Contrast Agent Selection to Prevent Recurrent Severe Hypersensitivity Reaction to Iodinated Contrast Media Based on Nationwide Database.

OBJECTIVE: To investigate the incidence of severe iodinated contrast media (ICM)-related hypersensitivity reaction (HSR) and to find the optimal alternative ICM to reduce the risk of severe HSR recurrence. METHODS: We retrospectively reviewed 23,383,183 cases of ICM administration between January 2015 and December 2019 from the nationwide health insurance database. We classified ICMs based on generic profiles and the presence of N-(2,3-dihydroxypropyl) carbamoyl side chains. The incidence of severe and recurrent severe HSRs was calculated, and χ2 tests were performed to compare the prevalence of severe HSR according to ICM groups. In addition, logistic regression analyses were used to assess differences between ICM groups. RESULTS: The incidence of severe HSRs was 1.92% (450,067 of 23,282,183). Among 1,875,245 individuals who received ICM twice on different days, severe HSR occurred in 40,850 individuals, and severe HSR recurred in 3319 individuals (8.12%). The risk of recurrence significantly decreased when the ICM changed (9.24% vs 7.08%, P < 0.001), especially when the ICM changed to one with a different side chain (6.74%, P < 0.001). In addition, compared with the reuse of the culprit agent, using combinations of iobitridol/iohexol (odds ratio [OR], 0.696; P = 0.04), iohexol/iopamidol (OR, 0.757; P = 0.007), iopamidol/iohexol (OR, 0.447; P < 0.001), and ioversol/iohexol (OR, 0.683; P = 0.04) reduced the risk of recurrence of severe HSR. CONCLUSIONS: Changing the culprit ICM to that with a different side chain can reduce severe HSR recurrence. The optimal choice of an alternative ICM depends on the causative agent.

Morphologic and molecular biologic analyses of the skin rejuvenation effect of the fractional 1064-nm picosecond laser: An animal study.

OBJECTIVES: Application of the picosecond laser in the field of dermatology has expanded from tattoo removal to skin rejuvenation on a clinical basis. Although various mechanisms of pigment removal have been elucidated, the molecular changes associated with skin rejuvenation have yet to be identified. The aim of this study was to explore the theoretical basis and to evaluate the efficacy of skin rejuvenation using a 1064-nm fractional picosecond laser in a mouse model. METHODS: We conducted an in vivo study using a fractional picosecond laser on the skin of old and young female hairless mice and performed topographical, histological, micro-, and electron microscopic assessments. RESULTS: The topography of the skin surface was enhanced and showed increased dermal thickness on histological examination. Electron microscopy revealed disarranged collagen bundles with microspaces and vascular leakage in the upper dermis. Levels of collagen synthesis markers and various inflammatory cytokines, such as procollagens, interleukin-1ß, tumor necrosis factor-α, and heat shock proteins, were elevated in the laser-treated skin. CONCLUSIONS: This study provides a possible mechanism for the skin rejuvenation effect of fractional picosecond laser that has been reported previously in clinical observations. Based on our findings, the fractional picosecond laser could be widely applied in clinical settings where dermal regeneration and promotion of skin rejuvenation is required.

Skin atrophy caused by topical glucocorticoids is less common in patients with atopic dermatitis than in those with psoriasis.

Although the long-term use of topical glucocorticoids (TGC) may induce skin atrophy including striae distensae (SD), patients with atopic dermatitis (AD) appear to have lesser degree of skin atrophy than those with psoriasis (PSO). Periostin, encoded by POSTN, is involved in tissue remodelling processes of chronic AD lesions. This study was designed to investigate the difference in the occurrence of skin atrophy in patients with AD or PSO when treated with TGC and to elucidate the association between skin atrophy and periostin. Big data analysis using Korean Health Claims Database was performed to determine the prevalence of SD in AD and PSO patients. Blood and skin eosinophils count and dermal fibrosis between AD and PSO patients were compared, and immunohistochemistry for periostin and mRNA sequencing in the dermis were performed. Animal experiments using AD and PSO murine model were conducted. Big data analysis revealed that patients with AD have significantly lesser degree of SD than patients with PSO. The ratio of the dermal fibrous tissues and eosinophil counts were significantly higher in AD patients. In AD skin, periostin was more widely distributed in the entire dermis and POSTN mRNAs were significantly upregulated. Dermal thickness and fibrosis were significantly higher in AD mice even after TGC treatment. A significant positive correlation was observed between dermal fibrosis and tissue eosinophil counts. Lesser skin atrophy in AD patients even after long-term TGC application could be resulted from skin fibrosis caused by increased tissue eosinophils and periostin deposition.

Decrease of ceramides with long-chain fatty acids in psoriasis: Possible inhibitory effect of interferon gamma on chain elongation.

Reportedly, decreases in fatty acid (FA) chain length of ceramide (CER) are associated with interferon-γ (IFN-γ), which shows increased expression in psoriasis. However, the underlying mechanism of this association remains unclear. Therefore, in this study, we aimed to clarify this association between FA chain length of CER, IFN-γ, and the major transcriptional factors involving psoriasis. CER profiling according to FA chain length and class was performed in murine epidermis (n = 10 BALB/c mice topically treated with imiquimod, n = 10 controls) and human stratum corneum (SC) (n = 12 psoriasis, n = 11 controls). The expression of lipid synthetic enzymes, including elongases (ELOVLs), in murine epidermis was also measured using RT-PCR. Furthermore, the association of IFN-γ with various enzymes and transcription factors involved in the generation of long-chain CERs was also investigated using in vitro keratinocyte. A significant decrease in the percentage of long-chain CERs was observed in psoriasis-like murine epidermis and human psoriatic SC. Additionally, the expression levels of ELOVL1, ELOVL4, and ceramide synthase3 (CerS3) were significantly decreased in psoriasis-like murine epidermis and IFN-γ-treated keratinocyte. There was also a significant decrease in the expression of transcriptional factors, including peroxisome proliferator-activated receptor (PPAR), in IFN-γ treated keratinocyte. Thus, it could be suggested that IFN-γ may regulate ELOVL and CerS levels by down-regulating the transcriptional factors. Additionally, given the possible involvement of PPARs or liver X receptor agonist in the CER elongation process, they may serve as potential therapeutic agents for lengthening the CER FAs in psoriasis.

Effects of Polynucleotide Dermal Filler in the Correction of Crow's Feet Using an Antera Three-Dimensional Camera.

BACKGROUND: Dermal fillers are gaining interest for tissue enlargement and skin improvement. Among them, polynucleotides have demonstrated multiple skin beneficial effects. The effects of polynucleotide fillers were objectively evaluated using an Antera 3D camera, subjectively evaluated by participants and investigators. METHODS: Thirty subjects with crow's feet were enrolled in the study. The subjects received polynucleotide filler for crow's feet. Crow's feet grading score (CFGS), global esthetic improvement scale (GAIS), and Antera 3D imaging results were evaluated. RESULTS: Twenty-eight subjects (93.3%) completed the study. An improvement in CFGS compared with that at baseline (p < 0.001) was observed 18 weeks after the first injection of polynucleotides. Additionally, at the final visit, there were improvements in wrinkle, texture, pore, depression, and Hb values compared with those at baseline (p < 0.05). However, no significant difference in melanin level was detected between the initial and final visits. CONCLUSIONS: Improvements in wrinkles, pores, texture, depression, and Hb level after polynucleotide filler injection were verified by objective and subjective evaluations. To the best of our knowledge, this is the first report on the objective evaluation of polynucleotide fillers in crow's feet using the Antera 3D camera. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A comparative clinical trial to evaluate efficacy and safety of the 308-nm excimer laser and the gain-switched 311-nm titanium:sapphire laser in the treatment of vitiligo.

BACKGROUND/PURPOSE: Ultraviolet B (UVB) laser irradiation in a targeted manner is a reasonable treatment option for localized vitiligo. Recently, narrow-band UVB gain-switched 311-nm titanium:sapphire lasers (TSL) were developed for the treatment of localized vitiligo. We aimed to compare efficacy, patient satisfaction, and safety between the conventional 308-nm excimer laser (EL) and gain-switched 311-nm TSL in patients with vitiligo. METHODS: The 13-paired lesions from 10 patients who had small vitiligo patches were included in this prospective intra-patient comparison trial. Each pair was randomly assigned to each laser treatment group and treated twice weekly for 12 weeks. The global photographic assessments by dermatologists, objective numerical assessments by imaging analyzer, and patient's satisfaction were used to evaluate the effectiveness. Adverse effects were also investigated at every visit. RESULTS: All treated lesions showed improvement of about 50% after 12 weeks. There was no significant difference between EL- and TSL-treated groups. Patient satisfaction and preference among the groups were also similar. Regarding safety, there were no serious adverse effects requiring cessation of the treatments; however, the severity score for persistent erythema (lasting >24 hours) was significantly lower in the TSL group than in the EL group. CONCLUSIONS: The gain-switched 311-nm TSL exhibited similar efficacy to the 308-nm EL in treating vitiligo as well as improved safety. Therefore, the 311-nm TSL is considered as a candidate device to replace the EL as a new and promising treatment option for localized vitiligo.

The Efficacy and Safety of 660 nm and 411 to 777 nm Light-Emitting Devices for Treating Wrinkles.

BACKGROUND: Low-level light therapy (LLLT) using light-emitting diodes (LEDs) is considered to be helpful for skin regeneration and anti-inflammation. OBJECTIVE: To evaluate the efficacy and safety of 2 types of LLLTs using 660 nm-emitting red LEDs and 411 to 777 nm-emitting white LEDs in the treatment of facial wrinkles. MATERIALS AND METHODS: A prospective, randomized, double-blinded, comparative clinical trial involving 52 adult female subjects was performed. The faces of the subjects were irradiated daily with 5.17 J of red or white LEDs for 12 weeks. RESULTS: In both groups treated with red and white LEDs, the wrinkle measurement from skin replica improved significantly from baseline at Week 12. The red LED group showed slightly better improvement, but there were no statistical differences. In assessments by blinded dermatologists, no significant differences were observed in both groups. In the global assessment of the subjects, the mean improvement score of the red LED group was higher than that of the white LED group. CONCLUSION: Low-level light therapy using 660 nm LEDs or 411 to 777 nm LEDs significantly improved periocular wrinkles. Especially, 660 nm LEDs could be an effective and tolerable treatment option for wrinkles.

Adiponectin corrects premature cellular senescence and normalizes antimicrobial peptide levels in senescent keratinocytes.

Stress-induced premature senescence or aging causes dysfunction in the human somatic system. Adiponectin (Acrp30) plays a role in functional recovery, especially with adenosine 3',5'-monophosphate (AMP)-activated protein kinase (AMPK) and silent mating type information regulation 2 homolog 1 (SIRT1). Acrp30 stimulation reduced the premature senescence positive ratio induced by hydrogen peroxide (H2O2) and restituted human ß-defensin 2 (hBD-2) levels in senescent keratinocytes. Acrp30 recovered AMPK activity in senescent keratinocytes and increased SIRT1 deacetylation activity. As a result, FoxO1 and FoxO3 transcription activity was recovered. Additionally, Acrp30 stimulation suppresses NFκB p65, which induces abnormal expression of hBD-2 induced by H2O2. In the present study, we have shown that Acrp30 reduces premature senescence and recovers cellular function in keratinocytes. These results suggest a role for Acrp30 as an anti-aging agent to improve impaired skin immune barriers.

Use of fractional CO2 laser decreases the risk of skin cancer development during ultraviolet exposure in hairless mice.

BACKGROUND: Nonmelanoma skin cancers are caused mainly by prolonged ultraviolet (UV) exposure. There is a growing interest in the prevention of skin cancer and antiaging treatment because of aging of the population. Currently, ablative fractional photothermolysis (FP) laser treatment is actively being performed for facial rejuvenation. OBJECTIVE: The objective of this study was to prove the suppressive effect of CO2 fractional laser (FL) on skin cancer development. MATERIALS AND METHODS: Two groups of hairless mice were treated with either CO2 FL or nothing at 3-week intervals during the 20 weeks of UV exposure period. The number of tumors was subsequently counted every 2 weeks over the 30-week period to the termination of the experiment. At 30 weeks, representative tumors were evaluated for tumor type. The authors also determined the messenger RNA (mRNA) expression levels of the matrix metalloproteinase 13 (MMP-13) and Type 1 procollagen. RESULTS: At 30 weeks, the UV- and FL-treated group showed a significantly lower tumor occurrence rate and a more benign progression of tumors than the UV-only treated group. The UV- and FL-treated group presented a higher mRNA level of Type 1 procollagen and a lower level of MMP-13 than the UV-only treated group. CONCLUSION: The occurrence of UV-induced skin tumors can be decreased by multiple sessions of ablative FP with CO2 laser.

Topical tacrolimus does not negatively impact acute skin wound healing.

Despite the increasing use of topical tacrolimus, there is little information about its effect on skin wound healing. To determine effects on acute cutaneous wound healing, two full-thickness skin wounds were imparted on the backs of 45 hairless mice, which were then divided into vehicle-, topical tacrolimus- and topical steroid-treated group. Each drug was topically applied once daily. The wound area was assessed by using dermoscopic images every two days after wounding. At 3, 7 and 11 days after wounding, 10 wounds in each group were collected for semi-quantitative analysis of histological features including re-epithelialization, polymorphonuclear leucocytes, fibroblasts and collagen. We also checked the mRNA expression levels of EGF, TGF-ß, TNF-α and IL-1α. While topical application of clobetasol propionate was found to delay re-epithelialization and infiltration of polymorphonuclear leucocyte, topical treatment with tacrolimus showed patterns similar to that of the vehicle. In the tacrolimus-treated group, mRNA expression levels of IL-1α and TGF-ß were slightly decreased, while the others were similar with the vehicle-treated group. Unlike steroid, topical tacrolimus, therefore, did not disturb the wound healing process in a murine skin wound model.

Solitary Keratoacanthoma at the Recipient Site of a Full-Thickness Skin Graft: A Case Report and Review of the Literature.

A 57-year-old man presented with a pigmented papule, 0.4 cm in diameter, on the left lower eyelid. Skin biopsy revealed a basal cell carcinoma, which was excised through a wide excision followed by a full-thickness skin graft (FTSG). Two weeks after the surgery, an erythematous nodule developed in the lower margin of the graft recipient site. The nodule size increased rapidly over 2 weeks, becoming dome-shaped with a central hyperkeratotic plug. A diagnosis of keratoacanthoma (KA) was made, and surgical excision was performed. Histological findings revealed a large, well-differentiated squamous tumor with a central keratin-filled crater and buttress. The human papilloma virus (HPV) genotyping results were negative. Risk factors for KA include trauma, old age, exposure to ultraviolet (UV) radiation, immunosuppression, and HPV infection. KA has most often been reported to develop at the donor site. Although the pathogenesis of KA is unclear, trauma is believed to act as a second insult to a preceding oncogenic insult, such as exposure to UV radiation, resulting in a koebnerization. Herein, we report a case of solitary KA at a FTSG recipient site. This report presents information that may provide guidance during dermatologic surgeries.

Split-face comparative study of 1550 nm fractional photothermolysis and trichloroacetic acid 15% chemical peeling for facial melasma in Asian skin.

Fractional photothermolysis (FP) therapy and chemical peels have been reported to be effective in patients with recalcitrant melasma. However, there is little information to compare the efficacy of single treatment session in Asian women. The aim of this study was to examine the efficacy, long-lasting outcomes and safety of a single session of 1550-nm erbium-doped FP in Asian patients, compared with trichloroacetic acid (TCA) peel with a medium depth. Eighteen Korean women (Fitzpatrick skin type III or IV) with moderate-to-severe bilateral melasma were randomly treated with a single session of 1550-nm FP on one cheek, and with a 15% TCA peel on the other cheek. Outcome measures included an objective melasma area severity index and subjective patient-rated overall improvement at 4 and 12 weeks after treatment. Melasma lesions were significantly improved 4 weeks after either treatment, but melasma recurred at 12 weeks. Post-inflammatory hyperpigmentation developed in 28% of patients at 4 weeks but resolved in all but one patient by 12 weeks. There was no difference between FP treatment and TCA peeling with respect to any outcome measure. FP laser and TCA peel treatments were equally effective and safe when used to treat moderate-to-severe melasma, but neither treatment was long-lasting. We suggest that multiple or periodic maintenance treatments and/or supplemental procedures may be required for the successful treatment of melasma in Asian women.

Screening of Plant-Derived Natural Extracts to Identify a Candidate Extract Capable of Enhancing Lipid Synthesis in Keratinocytes.

BACKGROUND: Reduced lipid content in the stratum corneum is a major cause of skin-barrier dysfunction in various pathological conditions. Promoting lipid production is a potential strategy to improve skin-barrier function. Recent evidence supports the beneficial effects of adiponectin on lipid metabolism and senescence in keratinocytes. OBJECTIVE: This study aimed to investigate whether plant extracts can enhance skin-barrier function. METHODS: We screened fruit and herb extracts that enhance the lipid synthesis of keratinocytes via AMP-activated protein kinase (AMPK) activation and SIRT1 signaling in the adiponectin pathway. The levels of major lipid synthesis enzymes and transcription factors as well as epidermal barrier lipids involved in adiponectin-associated epidermal barrier formation were evaluated in the herbal extracts- or adiponectin-treated human epidermal keratinocyte and equivalent models. The mRNA expression of major lipid synthesis enzymes increased following treatment with Lycii Fructus , Prunus tomentosa , and Melia toosendan extracts. RESULTS: The expression of transcription factors SIRT1, liver X receptor α, peroxisome proliferator-activated receptors (PPARs), and sterol regulatory element-binding proteins (SREBPs) were upregulated. Levels of free fatty acids, cholesterol, and ceramides were elevated. The expression of keratinocyte differentiation markers increased. In particular, among fruit extracts with a detectable effect, Melia toosendan induced the highest expression of lipid synthase. CONCLUSION: These results indicate that Melia toosendan is a promising candidate for improving skin-barrier function.

Comparison of the Efficacy and Safety of Biologics (Secukinumab, Ustekinumab, and Guselkumab) for the Treatment of Moderate-to-Severe Psoriasis: Real-World Data from a Single Korean Center.

Biologics are important treatment options for psoriasis; however, direct comparison of their efficacy, safety, and drug survival is insufficient in clinical practice. This retrospective single-center study aimed to compare the efficacy, safety, and drug survival of three commonly used psoriasis biologics (secukinumab, ustekinumab, and guselkumab) and identify the factors affecting drug survival in actual clinics in Korea. We enrolled 111 patients with moderate to severe psoriasis and for at least 56 weeks of follow-up; among these, 27, 23, and 61 were administered secukinumab, ustekinumab, and guselkumab, respectively. All groups were comparable with respect to their baseline characteristics. Secukinumab showed a rapid response, and guselkumab was superior in terms of a long-term response and complete remission compared with other biologics, while ustekinumab showed a lower efficacy compared with other biologics. All three biologics had a favorable and similar safety profile; however, allergic reactions and latent tuberculosis were more common with secukinumab and ustekinumab, respectively. Guselkumab was the most sustained biologic, and the survival rates of secukinumab and ustekinumab were similar. Drug survival was remarkably shorter in female patients and those with hypertension. Introduction of new biologics emerged as a negative factor for drug survival in clinical settings.

Efficacy and Safety of Treatment with Fractional 1,064-nm Picosecond Laser with Diffractive Optic Element for Wrinkles and Acne Scars: A Clinical Study.

BACKGROUND: Fractional picosecond lasers is effective for the treatment of wrinkles or acne scars. OBJECTIVE: To investigate the safety and efficacy of treatment with a fractional 1,064-nm picosecond laser with a diffractive optic element for facial wrinkles and acne scars. METHODS: This prospective open-labeled trial comprised 22 subjects with facial wrinkles or acne scars. Subjects received three laser treatments with a fractional 1,064-nm picosecond laser at 3-week intervals. The efficacy and safety were evaluated at every visit and 2 months after the final treatment (14 weeks from the first treatment session). Global photographic assessments were performed by three blinded dermatologists and the subjects. Skin profilometry was performed using three-dimensional digital photographs; viscoelasticity was measured. RESULTS: The overall mean global improvement scores assessed by the dermatologists at weeks 3, 6, and 14, were 1.8±1.46, 2.5±1.88, and 3.5±1.84, respectively, and those assessed by the subjects were 2.7±2.08, 4.1±2.24, and 5.0±2.52, respectively. Skin profilometry showed significant improvements in the skin wrinkles, texture, depressions, and pores. The gross elasticity and skin firmness significantly improved by 10.96% and 9.04%, respectively. The major adverse reactions were erythema, pruritus, and petechiae, which disappeared within 2~3 days. CONCLUSION: The fractional 1,064-nm picosecond laser is an effective and safe therapeutic modality for skin rejuvenation.

Consensus Update for Systemic Treatment of Atopic Dermatitis.

BACKGROUND: In 2015, the Korean Atopic Dermatitis Association (KADA) working group published consensus guidelines for treating atopic dermatitis (AD). OBJECTIVE: We aimed to provide updated consensus recommendations for systemic treatment of AD in South Korea based on recent evidence and experience. METHODS: We compiled a database of references from relevant systematic reviews and guidelines on the systemic management of AD. Evidence for each statement was graded and classified based on thestrength of the recommendation. Forty-two council members from the KADA participated in three rounds of voting to establish a consensus on expert recommendations. RESULTS: We do not recommend long-term treatment with systemic steroids forpatients with moderate-to-severe AD due to the risk of adverse effects. We recommend treatment with cyclosporine or dupilumab and selective treatment with methotrexate or azathioprine for patients with moderate-to-severe AD. We suggest treatment with antihistamines as an option for alleviating clinical symptoms of AD. We recommend selective treatment with narrowband ultraviolet B for patients with chronic moderate-to-severe AD. We do not recommend treatment with oral antibiotics for patients with moderate-to-severe AD but who have no signs of infection. We did not reach a consensus on recommendations for treatment with allergen-specific immunotherapy, probiotics, evening primrose oil, orvitamin D for patients with moderate-to-severe AD. We also recommend educational interventions and counselling for patients with AD and caregivers to improve the treatment success rate. CONCLUSION: We look forward to implementing a new and updated consensus of systemic therapy in controlling patients with moderate-to-severe AD.