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Abstract This case report describes an 80-year-old man who presented with a growing erythematous nodule with erosion, measuring 0.6 cm × 0.6 cm, on his right temple. This lesion was later diagnosed as atypical fibroxanthoma (AFX). Instead of undergoing Mohs surgery, the gold standard treatment, the patient opted to pursue a topical treatment regimen because of financial costs associated with surgical removal and repair. This topical regimen consisted of tazarotene cream, imiquimod cream, and 5-fluorouracil solution, applied for 30 days. The patient was directed to use this combination 5 days per week for 6 weeks. The specified dosage for each medication was a fifth of a packet of imiquimod 5% cream, an equivalent amount of tazarotene 0.1% cream, and a single drop of 5-fluorouracil 2% solution. These were combined on a bandage and placed on the lesion overnight. Following the treatment, a 3-week post-application examination revealed an erosion, 1.0 cm × 0.9 cm, amidst erythema. A subsequent incisional biopsy with histopathology and stains for CD10 and CD99, 3 weeks after treatment, and three punch biopsies with histopathology and stains for CD10 and CD99, 1-year post-treatment, confirmed the absence of AFX. AFX is a superficial variant of pleomorphic dermal sarcoma (PDS), which shares histologic similarities, yet the exact relationship between AFX/PDS and undifferentiated pleomorphic sarcoma is still not well understood. Previous studies have indicated a genomic similarity between AFX/PDS and cutaneous squamous cell carcinoma (cSCC), which suggests the potential efficacy of cSCC-targeted treatments for AFX/PDS. This case marks the first recorded instance of successful topical medical treatment of AFX, offering an alternative for patients who may opt out of surgical intervention. Continued research to assess the broader efficacy of this approach is encouraged.

Abstract Stasis dermatitis (SD) is a chronic inflammatory dermatosis that typically presents with nonspecific signs and symptoms such as pruritic and xerotic skin, aching legs, and areas of dyspigmentation (red or brown in lighter skin tones and brown, purple, gray, or ashen in darker skin tones). These signs and symptoms are often misdiagnosed as other conditions, such as cellulitis. Moreover, within healthcare systems, SD is often overlooked due to a lack of understanding of the magnitude and impact of the condition, as well as incomplete recognition of the various presenting clinical manifestations. Inadequate or inappropriate management may lead to disease progression, including worsening edema, pain, and itch as well as complications such as venous leg ulcers. When patients do seek medical attention (often upon worsening of the condition), a diagnosis of SD is often challenging because of physician lack of expertise and the plethora of disorders that may manifest similarly to SD. Furthermore, upon diagnosis, evidence‐based treatment options are limited, and adherence to SD treatment regimens is often low. SD significantly impacts patient and caregiver quality of life (QoL), with far‐reaching psychosocial and socioeconomic effects. In this review, we describe the patient journey associated with SD and the challenges associated with diagnosis, the burden of disease and impact on patient QoL, and the unmet needs that remain with current therapeutic options.

Plain Language Summary Stasis dermatitis is a skin disease that affects the legs, most often of older people, with chronic venous insufficiency. Chronic venous insufficiency is when veins cannot return blood from the legs back to the heart. This leads to high blood pressure in veins and causes blood in those veins to flow backwards. If stasis dermatitis is left untreated, complications, including skin ulcers, can result. Other skin symptoms of stasis dermatitis include itchiness, scaling, and discoloration. Such skin symptoms can have a negative effect on a person’s quality of life. Inflammation that lasts a long time is likely the main link between the skin changes seen in people with stasis dermatitis and the increased pressure in leg veins. Several molecules are associated with the inflammation observed in stasis dermatitis, including white blood cells, matrix metalloproteinases, phosphodiesterase 4, and interleukin-31. Treatment for stasis dermatitis should focus both on the underlying chronic venous insufficiency and the associated skin issues. Identifying inflammatory markers and pathways could help treat the signs and symptoms associated with stasis dermatitis, including the skin symptoms.

Chronic wounds such as diabetic foot ulcers and venous leg ulcers place a significant burden on the healthcare system and in some cases, have 5-year mortality rates comparable to cancer. They negatively impact patients’ quality of life due to pain, odor, decreased mobility, and social isolation. Skin substitutes are an advanced therapy recommended for wounds that fail to show decrease in size with standard care. The choice of substitute used should be based on evidence, which often differs based on wound etiology. There are more than 75 skin substitutes currently available, and that number is rising. In this review, we discuss current management and future directions of chronic wounds while providing a review of available randomized control trial data for various skin substitutes.

Jozic et al observe deregulated cytoskeleton components and elevated levels of cortisol and caveolin-1 in chronic wounds. They also show that inducible-keratinocyte specific Cav1 knockout or drug-induced cholesterol disruption in diabetic mice leads to accelerated wound closure suggesting a therapeutic approach for diabetic foot ulcers.

Diabetes mellitus is an increasingly prevalent chronic metabolic disease characterized by prolonged hyperglycemia that leads to long-term health consequences. It is estimated that impaired healing of diabetic wounds affects approximately 25% of all patients with diabetes mellitus, often resulting in lower limb amputation, with subsequent high economic and psychosocial costs. The hyperglycemic environment promotes the formation of biofilms and makes diabetic wounds difficult to treat. In this review, we present updates regarding recent advances in our understanding of the pathophysiology of diabetic wounds focusing on impaired angiogenesis, neuropathy, sub-optimal chronic inflammatory response, barrier disruption, and subsequent polymicrobial infection, followed by current and future treatment strategies designed to tackle the various pathologies associated with diabetic wounds. Given the alarming increase in the prevalence of diabetes, and subsequently diabetic wounds, it is imperative that future treatment strategies target multiple causes of impaired healing in diabetic wounds.

Chronic wounds develop when the orderly process of cutaneous wound healing is delayed or disrupted. Development of a chronic wound is associated with significant morbidity and financial burden to the individual and health-care system. Therefore, new therapeutic modalities are needed to address this serious condition. Mesenchymal stem cells (MSCs) promote skin repair, but their clinical use has been limited due to technical challenges. Extracellular vesicles (EVs) are particles released by cells that carry bioactive molecules (lipids, proteins, and nucleic acids) and regulate intercellular communication. EVs (exosomes, microvesicles, and apoptotic bodies) mediate key therapeutic effects of MSCs. In this review we examine the experimental data establishing a role for EVs in wound healing. Then, we explore techniques for designing EVs to function as a targeted drug delivery system and how EVs can be incorporated into biomaterials to produce a personalized wound dressing. Finally, we discuss the status of clinically deploying EVs as a therapeutic agent in wound care.

Giant basal cell carcinomas (GBCCs) are large basal cell carcinomas (BCCs;

Background The association between pyoderma gangrenosum (PG) and arthritis is well established. We have observed a refractory population of patients with arthritis-associated PG (PGA). We, therefore, tested the hypothesis that differences exist in response to treatment in patients with PGA compared with patients with PG without arthritis. Observations We performed a review of patients with PG during a 2-year period. Patients had noninfectious chronic ulcerations clinically typical for PG, exclusion of relevant differential diagnoses, and consistent histopathological features. Outcomes compared between patients with arthritis (PGA) and without arthritis (PG) included complete healing, percentage change in wound size, and duration of therapy. Of 10 PG ulcers, 7 healed, compared with 2 of 8 PGA ulcers. There was a greater mean percentage decrease in wound size in the PG vs the PGA ulcers (78.9% vs 23.4%; P = .10) and a shorter mean duration of treatment (8.7 vs 14.8 months; P = .18). Conclusions The ulcers of patients with PGA seem more refractory to treatment than the ulcers of patients with PG alone. Those with PGA ulcers represent a refractory subset of patients, and the ulcers are possibly secondary to unique pathophysiological features. [ABSTRACT FROM AUTHOR]

AbstractScleroderma is a common autoimmune disorder with no effective therapy. Current concepts of scleroderma include the hypothesis that scleroderma results from excess conversion of endothelial cells to fibroblast like cells, called endothelial mesenchymal transformation. This process is thought to be mediated by cytokines including transforming growth factor beta (TGFb), which causes increased collagen synthesis, resulting in fibrosis, the hallmark of the disease. In vitro studies have hypothesized that rapamycin may be of benefit in scleroderma due to antagonism of collagen synthesis. Given that rapamycin has antiangiogenic activities, inhibits wound healing, and prevents the synthesis of collagen in vivo, we tried rapamycin in a patient with scleroderma. We observed rapid improvement in skin stiffness and mobility. Our results provide the rationale for larger clinical trials of rapamycin in scleroderma and other fibrotic disorders. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers (DFUs) lead to nearly 100,000 lower limb amputations annually in the United States. DFUs are colonized by complex microbial communities, and infection is one of the most common reasons for diabetes-related hospitalizations and amputations. In this study, we examined how DFU microbiomes respond to initial sharp debridement and offloading and how the initial composition associates with 4 week healing outcomes. We employed 16S rRNA next generation sequencing to perform microbial profiling on 50 samples collected from 10 patients with vascularized neuropathic DFUs. Debrided wound samples were obtained at initial visit and after one week from two DFU locations, wound bed and wound edge. Samples of the foot skin outside of the wounds were also collected for comparison. We showed that DFU wound beds are colonized by a greater number of distinct bacterial phylotypes compared to the wound edge or skin outside the wound. However, no significant microbiome diversity changes occurred at the wound sites after one week of standard care. Finally, increased initial abundance of Gram-positive anaerobic cocci (GPAC), especially Peptoniphilus (p < 0.05; n = 5 subjects), was associated with impaired healing; thus, GPAC's abundance could be a predictor of the wound-healing outcome.

Larissa Zaulyanov, Robert S Kirsner Department of Dermatology and Cutaneous Surgery; University of Miami Miller School of Medicine, Miami, Florida, USAAbstract: Apligraf® (Organogenesis, Canton, MA) is a bi-layered bioengineered skin substitute and was the first engineered skin US Food and Drug Administration (FDA)-approved to promote the healing of ulcers that have failed standard wound care. Constructed by culturing human foreskin-derived neonatal fibroblasts in a bovine type I collagen matrix over which human foreskin-derived neonatal epidermal keratinocytes are then cultured and allowed to stratify, Apligraf provides both cells and matrix for the nonhealing wound. Its exact mechanism of action is not known, but it is known to produce cytokines and growth factors similar to healthy human skin. Initially approved by the FDA in 1998 for the treatment of venous ulcers greater than one-month duration that have not adequately responded to conventional therapy, Apligraf later received approval in 2000 for treatment of diabetic foot ulcers of greater than three weeks duration. Herein, we review the use of Apligraf in the treatment of chronic venous leg ulcers and diabetic foot ulcers. Our goal is to provide a working understanding of appropriate patient selection and proper use of the product for any physician treating this segment of the aging population.Keywords: wound healing, Apligraf®, venous leg ulcer, diabetic foot ulcer

Perforin-2 (MPEG1) is a pore-forming, antibacterial protein with broad-spectrum activity. Perforin-2 is expressed constitutively in phagocytes and inducibly in parenchymal, tissue-forming cells. In vitro, Perforin-2 prevents the intracellular replication and proliferation of bacterial pathogens in these cells. Perforin-2 knockout mice are unable to control the systemic dissemination of methicillin-resistant Staphylococcus aureus (MRSA) or Salmonella typhimurium and perish shortly after epicutaneous or orogastric infection respectively. In contrast, Perforin-2-sufficient littermates clear the infection. Perforin-2 is a transmembrane protein of cytosolic vesicles -derived from multiple organelles- that translocate to and fuse with bacterium containing vesicles. Subsequently, Perforin-2 polymerizes and forms large clusters of 100 Å pores in the bacterial surface with Perforin-2 cleavage products present in bacteria. Perforin-2 is also required for the bactericidal activity of reactive oxygen and nitrogen species and hydrolytic enzymes. Perforin-2 constitutes a novel and apparently essential bactericidal effector molecule of the innate immune system.

Diabetes Mellitus (DM) is a chronic, severe disease rapidly increasing in incidence and prevalence and is associated with numerous complications. Patients with DM are at high risk of developing diabetic foot ulcers (DFU) that often lead to lower limb amputations, long term disability, and a shortened lifespan. Despite this, the effects of DM on human foot skin biology are largely unknown. Thus, the focus of this study was to determine whether DM changes foot skin biology predisposing it for healing impairment and development of DFU. Foot skin samples were collected from 20 patients receiving corrective foot surgery and, using a combination of multiple molecular and cellular approaches, we performed comparative analyses of non-ulcerated non-neuropathic diabetic foot skin (DFS) and healthy non-diabetic foot skin (NFS). MicroRNA (miR) profiling of laser captured epidermis and primary dermal fibroblasts from both DFS and NFS samples identified 5 miRs de-regulated in the epidermis of DFS though none reached statistical significance. MiR-31-5p and miR-31-3p were most profoundly induced. Although none were significantly regulated in diabetic fibroblasts, miR-29c-3p showed a trend of up-regulation, which was confirmed by qPCR in a prospective set of 20 skin samples. Gene expression profiling of full thickness biopsies identified 36 de-regulated genes in DFS (>2 fold-change, unadjusted p-value ≤ 0.05). Of this group, three out of seven tested genes were confirmed by qPCR: SERPINB3 was up-regulated whereas OR2A4 and LGR5 were down-regulated in DFS. However no morphological differences in histology, collagen deposition, and number of blood vessels or lymphocytes were found. No difference in proliferative capacity was observed by quantification of Ki67 positive cells in epidermis. These findings suggest DM causes only subtle changes to foot skin. Since morphology, mRNA and miR levels were not affected in a major way, additional factors, such as neuropathy, vascular complications, or duration of DM, may further compromise tissue's healing ability leading to development of DFUs.

Use of new keratin-based wound dressings represent a novel approach to wound management. The authors present three patients with recalcitrant, venous and mixed venous, and arterial leg ulcers treated with these dressings. Improvement in each case was observed. [ABSTRACT FROM AUTHOR]

Vitiligo is one of the most common dermatological disorders, appearing as one or more white macules or patches and affecting up to two percent of the population worldwide. The undesirable aesthetic properties of vitiligo, especially facial, may result in significant negative psychosocial effects, particularly a rate of depression twice that of the general population. While there is no cure, there are several treatment options, notably depigmentation in severe cases. Monobenzone is the most potent depigmenting agent. However, its use is limited due to the permanent and potent nature of the drug. This case presents an example of when timely and aggressive treatment with monobenzone is warranted, demonstrating excellent clinical response, which resulted in a significant increase in the quality of life in a patient with severe vitiligo. [ABSTRACT FROM AUTHOR]

Abstract: Evidence to support available therapies for pyoderma gangrenosum (PG) is limited. Many patients do not respond to topical therapies such as tacrolimus or topical steroids. Currently favored oral systemic treatments (eg, cyclosporine and steroids) achieve complete remission in only 50% of patients and have unfavorable adverse effect profiles. There is a growing body of evidence to support biologic agents for the treatment of PG, but their exact role remains unclear. Here the authors present a patient with peristomal PG, the first reported case of PG responding to treatment with risankizumab, an anti-interleukin 23 monoclonal antibody. Risankizumab may represent an effective and relatively safe treatment for PG that merits additional exploration in prospective, controlled studies., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The purpose of this learning activity is to provide information about the etiology and treatment of atrophie blanche., Target Audience: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care., Objectives: After participating in this educational activity, the participant should be better able to:1. Discuss the pathophysiology of atrophie blanche.2. Explore treatment options for livedoid vasculopathy., Abstract: Atrophie blanche (AB) is a porcelain-white scar that may be seen at the base of a healed ulcer or in association with livedoid vasculopathy (LV). The term AB originally had been used synonymously with LV, whereas LV is a noninflammatory thrombotic condition presenting as either a primary or secondary event (often associated with coagulation).