Keloids and Hypertrophic Scars: Characteristic Vascular Structures Visualized by Using Dermoscopy

Background

Keloids and hypertrophic scars represent excessive scarring. They require different therapeutic approaches, which can be hampered because of an apparent lack of morphologic difference between the two diseases.

Objective

This study investigated the clinical and dermoscopic features of keloids and hypertrophic scars in order to help dermatologists distinguish these lesions better.

Methods

A total of 41 keloids and hypertrophic scars in 41 patients were examined clinically and by performing dermoscopy with a digital imaging system. Lesions were evaluated for vascular structures.

Results

Dermoscopy revealed vascular structures in most keloid lesions (90%) but in only 27% of hypertrophic scar lesions. The most common dermoscopic vascular structures in keloids were arborizing (52%), followed by linear irregular (33%) and commashaped (15%); these features were present but less evident in hypertrophic scars (9% for all types). The distribution frequency of the vascular structures differed significantly between diseases (p<0.001).

Conclusion

A strong association of vascular structures with keloids was observed on dermoscopic examination. The results suggest dermoscopic examination of vascular structures is a clinically useful diagnostic tool for differentiating between keloids and hypertrophic scars.     

Pilot Study of the Efficacy of 578 nm Copper Bromide Laser Combined with Intralesional Corticosteroid Injection for Treatment of Keloids and Hypertrophic Scars

Background

Treatments including intralesional corticosteroid injection, pressure therapy, cryotherapy, and various laser therapies have had limited success for keloids and hypertrophic scars.

Objective

This trial evaluated the efficacy of a combination of 578 nm copper bromide laser and the more traditional intralesional corticosteroid injection for the treatment of keloids and hypertrophic scars with respect to scar color.

Methods

Keloids or hypertrophic scars of 12 Korean patients were treated five times by the combined treatment at 4-week intervals. Clinical improvement was assessed by the physicians'' global assessment (PGA) comparing pre- and post-treatment photographs, as well as 4 weeks after the last treatment. Erythema intensity was quantified using a mexameter.

Results

Most scars showed significant clinical improvement in PGA and decreased erythema intensity after 5 treatments. All patients showed improvements in symptoms like pruritus.

Conclusion

The combined treatment is effective for keloids and hypertrophic scars, especially when the telangiectatic portion of the scars is prominent. The adjunctive use of 578 nm copper bromide laser decreased the telangiectatic side effects of an intralesional corticosteroid injection by reducing the vascular components of scars.     

Expression of the c-Met Proteins in Malignant Skin Cancers

Background

The expression of c-Met is substantially elevated in most malignant human cancers. We therefore searched for c-Met expression and compared the expression level among malignant skin cancers.

Objective

The aim of this study was to determine the c-Met expression pattern and the protein expression level in selected malignant cutaneous tumors.

Methods

G361 cells (malignant melanoma cell line) and A431 cells (squamous cell carcinoma cell line) were cultured and analyzed, using immunoprecipitation and Western blot analysis, for expression of c-Met. Additionally, 16 separate specimens of malignant melanomas (MMs), 16 squamous cell carcinomas (SCCs), 16 basal cell carcinomas (BCCs) and 16 normal tissues were analyzed for the expression of c-Met using immunohistochemical studies.

Results

Based on cultured cell immunoprecipitation and Western blot analysis, both A431 cells and G361 cells expressed c-Met, however, c-Met was expressed substantially more in G361 cells. Immunohistochemical examination of c-Met showed that it was over-expressed in all malignant skin cancers. In addition, c-Met expression was more increased in MM compared to other cancers.

Conclusion

In our study, c-Met is involved in malignant skin cancer development and the level of its expression is thought to be related to the degree of malignancy in melanoma cancers.     

Comparison of Gene Expression Profiles between Keratinocytes,Melanocytes and Fibroblasts

Background

The skin has many important functions such as protection, preservation, temperature regulation, and vitamin D synthesis. It is composed of a variety of cell types including keratinocytes, melanocytes and fibroblasts.

Objective

We attempted to compare the gene expression profiles between keratinocytes, melanocytes and fibroblast, using cDNA microarray.

Methods

Keratinocytes, melanocytes and fibroblasts were primary cultured from five foreskin specimens. Total RNAs were extracted and pooled to reduce the individual variations, and then used for cDNA microarray.

Results

Total 12,028 genes were selected as the reliable genes whose expression was detected in at least one of the three cell types. By comparing the relative expression levels with cutoff limitation as a fourfold change, we obtained 126 fibroblast-specific, 179 keratinocyte-specific and 173 melanocyte-specific genes, many of which are known to be characteristically expressed in each cell type. In addition, we identified many genes whose skin-specific functions have not yet been determined.

Conclusion

Our data provide important information on which to base further investigation into the specification of skin cell types.     

Changes in Transepidermal Water Loss and Skin Hydration according to Expression of Aquaporin-3 in Psoriasis

Background

Aquaporins (AQPs) are a family of water transporting proteins present in many mammalian epithelial and endothelial cell types. Among the AQPs, AQP3 is known to be a water/glycerol transporter expressed in human skin.

Objective

The relationship between the expression level of AQP3 and transpidermal water loss (TEWL) in the lesional and peri-lesional skin of psoriasis-affected patients, and skin hydration in the lesional and peri-lesional skin of psoriasis patients, was investigated.

Methods

The expression of AQP3 in psoriasis-affected and healthy control skin was determined using immunohistochemical and immunofluroscence staining. TEWL and skin hydration were measured using a Tewameter® TM210 (Courage & Khazaka, Cologne, Germany) and a Corneometer® CM 820 (Courage & Khazaka), respectively.

Results

AQP3 was mainly expressed in the plasma membrane of stratum corneum and the stratum spinosum in normal epidermis. Unlike the normal epidermis, AQP3 showed decreased expression in the lesional and peri-lesional epidermis of psoriasis. TEWL was increased, and skin hydration was decreased, in the lesional and peri-lesional skin of psoriasis patients, compared with the healthy control sample.

Conclusion

Although various factors contribute to reduced skin hydration in the lesional and peri-lesional skin of psoriasis, AQP3 appears to be a key factor in the skin dehydration of psoriasis-affected skin.     

Enhancement of Keratinocyte Differentiation by Rose Absolute Oil

Background

Through differentiation processes, keratinocytes provide a physical barrier to our bodies and control skin features such as moisturization, wrinkles and pigmentation. Keratinocyte differentiation is disturbed in several skin diseases such as psoriasis and atopic dermatitis.

Objective

The aim of this study is to evaluate the keratinocyte differentiation-enhancing effect of rose absolute oil (RAO).

Methods

Primary cultured human normal keratinocytes were treated with RAO, and differentiation then checked by the expression of marker genes.

Results

RAO did not induce cytotoxicity on cultured keratinocytes at a dose of 10µM. The level of involucrin, an early marker for keratinocyte differentiation, was significantly increased by RAO. Concomitantly, RAO increased involucrin promoter activity, indicating that RAO increased involucrin gene expression at the mRNA level. Furthermore, RAO increased the level of filaggrin in cultured keratinocytes, and in the granular layer of mouse skin. In line with these results, RAO decreased the proliferation of keratinocytes cultured in vitro. When RAO was applied topically on the tape-stripped mouse skins, it accelerated the recovery of disturbed barrier function.

Conclusion

These results suggest that RAO may be applicable for the control of skin texture and keratinocyte differentiation-related skin diseases.     

Characterizing Cutaneous Elastic Fibers by Eosin Fluorescence Detected by Fluorescence Microscopy

Background

Though elastic fibers are as important as collagen fibers in interpretation of the histopathologic findings, it is impossible to observe them on the hematoxylin & eosin (H&E) stained specimen.

Objective

Characterizing eosin fluorescence emitted by elastic fibers in H&E stained specimens.

Methods

Normal skin tissue sections were stained in 4 different ways (unstained, hematoxylin only, eosin only, H&E) and observed under a fluorescence microscope using a FITC filter set. Fluorescent findings of 30 H&E-stained specimens showing abnormal dermal findings were compared with bright field findings of Miller''s elastic stained specimen.

Results

Strong eosin fluorescence was related to the differential binding property of eosin with elastic fibers. Hematoxylin stain quenched excessive eosin fluorescence from other tissue components and contributed to better contrast. Fluorescence microscopy of H&E-stained sections was found to be especially useful in observing mature elastic fibers in the reticular dermis. In 74% of the specimens, eosin fluorescence findings of elastic fibers in reticular dermis matched well with that of specimens with elastic fiber special stain.

Conclusion

Analysis of skin elastic fibers by fluorescence microscopy is a useful and complementary method to reveal hidden elastic fibers in H&E-stained specimens.     

Analysis of MAST-CLA Results as a Diagnostic Tool in Allergic Skin Diseases

Background

Urticaria and atopic dermatitis are representative allergic skin diseases that can be mediated by IgE. Measuring levels of specific IgE can be used to confirm causative agents of these skin diseases.

Objective

To analyze results from the multiple allergosorbent test chemiluminescent assay (MAST-CLA), which measures specific IgE in the presence of a causative agent/allergen, in IgE-mediated skin diseases.

Methods

A total of 404 patients with urticaria, atopic dermatitis or pruritus were enrolled in the present study. Positive rates of specific IgE as well as total serum IgE from the MAST-CLA were compared.

Results

Positive rates of specific IgE were highest in atopic dermatitis patients, followed by urticaria, and then pruritus, with 57.0%, 37.1%, and 20.8%, respectively (p<0.05). House dust mite species were the most common allergens in both atopic dermatitis and urticaria skin diseases. There were no differences in the overall MAST-CLA results between acute and chronic urticaria. The relative positive rate of inhalant allergen was significantly higher in adult than in child atopic dermatitis patients.

Conclusion

Results from the MAST-CLA showed diversity among the three disease groups, and within each disease group, with different positive rates of specific IgE, a different mean allergen number per patient, and so on. Therefore, we concluded that MAST-CLA could be a useful diagnostic tool for various allergic skin diseases.     

Decreased Expression of Type 5 17β-Hydroxysteroid Dehydrogenase (AKR1C3) Protein Identified in Human Diabetic Skin Tissue

Background

Diabetes is characterized by chronic hyperglycemia, and hyperglycemia can increase reactive oxygen species (ROS) production from the mitochondrial electron transport chain. The formation of ROS in cells induces oxidative stress and activates oxidative damage-inducing genes. There is no research on the protein levels of oxidative damage-related genes AKR1C3 in human diabetic skin. We explored the expression of AKR1C3 in diabetic skin compared with normal skin tissue.

Objective

To compare the expression of AKR1C3 in normal skin versus diabetic skin.

Methods

AKR1C3 expression was evaluated by western blotting in 6 diabetic skin tissue samples and 6 normal skin samples. Immunohistochemical staining was carried out to analyze AKR1C3 expression in the 6 diabetic skin tissue samples (July 2009 to December 2011; Department of Plastic and Reconstructive Surgery at Soonchunhyang University Seoul Hospital, Seoul, Korea).

Results

The western blotting showed a significant reduction in AKR1C3 protein expression in diabetic skin tissue compared to normal tissue. Immunohistochemical examination of AKR1C3 showed that it was weakly expressed in all diabetic skin samples.

Conclusion

We believe that AKR1C3 is related to diabetic skin in altered metabolic states which elevate ROS production.     

Comparison of the Expression Profile of JunB, c-Jun, and S100A8 (Calgranulin A) in Psoriasis Vulgaris and Guttate Psoriasis

Background

Psoriasis is a chronic, inflammatory, immune-mediated skin disease. Recently, several psoriasis-linked genetic loci have been reported; PSORS4 contains S100A8 (calgranulin A), and PSOR6 (19p13) locus harbors JunB (19p13.2). S100A8 is considered to be a marker of inflammation in a variety of diseases. The expression of JunB and c-Jun have been reported to be reduced in psoriatic lesions.

Objective

We attempted to assess the role and correlation of S100A8, JunB, and c-Jun in the pathogenesis of guttate psoriasis and psoriasis vulgaris by studying whether any difference of immunohistochemical expression existed.

Methods

Skin biopsy specimens from patients with psoriasis vulgaris (n=37) and guttate psoriasis (n=17), and a normal skin controls (n=9) were utilized in the study. Formalin-fixed and paraffin-embedded tissue sections were prepared and JunB, c-Jun, and calgranulin A were immunohistochemically stained in order to compare the expression of those three proteins in each group.

Results

Reduced JunB expression was observed in patients with psoriasis vulgaris and guttate psoriasis, as compared to patients in the control group; however, c-Jun expression was reduced only in the psoriasis vulgaris group. The expression of S100A8 increased in the psoriasis groups as compared to the control group. In addition, the expression of S100A8 was different between the psoriasis vulgaris and guttate psoriasis groups; S100A8 was expressed more profoundly in the guttate psoriasis group (p<0.05).

Conclusion

Our results indicate that S100A8 contributes to the pathogenesis of guttate psoriasis, and it may be a good target for therapy for guttate psoriasis provoked by microorganisms.     

Epidermal Hyperplasia and Elevated HB-EGF are More Prominent in Retinoid Dermatitis Compared with Irritant Contact Dermatitis Induced by Benzalkonium Chloride

Background

''Retinoid dermatitis'' is a retinoid-induced irritant contact dermatitis (ICD). The mechanism of retinoid dermatitis may be different from that of other ICDs. However, it remains uncertain how topical retinoid induce ICD.

Objective

We compared several aspects of contact dermatitis induced by topical retinol and benzalkonium chloride (BKC) on hairless mice skin.

Methods

2% retinol or 2.5% BKC was applied to hairless mice and transepidermal water loss (TEWL), ear thickness, histologic and immunohistochemical findings were compared. We also compared mRNA expression of inflammatory cytokines, epidermal differential markers, cyclooxygenases (COXs) and heparin binding epidermal growth factor like growth factor (HB-EGF).

Results

Topical application of 2% retinol and 2.5% BKC increased TEWL and ear thickness in similar intensity. Epidermal hyperplasia was more prominent in retinol treated skin. Proliferating cell nuclear antigen, involucrin and loricrin expression were higher in retinol-treated skin than in BKC-treated skin. Filaggrin, however, was more expressed in BKC-treated skin. The mRNA expression of IL-8, TNF-α, COX-2, involucrin, loricrin and filaggrin were increased in both retinol- and BKC-treated skin in similar intensity. HB-EGF was more significantly increased in retinol-treated skin.

Conclusion

Elevated HB-EGF and epidermal hyperplasia are more prominent features of retinoid dermatitis than in BKC-induced ICD.     

Merkel Cell Polyomavirus Is Frequently Detected in Korean Patients with Merkel Cell Carcinoma

Background

Merkel cell carcinoma (MCC) is an increasingly common neuroendocrine cancer of the skin. Merkel cell polyomavirus (MCPyV) is one of the causative agents of MCC. The prevalence of MCPyV in primary MCC and sun-exposed non-MCC tumors has been known to have different results depending on where it was investigated.

Objective

This study assesses the prevalence of MCPyV from primary MCC and sun-exposed non-MCC tumors in Korea.

Methods

A molecular pathology study was performed on 7 tissue specimens of MCC, 1 tissue specimen of metastatic small cell carcinoma of the lung, and 32 tissue specimens of non-MCC tumors occurring from sun-exposed areas [8 basal cell carcinomas (BCCs), 8 squamous cell carcinomas (SCCs), 8 actinic keratoses (AKs), and 8 seborrheic keratoses (SKs)]. All specimens were analyzed to determine the presence of MCPyV-DNA using both polymerase chain reaction (PCR) and real-time quantitative PCR. Immunohistochemistry with monoclonal antibody of MCPyV large T antigen (CM2B4) was also conducted.

Results

Using both PCR, MCPyV sequences were detected in six of seven MCC tissue specimens (85.7%). Five (71%) of seven MCC tumors were immunoreactive for CM2B4. All five immunoreactive cases were positive for MCPyV. However, there was no association of MCPyV with BCC, SCC, AK, and SK.

Conclusion

Our results implicate that MCPyV may contribute to the pathogenesis of primary MCC, not of non-MCC skin tumors in Korea, and the persons with MCPyV infection are unusual in Korea compared to other areas.     

Postoperative Electron Beam Radiotherapy for Keloids: Treatment Outcome and Factors Associated with Occurrence and Recurrence

Background

In the treatment of keloids, the recurrence after surgical excision is relatively high. Various types of adjuvant therapy such as radiotherapy and corticosteroid injection have been used to reduce the recurrence.

Objective

The aim of this study was to determine the appropriate time for initiating postoperative radiotherapy and to analyze factors associated with the occurrence and recurrence of keloids.

Methods

Of these 37 lesions, 22 were located in the ear lobe, 6 in the helix of the auricle, 4 on the shoulder, 3 on the chest wall, and 2 on the abdomen. Causative factors were piercings (n=24), trauma (n=5), previous surgical lesions or bacillus Calmette-Guerin vaccination lesions (n=3) and acne (n=2). Radiation therapy was initiated within 24 h in 24 lesions, between 24 and 72 h in 6 lesions, and after more than 72 h in 7 lesions.

Results

Seven lesions recurred, including 5 recurrences in high stretch-tension regions (p=0.010). Initial treatments were administered within 24 h in 1 lesion and more than 72 h after surgical excision in 6 lesions (p<0.0001). In the 19 patients with family histories, maternal and paternal genetic predispositions were present in 14 and 5 patients, respectively (p=0.033).

Conclusion

Radiotherapy should be initiated within 72 h of surgical excision. Location in a high stretch-tension region was significantly associated with recurrence. Patients with a family history showed a significant tendency toward maternal genetic predisposition. Therefore, combination therapy should be considered to reduce the occurrence and recurrence of keloids, and careful observation is required.     

Observational descriptive study of cutaneous manifestations in patients from Mato Grosso with viral chronic hepatitis

BACKGROUND

Extrahepatic manifestations are seen in association with chronic infection by hepatitis B or C virus including cutaneous disorders. The frequency of these findings seems to vary among different places and reports. There is a lack of information about this issue in Brazil.

OBJECTIVES

To estimate the prevalence of cutaneous findings affecting HBV or HCV carriers from a reference outpatient unit in Mato Grosso.

METHODS

A cross-sectional observational study.

RESULTS

108 patients were studied. 88.9% presented some cutaneous findings but must of them were nonrelated to chronic viral infection. Four patients had cutaneous or autoimmune syndromes that may be HBV or HCV related.

CONCLUSION

In our study we found no statistical association between viral hepatitis and skin diseases.     

Assessing depression and anxiety in the caregivers of pediatric patients with chronic skin disorders

BACKGROUND

The literature has shown that the presence of emotional disturbances in caregivers of children with skin diseases affects the course and treatment of the disease. Anxiety and depression are among the most frequently reported psychiatric diagnoses related to this fact.

OBJECTIVE

To evaluate the presence of anxiety and depression in caregivers of pediatric patients with chronic skin disorders, exemplified by atopic dermatitis, psoriasis and vitiligo, and correlate them to the quality of life of the patients.

METHODS

The sample consisted of 118 patients with atopic dermatitis, vitiligo and psoriasis, monitored by their main caregiver. The levels of anxiety and depression in the caregivers were assessed using the Hamilton Anxiety Scale and the Beck Depression Inventory, respectively. The Children''s Dermatology Life Quality Index was applied.

RESULTS

Anxiety was observed in 36% of the caregivers of the patients with atopic dermatitis, in 36% of those of children affected by psoriasis, and in 42% of those responsible for pediatric patients with vitiligo. Depression occurred in 36% of the caregivers of patients with atopic dermatitis, in 36% of those of children affected by psoriasis and in 26% of those responsible for pediatric patients with vitiligo. There was a significant correlation between poor quality of life scores in patients with vitiligo and the presence of depression and anxiety in their caregivers.

CONCLUSION

Emotional disorders tend to be present among close family members of children with the chronic skin diseases studied and their prevention can help in controlling and treating these diseases.     

Clinical study of skin changes in low and high risk pregnant women

BACKGROUND

During pregnancy there is immunological, metabolic, endocrine and vascular changes responsible for physiological and pathological skin changes.

OBJECTIVES

determine the prevalence of specific physiological changes and pregnancy, comparing the period of gestation of their appearances and compare type of prenatal care as the skin changes.

METHODS

A cross-sectional study with 905 pregnant women.

RESULTS

The prevalence of physiological skin changes was 88.95% and the most common was pigment. The prevalence of specific dermatoses was 8.72% and atopic eruption was the most common.

CONCLUSION

Physiological changes were seen more in the 3rd quarter, as well as the specific dermatoses. No statistical difference in prenatal low risk compared to high risk was observed, whereas the cutaneous physiological changes and specific pregnancy dermatoses.     

Oxidative Damage and Nuclear Factor Erythroid 2-Related Factor 2 Protein Expression in Normal Skin and Keloid Tissue

Background

Reactive oxygen species (ROS) play an important role in the induction of apoptosis under pathological conditions. Recently, a significant increase in ROS production and disrupted apoptosis mechanisms in keloids have been reported. Nuclear factor erythroid 2-related factor 2 (Nrf2) represents one of the most important cellular defense mechanisms against oxidative stress and is implicated in the regulation of apoptosis. Recently, it has been reported that Nrf2 upregulates Bcl-2, an anti-apoptotic protein.

Objective

To compare Nrf2 protein expression in normal skin tissues to keloid tissues.

Methods

ROS generation in keloid tissues was evaluated with OxyBlot analysis. Western blotting and/or immunohistochemical staining approaches were used to study expression of Nrf2 or Bcl-2 in keloid and normal skin tissues. Cellular fractionation was performed to examine subcellular distribution of Nrf2. Transfection of fibroblasts with Nrf2-specific small interfering RNA (siRNA) was conducted to understand the relationship between Nrf2 expression and apoptosis induction.

Results

Protein oxidation, a marker of oxidative stress, is increased in keloid tissues. Western blot analysis clearly showed that Nrf2 and Bcl-2 are downregulated in keloid tissues. Immunohistochemical staining of Nrf2 confirmed the results of the western blot analysis. Transfection of fibroblasts with the Nrf2-specific siRNA results in increased apoptosis and decreased cell viability.

Conclusion

Collectively, our data indicate that Nrf2 expression is downregulated in keloid tissues, and that Nrf2 is involved in the development of apoptosis in Nrf2 siRNA-transfected fibroblasts. We propose that a defective antioxidant system and apoptotic dysregulation may participate in keloid pathogenesis.     

The Immunohistochemical Patterns of Calcification-related Molecules in the Epidermis and Dermis of the Zebrafish (Danio rerio)

Background

The scales of bony fish represent a significant reservoir of calcium and calcification of the elasmoid scale is known to be associated with deposition of mineral crystals from the epidermis to dermis. However, little is known about the exact mechanisms of calcium deposition, mobilization and regeneration occurring in the zebrafish skin.

Objective

The purpose of this study was to investigate the expression of calcification-related molecular mediators in both the epidermis and dermis of the zebrafish (Danio rerio), using immunohistochemical study.

Methods

We examined the skin of zebrafish in four populations of different ages (i.e. 20 days post-fertilization (dpf), 35 dpf, 50 dpf, and the adult zebrafish), using several immunohistochemical markers, including bone morphogenetic protein 4 (BMP-4), β-catenin, osteocalcin, osteopontin and osteonectin.

Results

BMP-4, osteopontin and osteonectin were moderately expressed in the epidermis of zebrafish after 35 dpf. Also, some of the cells in the upper dermis showed strong positivity for BMP-4, osteocalcin, osteopontin and osteonetin.

Conclusion

Our results suggest that BMP-4, osteocalcin, osteopontin and osteonectin may play a role in the process of calcification of the elasmoid scale.