Guanine Deaminase in Human Epidermal Keratinocytes Contributes to Skin Pigmentation.

Epidermal keratinocytes are considered as the most important neighboring cells that modify melanogenesis. Our previous study used microarray to show that guanine deaminase (GDA) gene expression is highly increased in melasma lesions. Hence, we investigated the role of GDA in skin pigmentation. We examined GDA expression in post-inflammatory hyperpigmentation (PIH) lesions, diagnosed as Riehl's melanosis. We further investigated the possible role of keratinocyte-derived GDA in melanogenesis by quantitative PCR, immunofluorescence staining, small interfering RNA-based GDA knockdown, and adenovirus-mediated GDA overexpression. We found higher GDA positivity in the hyperpigmentary lesional epidermis than in the perilesional epidermis. Both UVB irradiation and stem cell factor (SCF) plus endothelin-1 (ET-1) were used, which are well-known melanogenic stimuli upregulating GDA expression in both keratinocyte culture alone and keratinocyte and melanocyte coculture. GDA knockdown downregulated melanin content, while GDA overexpression promoted melanogenesis in the coculture. When melanocytes were treated with UVB-exposed keratinocyte-conditioned media, the melanin content was increased. Also, GDA knockdown lowered SCF and ET-1 expression levels in keratinocytes. GDA in epidermal keratinocytes may promote melanogenesis by upregulating SCF and ET-1, suggesting its role in skin hyperpigmentary disorders.

Anesthetic cream relieves pain after cryotherapy treatment of plantar and palmar warts.

Cryotherapy using liquid nitrogen is an effective and commonly used treatment for palmoplantar warts. However, pain can be a limiting factor in the effective use of cryotherapy. In this study, we found that a single application of anesthetic cream following cryotherapy treatment of warts reduced posttreatment pain and led to improved tolerability of the procedure.

The ion channel activator CyPPA inhibits melanogenesis via the GSK3ß/ß-catenin pathway.

Research into materials that inhibit melanogenesis in skin has gained interest. Screening for such compounds in B16F10 cells revealed that cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA), a positive modulator of small-conductance Ca2+-activated K+ channels, is a strong inhibitor of melanogenesis. We investigated the anti-melanogenic activity of CyPPA and the molecular mechanism by which CyPPA reduced melanin production in normal human melanocytes (NHM). CyPPA treatment resulted in a significant concentration-dependent reduction in melanin content without significant cytotoxicity; treatment likewise resulted in a significant time-dependent reduction in tyrosinase (TYR) activity. Treatment with CyPPA also decreased transcription of melanogenesis-related genes, including the gene encoding microphthalmia-associated transcription factor (MITF). In addition, visual evaluation of the MelanoDerm™ human skin model revealed significantly lower melanin content in the CyPPA-treated condition than in the untreated control. CyPPA was determined to modulate glycogen synthase kinase-3ß (GSK3ß) activity, thereby leading to a decrease in ß-catenin/MITF expression. Thus, CyPPA acts as a melanogenesis inhibitor by modulating the GSK3ß/ß-catenin/MITF pathway.

Alopecia areata and overt thyroid diseases: A nationwide population-based study.

An association between alopecia areata (AA) and other autoimmune diseases has been reported. We investigated the associations between AA and overt autoimmune thyroid diseases. A nationwide, population-based, cross-sectional study was performed using the Korea National Health Insurance claims database. We defined patients with AA as those whose records showed at least four physician contacts in which AA, alopecia totalis (AT) or alopecia universalis (AU) was the principal diagnosis. We also established an age- and sex-matched control group without AA. In a subgroup analysis, patients with AT or AU were classified into the severe AA group, and the remainder were classified into the mild to moderate AA group. Patients with AA were at an increased risk of Graves' disease (odds ratio [OR], 1.415; 95% confidence interval [CI], 1.317-1.520) and Hashimoto thyroiditis (OR, 1.157; 95% CI, 1.081-1.237), and the associations were stronger in the severe AA group (Graves' disease: OR, 1.714; 95% CI, 1.387-2.118; Hashimoto thyroiditis: OR, 1.398; 95% CI, 1.137-1.719). In conclusion, AA was significantly associated with overt autoimmune thyroid diseases. Furthermore, the risk was much higher in the severe AA group.

Treatment of Melasma and Post-Inflammatory Hyperpigmentation by a Picosecond 755-nm Alexandrite Laser in Asian Patients.

The picosecond lasers have shown to effectively treat tattoo pigments that are intractable to previous multiple Q-switched (QS) laser treatments. Therefore we hypothesized that a picosecond laser would show better efficacy with minimal adverse events in the treatment of melasma and post-inflammatory hyperpigmentation (PIH) that are difficult to treat with conventional QS lasers. Two patients with melasma and one patient with PIH were treated with a Picosecond 755-nm Alexandrite Laser (Cyanosure, USA). All patients were Korean with skin type IV and no longer responding to QS laser treatments. Laser treatment was well tolerated in all the patients. Adverse events such as PIH were not reported during 8 weeks of follow up period. After the multiple treatment sessions, one patient reported fair improvement and two patients reported good improvement. Consistent with the clinical results, ex vivo skin model irradiated with a Picosecond 755-nm Alexandrite Laser also showed decreased epidermal keratinocyte necrosis compared with the 532-nm QS Neodymium-Doped Yttrium Aluminium Garnet Laser (Lutronic, Korea) yet decreased melanin content. In conclusion, the Picosecond 755-nm Alexandrite Laser may be useful for effective treatment of intractable melasma and PIH with fewer adverse events in dark Asian skin.

Novel Anti-Melanogenesis Properties of Polydeoxyribonucleotide, a Popular Wound Healing Booster.

Polydeoxyribonucleotide (PDRN), a deoxyribonucleotide polymer, is popularly used for faster healing of cutaneous wounds and boosting of neocollagenesis of photoaged skin among current dermatologic practitioners. Some patients receiving PDRN injection treatment also reported improvement of photoaging-associated mottled pigmentation (PMP). To investigate the effect of PDRN on cutaneous melanogenesis, we examined the effect of PDRN and an available product (Placentex(®)) containing PDRN on melanogenesis using human melanocytes-keratinocytes cocultures and mouse melanocytes. Melanin content, tyrosinase activity, and levels of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein (TRP-1) were determined. Intracellular signaling pathways were assessed by Western blotting. PDRN and Placentex(®) led to decreases in melanin content, tyrosinase activity, and MITF and TRP-1 expression with concomitant increases in phosphorylated forms of extracellular signal-regulated protein kinase (ERK) and AKT in mouse melanocytes. More importantly, both PDRN and Placentex(®) significantly suppressed the melanin content in human melanocyte-keratinocyte cocultures. Clinical evaluation of six female patients with facial hyperpigmentation after three sessions of intradermal PDRN injections using a 5-point scale revealed that PDRN led to more than noticeable improvements in hyperpigmented lesions. This is the first study to demonstrate that PDRN, which is known for its wound-healing properties, may have novel anti-melanogenesis and potential skin whitening properties.

Effects of highly concentrated hyaluronic acid filler on nasolabial fold correction: A 24-month extension study.

BACKGROUND: A previous 6-month study using a more highly concentrated novel hyaluronic acid (HA) filler, PP-501-B, found nasolabial fold (NLF) improvements with increased tolerability. OBJECTIVE: We investigated the long-term efficacy, durability and safety of PP-501-B in the correction of NLFs. METHODS: Subjects completing the initial six-month study were enrolled in this 24-month, randomized, multicenter, double-blind, split-face, extension study. The injection areas and treatment procedures were identical to those of the initial study: each subject was injected with PP-501-B in one NLF and with Restylane Perlane (Q-med) in the contralateral NLF. We reassessed wrinkle improvement using the five-point Wrinkle Severity Rating Scale (WSRS) and changes in the Global Aesthetic Improvement Scale at 12, 18 and 24 months after the initial treatment. RESULTS: Of the 81 patients enrolled, 72 completed the study. The WSRS score significantly decreased from baseline throughout the follow-up period after retreatment with both fillers. There was no significant difference in the WSRS scores between the two fillers at 24 months. Both fillers were well tolerated with no severe complications or adverse reactions. CONCLUSION: The new HA filler PP-501-B is safe and effective in the long term for the correction of moderate-to-severe NLFs, even after a second treatment.

Q-Switched 660-nm Versus 532-nm Nd: YAG Laser for the Treatment for Facial Lentigines in Asian Patients: A Prospective, Randomized, Double-Blinded, Split-Face Comparison Pilot Study.

BACKGROUND: Q-switched (QS) 532-nm lasers are widely used to treat solar lentigines. OBJECTIVE: To compare the efficacy and safety of 660-nm and 532-nm QS neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers in the treatment for lentigines in Asians. MATERIALS AND METHODS: The halves of each face (randomly chosen) of 8 Korean Fitzpatrick Skin Type III-IV women with facial solar lentigines were treated with either 660-nm or 532-nm lasers. Pigmentation was measured objectively using a profilometric skin analysis tool and subjectively using the pigmentation area and severity index (PSI) score, global assessment of the aesthetic improvement scale (GAIS), and a patient satisfaction score at Weeks 4 and 8. RESULTS: Seven patients completed the study. No significant differences were found in the PSI, GAIS, patient satisfaction score, and melanin average score between the lasers. The melanin average level was significantly reduced by the 660-nm laser but not the 532-nm laser at Week 8 compared with the baseline. CONCLUSION: Both 660-nm and 532-nm QS Nd:YAG lasers effectively reduce pigmentation for up to 8 weeks with high patient satisfaction. The new 660-nm laser therefore increases the treatment options for lentigines in Asian skin.

Gene expression profiling in melasma in Korean women.

BACKGROUND: There has been a paucity of data about the difference in gene expression between melasma lesional skin and normal adjacent one. OBJECTIVE: Our aim was to identify novel genes involved in the pathogenesis of melasma. METHODS: We performed a microarray analysis and confirmed the results on quantitative real-time polymerase chain reaction (qRT-PCR) in Korean women with melasma. RESULTS: There were 334 genes whose degree of expression showed a significant difference between melasma lesional skin and normal adjacent one. Of these, five were confirmed on qRT-PCR. In melasma lesional skin, there were down-regulation of genes involved in the PPAR signaling pathway and up-regulation of genes involved in neuronal component and the functions of stratum corneum barrier. CONCLUSION: This result suggests that the pathogenesis of melasma might be associated with novel genes involved in the above signaling pathway in Korean women.

Inflammatory features of melasma lesions in Asian skin.

Melasma is triggered by various factors including ultraviolet radiation and estrogen; however, its pathogenesis is unclear. To investigate the inflammatory features of melasma lesions as triggers for this disorder, 197 women with melasma who attended Asan Medical Center and Kangskin Clinic, Seoul, from June 2011 to October 2011 completed a questionnaire concerning triggering or aggravating factors. These cases were divided into "non-inflammatory" and "inflammatory" groups. Skin biopsies and immunostaining for CD68, CD117, and leukocyte common antigen (LCA) were performed in the lesional and peri-lesional skin of ten cases in the non-inflammatory group and nine cases in the inflammatory group. Among the 197 subjects (mean age, 41.5 years; mean age of melasma onset, 33.8 years), 50 patients (25.4%) were categorized into the inflammatory group. This group comprised cases that had inflammatory symptoms and events that triggered the melasma lesions. The lesional dermis contained more CD68(+) melanophages, CD117(+) mast cells, and LCA(+) leukocytes in the inflammatory group than in the non-inflammatory group. Inflammatory clinical features and an increased number of inflammatory cells in the lesion may be involved in the development of melasma in Asian skin.

Efficacy and safety of a new monophasic hyaluronic acid filler in the correction of nasolabial folds: a randomized, evaluator-blinded, split-face study.

BACKGROUND: Hyaluronic acid (HA) fillers are frequently used for the correction of facial soft-tissue defects. OBJECTIVE: To compare the efficacy and safety of a novel monophasic HA filler (mono-HA), and a well-studied biphasic HA filler (bi-HA), in the treatment of moderate to severe nasolabial folds. METHODS: In this randomized, evaluator-blinded, split-face comparative study, subjects were randomized for injections with mono-HA or bi-HA on the left or right side of the face. Efficacy was determined by calculating the change in the Wrinkle Severity Rating Score (WSRS) relative to baseline. Local safety was assessed on the basis of subject diary entries which recorded erythema, swelling, induration, pruritus, irritation, mass, hematoma, pain, and dryness. RESULTS: At week 24, the mean improvement in the WSRS from baseline was 2.18 ± 0.42 for the mono-HA side and 2.16 ± 0.41 for the bi-HA side. Both fillers were well-tolerated and adverse reactions were mild and transient in most cases. CONCLUSIONS: Mono-HA has a non-inferior efficacy to bi-HA in the treatment of moderate to severe nasolabial folds.

Formation of new melasma lesions in the periorbital area following high-fluence, 1064-nm, Q-switched Nd/YAG laser.

Although ultraviolet (UV) light or exogenous hormones have been associated with the development or exacerbation of melasma, the use of laser as a treatment modality has not been cited as a factor linked to the development of melasma lesions. It is unclear whether epidermal trauma caused by laser or other treatment can lead to the formation of a new melasma lesion. We report on the formation of new melasma lesions in a patient who was treated for acquired bilateral nevus of Ota-like macules (ABNOM) with a high-fluence 1064 nm Q-switched (QS) neodymium-doped yttrium aluminum garnet (Nd/YAG) laser.

Atypical molluscum contagiosum accompanied by CD30-positive lymphoid infiltrates.

Atypical presentations of molluscum contagiosum require histophathologic examination and may show pleomorphic lymphocytic infiltrates of a reactive nature, mimicking cutaneous lymphoproliferative diseases. Serial sections of specimens or polymerase chain reactions to show T-cell receptor clonality may be helpful for differential diagnosis. We report a case of atypical molluscum contagiosum accompanied by atypical lymphocytic infiltration showing CD30 positivity.

Granular parakeratosis of eccrine ostia.

Granular parakeratosis is a recently recognized disorder of keratinization that is usually confined to intertriginous areas. The histopathologic features are distinctive and diagnostic. Rarely, histopathologic variants such as follicular granular parakeratosis and granular parakeratosis of eccrine ostia have been described. In this report, we describe a rare case of granular parakeratosis mostly confined to eccrine ostia.