Effect of the Recombinant Human Epidermal Growth Factor Ointment on Cutaneous Surgical Wounds Compared to Antibiotic Ointment.

BACKGROUND: Applying antibiotic ointment after skin surgery can decrease infection and improve scar. Epidermal growth factor (EGF) is known to be able to promote the growth and movement of epidermal cells to stimulate wound healing. Recombinant human EGF (rhEGF) ointment can be used in wet closed dressing to promotes wound healing and prevent complications by maintaining a wet environment. OBJECTIVE: To compare the efficacy of rhEGF ointment and conventional antibiotic ointment after cutaneous resection. METHODS: Patients who had excision procedures in two or more sites were enrolled. Each wound was assigned to the rhEGF group or the antibiotic ointment group. Wounds were subjected to Physician Global Assessment (PhGA), Patient Global Assessment (PGA), and Patient satisfaction assessment (PSA). The length and area of wounds, and melanin and erythema index (MI and EI) were also assessed for these wounds. RESULTS: Among 11 patients with a total of 20 pairs of resection sites, PhGA, PGA, MI, and EI showed no significant difference between rhEGF and antibiotic ointment groups. However, changes in length and area of wounds showed significant differences between the two groups. CONCLUSION: RhEGF ointment showed similar short-term cosmetic results with antibiotic ointment, and improved surgical results in regards of the wound size. Applying rhEGF could reduce the use of antibiotic ointments for cutaneous clean (class I) wound surgery.

Dermoscopic Findings and the Clinicopathologic Correlation of Pigmented Purpuric Dermatosis: A Retrospective Review of 60 Cases.

BACKGROUND: Pigmented purpuric dermatosis (PPD) is known as a chronic recurrent eruption which usually presents with petechiae and pigmented macules on the lower extremities. Dermoscopy is a noninvasive diagnostic tool in identifying pigmented and vascular lesions, which can also be beneficial in the evaluation of PPD. OBJECTIVE: We aimed to analyze the common dermoscopic characteristics of PPD, and correlate those findings with the histopathologic features. Additionally, dermoscopic and pathological findings in this study population were compared with other similar studies from the literature review. METHODS: A retrospective analysis was performed using data of 60 patients who were diagnosed as PPD by skin biopsy and had dermoscopic examination. The pathologic analysis was performed by categorizing the pattern into lichenoid, perivascular, interface, and spongiotic subtype, and the dermoscopic assessment was performed by the three authors independently. RESULTS: In dermoscopy, 96.7% of the patients showed red globules and dots, followed by brownish patch, coppery-red pigmentation, and annular comma-like vessels. The pathologic pattern analysis revealed statistically significant association of lichenoid pattern with coppery red pigmentation, perivascular pattern with annular/comma-like vessels, and spongiosis pattern with reticular pigmented network and linear vessels. The interrater similarity test showed total kappa value of 0.811 which referred to "very good". CONCLUSION: In this study, the prevalence of dermoscopic features in Asian PPD patients was identified, which was similar with previous studies. The dermoscopic-pathologic correlation was found in four dermoscopic features. We suggest that dermoscopic examination is helpful in clinical diagnosis and pathological prediction of PPD.

TGF-ß3 suppresses melanogenesis in human melanocytes cocultured with UV-irradiated neighboring cells and human skin.

BACKGROUND: Ultraviolet radiation (UVR) is the most well-known cause of skin pigmentation accompanied with photoaging. Transforming growth factor (TGF)-ß1 was previously shown to have anti-melanogenic property; however, it can induce scarring in skin. OBJECTIVE: We investigated the effect of TGF-ß3 on melanogenesis in human melanocytes cocultured with UV-irradiated skin constituent cells, and UV-irradiated human skin. METHODS: UVB irradiation or treatment with stem cell factor (SCF) and endothelin-1 (ET-1) was applied to human melanocytes cocultured with keratinocytes and/or fibroblasts and ex vivo human skin. Mechanistic pathways were further explored after treatment with TGF-ß3. RESULTS: While UVB irradiation or SCF/ET-1 enhanced melanogenesis, TGF-ß3 effectively inhibited melanin accumulation and tyrosinase activity via downregulation of the extracellular signal-regulated kinase (ERK)/microphthalmia-associated transcription factor (MITF) pathway. TGF-ß3 increased the expression of differentiation markers of keratinocytes. CONCLUSION: TGF-ß3 effectively suppressed UVR-stimulated melanogenesis indicating that topical TGF-ß3 may be a suitable candidate for the treatment of UV-associated hyperpigmentation disorders.

Loratadine, an H1 Antihistamine, Inhibits Melanogenesis in Human Melanocytes.

It has long been believed that histamine is associated with cutaneous melanogenesis. Specifically, H2-receptor antagonists reportedly inhibit melanogenesis, but H1-receptor antagonists, which are some of the most commonly prescribed medicines in dermatology, have not been studied to determine whether and how they regulate melanogenesis. Therefore, we screened H1-receptor antagonists to determine whether they inhibit melanogenesis and found that loratadine was particularly effective, in this regard without compromising cellular viability. Loratadine downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase in melanocytes. To determine the intracellular signaling pathways, Akt was consistently activated by loratadine. PI3K/Akt pathway inhibitor, LY294002, restored the reduced melanin content that was induced by loratadine. In addition, phospho-GSK-3ß also was found to be increased following loratadine treatment. Loratadine reduced the amount of PKC-ßII in the membrane fraction, thereby decreasing its activity. Taken together, our data indicate that loratadine regulates melanogenesis via Akt/MITF and PKC-ßII signaling, thereby leading to the inhibition of melanogenic proteins. The antimelanogenic effects of loratadine have potentially significant and useful roles in dermatologic practice, although further clinical studies will be required to test this.

The efficacy of powdered polydioxanone in terms of collagen production compared with poly-L-lactic acid in a murine model.

BACKGROUND: There are many collagen-stimulating fillers, including calcium hydroxyapatite, polycaprolactone (PCL), and poly-L-lactic acid (PLLA), and other materials have been tested. Polydioxanone (PDO) has recently been used as absorbable thread-lifting material due to its collagen-forming effects. PDO in powdered form is expected to be a good material for collagen-producing fillers. OBJECTIVES: To evaluate the collagen-producing effects of powdered PDO injection compared with PLLA injection in a murine model. MATERIALS AND METHODS: Powdered PDO mixed with sodium carboxymethyl cellulose, PLLA, and phosphate-buffered saline was injected on dorsal skin of 8-week-old rat. Tissue samples were obtained 1, 2, and 12 weeks after the procedures for histopathologic review and for real-time PCR to quantify collagen and tissue growth factors. RESULTS: Both PLLA and powdered PDO injections induced granulomatous reactions. Collagen type 1, collagen type 3, TGF-ß1, TGF-ß2, and TGF-ß3 showed increases 2 weeks after injection but decreased 12 weeks after injection for both powdered PDO and PLLA. CONCLUSION: Our results suggested that powdered PDO injection induces collagen formation more effectively than PLLA injection. Therefore, PDO can be a good option for forming collagen.

Comparative efficacy of short-pulsed intense pulsed light and pulsed dye laser to treat rosacea.

Background: Laser and light-based therapies have often been used successfully to treat rosacea. Recently, short-pulsed intense pulsed light (IPL) that emitted pulse durations down to 0.5 ms was found to be effective for rosacea treatment. Objective: This study evaluated the efficacy of short-pulsed IPL in the treatment of rosacea compared with pulsed dye laser (PDL) using same pulse duration and fluence. Materials and Methods: Nine patients with rosacea were enrolled in a randomized, split-face trial. Each treatment consisted of four sessions at three-week intervals and followed up until three weeks after the last treatment. Efficacy was assessed by erythema, melanin index, physician's subjective evaluation, and patient's satisfaction. Results: The mean change in erythema index was -4.93 ± 1.59 for the short-pulsed IPL group and -4.27 ± 1.23 for the PDL group. The mean change in melanin index was -2.52 ± 2.45 for the short-pulsed IPL group and -1.95 ± 1.41 for the PDL group. There was no significant difference in either melanin or erythema index between short-pulsed IPL and PDL treatments, and there were no noticeable adverse events. Conclusions: There was no significant difference between PDL and short-pulsed IPL treatment using the same energies and pulse. Both PDL and short-pulsed IPL were satisfactory and safe for rosacea treatment.

Comparative effects of various absorbable threads in a rat model.

BACKGROUND: Conventional procedures including botulinum toxin and filler injections have their limitations in improving deep wrinkles and decreasing tissue laxity, and possess the propensity for vascular accidents. Absorbable thread is a recently commercialized field, but there is little evidence on comparative superiority. OBJECTIVES: We observed the effects of polydiaxanone (PDO) threads with different number of strands in relation to collagen production and histopathology in a rat model. MATERIALS AND METHODS: Dorsal skin of rat was divided into five different compartments and four different PDO threads and monofilament poly-lactic acid (PLA) thread were inserted. Tissue samples were obtained at week 1, 2, and 12 after the procedure for histopathologic review and real-time PCR for quantification of collagen. RESULTS: Multiple PDO filaments produced more collagen at 2 weeks. Single-stranded PLA thread insertion resulted in more Col1α1 levels than the double PDO thread and also showed the most Col1α3 production at week 2. The amount of collagen showed a sharp decline at week 12. Histologic evaluation showed retained threads surrounded by fibrous capsule-like structure at week 12. CONCLUSION: We were able to observe more collagen production in multiple stranded PDO threads compared to a single strand and that increasing number of threads leads to more collagen synthesis.

Acquired bilateral telangiectasia macularis eruptiva perstans: A unique clinical feature of photodamaging rather than a subtype of cutaneous mastocytosis.

Telangiectasia macularis eruptiva perstans (TMEP) is a rare subtype of cutaneous mastocytosis, characterized by telangiectatic tan to brown macules on the trunk and extremities. Although TMEP has been descried as an uncommon disease in the literature, we often encounter patients with TMEP lesions in the outpatient clinic. We aimed to assess the clinical and histopathological characteristics of acquired bilateral TMEP, and the pathophysiological mechanism of acquired bilateral TMEP among these patients. We retrospectively reviewed 30 patients (28 men and 2 women) with acquired bilateral TMEP; multiple telangiectatic dark red to brown macules that were symmetrically distributed. The clinical characteristics and general histopathological findings of lesional skin were investigated. The number of mast cells was evaluated using immunohistochemical analysis with an antibody directed against c-kit (CD117). Acquired bilateral TMEP was predominantly localized on the sun-exposed area: the upper arm in 30 patients (100%), forearm in 19 patients (63.3%) and anterior chest in 15 patients (50%). A total of 16 patients (53.3%) showed at least one aggravating factor, including UV irradiation, alcohol use and heat exposure. Compared with the mast cell numbers in 19 age- and biopsy site-matched healthy controls (91 ± 29.0/mm2 ), the number of mast cells in the papillary dermal skin of acquired bilateral TMEP patients was significantly increased (159 ± 37.2/mm2 , P < 0.01). In addition, a significant difference in vessel numbers in the papillary dermis was observed between acquired bilateral TMEP patients and healthy controls (10.5 ± 1.9 vs 5.4 ± 1.0/mm2 , P < 0.01). Acquired bilateral TMEP is a relatively common disorder in middle-aged Asian men. An increased number of mast cells and dilated vessels might be a photoaging-related reactive process of chronic sun-exposure, which consequently leads to the formation of characteristic telangiectatic hyperpigmentary macules through certain melanogenic mediators.

Novel regulation of melanogenesis by adiponectin via the AMPK/CRTC pathway.

Several studies observed that adiponectin, an important adipokine that improves glucose metabolism by regulating AMP-activated protein kinase (AMPK) signaling, is dermatologically beneficial. In our recent microarray data, we found that adiponectin expression was lower in lesional skin than in non-lesional skin of melasma patients. Given that AMPK is a key adiponectin signaling mediator, we investigated the role of adiponectin and AICAR, a cell-permeable AMPK activator, in melanogenesis. We herein showed that adiponectin and AICAR downregulated MITF, tyrosinase, TRP-1, and DCT expression and reduced melanin content in normal human and mouse melanocytes. The depigmenting effect of adiponectin was mediated via AMPK activation, which induced the inhibitory phosphorylation of CREB-regulated transcription co-activators (CRTCs) and subsequent suppression of the novel CRTC/CREB pathway in melanocytes. These findings suggest that adiponectin and its analogs are useful as a clinical strategy for treating hyperpigmentation disorders.

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.

Histological and molecular analysis of the long-pulse 1,064-nm Nd:YAG laser irradiation on the ultraviolet-damaged skin of hairless mice: In association with pulse duration change.

BACKGROUND: Nonablative lasers have been widely used to improve photodamaged skin, although the mechanism underlying dermal collagen remodeling remains unclear. OBJECTIVE: To investigate the effects and the molecular mechanisms of long-pulse neodymium-doped yttrium aluminum garnet (Nd:YAG) laser irradiation on dermal collagen remodeling in association with different pulse durations. MATERIAL AND METHODS: Five hairless mice were pretreated with ultraviolet B irradiation for 8 weeks. The dorsal quadrant of each mouse was then irradiated twice at 1-week intervals at a pulse duration of 1 ms, 12 ms, or 50 ms, and a constant fluence of 20 J/cm(2). The levels of dermal collagen, mRNAs of procollagens, matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and various growth factors were analyzed after 4 weeks. RESULTS: Long-pulse Nd:YAG treatment increased the dermal collagen level. A substantial increase in the level of procollagens, MMPs, TIMPs, and various growth factors was also observed irrespective of pulse duration, with a trend toward maximal increase at a pulse duration of 12 ms. CONCLUSION: Long-pulse 1,064-nm Nd:YAG laser irradiation promotes wound-healing process, which is characterized by the induction of growth factor expression and subsequent increase in MMPs and TIMPs, followed by matrix remodeling as confirmed by new procollagen production.

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.

Superficial and deep infiltrating congenital juvenile xanthogranuloma involving multiple skeletal muscles and associated with ulceration and generalized postinvolution atrophy.

We present a 2-day-old boy with a deep-seated giant juvenile xanthogranuloma infiltrating the skeletal muscles on his right lower limb. Unlike typical juvenile xanthogranuloma, the lesion has shown only partial spontaneous regression with large atrophic scar. However, despite the involvement multiple muscle on the right thigh, the patient has no evidence of orthopaedic sequelae.

Effect of an epidermal growth factor-containing cream on postinflammatory hyperpigmentation after Q-switched 532-nm neodymium-doped yttrium aluminum garnet laser treatment.

BACKGROUND: Topical application of epidermal growth factor (EGF) promotes wound healing and may reduce the risk of laser-induced postinflammatory hyperpigmentation (PIH). OBJECTIVE: To investigate the effect of an EGF-containing cream on the incidence of laser-induced PIH. METHODS: Twenty-five Korean patients with senile lentigines were recruited and underwent 532-nm Q-switched Nd:YAG laser treatment. Postoperatively, patients applied either an EGF-containing cream or a control cream to the laser-treated area. Skin color and transepidermal water loss (TEWL) were measured on Days 0, 3, 7, and 35 using a Mexameter and Tewameter, respectively. RESULTS: The EGF-containing cream resulted in a nonsignificant reduction in the laser-induced increase in TEWL (p = .052 on Day 7) but significantly decreased the melanin index and incidence of PIH on Day 35 (p = .031 and p = .027, respectively). CONCLUSION: Epidermal growth factor-containing creams may be an effective measure to prevent laser treatment-induced PIH in Asian patients.

Generalised hyperpigmentation caused by ectopic adrenocorticotropic hormone syndrome with recurrent thymic neuroendocrine carcinoma.

Ectopic adrenocorticotropic hormone (ACTH) syndrome is a rare cause of generalised hyperpigmentation. The clinical features are due to the excessive ectopic secretion of adenocorticotropin by diverse neuroendocrine or non-endocrine tumours. Here, we describe a rare case of ectopic ACTH syndrome developing from recurring thymic neuroendocrine carcinoma, which first presented as generalised hyperpigmentation.