Papillary fibroblasts differentiate into reticular fibroblasts after prolonged in vitro culture

The dermis can be divided into two morphologically different layers: the papillary and reticular dermis. Fibroblasts isolated from these layers behave differently when cultured in vitro. During skin ageing, the papillary dermis decreases in volume. Based on the functional differences in vitro, it is hypothesized that the loss of papillary fibroblasts contributes to skin ageing. In this study, we aimed to mimic certain aspects of skin ageing by using high‐passage cultures of reticular and papillary fibroblasts and investigated the effect of these cells on skin morphogenesis in reconstructed human skin equivalents. Skin equivalents generated with reticular fibroblasts showed a reduced terminal differentiation and fewer proliferating basal keratinocytes. Aged in vitro papillary fibroblasts had increased expression of biomarkers specific to reticular fibroblasts. The phenotype and morphology of skin equivalents generated with high‐passage papillary fibroblasts resembled that of reticular fibroblasts. This demonstrates that papillary fibroblasts can differentiate into reticular fibroblasts in vitro. Therefore, we hypothesize that papillary fibroblasts represent an undifferentiated phenotype, while reticular fibroblasts represent a more differentiated population. The differentiation process could be a new target for anti‐skin‐ageing strategies.     

In vivo animal histology and clinical evaluation of multisource fractional radiofrequency skin resurfacing (FSR) applicator

Abstract

Objective. Acne scars are one of the most difficult disorders to treat in dermatology. The optimal treatment system will provide minimal downtime resurfacing for the epidermis and non-ablative deep volumetric heating for collagen remodeling in the dermis. A novel therapy system (EndyMed Ltd., Cesarea, Israel) uses phase-controlled multi-source radiofrequency (RF) to provide simultaneous one pulse microfractional resurfacing with simultaneous volumetric skin tightening. Methods. The study included 26 subjects (Fitzpatrick's skin type 2–5) with moderate to severe wrinkles and 4 subjects with depressed acne scars. Treatment was repeated each month up to a total of three treatment sessions. Patients’ photographs were graded according to accepted scales by two uninvolved blinded evaluators. Results. Significant reduction in the depth of wrinkles and acne scars was noted 4 weeks after therapy with further improvement at the 3-month follow-up. Conclusion. Our data show the histological impact and clinical beneficial effects of simultaneous RF fractional microablation and volumetric deep dermal heating for the treatment of wrinkles and acne scars.     

Familial anetoderma

A 31-year-old Caucasian male presented with a history of erythematous, saccular outpouchings of the skin on his back, shoulders, and upper extremities (Fig. 1). The patient reported that his mother and aunt had a similar skin disorder, which initially began with inflammation, but healed leaving lax skin in its wake. He did not recall the name of the skin condition. Physical examination revealed large confluent zones of sac-like protrusions of erythematous skin on the back and shoulders. Histopathologic examination of the excisional biopsy revealed a relatively unremarkable epidermis. Perivascular lymphocytes were present in small numbers in the papillary dermis. Adnexal structures and deep dermis remained intact. The acid-orcein-Giemsa stain highlighted the absence of elastic fibers within the mid and lower reticular dermis (Fig. 2a,b), consistent with anetoderma.     

Nevus anelasticus: how should such lesions be classified?

Nevus anelasticus represents a rare entity that is most commonly classified as a connective tissue nevus. It typically presents before 20 years of age with asymmetrically distributed white‐to‐skin‐toned or pink‐to‐red papules or plaques on the trunk and upper extremities. The lesion is defined histopathologically by the absence or degeneration of elastic fibers in the dermis. We report the case of a healthy 17‐year‐old female who presented with an asymptomatic slowly progressive plaque on the right inferior areola. Histopathologic examination showed the absence of elastic fibers in the papillary and upper reticular dermis and fragmented elastic tissue fibers in the deep reticular dermis. Although there is ongoing controversy regarding the nosology of this uncommon disorder, we propose that it is a distinct entity based on its histopathologic and clinical features.     

Comparison of effect between high intense focused ultrasound devices for facial tightening: Evaluator-blinded,split-face study

Background: Various high intense focused ultrasound (HIFU) devices have been introduced in recent years for improving skin laxity, with satisfactory results. However, there is no comparative study on the efficacy and safety of available HIFU devices. Objective: To compare the efficacy and safety of two HIFU devices for facial skin tightening and subsequently, to validate the quantitative assessment. Methods and materials: We performed a split-face comparative study in 20 Korean patients. Two different HIFU devices were used on each side of the face. Patients received one treatment session on the same number of coagulative zones. Patient assessments were recorded. Three blinded clinicians evaluated paired pretreatment and post-treatment photographs. Quantitative assessment using a fixed point as well as a variable point was additionally performed for objective evaluation. Results: Qualitative assessments of both HIFU devices conducted by both clinicians and patients generally showed mild to moderate improvement, similar to previous studies. The two devices had similar efficacy in blinded clinician and quantitative assessment, although there were some differences in patient satisfaction and degree of pain. There was a correlation between clinician qualitative scores and quantitative values, which suggests successful skin tightening. Conclusion: To the author's knowledge, both HIFU devices tested can be used safely and effectively for facial tightening.     

不同年龄真皮纤维网结构的扫描电镜观察 Ⅰ. 胶原纤维

作者用扫描电镜观察了1岁以内婴儿,20-40岁成人及70岁以上老年的上臂、腹部和足跟部皮肤的真皮胶原纤维网.发现婴儿的胶原纤维较细,排列方向主要与表面平行,乳头层和网状层分界不清,各部位间无明显差异;成人的胶原纤维较粗,走向完全凌乱,乳头层和网状层分界清晰,有"中间带"将二者分开,足跟部纤维网较上臂和腹部者致密;老年真皮胶原纤维网较成人者更为致密而凌乱,纤维较直且相互交织较疏松,可见纤维束散开现象,足跟部纤维束堆聚非常紧密.作者对纤维网结构差异的原因及与皮肤生物学特性的关系进行了讨论.     

Differential effect of extracellular matrix derived from papillary and reticular fibroblasts on epidermal development <Emphasis Type="Italic">in vitro</Emphasis>

Background

Papillary and reticular fibroblasts have different effects on keratinocyte proliferation and differentiation.

Objectives

The aim of this study was to investigate whether these effects are caused by differential secretion of soluble factors or by differential generation of extracellular matrix from papillary and reticular fibroblasts.

Materials & Methods

To study the effect of soluble factors, keratinocyte monolayer cultures were grown in papillary or reticular fibroblast-conditioned medium. To study the effect of extracellular matrix, keratinocytes were grown on papillary or reticular-derived matrix.

Results

Conditioned medium from papillary or reticular fibroblasts did not differentially affect keratinocyte viability or epidermal development. However, keratinocyte viability was increased when grown on matrix derived from papillary, compared with reticular, fibroblasts. In addition, the longevity of the epidermis was increased when cultured on papillary fibroblast-derived matrix skin equivalents compared with reticular-derived matrix skin equivalents.

Conclusion

The findings indicate that the matrix secreted by papillary and reticular fibroblasts is the main causal factor to account for the differences in keratinocyte growth and viability observed in our study. Differences in response to soluble factors between both populations were less significant. Matrix components specific to the papillary dermis may account for the preferential growth of keratinocytes on papillary dermis.

     

A novel non-invasive radiofrequency dermal heating device for skin tightening of the face and neck

Background: Loose, lax skin is a common cosmetic complaint. Previous non-invasive skin tightening devices had modest efficacy and were associated with pain or downtime. New technologies may allow for effective skin tightening with a series of radiofrequency (RF) treatments with no downtime. Objective: To evaluate the efficacy and safety of a novel bipolar RF device for skin tightening. Methods: Fifteen consecutive female patients were enrolled in the case series; 14 completed the study and were included in the analysis. The device under investigation is a novel, bipolar RF device allowing for achievement and maintenance of optimal dermal temperatures to stimulate collagen remodeling and skin tightening. Patients underwent a series of 4–6 weekly treatments. Three blinded, experienced cosmetic physicians evaluated paired pre-treatment and post-treatment photographs and determined the associated improvement, if any. Results: All patients (14/14) were determined to have a clinical improvement, as the pre-treatment and post-treatment photographs were correctly identified by the evaluators. It was observed that 21% (3/14) of patients had significant improvement, 50% (7/14) had moderate improvement, and 29% (4/14) had mild improvement. No pain, side effects, or adverse events were observed. Conclusions: This novel bipolar RF device represents a safe, effective treatment option for non-invasive skin tightening.     

网状红斑黏蛋白病1例

报告1例网状红斑黏蛋白病。患者男，49岁。头面部、胸背部红斑、丘疹伴瘙痒10年，日晒后皮损无明显改变。组织病理检查示真皮乳头层，网状层上部血管及毛囊周围淋巴细浸润，真皮胶原束之间有阿新蓝染色阳性的黏蛋白沉积。     

TGF-β1 induces differentiation of papillary fibroblasts to reticular fibroblasts in monolayer culture but not in human skin equivalents

Abstract

Fibroblasts isolated from the papillary and reticular dermis are different from each other in vitro. If papillary fibroblasts are subjected to prolonged serial passaging they will differentiate into reticular fibroblasts. Reticular fibroblasts have been shown to resemble myofibroblasts in severalways. TGF-β1 is the most important factor involved in myofibroblastdifferentiation.

Aims

we investigated if TGF-β1 can induce differentiation of papillary fibroblasts into reticular fibroblasts, in monolayer cultures and in human skin equivalents.

Method

Monolayer cultures of and human skin equivalents generated with papillary fibroblasts were stimulated with TGF-β1. The expression of markers specific for reticular and papillary fibroblasts was measured by qPCR and immunohistochemical analysis in monolayer cultures. In human skin equivalents, the morphology and the expression of several markers was analysed and compared to untreated papillary and reticular human skin equivalents.

Results

Monolayer cultures of papillary fibroblasts started to express a reticular marker profile after stimulation with TGF-β1. Human skin equivalents generated with papillary fibroblast and stimulated with TGF-β1 were similar to papillary control equivalents and did not obtain reticular characteristics. Expression of reticular markers was only found in the lower layers of TGF-β1-stimulated papillary skin equivalents.

Conclusions

TGF-β1 can induce differentiation to reticular fibroblasts in monolayer cultures of papillary fibroblasts. In skin equivalents no such effects were found. The major difference between these experiments is the presence of extracellular matrix in skin equivalents. Therefore, we hypothesize that the matrix secreted by papillary fibroblasts protects them from TGF-β1 induced differentiation.

     

Fibroelastolytic papulosis: histopathologic confirmation of disease spectrum variants in a single case

Fibroelastolytic papulosis is a rare, acquired fibroelastolytic disorder that presents clinically as white‐to‐yellow papules and plaques most commonly occurring on the neck of elderly patients. The term fibroelastolytic papulosis encompasses two closely related conditions previously described as pseudoxanthoma elasticum‐like papillary dermal elastolysis (PDE) and white fibrous papulosis of the neck (WFPN). Here we present a case of a 78‐year‐old white female with a several‐year history of numerous, asymptomatic 2–3 mm yellowish, non‐follicular papules distributed symmetrically over the posterior neck, axillae, arm and antecubital fossae. Histopathologic examination revealed thickened and clumped elastotic fibers admixed with thick, sclerotic appearing collagen bundles in the mid and deep reticular dermis. Rare melanophages, loss of vertically oriented elastic fibers and scattered elastotic globes were noted in the papillary dermis. Based on the shared clinicopathologic features showed in this case, strong consideration should be made for the additional inclusion of papillary dermal elastosis as existing along the disease continuum of fibroelastolytic papulosis. This occurrence of fibroelastolytic papulosis shows unique histopathologic findings of pseudoxanthoma elasticum‐like PDE, papillary dermal elastosis and WFPN, further supporting the theory that these entities exist as variants along the fibroelastolytic papulosis spectrum.     

The efficacy and safety of the high-intensity parallel beam ultrasound device at the depth of 1.5 mm for skin tightening

Background

High-intensity parallel beam ultrasound (US) is a novel device equipped with Synchronous Ultrasound Parallel Beam (SUPERB) technology applied in anti-aging treatment. The system is aimed at pathways stimulating neocollagenesis and neoelastinogenesis in the dermis leading to skin tightening and rejuvenation.

Aims

Evaluate the efficacy and safety of the high-intensity parallel beam US device at the depth of 1.5 mm for skin tightening treatment.

Methods

Thirty-six participants were enrolled in the study. Digital photographs and Antera 3D photographs were taken at baseline, 1 and 3 months post-treatment. The depression volume of nasolabial folds (NLFs) and marionette lines (MLs) in each visit was evaluated using Antera 3D imaging program. Pain was evaluated by pain measurement scales immediately after treatment. Any procedure related side effects were documented and examined.

Results

Post-treatment results were compared to the baseline; statistically significant mean depression volume (MDV) change of NLFs and MLs were found at 1 and 3 months post-treatment. No significant MDV change from 1 to 3 months post-treatment could be demonstrated. The mean pain score was 6.64 on a 0–10 scale. No adverse events were reported.

Conclusions

Our study demonstrates that the novel high-intensity parallel beam US device is clinically safe and effective for skin tightening in the lower face area. We noticed a reduction in NLFs and MLs in more than 60% of our participants already as early as 1 month post-treatment.     

Complementary clinical effects of topical tightening treatment in conjunction with a radiofrequency procedure

Abstract

Background: Skin laxity and cellulite on the buttocks and thighs are two common cosmetic concerns. Skin tightening with radiofrequency (RF) devices has become increasingly popular. Objective: The purpose of this study is to evaluate the efficacy and safety of a topical skin laxity tightening agent when used in combination with an RF device. Methods: A double-blinded, randomized clinical trial enrolled twenty females with mild-to-moderate skin laxity on the posterior thighs/buttocks. Each subject underwent two monthly treatments with an RF source (Alma Accent) to both legs. Subjects were then randomized to apply a topical agent (Skinceuticals Body Tightening Concentrate) twice daily to only one designated thigh/buttock throughout the eight-week duration of the study. All subjects were evaluated for improvement in lifting, skin tone, radiance, firmness/tightness, skin texture, and overall appearance based on photographic evaluation by blinded investigators at 12 weeks following the final RF treatment. Results: A statistically significant improvement was found in the overall appearance on both sides treated with the RF device when compared to baseline. However, the area treated with the topical agent showed a statistically significantly greater degree of improvement than the side where no topical agent was applied. No adverse effects were reported. Conclusion: The use of a novel skin tightening agent used after RF procedures is both safe and effective for treatment of skin laxity on the buttocks and thighs. Combined therapy leads to a better result.     

白色纤维性丘疹病

报告1例白色纤维性丘疹病。患者女，44岁。躯干四肢丘疹3年，无自觉症状。丘疹直径3-5mm，象牙白色或肤色，部分皮损萎缩。皮损组织病理检查显示真皮乳头层及网层上方胶原纤维增生，呈均质化改变。弹性纤维染色显示真皮浅层带状弱弹性纤维消失。     

完全型Melkersson-Rosenthal综合征1例

患者女,50岁。反复口角歪斜23年,上唇肿胀10年,加重2年。上唇组织病理示:非干酪样上皮细胞炎性肉芽肿。诊断:完全型Melkersson-Rosenthal综合征。     

Analysis of mast cell subpopulations (MCT, MCTC) in cutaneous inflammation using novel enzyme-histochemical staining techniques

Abstract In order to gain insights into the dynamics of mast cell subpopulations in normal and diseased skin, a novel enzyme-histochemical double and triple staining method was employed that allowed the detection of metachromasia (toluidine blue) and the mast cell proteases tryp-tase and chymase within the same cell. Cryostat sections were used of skin biopsies from the following specimens: normal skin (N=4), psoriasis (N=13), atopic eczema (N=7), lichen planus (N=6), interferon α2a injection sites (N=l) of a leukemic infiltrate and corresponding normal skin of the same patient before and after treatment. (i) Equal numbers of tryptase-and chymase-positive mast cells (MCTC) were obtained in all normal and diseased specimens in papillary and reticular dermis, with threefold increases around appendages, (ii) Tryptase-positive mast cells (MCT) were absent in normal skin, but were markedly increased in a disease-specific pattern within the papillary dermis, the inflammatory infiltrate and around appendages, (iii) Marked increases of MCT were also noted at interferon injection sites within the leukemic infiltrate, but not in the normal skin of the same patient. These data suggest that disease-dependent mast cell dynamics involve only MCT in cutaneous inflammation and that MCT numbers are controlled by distinct, disease-specific local tissue factors.     

Split-face histological and biochemical evaluation of tightening efficacy using temperature- and impedance-controlled continuous non-invasive radiofrequency energy

Background: Bipolar radiofrequency (RF) is capable of heating dermal collagen fibers and inducing skin tightening by collagen remodeling. Objective: To substantiate safety and improvement of skin laxity following skin heating with a novel temperature- and impedance-controlled non-invasive radiofrequency (RF) device by histological and biochemical evaluations. Methods: A split-face study was performed on 4 subjects who underwent 8 weekly RF sessions on one side of their face, leaving the other side an untreated control and then underwent facelift procedure. Clinical evaluation by photographs was done prior to the surgical procedure. Ex vivo fragments were harvested from both sides and compared. Morphometric analysis of dermal collagen fibers, collagen synthesis, and elastin synthesis evaluations were compared in triplicates. Results: Facial skin tightening was apparent in split-face photographs. A significant increase of 7.9% in dermal collagen content, and a significant increase of 34.7% in collagen synthesis were demonstrated in the treated samples. No statistically significant effect on elastin synthesis was detected. Conclusions: Skin tightening following treatment with non-invasive RF has proven histologically and biochemically to derive from increase in dermal collagen synthesis and content.     

Familial acral localized late-onset focal dermal elastosis

Late-onset focal dermal elastosis is a rare disorder of elastic tissue, characterized by a local accumulation of elastic fibers in the mid and deep reticular dermis. This disorder occurs mainly in elderly people and consists of multiple yellow papules that are typically distributed on the sides of the neck and flexural areas, closely resembling pseudoxanthoma elasticum from the clinical point of view. We report 2 sisters who have presented with a 20-year history of multiple yellow papules, mainly located on the dorsum of their hands. They also had few lesions of similar morphology scattered on the anterior aspects of their wrists, thighs, and lower abdomen. Histopathologic study demonstrated a focal increase in thick, interlacing elastic fibers in the mid and deep reticular dermis. The most striking features of our cases were the early age of clinical presentation, the familial involvement, and the predominantly acral distribution of the lesions.     

Specificity of dermal mucin in the diagnosis of lupus erythematosus: comparison with other dermatitides and normal skin

Increased dermal mucin is a feature of lupus erythematosus (LE); however, its amount and distribution have not been well characterized. The differentiation of LE from other forms of dermatitis can be challenging when other features of LE are subtle or equivocal. One hundred and thirty‐five skin specimens showing LE, graft vs. host disease, erythema multiforme/fixed drug eruption, lichen planus, polymorphous light eruption (PMLE), urticaria, eczematous dermatitis and psoriasis and normal skin with and without photodamage were collected. The amounts of mucin in the papillary, superficial reticular and deep reticular dermis were scored from 0 to 3 on hematoxylin–eosin (H&E) and alcian blue (AB) stains, and compared between groups. The mean scores in the reticular dermis were significantly higher in LE than in other categories except PMLE and eczematous dermatitis. A combined H&E + AB score of ≥5 in the superficial reticular dermis gave an overall specificity of 85.7% for LE. Mucin in the papillary dermis failed to distinguish among entities. Normal photodamaged skin showed significantly more mucin in the superficial reticular dermis compared to non‐photodamaged skin. While LE is associated with increased mucin deposition, scant to moderate amount of mucin alone has limited specificity and is common in other dermatitides or photodamaged skin.     

Pseudoxanthomatous mastocytosis

A 50‐year‐old woman presented with itchy, multiple, flat, yellowish, waxy papules and plaques diffusely involving her face, trunk, and upper extremities for 5 years ( Fig. 1 ). Itching was moderate to severe in intensity and was episodic, without any identifiable aggravating or relieving factors. On rubbing the lesions with a blunt object erythema was elicited. Her ophthalmological examination was normal. Her complete hemogram was normal along with other routine investigations. Patient's slit skin smear for acid‐fast bacilli and rk39 dip‐stick ELISA for post‐kala‐azar dermal leishmaniasis were negative. Ultrasound examination of her abdomen was normal and skeletal survey showed no evidence of bony changes. Histological examination showed diffuse dense infiltrate of numerous mast cells filling up the papillary dermis and most of upper‐ and mid‐reticular dermis. Overlying epidermis showed moderate epidermal hyperplasia and hyperpigmentation. There was sparse scattering of neutrophils within the infiltrate. Extracellular mast cells granules were also seen ( Fig. 2 ). Diagnosis of diffuse cutaneous mastocytosis of pseudoxanthomatous variety was made.

Figure 1 Open in figure viewer PowerPoint Pretreatment photographs of the patient; (a) face; (b) trunk