of LC3 in melanosome-associated pigment-rich melanocytic nevi of sun-exposed skin, as indicated by patterns of melanosomal protein MART1 expression. Rapamycin-induced autophagy significantly increased the melanin index, tyrosinase activity and expression of several proteins linked to melanosome biogenesis, including microphthalmia transcription factor (MITF), pre-melanosome protein and tyrosinase, in Melan-a melanocytes. siRNA-mediated knockdown of LC3, but not beclin-1 or ATG5, decreased melanin content and tyrosinase activity. LC3 knockdown also markedly inhibited MITF expression and subsequent rapamycin-induced melanosome formation. More importantly, LC3 knockdown suppressed α-MSH-mediated melanogenesis by attenuating cAMP response element-binding protein (CREB) phosphorylation and MITF expression in Melan-a cells via decreased extracellular signal-regulated kinase (ERK) activity. Overexpression of constitutively active ERK reversed the effect of LC3 knockdown on CREB phosphorylation and MITF expression. These findings demonstrate that LC3 contributes to melanogenesis by increasing ERK-dependent MITF expression, thereby providing a mechanistic insight into the signaling network that links autophagy to melanogenesis.

A Randomized, Evaluator-Blinded, Split-Face Comparison Study of the Efficacy and Safety of a Novel Mannitol Containing Monophasic Hyaluronic Acid Dermal Filler for the Treatment of Moderate to Severe Nasolabial Folds.

BACKGROUND: Mannitol containing monophasic filler with higher crosslinking has not been well studied for moderate and severe nasolabial fold (NLF) correction. OBJECTIVE: To compare the efficacy and safety of a novel mannitol containing hyaluronic acid (HA) filler (HA-G) with biphasic HA filler (HA-P) for moderate and severe NLF correction. METHODS: Thirteen subjects with symmetric moderate to severe NLF received HA-G (in one NLF) and HA-P (in other NLF) and were evaluated for 24 weeks. RESULTS: At both 12 and 24 weeks, the mean improvement in Genzyme 6-point grading scale from baseline was significantly greater in the side of face that was treated with HA-G than HA-P (1.96±0.91 vs. 1.54±0.73 at week 12; p=0.044, 1.88±0.78 vs. 1.3±0.79 at week 24; p=0.027, respectively). At 12 weeks, the mean Global Aesthetic Improvement Scale score was 2.92±0.93 for HA-G and 2.31±0.95 for HA-P (p=0.008). Both fillers were well tolerated. CONCLUSION: The HA filler HA-G provides better efficacy and similar local tolerability compared with HA-P in 6 months following treatment for moderate and severe NLF.

Identification of Ten Additional Susceptibility Loci for Ulcerative Colitis Through Immunochip Analysis in Koreans.

BACKGROUND: Recent genetic association studies identified more than 160 susceptibility loci for inflammatory bowel disease in Caucasian populations, but studies in Asian populations are limited. We have previously reported 3 loci associated with Korean ulcerative colitis (UC). METHODS: Using the Immunochip custom single nucleotide polymorphisms (SNP) array designed for dense genotyping of 186 known disease loci from 12 immune-mediated diseases, we analyzed 705 patients with UC and 1178 controls for 536,821 SNPs (89,057 genotyped and 447,764 imputed) in the discovery stage followed by replication in additional 980 affected individuals and 2694 controls in a Korean population. RESULTS: We confirmed the associations of 10 known UC risk loci in Koreans: rs76418789 in IL23R (combined P = 1.25 × 10), rs4728142 in IRF5 (combined P = 3.17 × 10), rs1830610 near JAK2 (combined P = 2.28 × 10), rs1555791 near TNFRSF14 (combined P = 1.62 × 10), rs880790 between IL10-IL19 (combined P = 3.73 × 10), rs10185424 between IL1R2-IL1R1 (combined P = 1.54 × 10), rs6478108 in TNFSF15 (combined P = 9.28 × 10), rs861857 between UBE2L3-YDJC (combined P = 3.05 × 10), rs1801274 in FCGR2A (discovery P = 1.54 × 10), and rs17085007 between GPR12-USP12 (discovery P = 3.64 × 10). The percentage of phenotype variance explained by the 13 risk loci (including 3 previously reported loci) was 5.61% in Koreans (on the liability scale, population prevalence = 0.0308%). CONCLUSIONS: Our study increased the number of UC susceptibility loci in Koreans to 13 and highlighted the extensive sharing of genetic risk across populations of UC.

A prospective, randomized, double-blind comparison of an ablative fractional 2940-nm erbium-doped yttrium aluminum garnet laser with a nonablative fractional 1550-nm erbium-doped glass laser for the treatment of photoaged Asian skin.

BACKGROUND: As compared with ablative fractional CO2 laser, ablative fractional erbium-doped yttrium aluminum garnet (Er:YAG) laser is considered to be a more suitable treatment option for photoaged skin in Asians due to the lower incidence of postinflammatory hyperpigmentation. OBJECTIVE: To compare the efficacy and safety of ablative fractional Er:YAG laser (ablative fractional resurfacing [AFR]) and nonablative fractional 1550-nm Er:glass laser (non-AFR [NAFR]) in the treatment of photoaging. METHODS: This was a prospective, randomized, double-blinded comparative study. In three sessions, at four-week intervals, 19 patients received Er:YAG AFR, and 15 patients received Er:glass NAFR. Pigmentation, uneven tone/erythema, wrinkles and overall features of photoaging were scored. Patient satisfaction, adverse effects and pain scores were recorded. Melanin and erythema indexes were measured. RESULTS: Reductions in pigmentation and uneven tone/erythema scores were significantly greater after Er:YAG AFR, while wrinkle score reduction was significantly greater after Er:glass NAFR. Physician and patient assessments for the overall features showed greater improvement in the Er:glass NAFR. Treatment-related pain or adverse events were less in the Er:YAG AFR. CONCLUSION: Both Er:YAG AFR and Er:glass NAFR are effective and safe and could be used in a complementary manner for treating photoaged Asian skin.

Concomitant use of azathioprine/6-mercaptopurine decreases the risk of anti-TNF-induced skin lesions.

BACKGROUND: Anti-tumor necrosis factor (anti-TNF) agents are widely used to treat patients with moderate-to-severe inflammatory bowel disease (IBD). We aimed to identify the risk factors for adverse skin lesions in patients with IBD receiving anti-TNF agents and assess the effect of concomitant use of azathioprine/6-mercaptopurine (AZA/6 MP). METHODS: A total of 500 patients (404 with Crohn's disease, 96 with ulcerative colitis) who received anti-TNF agents between June 2002 and July 2013 were identified and retrospectively investigated. We compared 47 patients with IBD with skin lesions with 443 patients with IBD without skin lesions to identify risk factors by univariate and multivariate analysis. The Kaplan-Meier method was used to estimate the cumulative incidence of adverse skin lesions in relation to the concomitant use of AZA/6 MP. RESULTS: Eczematiform eruptions (n = 18, 38%) were the most common skin lesion type, followed by psoriasiform lesions (n = 13, 28%). A response to topical steroids was seen in 70% (33/47) of patients with skin lesions, and anti-TNF agents had to be discontinued in 9% (4/47). Concomitant use of AZA/6 MP decreased the risk of skin lesions in univariate (hazard ratio, 0.452; 95% CI, 0.251-0.814; P = 0.008) and multivariate (hazard ratio, 0.437; 95% CI, 0.242-0.790; P = 0.006) analysis. In addition, the cumulative incidence of adverse skin lesions was lower in patients on concomitant maintenance with AZA/6 MP (P = 0.009) than in those on anti-TNF monotherapy. CONCLUSIONS: Concomitant use of AZA/6 MP may decrease the occurrence of adverse skin lesions in patients receiving anti-TNF therapy.

Adverse events associated with botulinum toxin injection: a multidepartment, retrospective study of 5310 treatments administered to 1819 patients.

BACKGROUND: The injection of botulinum toxin is now commonly used for many therapeutic and cosmetic purposes but because of its increased use more adverse events are being reported. OBJECTIVE: To retrospectively evaluate and analyze the safety of botulinum toxin injections in terms of purpose and the type of toxin administered. MATERIALS AND METHODS: Data were collected on 1819 patients who underwent a total of 5310 treatments between 2005 and 2011 at a single tertiary medical center. Information on the dosage, treatment purpose, type of botulinum toxin, and any adverse events associated with these treatments were collected and analyzed. The generalized estimating equation (GEE) with the logistic link function was used to estimate the overall frequencies of adverse events. A multivariable GEE with the logistic link function was used to identify the factors associated with adverse events. RESULTS: Among the 5310 botulinum toxin treatments in our study cohort, 2258 of which (42.5%) were used to treat hemifacial spasm, 184 adverse events (3.73%) were recorded, 114 (2.26%) muscle-related, and 71 (1.47%) muscle-unrelated. The highest number of adverse events (8.29%) was associated with the treatment of blepharospasm and the lowest (1.07%) with masseter hyperplasia. By multivariate analysis, the odds ratio for females was 1.577 (95% confidence interval [CI] = 1.052-2.364; p = 0.027) and for the dose was 1.006 (95% CI = 1.002-1.010; p = 0.005). When compared with upper face wrinkles, the odds ratio was 2.510 (95% CI = 1.400-4.499; p = 0.002) for blepharospasm, 0.375 (95% CI = 0.202-0.695; p = 0.002) for cervical dystonia, and 0.114 (95% CI: 0.015-0.862; p = 0.035) for masseter hyperplasia. CONCLUSION: When injecting botulinum toxin for cosmetic purposes, practitioners should be cautious, especially when targeting the areas around the eyes, as these treatments are prone to cause adverse events.

Role of CD4CD25FOXP3 Regulatory T Cells in Psoriasis.

BACKGROUND: CD4(+)CD25(high+)regulatory T cells (Tregs) are considered to be of vital importance for maintaining immunologic self-tolerance and preventing autoimmune diseases. These cells have been found to be deficient in skin lesions and in the peripheral blood of patients with psoriasis. OBJECTIVE: To investigate the role of Tregs in the pathogenesis of psoriasis and to evaluate the changes in Tregs in relation to the severity and the clinical course of psoriasis. METHODS: Immunohistochemistry (CD3, 4, 8, 79 and FOXP3) was performed in 22 psoriatic patients compared to 5 normal controls. Flow cytometry (CD3, 4, 8, 25 and FOXP3) was performed in 18 psoriatic patients and 8 normal volunteers and reverse transcriptase polymerase chain reaction (foxp3 mRNA) was performed in 8 psoriasis patients. RESULTS: An increase in the FOXP3(+) cell fraction was detected in the lesional psoriatic skin irrespective of the severity of psoriasis as compared with the normal skin. However, a decrease in FOXP3(+) cells was observed in the samples obtained from psoriasis of 'acute course'. FOXP3(+) Treg populations in the blood of the 'acute course' psoriasis was not different compared to that of 'chronic course' psoriasis and normal controls. CONCLUSION: The deficiency of FOXP3(+) Tregs in the lesional psoriatic skin might be responsible for the exacerbation of psoriasis.