Jung U Shin

The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization

BACKGROUND Atopic dermatitis (AD) shows very high prevalence in Asia, with a large unmet need for effective therapeutics. Direct comparisons between European American (EA) and Asian patients with AD are unavailable, but earlier blood studies detected increased IL-17(+)-producing cell counts in Asian patients with AD. OBJECTIVE We sought to characterize the Asian AD skin phenotype and compare it with the EA AD skin phenotype. METHODS We performed genomic profiling (real-time PCR) and immunohistochemistry on lesional and nonlesional biopsy specimens from 52 patients with AD (25 EAs and 27 Asians), 10 patients with psoriasis (all EAs), and 27 healthy subjects (12 EAs and 15 Asians). RESULTS Although disease severity/SCORAD scores were similar between the AD groups (58.0 vs 56.7, P = .77), greater acanthosis, higher Ki67 counts, and frequent parakeratosis were characteristics of lesional epidermis from Asian patients with AD (P < .05). Most (24/27) Asian patients had high IgE levels. A principal component analysis using real-time PCR data clustered the Asian AD phenotype between the EA AD and psoriasis phenotypes. TH2 skewing characterized both Asian and EA patients with AD but not patients with psoriasis. Significantly higher TH17 and TH22 (IL17A, IL19, and S100A12 in lesional and IL-22 in nonlesional skin; P < .05) and lower TH1/interferon (CXCL9, CXCL10, MX1, and IFNG in nonlesional skin; P < .05) gene induction typified AD skin in Asian patients. CONCLUSION The Asian AD phenotype presents (even in the presence of increased IgE levels) a blended phenotype between that of EA patients with AD and those with psoriasis, including increased hyperplasia, parakeratosis, higher TH17 activation, and a strong TH2 component. The relative pathogenic contributions of the TH17 and TH2 axes in creating the Asian AD phenotype need to be tested in future clinical trials with appropriate targeted therapeutics.

Oral Tranexamic Acid Enhances the Efficacy of Low‐Fluence 1064‐Nm Quality‐Switched Neodymium‐Doped Yttrium Aluminum Garnet Laser Treatment for Melasma in Koreans: A Randomized, Prospective Trial

Background Tranexamic acid (TA) has recently gained in popularity in the treatment of pigmentary disorders. Objective To evaluate the clinical efficacy and safety of oral TA combined with low‐fluence 1064‐nm quality‐switched neodymium‐doped yttrium aluminum garnet (QSNY) laser for the treatment of melasma. Materials and methods Forty‐eight patients with melasma were enrolled in the study and subsequently divided into two groups: a combination group and a laser treatment group. All patients were treated with two sessions of low‐fluence QSNY laser, and patients in the combination group took 8 weeks of oral TA. Two blinded dermatologists evaluated patients using the Modified Melasma Area and Severity Index (mMASI) and a clinical improvement scale. Results Mean mMASI score 4 weeks after the second treatment decreased significantly in both groups from base line. Based on overall clinical improvement, a greater number of patients scored as grade 3 and more in the combination group; no patients were scored as grade 4 in the laser‐alone group. Conclusions Oral TA may prove a safe and efficient treatment option for melasma in combination with low‐fluence QSNY laser therapy.

DAMP molecules S100A9 and S100A8 activated by IL‐17A and house‐dust mites are increased in atopic dermatitis

S100A9 and S100A8 are called damage‐associated molecular pattern (DAMP) molecules because of their pro‐inflammatory properties. Few studies have evaluated S100A9 and S100A8 function as DAMP molecules in atopic dermatitis (AD). We investigated how house‐dust mites affect S100A9 and S100A8 expression in Th2 cytokine‐ and Th17 cytokine‐treated keratinocytes, and how secretion of these molecules affects keratinocyte‐derived cytokines. Finally, we evaluated expression of these DAMP molecules in AD patients. S100A9 expression and S100A8 expression were strongly induced in IL‐17A‐ and Dermatophagoides (D.) farinae‐treated keratinocytes, respectively. Furthermore, co‐treatment with D. farinae and IL‐17A strongly increased expression of S100A9 and S100A8 compared with D. farinae‐Th2 cytokine co‐treatment. The IL‐33 mRNA level increased in a dose‐dependent manner in S100A9‐treated keratinocytes, but TSLP expression did not change. S100A8/A9 levels were also higher in the lesional skin and serum of AD patients, and correlated with disease severity. Taken together, S100A9 and S100A8 may be involved in inducing DAMP‐mediated inflammation in AD triggered by IL‐17A and house‐dust mites.

Endothelial‐to‐mesenchymal transition induced by Wnt 3a in keloid pathogenesis

Endothelial‐to‐mesenchymal transition is a phenotypic conversion characterized by down‐regulation of vascular endothelial markers and the acquisition of a mesenchymal phenotype. We hypothesized that keloid fibroblasts are of endothelial origin and that endothelial‐to‐mesenchymal transition substantially contributes to collagen accumulation during the development and progression of keloids. Wingless protein (Wnt‐3a) protein expression was examined using immunohistochemistry in keloid tissues. Human dermal microvascular endothelial cells (HDMECs) were treated with Wnt‐3a. mRNA and protein expression of endothelial (vascular endothelial cadherin) and mesenchymal (vimentin, snail family transcription factor [slug], and α‐smooth muscle actin) cell markers were measured using real‐time RT‐PCR and immunocytochemistry, respectively. Additionally, coexpression of CD31 (cluster of differentiation 31), and endothelial cell marker, and vimentin in the vascular endothelium of keloid tissues was examined using immunofluorescence. Wnt‐3a overexpression was observed in human keloid tissues. Wnt‐3a treatment significantly reduced vascular endothelial cadherin mRNA expression and induced vimentin and slug mRNA expression in HDMECs. HDMECs became spindle‐shaped and exhibited reduced expression of CD31 and increased expression of vimentin, slug, and α‐smooth muscle actin. Moreover, coexpression of CD31 and vimentin was observed in the dermal vascular endothelium of keloid tissues from two patients with clinically active keloids. In conclusion, transient conversion of HDMECs to a mesenchymal phenotype may contribute to dermal fibrosis of keloid and hypertrophic scars.

Comparison of non‐ablative and ablative fractional laser treatments in a postoperative scar study

Postoperative scarring after thyroidectomy is a problem for both patients and clinicians. Recently, both non‐ablative and ablative fractional laser (NFL and AFL) systems have attracted attention as potential therapies for the revision of thyroidectomy scars. The present split‐scar study was designed to directly compare the efficacy of these two methods for the treatment of post‐thyroidectomy scars.

A Case of Hand-foot-mouth Disease in an Immunocompetent Adult

Hand-foot-mouth (HFM) disease is primarily a disease of children, although it can be seen in immunocompromised adults. We describe a case of HFM disease in a 35-year-old immunocompetent male. He presented with multiple, 1~2 mm sized, erythematous vesicular papules on both hands and feet. Histopathological findings of a skin biopsy showed superficial perivascular lymphocytic infiltration, focal keratinocyte necrosis, and reticular degeneration. Because delayed diagnosis can cause spread of the disease to children, dermatologists should be aware that HFM disease can occur in adults with intact immune systems.

The effect of succinylated atelocollagen and ablative fractional resurfacing laser on striae distensae

Abstract Striae distensae are dermal atrophic scars with epidermal thinning and decreased collagen and elastic fiber. There is no ‘gold standard’ treatment modality in the treatment of striae distensae. Collagen is a major extracellular matrix component and is important in wound healing. The ablative CO2 fractional laser is effective in various cutaneous scars and this study was attempted to evaluate the effect of succinylated atelocollagen and ablative CO2 fractional laser in the treatment of striae distensae. Participants were divided into two groups and received three laser treatments at a 4-week interval. Clinical improvement was evaluated by participants and two blinded physicians by observing the comparative photographs. Skin biopsies were randomly taken from six participants. The ablative fractional resurfacing laser was effective in the clinical improvement of striae distensae. Statistically significant differences were partly observed between the collagen and placebo groups. Clinical improvement scored by doctors showed more improvement in the collagen group. However, scoring by participants did not show significant differences between the collagen and placebo groups. In conclusion, the ablative fractional resurfacing laser is effective in the treatment of striae distensae and succinylated atelocollagen may also be effective for striae distensae treatment. However, to prove the effect of succinylated atelocollagen, further research with a larger group of participants is needed.

Treatment of Epidermal Growth Factor Receptor Inhibitor-Induced Acneiform Eruption with Topical Recombinant Human Epidermal Growth Factor

Background: Epidermal growth factor receptor (EGFR) inhibitors have been used as anticancer agents for the treatment of a variety of solid tumors. Related skin toxicities are the most common adverse effects and occur with all EGFR inhibitors. Several treatment approaches, such as antiseptic soaps, topical and oral antibiotics, and topical and oral corticosteroids, have been reported; however, the responses have been varied. Acneiform eruption induced by EGFR inhibitor treatment results from disturbed normal keratinocyte and hair follicle biology and may therefore benefit from local restoration of EGF pathway. Observations: We treated HaCaT cells with EGFR inhibitor and evaluated the expression of EGFR. After treatment of cells with EGFR inhibitor, EGFR expression was increased in a dose-dependent manner. We hypothesized that newly synthesized EGFR, not inhibited by EGFR inhibitors, may perform their biological action in keratinocytes in the presence of additional EGF. In this study, we therefore treated acneiform eruption patients with topical recombinant human EGF (rhEGF) with institutional review board approval. Here, we report three cases of such eruptions who responded to topical rhEGF. Conclusion: Topical rhEGF may be an effective treatment option for EGFR inhibitor-induced acneiform eruption.

Lupus miliaris disseminatus faciei without facial involvement.

Sir, Lupus miliaris disseminatus faciei (LMDF) is a papular eruption characterized by discrete red-brown, domeshaped papules on the medial and lateral areas of the face, which often extends onto the neck and chin (1). Extrafacial manifestations are not uncommon and may affect the axilla, shoulders, arms, hands, groins and legs. There has been a previous report of concurrent involvement of the face, neck and chest (2). However LMDF occurring on the neck and chest without facial involvement has not been reported previously. We report here a rare case of LMDF on the neck and chest of a patient without any facial manifestations.

Retrospective Analysis on the Effects of House Dust Mite Specific Immunotherapy for More Than 3 Years in Atopic Dermatitis

Purpose In extrinsic atopic dermatitis (AD), house dust mites (HDM) play a role in eliciting or aggravating allergic lesions. The nature of skin inflammation in AD has raised a growing interest in allergen-specific immunotherapy (SIT). Thus, we assessed clinical improvement and laboratory parameters for evaluation of the benefit of long-term SIT. Materials and Methods A total of 217 AD patients who were treated with SIT for at least 3 years were retrospectively assessed, by using their investigator global assessment, pruritus scores, loss of sleep (LOS), total serum IgE, and eosinophil counts collected. Patients were additionally classified into subgroups according to age, initial AD severity and mono- or multi-sensitization to include different individual factors in the evaluation of SIT efficacy. Lastly, we compared laboratory data of good responders to SIT with that of poor responders to SIT. Results Improvement after SIT therapy was observed in 192 out of 217 patients (88.4%). Among these patients, 138 (63.5%) achieved excellent, near-complete or complete clinical remission. Significant reduction of pruritus, LOS, and the mean value of total serum IgE were observed (p<0.01). Better outcome was found in patients younger than 12 years of age (p=0.024). Patients with moderate to severe AD showed better treatment outcomes (p=0.036). Patients sensitized only to HDM had the better response to treatment, but SIT was also effective in multi-sensitized groups (p=1.051). No significant differences in baseline laboratory results were observed between good and poor responders (p>0.05). Conclusion We emphasize the usefulness of long-term HDM SIT as a disease-modifying therapy for AD.