Review

Authors: Rei Ogawa

Keloids and hypertrophic scars are caused by cutaneous injury and irritation, including trauma, insect bite, burn, surgery, vaccination, skin piercing, acne, folliculitis, chicken pox, and herpes zoster infection. Notably, superficial injuries that do not reach the reticular dermis never cause keloidal and hypertrophic scarring. This suggests that these pathological scars are due to injury to this skin layer and the subsequent aberrant wound healing therein. The latter is characterized by continuous and histologically localized inflammation. As a result, the reticular layer of keloids and hypertrophic scars contains inflammatory cells, increased numbers of fibroblasts, newly formed blood vessels, and collagen deposits. Moreover, proinflammatory factors, such as interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α are upregulated in keloid tissues, which suggests that, in patients with keloids, proinflammatory genes in the skin are sensitive to trauma. This may promote chronic inflammation, which in turn may cause the invasive growth of keloids. In addition, the upregulation of proinflammatory factors in pathological scars suggests that, rather than being skin tumors, keloids and hypertrophic scars are inflammatory disorders of skin, specifically inflammatory disorders of the reticular dermis. Various external and internal post-wounding stimuli may promote reticular inflammation. The nature of these stimuli most likely shapes the characteristics, quantity, and course of keloids and hypertrophic scars. Specifically, it is likely that the intensity, frequency, and duration of these stimuli determine how quickly the scars appear, the direction and speed of growth, and the intensity of symptoms. These proinflammatory stimuli include a variety of local, systemic, and genetic factors. These observations together suggest that the clinical differences between keloids and hypertrophic scars merely reflect differences in the intensity, frequency, and duration of the inflammation of the reticular dermis. At present, physicians cannot (or at least find it very difficult to) control systemic and genetic risk factors of keloids and hypertrophic scars. However, they can use a number of treatment modalities that all, interestingly, act by reducing inflammation. They include corticosteroid injection/tape/ointment, radiotherapy, cryotherapy, compression therapy, stabilization therapy, 5-fluorouracil (5-FU) therapy, and surgical methods that reduce skin tension.

Topics: Animals; Cicatrix, Hypertrophic; Dermis; Humans; Interleukins; Keloid

PubMed: 28287424
DOI: 10.3390/ijms18030606

Review

Authors: Claudio Conforti, Iris Zalaudek, Roberta Vezzoni...

The skin is a dynamic organ that continuously eliminates an infinite number of keratinized cells through physiological mechanism. Chemical peeling is a widely used cosmetic procedure in medical practice. This technique consists of the application of one or more chemical ablative agents to the skin's surface in order to induce keratolysis or keratocoagulation. Exfoliation is followed by skin and epidermal regeneration from the adjacent epithelium and skin adnexa. Moreover, through an inflammatory reaction and the activation of the inflammation mediators, an increase in fibroblastic synthesis and in the production of new collagen and glycosaminoglycan fibers is induced. After the first treatment session, the appearance and the texture of the skin are significantly improved. Peeling agents may be divided into superficial (epidermis-papillary dermis), medium-depth (papillary to upper reticular dermis) and deep subtypes based on the depth of their penetration (mid-reticular dermis). Superficial peel is mainly used for dyschromia, acne, post-inflammatory hyperpigmentation, melasma and actinic keratosis. Medium depth peel mainly treats solar keratosis or lentigines, pigmentary disorders and superficial scars. Skin photo-ageing, deep scars or wrinkles and precancerous skin lesions require a deep chemical peeling. The aim of this article is to review recent advances in chemical peel of melasma and acne.

Topics: Acne Vulgaris; Chemexfoliation; Cicatrix; Humans; Hyperpigmentation; Keratolytic Agents; Melanosis; Skin Aging; Skin Diseases

PubMed: 31804050
DOI: 10.23736/S0392-0488.19.06425-3

Review

Authors: Alexandra L Rippa, Ekaterina P Kalabusheva, Ekaterina A Vorotelyak...

There are many studies on certain skin cell specifications and their contribution to wound healing. In this review, we provide an overview of dermal cell heterogeneity and their participation in skin repair, scar formation, and in the composition of skin substitutes. The papillary, reticular, and hair follicle associated fibroblasts differ not only topographically, but also functionally. Human skin has a number of particular characteristics that are different from murine skin. This should be taken into account in experimental procedures. Dermal cells react differently to skin wounding, remodel the extracellular matrix in their own manner, and convert to myofibroblasts to different extents. Recent studies indicate a special role of papillary fibroblasts in the favorable outcome of wound healing and epithelial-mesenchyme interactions. Neofolliculogenesis can substantially reduce scarring. The role of hair follicle mesenchyme cells in skin repair and possible therapeutic applications is discussed. Participation of dermal cell types in wound healing is described, with the addition of possible mechanisms underlying different outcomes in embryonic and adult tissues in the context of cell population characteristics and extracellular matrix composition and properties. Dermal white adipose tissue involvement in wound healing is also overviewed. Characteristics of myofibroblasts and their activity in scar formation is extensively discussed. Cellular mechanisms of scarring and possible ways for its prevention are highlighted. Data on keloid cells are provided with emphasis on their specific characteristics. We also discuss the contribution of tissue tension to the scar formation as well as the criteria and effectiveness of skin substitutes in skin reconstruction. Special attention is given to the properties of skin substitutes in terms of cell composition and the ability to prevent scarring.

Topics: Animals; Cicatrix; Dermis; Extracellular Matrix; Fibroblasts; Hair Follicle; Humans; Keloid; Myofibroblasts; Regeneration; Skin; Skin Physiological Phenomena; Skin, Artificial; Wound Healing

PubMed: 31216669
DOI: 10.3390/cells8060607

Review

Authors: Sabrina Guillen Fabi

Microfocused ultrasound (MFU) has been recently developed to meet the ever-growing public demand for achieving significant, noninvasive skin lifting and tightening. MFU can be focused on subcutaneous tissue where the temperature briefly reaches greater than 60°C, producing small (<1 mm(3)) thermal coagulation points to a depth of up to 5 mm within the mid-to-deep reticular layer of the dermis and subdermis. The intervening papillary dermal and epidermal layers of skin remain unaffected. The application of heat at these discrete thermal coagulation points causes collagen fibers in the facial planes such as the superficial musculoaponeurotic system and platysma, as well as the deep reticular dermis, to become denatured, contracting and stimulating de novo collagen. A commercially available device combines MFU with high-resolution ultrasound imaging (MFU-V), which enables visualization of tissue planes to a depth of 8 mm and allows the user to see where the MFU energy will be applied (Ultherapy(®); Ulthera Inc., Mesa, AZ, USA). Using different transducers, MFU-V treatment can be customized to meet the unique physical characteristics of each patient by adjusting energy and focal depth of the emitted ultrasound. By targeting the facial superficial musculoaponeurotic system, noninvasive tightening and lifting of sagging facial and neck skin and improvements in the appearance of wrinkles can be achieved. MFU-V can also improve lines and wrinkles of the décolleté. Treatment protocols for the use of MFU-V continue to be refined, and its use in combination with other rejuvenation techniques has been demonstrated. Brief discomfort that often occurs during treatment can be minimized with oral nonsteroidal anti-inflammatory drugs. Other treatment-related adverse events include transient erythema, edema, and occasional bruising. MFU-V is best suited for patients with mild-to-moderate skin and soft tissue laxity. For older patients with severe skin laxity and marked platysmal banding, surgical treatment should be considered.

PubMed: 25709486
DOI: 10.2147/CCID.S69118

Review

Authors: Valérie Haydont, Bruno A Bernard, Nicolas O Fortunel...

Ageing is today a major societal concern that is intrinsically associated with the increase of life expectancy. Outside the context of severe degenerative diseases that affect the elderly populations, normal visible signs of ageing, notably skin sagging and wrinkles, influence the social and individual perception of peoples. Accordingly, there is a strong demand for researches on skin ageing. Deciphering the cellular and molecular processes of skin evolution through ageing is thus an active scientific domain, at the frontier of tissue developmental and ageing biology. The focus of the present article is to provide an overview of the current knowledge concerning the evolution of dermis characteristics at different life stages, from intra-uterine to post-natal life. The description will integrate stage-specific and age-related changes in dermis characteristics at the tissue, cell, and molecular levels.

Topics: Aging; Animals; Dermis; Extracellular Matrix; Humans; Skin Aging

PubMed: 29548941
DOI: 10.1016/j.mad.2018.03.006

Review

Authors: Hiroki L Yamaguchi, Yuji Yamaguchi, Elena Peeva...

Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment loss, respectively. In AA, inflammatory cell infiltrates are in the deep reticular dermis close to the hair bulb (swarm of bees), whereas in vitiligo the inflammatory infiltrates are in the epidermis and papillary dermis. Immune privilege collapse has been extensively investigated in AA pathogenesis, including the suppression of immunomodulatory factors (e.g., transforming growth factor-β (TGF-β), programmed death-ligand 1 (PDL1), interleukin-10 (IL-10), α-melanocyte-stimulating hormone (α-MSH), and macrophage migration inhibitory factor (MIF)) and enhanced expression of the major histocompatibility complex (MHC) throughout hair follicles. However, immune privilege collapse in vitiligo remains less explored. Both AA and vitiligo are autoimmune diseases that share commonalities in pathogenesis, including the involvement of plasmacytoid dendritic cells (and interferon-α (IFN- α) signaling pathways) and cytotoxic CD8+ T lymphocytes (and activated IFN-γ signaling pathways). Blood chemokine C-X-C motif ligand 9 (CXCL9) and CXCL10 are elevated in both diseases. Common factors that contribute to AA and vitiligo include oxidative stress, autophagy, type 2 cytokines, and the Wnt/β-catenin pathway (e.g., dickkopf 1 (DKK1)). Here, we summarize the commonalities and differences between AA and vitiligo, focusing on their pathogenesis.

Topics: Alopecia Areata; Humans; Vitiligo; Animals; Immune Privilege; Cytokines

PubMed: 38673994
DOI: 10.3390/ijms25084409

Authors: Mariana Pereira, Rita Ramos Pinheiro, André Lencastre...

Scleredema of Buschke is a rare connective tissue disease with a poorly understood pathogenesis. Three types of scleredema have been distinguished according to its association with preceding or underlying conditions. Type 1 is usually secondary to a febrile infection, type 2 is mostly associated with paraproteinemia and type 3, usually named scleredema diabeticorum, has a strict association with Diabetes mellitus. A diffuse, non-pitting swelling and induration of the skin define this disease. The skin histology is characterized by a normal or slightly thinned epidermis, and the dermis containing a decreased number of elastic fibers and thick large swollen collagen bundles separated by mucopolysaccharide deposits in the deep reticular dermis. In this report we present a 58-year-old man with scleredema diabeticorum controlled with a topical steroid cream and an optimization of glycemic control. We reviewed clinical, histopathological characteristics and the various possible treatments.

PubMed: 36483221
DOI: 10.4081/dr.2022.9477

Authors: Ryan R Driskell, Beate M Lichtenberger, Esther Hoste...

Fibroblasts are the major mesenchymal cell type in connective tissue and deposit the collagen and elastic fibres of the extracellular matrix (ECM). Even within a single tissue, fibroblasts exhibit considerable functional diversity, but it is not known whether this reflects the existence of a differentiation hierarchy or is a response to different environmental factors. Here we show, using transplantation assays and lineage tracing in mice, that the fibroblasts of skin connective tissue arise from two distinct lineages. One forms the upper dermis, including the dermal papilla that regulates hair growth and the arrector pili muscle, which controls piloerection. The other forms the lower dermis, including the reticular fibroblasts that synthesize the bulk of the fibrillar ECM, and the preadipocytes and adipocytes of the hypodermis. The upper lineage is required for hair follicle formation. In wounded adult skin, the initial wave of dermal repair is mediated by the lower lineage and upper dermal fibroblasts are recruited only during re-epithelialization. Epidermal β-catenin activation stimulates the expansion of the upper dermal lineage, rendering wounds permissive for hair follicle formation. Our findings explain why wounding is linked to formation of ECM-rich scar tissue that lacks hair follicles. They also form a platform for discovering fibroblast lineages in other tissues and for examining fibroblast changes in ageing and disease.

Topics: Adipocytes; Animals; Cell Lineage; Dermis; Female; Fibroblasts; Hair Follicle; In Vitro Techniques; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Transgenic; Muscle, Smooth; Skin; Wound Healing; beta Catenin

PubMed: 24336287
DOI: 10.1038/nature12783

Authors: Kellen J Cavagnero, Fengwu Li, Tatsuya Dokoshi...

The skin provides an essential barrier for host defense through rapid action of multiple resident and recruited cell types, but the complex communication network governing these processes is incompletely understood. To define these cell-cell interactions more clearly, we performed an unbiased network analysis of mouse skin during invasive S. aureus infection and revealed a dominant role for CXCL12+ fibroblast subsets in neutrophil communication. These subsets predominantly reside in the reticular dermis, express adipocyte lineage markers, detect IL-17 and TNFα, and promote robust neutrophil recruitment through NFKBIZ-dependent release of CXCR2 ligands and CXCL12. Targeted deletion of Il17ra in mouse fibroblasts resulted in greatly reduced neutrophil recruitment and increased infection by S. aureus. Analogous human CXCL12+ fibroblast subsets abundantly express neutrophil chemotactic factors in psoriatic skin that are subsequently decreased upon therapeutic targeting of IL-17. These findings show that CXCL12+ dermal immune acting fibroblast subsets play a critical role in cutaneous neutrophil recruitment and host defense.

Topics: Mice; Animals; Humans; Interleukin-17; Neutrophil Infiltration; Staphylococcus aureus; Skin; Fibroblasts; Chemokine CXCL12

PubMed: 38393304
DOI: 10.1084/jem.20231425