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Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The study aimed to investigate the prevalence and characteristics of pain in different ulcer types and to identify factors associated with pain experience in patients with lower-extremity ulcers. A cross-sectional single-centre study was performed, including 130 newly referred outpatients with lower-extremity ulcers. Pain intensity was measured with a visual analog scale (VAS) and pain characteristics with the short form mcgill pain questionnaire-2 (SF-MPQ-2). The mean pain intensity was 29.5 (SD 31.8) at rest and 35.5 (SD 34.1) during movement (0-100 VAS). 61.5% of the patients experienced pain (VAS > 0) at rest and 70.8% during movement. Moderate to severe pain at rest was seen in 39.2% and in 43.8% of patients during movement. The mean total score on SF-MPQ-2 (range 0-220) was 35.9 (SD 32.6). Most of the patients described pain as intermittent (mean 11.8 SD 13.9). Analgesics were prescribed for 78% of the patients. Ulcer type (i.e., arterial, immunological, pressure and venous) and age were associated with pain severity, and women had a significantly lower well-being score than men. Prevalence of pain in patients with lower-extremity ulcers was high across different ulcer aetiologies. Pain intensity and quality must be assessed to obtain adequate pain management., (© 2024 The Authors. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

Leg ulcers are a major complication of sickle cell disease (SCD). They are particularly challenging to treat and innovative therapies are needed. We previously showed that the healing of SCD ulcers is delayed because of decreased angiogenesis. During pregnancy, fetal microchimeric cells (FMC) transferred to the mother are recruited to maternal wounds and improve angiogenesis. After delivery, FMC persist in maternal bone marrow for decades. Here, we investigated whether fetal cells could also improve SCD ulcers in the post-partum setting. We found that skin healing was similarly improved in post-partum mice and in pregnant mice, through increased proliferation and angiogenesis. In a SCD mouse model that recapitulates refractory SCD ulcers, we showed that the ulcers of post-partum SCD mice healed more quickly than those of virgin mice. This was associated with the recruitment of fetal cells in maternal wounds where they harbored markers of leukocytes and endothelial cells. In a retrospective cohort of SCD patients, using several parameters we found that SCD women who had ever had a baby had less of a burden related to leg ulcers compared to nulliparous women. Taken together, these results indicate that healing capacities of FMC are maintained long after delivery and may be exploited to promote wound healing in post-partum SCD patients.

Sickle cell disease is a common and highly morbid genetic condition that is characterized by multi-system involvement, including numerous cutaneous manifestations. Persistent and recurrent leg ulceration has long been considered the dermatological hallmark of those with sickle cell disease, but there have been recent descriptions of associated infection with rare pathogens and episodes of liverdoid vasculopathy. Growing considerations for this population in the literature include cutaneous reactions to common treatments such as hydroxyurea and clinical management of the intersection between sickle cell disease and conditions like plaque psoriasis. Recent studies have also demonstrated an increased resistance to skin carcinogenesis for those with sickle cell disease through unclear mechanisms. However, though the body of knowledge regarding cutaneous manifestations and considerations of sickle cell disease is slowly expanding, it does not match the considerable disease and symptom burden faced by these patients. More research is needed to better delineate our understanding of these cutaneous manifestations of sickle cell disease to improve outcomes and further management., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: BCC is a malignancy that arises from the basal cells of the epidermis. Despite being the most common cancer worldwide, it rarely occurs in the setting of long-standing ulceration. Malignant transformation of wounds and scars is typically associated with the development of SCC, as with an MU. Reports in the literature of BCC arising within nonhealing, lower extremity wounds are limited., Case Report: The authors report a case of a 65-year-old man with several comorbidities who presented to the clinic with a nonhealing wound on the right lateral ankle. The wound first began as warts during childhood that had necessitated frequent debridement. The lesions persisted and, 7 years ago, developed into an ulcer with a large fungating mass associated with pain, bleeding, and foul-smelling exudate. Biopsy findings were consistent with infiltrative-type BCC. He was not a surgical candidate given his comorbidities and was instead treated with radiation therapy. No evidence of metastasis was seen on follow-up imaging., Conclusion: This case highlights the importance of prompt biopsy and cultures in patients with suspicious ulcers and wounds that do not respond to appropriate treatment.

Objective: To define the prevalence of leg ulcers and identify the clinical and laboratory factors associated with leg ulcers in adult participants., Methods: The authors conducted a cross-sectional study of 1,109 patients who were 18 years or older with SS or Sβ0-thalassemia genotypes from a Brazilian cohort. Investigators assessed the prevalence of factors associated with leg ulcers from 2013 to 2017., Results: The prevalence of leg ulcers was 21%. Increasing age (odds ratio [OR], 1.07; range, 1.06-1.09), male sex (OR, 2.03; range, 1.44-2.87), treatment with chronic transfusion therapy (OR, 1.88; range, 1.15-3.03), higher indirect bilirubin levels (OR, 1.48; range, 1.02-2.16), and low hemoglobin levels (OR, 2.17; range, 1.52-3.11) were associated with leg ulcers. Participants who self-reported as Black (OR, 6.75; range, 2.63-21.32), mixed (OR, 3.91; range, 1.55-12.20), and other/unknown (OR, 3.84; range, 1.04-15.24) were more likely to have leg ulcers compared with those who self-reported as White., Conclusions: The prevalence of leg ulcers in this Brazilian cohort was higher than the prevalence reported in developed countries. Known factors such as age and male sex were corroborated. The increased bilirubin level and decreased hemoglobin levels among participants with leg ulcers support the hypothesis that hemolysis is correlated with leg ulcer pathogenesis. Self-reported black skin color was an independent predictor of leg ulcers and warrants further study to understand the etiology and implications of this finding., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Lanolin is a complex mixture of high molecular weight esters, aliphatic alcohols, sterols, fatty acids, and hydrocarbons that has been widely used for centuries for its emollient properties. The purification of crude lanolin into lanolin wax and the processing of this wax into various derivatives began in 1882 and continue to this day with newer highly purified anhydrous lanolins. Controversy as to lanolin's allergenicity began in the 1920s and remains an issue. The most appropriate patch test preparation(s) for detecting allergy remain disputed. Detection of lanolin-induced contact dermatitis in diseased skin by patch testing on normal skin may lead to false negative results. Patients with a positive patch test to lanolin may tolerate use of lanolin on normal skin. Although lanolin is a weak sensitizer and the frequency of contact allergy to it in the European population reportedly is 0.4%, there are high-risk concomitant conditions: stasis dermatitis, leg ulcers, perianal/genital dermatitis, and atopic dermatitis (AD). Children and the elderly are also at greater risk of developing contact allergy to lanolin, partly because of comorbidities (AD and stasis dermatitis/leg ulcers, respectively). Finally, in the United States, non-Hispanic white patients are more likely than their non-Hispanic black counterparts to be lanolin allergic.

Patients with sickle cell disease and/or (rarely) trait are at increased risk for developing recurrent episodes of priapism, also known as stuttering priapism, and major ischemic priapism. Treatment of acute ischemic priapism is reactive; whereas ideal management consists of preventative approaches to ultimately promote the best improvement in patient's quality of life. Leg ulcers in patients with sickle cell disease (SCD) are quite common, with ∼20 % of patients with HBSS reporting either having an active or a past ucler. They can be confused with venous ulcers, with lower extremity hyperpigmentation confounding further the diagnosis. Several factors believed to contribute to the development of leg ulcers in patients with SCD are discussed in this article. Sickle cell liver disease (SCLD) occurs because of a wide variety of insults to the liver that happen during the lifetime of these patients. SCLD includes a range of complications of the hepatobiliary system and is increasing in prevalence with the aging adult sickle population. Liver nodular regenerative hyperplasia (NRH) is more common than realized and underappreciated as a diagnosis and requires liver biopsy with reticulin staining. Undiagnosed, the insidious damage from liver NRH can lead to noncirrhotic portal hypertension or cirrhosis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Venous leg ulcers are slow to heal, and recurrence is frequent. Living with venous leg ulcers can affect physical and psychological health, and result in financial burden for individuals. Physiological and psychosocial factors are associated with venous leg ulcer recurrence. As over 50% of venous leg ulcers will recur within 12 months of healing, a comprehensive knowledge of holistic risk factors associated with recurrence is required by health professionals involved in the care of the person with venous leg ulcers., Aim: To develop a systematic review protocol to determine the risk factors for recurrence of venous leg ulcers in adults., Method and Analysis: This protocol was developed according to the Preferred Reporting Items Form Systematic Review and Meta-Analysis Protocols (PRISMA-P). The inclusion criteria will be based on the PICOS mnemonic-adults with a history of venous leg ulcer/s (participants), risk factor/s under physiological (general/medical), clinical, demographics, psychosocial categories (I (intervention) or E (exposure), venous leg ulcer non-recurrence (comparison group), venous leg ulcer recurrence (outcomes to be measured) and will include study designs of original qualitative, quantitative and mixed method studies (study designs to be included). Methodological quality will be assessed using the Mixed Methods Appraisal Tool. This Systematic Review Protocol was registered in PROSPERO [CRD42021279792]., Results: If meta-analysis is not possible, a narrative review of results will be presented., Conclusions: This systematic review on recurrence of venous leg ulcers can provide evidence-based information for preventive strategies for recurrence of a healed venous leg ulcer. The standardised approach outlined in this systematic review protocol offers a rigorous and transparent method to conduct the review., Competing Interests: Declaration of competing interest No conflict of interest has been declared by the authors., (Copyright © 2022 Tissue Viability Society / Society of Tissue Viability. Published by Elsevier Ltd. All rights reserved.)

Prolidase deficiency is a rare cause of chronic ulceration with less than 100 reported cases in the literature. This article highlights to clinicians the features of this uncommon genodermatosis, the challenge of diagnosis, and treatment options., (© 2022 British Association of Dermatologists.)

Chronic ulcers are most often seen as a complication to venous leg ulcers, diabetic foot ulcers and pressure ulcers. Ulcers often display an underlying medical condition, which makes it mandatory to treat these individuals in a multidisciplinary setting. Modern ulcer therapy has changed over the latest decade, and as described in this review a number of new modalities have been included. The major group of ulcers often presents with well-defined features, but attention should be directed towards ulcers with atypic appearance such as ulcers related to calciphylaxis, hypertension (Martorell) and pyoderma.

Sickle leg ulcers (SLU) are malleoli lesions with exuberant hemolytic pathophysiology. The microRNAs are potential genetic biomarkers for several pathologies. Thereby, we aimed to assess the expression of circulating miR-199a-5p, miR-144, and miR-126 in association with hemolytic biomarkers in SLU. This cross-sectional study included 69 patients with sickle cell disease, 52 patients without SLU (SLU-) and 17 patients with active SLU or previous history (SLU+). The results demonstrated elevated expression of circulating miR-199a-5p and miR-144 in SLU+ patients while miR-126 expression was reduced. Circulating miR-199a-5p and miR-144 were associated with hemolytic biomarkers such as LDH, indirect bilirubin, AST, GGT, iron, ferritin, RBC, hemoglobin, and NOm, in addition to association with impaired clinical profile of SLU. Furthermore, in silico analyses indicated interactions of miR-199a-5p with HIF1A, Ets-1, and TGFB2 genes, which are associated with vasculopathy and reduced NO. In contrast, miR-126 was associated with an attenuating clinical profile of SLU, in addition to not characterizing hemolysis. In summary, this study demonstrates, for the first time, that hemolytic mechanism in SLU can be characterized by circulating miR-199a-5p and miR-144. The circulating miR-126 may play a protective role in SLU. Thus, these microRNAs can support to establish prognosis and therapeutic strategy in SLU.

Background: Leg ulcers are a frequent complication in patients with the inherited hemoglobin disorders. In thalassemia, the literature is limited, and factors associated with the development of leg ulcers in hemoglobin E (HbE) beta thalassemia, the most common form of severe beta-thalassemia worldwide, have not previously been reported., Methods: We reviewed all available medical records of patients with HbE beta thalassemia to document the onset of leg ulcers at the 2 largest treatment centers in Sri Lanka. We reviewed the literature to identify studies reporting outcomes of interventions for ulcers in severe thalassemia., Results: Of a total of 255 actively registered patients with HbE thalassemia in the 2 centers, 196 patient charts were evaluable. A leg ulcer with a documented date of onset was recorded in 45 (22%) of 196 evaluable patients, aged (mean ± SEM) 22.2 ± 1.4 years. Most had been irregularly transfused; steady-state hemoglobin was 6.4 ± 0.2 g/dL. Treatment achieving healing in 17 patients included transfusions, antibiotics, oral zinc, wound toileting, and skin grafting., Conclusion: Leg ulcers may be more common in HbE beta thalassemia than in other forms of thalassemia. A systematic approach to treatment will be needed to document the prevalence and factors placing such patients at risk for leg ulcers. Controlled trials to evaluate the optimal treatment of this common complication are indicated., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Sickle cell disease is a disorder characterized by chronic hemolytic anemia and multiorgan disease complications. Although vaso-occlusive episodes, acute chest syndrome, and neurovascular disease frequently result in complication and have well-documented guidelines for management, the management of chronic hemolytic and vascular-related complications, such as priapism, leg ulcers, and pulmonary hypertension, is not as well recognized despite their increasing reported prevalence and association with morbidity and mortality. This chapter therefore reviews the current updates on diagnosis and management of priapism, leg ulcers, and pulmonary hypertension., (Copyright © 2021 by The American Society of Hematology.)

Objective: To understand the experience of a woman with systemic lupus erythematosus and leg ulcers with cutaneous calcinosis., Methods: An experience report based on the social phenomenology of Alfred Schutz, conducted with a young woman undergoing treatment in an outpatient service., Results: The disease manifested itself in adolescence and brought emotional instability associated with body image concern and social isolation. The discontinuation of the studies triggered financial limitations with implications for treatment. The presence of ulcers aggravated by skin calcification makes the process of getting sick tiring and painful. Interpersonal relationships are resources for coping with situations experienced., Final Considerations: Patients with lupus may have social, affective, and family life, even in the face of the limitations imposed by the disease. However, the emergence of leg ulcer with calcinosis changes this situation.

Objective: To evaluate the presence of anemia in patients with chronic lower limb ulcers based on profile and hematometric indices., Method: This is a cross-sectional study carried out in a university hospital in Rio de Janeiro. The sample was composed of 64 participants with lower limb ulcers and evolution time greater than 12 weeks. Data was collected between May/2016 and December/2017 from hematological analyses, records from medical records, and wound assessment form., Results: 36 (56.2%) were male; 38 (59.4%) between 60 and 80 years old; 56 (87.5%) with chronic diseases and 52 (81.2%) with venous ulcers. 6 years mean of active ulceration. Anemia was detected in 36 (56.2%), 27 (75%) of which were normochromic and normocytic; 14 (38.8%) had deficiency anemia recorded in their medical chart., Conclusion: The low hemoglobin concentration is recurrent among the participants characterizing an anemia condition, whose profile reveals congruence to the anemia of chronic disease.

Objectives: The general anesthetic sevoflurane is being repurposed as a topical analgesic for painful chronic wounds. We conducted a Bayesian cost-effectiveness analysis (CEA) comparing the addition of domiciliary topical sevoflurane to conventional analgesics (SEVOFLURANE, n = 38) versus conventional analgesics alone (CONVENTIONAL, n = 26) for the treatment of nonrevascularizable painful leg ulcers in an outpatient Pain Clinic of a Spanish tertiary hospital., Methods: We used real-world data collected from charts to conduct this CEA from a public healthcare perspective and with a one-year time horizon. Costs of analgesics, visits and admissions were considered, expressed in €2016. Analgesic effectiveness was measured with SPID (Sum of Pain Intensity Difference). A Bayesian regression model was constructed, including "treatment" and baseline characteristics for patients ("arterial hypertension") and ulcers ("duration", "number", "depth", "pain") as covariates. The findings were summarized as a cost-effectiveness plane and a cost-effectiveness acceptability curve. One-way sensitivity analyses, a re-analysis excluding those patients who died or suffered from leg amputation, and an extreme scenario analysis were conducted to reduce uncertainty., Results: Compared to CONVENTIONAL, SEVOFLURANE was associated with a 46% reduction in costs, and the mean incremental effectiveness (28.15±3.70 effectiveness units) was favorable to SEVOFLURANE. The estimated probability for SEVOFLURANE being dominant was 99%. The regression model showed that costs were barely influenced by any covariate, whereas effectiveness was noticeably influenced by "treatment". All sensitivity analyses showed the robustness of the model, even in the extreme scenario analysis against SEVOFLURANE., Conclusions: SEVOFLURANE was dominant over CONVENTIONAL as it was less expensive and much more effective., Competing Interests: Dr. Selva-Sevilla and Dr. Cortiñas-Sáenz have nothing to disclose. Dr. Fernández-Ginés has a patent “Analgetic microspheres comprising a volatile halogenated anaesthetic” issued to Dámaso Fernández-Ginés. Dr. Gerónimo-Pardo owned stock options from Vapogenix Inc, and he had a personal interest in the issue since he started the repurposing process for the inhalation general anesthetic sevoflurane to be used as a topical analgesic. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aims and Objectives: The aims of this study were to explore the prevalence of background pain and identify demographic, clinical and psychosocial factors associated with moderate to severe background pain in persons with leg ulcers., Background: All chronic leg ulcers are potentially painful. Research indicates that 80% of persons with chronic leg ulcers experience wound-related background pain. However, studies on factors associated with pain have small samples and findings are inconclusive., Design: Exploratory cross-sectional study., Method: This quantitative study recruited persons with chronic leg ulcers (N = 252) from two wound care clinics using consecutive sampling method. Data were obtained through screening interview, clinical examination and questionnaires. Logistic regression with stepwise backwards elimination was used to identify factors associated with moderate to severe background pain. The STROBE checklist for cross-sectional studies was used for reporting this study., Results: Background pain was reported by 64% of the participants. Inferential statistical analyses suggest that between 58% and 69% of persons with chronic leg ulcers suffer from this type of pain. Factors associated with moderate to severe pain were older age, female gender, reduced sleep quality and diminished health status. In the final model, reduced sleep quality increased the likelihood of having moderate to severe pain in persons with good health status while not in persons with diminished health status., Conclusion: Ulcer-related background pain is common in persons with chronic leg ulcers. Older females reporting insomnia symptoms also had increased risk of moderate to severe ulcer-related background pain. These participants also perceived their health status to be better., Relevance to Clinical Practice: This study demonstrates that ulcer-related background pain and associated factors needs more attention in clinical practice. Furthermore, nurses and other healthcare professionals should integrate biopsychosocial strategies to assess and manage ulcer-related background pain., (© 2021 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Objective: Management and outcomes of superficial vein thrombosis (SVT) are highly variable and not well described. Therefore, the INvestigating SIGnificant Health TrendS in the management of SVT (INSIGHTS-SVT) study collected prospective data under real life conditions., Methods: Prospective observational study of objectively confirmed acute isolated SVT. The primary outcome was a composite of symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), and extension or recurrence of SVT at three months. The primary safety outcome was clinically relevant bleeding., Results: A total of 1 150 patients were included (mean age 60.2 ± 14.7 years; 64.9% women; mean BMI 29.4 ± 6.3 kg/m 2 ). SVT was below the knee in 54.5%, above the knee in 26.7%, above and below the knee in 18.8%. At baseline, 93.6% received pharmacological treatment (65.7% fondaparinux, 23.2% heparins, 4.3% direct oral anticoagulants [DOACs], 14.5% analgesics), 77.0% compression treatment, and 1.9% surgery; 6.4% did not receive any anticoagulation. The primary outcome occurred in 5.8%; 4.7% had recurrent or extended SVT, 1.7% DVT, and 0.8% PE. Clinically relevant non-major bleeding occurred in 1.2% and major bleeding in 0.3%. Complete clinical recovery of SVT was reported in 708 patients (62.4%). Primary outcome adjusted by propensity score and for treatment duration was lower with fondaparinux compared with low molecular weight heparin (4.4% vs. 9.6%; hazard ratio [HR] 0.51; 95% confidence interval [CI] 0.3 - 0.9; p = .017). On multivariable analysis, associated factors for primary outcome included another SVT prior to the present SVT event (HR 2.3), age per year (HR 0.97), duration of drug treatment per week (HR 0.92), and thrombus length (HR 1.03)., Conclusion: At three month follow up, patients with isolated SVT are at risk of thromboembolic complications (mainly recurrent or extended SVT), despite anticoagulation. In this real life study, about one third had received either heparins, oral anticoagulants, or no anticoagulation., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Non-Uremic Calciphylaxis (NUC) is a rare condition that often manifests as intractable and painful integumentary wounds, afflicting patients with a high burden of co-morbidity. The Endocannabinoid System (ECS) is a ubiquitous signalling system that is theorised to be dysregulated within wound beds and associated peri-wound tissues. Preclinical research has shown that the dominant chemical classes derived from the cannabis plant, cannabinoids, terpenes, and flavonoids, interact with the integumentary ECS to promote wound closure and analgesia. This is a prospective open label cohort study involving two elderly Caucasian females with recalcitrant NUC leg ulcers of greater than 6 months duration. Topical Cannabis-Based Medicines (TCBM) composed of cannabinoids, terpenes, and flavonoids were applied daily to both the wound bed and peri-wound tissues until complete wound closure was achieved. Wounds were photographed regularly, and the digital images were subjected to planimetric analysis to objectively quantify the degree of granulation and epithelization. Analgesic utilisation, as a surrogate/proxy for pain scores, was also tracked. The cohort had a mean M3 multimorbidity index score of 3.31. Complete wound closure was achieved in a mean of 76.3 days. Additionally, no analgesics were required after a mean of 63 days. The treatments were well tolerated with no adverse reactions. The positive results demonstrated in very challenging wounds such as NUC, among highly complex patients, suggest that TCBM may have an even broader role within integumentary and wound management. This treatment paradigm warrants being trialled in other wound types and classes, and ultimately should be subjected to randomised controlled trials., (© 2020 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Soft tissue ulceration resulting from chronic venous insufficiency is a common condition that requires standardised long-term therapy, which has been thoroughly established. We report a patient with a five-year history of persistent venous stasis ulcers despite treatment consistent with traditional wound care. Resolution of the ulcers began only upon deviation from conventional therapy. This report considers non-standard treatments in patients with venous ulcers that do not progress.

General Purpose: To provide information about the effectiveness of topical analgesic and local anesthetic agents for reducing pain associated with chronic leg ulcers., Target Audience: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care., Learning Objectives/outcomes: After participating in this educational activity, the participant will:1. Distinguish adverse reactions to topical analgesics and local anesthetic agents.2. Evaluate the effectiveness of topical analgesics and local anesthetic agents for pain associated with chronic leg ulcers.3. Identify substances used as topical analgesics and local anesthetic agents and the application of those agents., Abstract: To examine the evidence related to the effectiveness of topical analgesic and topical local anesthetic agents for reducing pain associated with chronic leg ulcers.A systematic search and review of the literature were undertaken using key search terms such as leg ulcers, topical anesthetics, topical analgesics, and pain. Six databases were electronically searched for articles published between January 1990 and August 2019.A total of 23 articles were identified that met the inclusion criteria. Data were extracted using content analysis. Most of the included studies were randomized controlled trials; however, the reported methodology for most of studies was poor, so the validity and reliability of the evidence are uncertain. Lidocaine/prilocaine cream, ibuprofen foam, and morphine gel were the most examined topical agents. Lidocaine/prilocaine cream significantly improved wound-related pain compared with all other studied agents. For topical analgesic agents, ibuprofen foam reduced chronic leg ulcer pain significantly, whereas morphine gel was ineffective.Lidocaine/prilocaine cream and ibuprofen foam are effective agents for reducing wound-related pain associated with chronic leg ulcers. Effective use of topical agents could reduce the need for systemic pain relief agents, mitigating potential adverse effects, while giving clinicians another treatment option to manage wound-related pain associated with chronic leg ulcers.

Background and Objectives: In patients with lymphedema, the disruption of the lymphatic network increases skin turgor and fibrosis of subcutaneous tissue, delays wound healing, causing recurrent ulcerations and infections. In these cases, management of ulcers can be challenging., Methods: Between January 2016 and June 2018, patients presenting with lymphedema were enrolled at our Institution. We selected patients with severe lymphedema and ulcers of lower limbs and we performed a surgical approach, involving free gastroepiploic lymph nodes and omentum flap, harvested through laparoscopy., Results: We enrolled 135 patients presenting for lymphedema. Among them, 10 eligible cases underwent excision of the ulcer and reconstruction with omentum flap. Mean age was 57.8 years and average follow-up 24.1 months. Circumferences and skin tonicity significantly decreased from the preoperative period. Lymphoscintigraphy showed improvement of the lymphatic drainage and restoration of lymphatic network. No episodes of infection were recorded in the postoperative period., Conclusions: Our combined procedure merges free flap techniques and lymphedema surgery: omentum covers the defect while providing a new source of lymph nodes, improving the lymphatic networks of the affected limb. This technique can highly increase the quality of life of the patient in a single-stage operation with fast recovery and low donor site morbidity., (© 2019 Wiley Periodicals, Inc.)

There is a paucity of studies regarding pruritus in patients with chronic leg ulcers. Data were collected using newly developed questionnaires for patients and physicians to evaluate pruritus in individuals with chronic leg ulcers. The results show that a total of 50 patients with chronic leg ulcers were included in this prospective study. Frequent pruritus was observed in 32.0% of the participants, while 36.0% reported occasional pruritus. The average pruritus intensity was 3.5 points (0-10 numeric rating scale [NRS]) and was found to increase with age. Patients experiencing pruritus achieved a higher Wound-quality of life (QoL) score (32.1) as that of patients without pruritus (25.8). Additional dermatological findings around the wounds included xerosis (26.0%), eczema (4.0%), and excoriations (2.0%). Pruritus was reported by all subjects with eczema and 84.6% of those with xerosis. The pruritus lasted significantly longer in women (average 98.4 months) vs men (average 37.5 months). Interestingly, men reported more intense pruritus than women (4.4 vs 2.8). Females reported more frequent use of skin care products than males. In conclusion, the current data show that two-thirds of patients with chronic leg ulcers suffer from moderate intense pruritus. Therefore, pruritus is a frequent and often neglected problem that should be regularly evaluated in all patients with chronic leg ulcers and considered in future therapy concepts., (© 2019 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Histopathologic vasculitis is often reported in periulcer specimens, but the frequency and clinical significance of this finding have not been evaluated., Objective: We evaluated the sensitivity, specificity, negative predictive value, and positive predictive value of histopathologic vasculitis from the periulcer edge for detecting ulcers due to cutaneous vasculitis., Methods: We performed a retrospective chart review of patients with leg ulcers at a tertiary hospital between 2009 and 2016. Histopathologic slides were evaluated by 2 dermatopathologists who were blinded to the etiology of ulcer. Focal vasculitis was defined as involvement of fewer than 3 vessels., Results: Vasculitis at the periulcer edge was seen in 51.6% of the specimens (32 of 62). Of the specimens with histopathologic vasculitis, focal vasculitis was seen in the majority of specimens (71.9% [23 of 32]), whereas diffuse vasculitis was observed in 28.1% (9 of 32). Periulcer vasculitis yielded a high sensitivity (100% [95% confidence interval, 29%-100%]). Furthermore, the specificity was low (50.9% [95% confidence interval, 38.1%-63.6%]) for detecting vasculitis-induced ulcers., Limitations: Small number of vasculitis-induced ulcers., Conclusion: Focal vasculitis from the periulcer edge is a nonspecific finding and provides little diagnostic value in determining the etiology of lower leg ulcers. Emphasis should be placed on the combination of clinical history and examination, histology, and laboratory findings when diagnosing ulcers., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Pseudohyperaldosteronism, or Liddle syndrome, is a rare, autosomal dominant condition characterized by early-onset hypertension, often associated with hypokalemia and metabolic alkalosis. Martorell hypertensive ischemic leg ulcer is a rare, underdiagnosed ulcer characterized by subcutaneous arteriolosclerosis, classically appearing over the dorsolateral lower extremity or Achilles tendon in patients with hypertension and diabetes. It presents an important diagnostic challenge because it can appear grossly similar to other entities such as pyoderma gangrenosum or venous stasis ulcers, but requires surgical intervention. This article presents a case study of surgical management of a Martorell ulcer in a 69-year-old woman with Liddle syndrome. To the authors' knowledge, this is the first case reported in the literature of this rare ulcer occurring secondary to this rare cause of hypertension.

Aim: An investigator-initiated clinical study was carried out to evaluate the therapeutic potency of SR-0379 for the treatment of leg ulcers in patients with Werner syndrome., Methods: A multicenter, open-label study was carried out from September 2017 to February 2018. The inclusion criteria for leg ulcers were: (i) leg ulcers in patients with Werner syndrome, diabetes or critical limb ischemia/venous stasis; and (ii) a wound size of >1 cm and <6 cm in diameter. Four individuals with Werner syndrome and diabetic ulcers, respectively, were enrolled. SR-0379 (0.1%) was sprayed on skin ulcers once per day for 4 weeks. Efficacy was evaluated by determining the rate of wound size reduction as a primary end-point at 4 weeks after the first treatment compared with the pretreatment wound size. As secondary end-points, the DESIGN-R score index, the 50% wound size reduction ratio, time to wound closure and quantification of wound bacteria were also evaluated. The safety of SR-0379 was evaluated during the study period., Results: The reduction rate of ulcer size treated with 0.1% SR-0379 was 22.90% (mean) in the Werner syndrome ulcers group (n = 4) and 35.70% (mean) in the diabetic ulcers group (n = 4), respectively. The DESIGN-R score decreased by 4.0 points in the Werner syndrome ulcers group and 4.3 points in the diabetic ulcers group. Two mild adverse events were reported in two patients, and causal relationships were denied in any events., Conclusion: Treatment with SR-0379 was safe, well-tolerated, and effective for leg ulcers of both Werner syndrome and diabetes patients. Geriatr Gerontol Int 2019; 19: 1118-1123., (© 2019 Japan Geriatrics Society.)

Cases: We describe 2 cases of nonagenarians with periprosthetic knee fractures that were not amenable to either standard internal fixation nor prosthesis revision because of infected leg ulcers in the same limb. The fractures were internally fixed by percutaneous insertion of medial and lateral plates that spanned the knee. Both patients returned to their baseline level of activity without developing surgical site infections., Conclusions: Percutaneous bridging plates that span the knee are a useful option for treating these difficult cases.

Objective: A wound is defined as chronic when it requires more than 6 weeks to heal. The link between chronic wounds and depression was first pointed out by House and Hughes in 1996 and later evaluated by other numerous studies. Several studies demonstrate that among chronic skin wounds causing chronical physical disease, the leg ulcers are the most frequently associated with depression. The aim of our study is to evaluate the prevalence of depression in patients with different types of chronic wounds., Patients and Methods: We enrolled a total of 33 patients with chronic wounds and 33 healthy controls matched by sex and age. Both patients and controls underwent a BDI II survey. We evaluated 33 patients, with a mean age of 71 years (range 25-87), and 33 controls, with a mean age of 73 years (range 31-88)., Results: The average score at the BDI II questionnaire was 14.5 and 8, respectively., Conclusions: The depression among patients with chronic wounds has a multifactorial origin that should be treated with a multidisciplinary approach. Since the improvement of the psycho-emotional state means better compliance of the patient, we can also expect a better result in terms of efficacy in chronic wound treatment.

Venous insufficiency is related to aging. Edema, pathological evolution of venous insufficiency, favors the appearance of venous ulcers as the main complication. Leg ulcers can be treated with compression, the Unna's boot being one of them, and noncompression therapies (conventional dressing). Bioelectrical impedance analysis accurately measures the patient's body fluids. The objective of this study was to evaluate the edema evolution of the venous ulcer-affected lower limb by means of electric bioimpedance with the use of Unna's boot and noncompressive dressing. Fifteen legs with active ulcers were treated from September 2014 to December 2016. The legs were treated with Unna's boot and noncompression therapies on different days with randomized order of events. Bioimpedance was performed in the morning and afternoon to evaluate the increase in edema over the day. All patients were female with ages ranging from 50 to 76 years (mean age: 63 years). According to bioimpedance, the volume of the legs increased with both types of therapy. However, compression therapy was significantly more effective than noncompression therapy. Bioimpedance confirmed that compression therapy (Unna's boot) gives better results than noncompression therapy in relation to the formation of edema over a day in patients with chronic venous ulcers., (Copyright © 2018 Society for Vascular Nursing. Published by Elsevier Inc. All rights reserved.)

Angiosarcoma is a vascular malignancy that can affect various anatomic sites. Although rare, cutaneous angiosarcoma is the most common clinical manifestation, accounting for approximately 50% to 60% of cases. Cutaneous angiosarcoma typically is known to occur in 3 settings: (1) idiopathic, (2) following radiation treatment, and (3) in the setting of chronic lymphedema following mastectomy (known as Stewart-Treves syndrome). The clinical manifestation of angiosarcoma can mimic other processes. We present a case of cutaneous angiosarcoma on the leg in an elderly woman in the setting of a chronic nonhealing wound and lymphedema. We also discuss the differential diagnosis and treatment options.

β-Thalassemia intermedia is a clinical condition of intermediate gravity between β-thalassemia minor, the asymptomatic carrier, and β-thalassemia major, the transfusion-dependent severe anemia. It is characterized by a significant clinical polymorphism, which is attributable to its genetic heterogeneity. Ineffective erythropoiesis, chronic anemia, and iron overload contribute to the clinical complications of thalassemia intermedia through stepwise pathophysiological mechanisms. These complications, including splenomegaly, extramedullary erythropoiesis, iron accumulation, leg ulcers, thrombophilia, and bone abnormalities can be managed via fetal hemoglobin induction, occasional transfusions, chelation, and in some cases, stem cell transplantation. Given its clinical diversity, thalassemia intermedia patients require tailored approaches to therapy. Here we present an overview and novel approaches to the genetic basis, pathophysiological mechanisms, clinical complications, and optimal management of thalassemia intermedia.

We present a case of a 69-year-old woman with rheumatoid arthritis. The patient's condition was managed with steroid therapy for more than 12 years. She had a coexisting infected chronic ulceration in the left leg, which was treated with negative pressure wound therapy for 52 days. Use of this therapy within the wound reduced exudate and the bacterial count, which dramatically accelerated the process of wound healing.

Venous insufficiency is the most common cause of leg ulceration, but the impact of venous leg ulceration on health-related quality of life has not been adequately assessed. This study compared data from randomized controlled trials to population norms obtained from a large national population survey. We combined the baseline Short Form-36 (SF-36) version 1 data from two New Zealand randomized controlled trials that recruited participants with VLU and compared the pooled data to the population scores obtained from the New Zealand Health Survey using general linear regression to adjust for age, sex, and ethnicity differences between the cohorts. Baseline SF-36 scores obtained from 618 trial participants were compared to the SF-36 scores obtained from the 12,529 participants in the New Zealand Health Survey. Participants with VLU had significantly lower crude SF-36 scores across all eight SF-36 domains, but there was interaction between age and group. Adjusted mean differences for participants aged 65 years or younger were -25.8, -32.1, -21.2, -9.6, -7.6, -23.9, -21.5, and -9.3, respectively, for Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health whereas the adjusted mean differences for older participants were -15.7, -23.8, -13.8, -0.3 (nonsignificant), -4.6, -15.3, -21.2, and -6.6. This study is the first to compare a VLU population to norms from a general population survey and the first to show VLU interacts with age creating stronger impact in younger patients compared their age cohort. Younger patients may have need of more pastoral care as a consequence., (© 2018 by the Wound Healing Society.)

Chromoblastomycosis is a chronic infection, caused by pigmented fungi affecting skin and subcutaneous tissues characterized by verrucous nodules or plaques. Fonsecaea pedrosoi and Cladophialophora carrionii are the prevalent agents in the endemic areas. Phoma is an uncommon agent of human infection and involved mainly with phaeohyphomycosis cases. The case of a patient with a history of laceration in foot followed by verrucous aspect and scaly lesions, which had evolved for 27 years is presented. On physical examination disease was clinically compatible with chromoblastomycosis and the microscopic examination of scales showed fumagoid cells. On culture a dematiaceous fungus was grown. The agent was confirmed to be Phoma insulana based on its morphology and PCR-sequencing. This fungal agent has not been previously reported in association with this pathology., (Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Martorell hypertensive ischemic ulcer can be a real clinical and therapeutic challenge. Controversy exists regarding both the underlying triggers of the disease and the type of treatment that should be established. Early skin grafting has been suggested as an effective treatment to enhance pain reduction and wound healing in these patients. The authors present the case of a 68-year-old woman with well-controlled hypertension and diabetes who developed extremely painful, rapidly progressing bilateral ulcers on the distal aspect of her legs. Without previous surgical debridement, the lesions were covered with punch grafts. Pain and necrotic progression were immediately controlled and complete epithelialization was achieved in 7 weeks.

We present the case of a 58-year-old man who presented to our wound care centre with a 7 -month history of a progressive unilateral leg ulcer. He reported intermittent, heavy bleeding at the ulcer. The duplex sonography showed a bilateral incompetence of the saphenofemoral junctions and the entire course of the great saphenous veins and, surprisingly, also a bilateral reversed arterial-like pulsating flow in the great and small saphenous veins as well as in the deep veins of the lower extremities. During cardiac examination by auscultation and echocardiography, we detected a previously undescribed severe tricuspid insufficiency with strongly reduced systolic ejection of both the left and the right ventricle and repercussions on the peripheral venous system as a cause for the pulsating veins. This case report highlights that, although infrequent, the presence of pulsating varicose veins points to the presence of cardiac abnormalities, especially severe tricuspid insufficiency, and should direct clinicians to initiate a thorough cardiological examination. Our case highlights that consequent compression therapy can be sufficient for wound healing in such cases and should be initially considered. These patients are at risk of severe bleeding, and therefore, interventions should be carefully planned., (© 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Coagulation disorders contribute to the development of livedoid vasculopathy (LV). Elevated plasma levels of lipoprotein(a) [Lp(a)] are an independent risk factor for the development of cardiovascular disease and associated with hypercoagulable states. Increased serum Lp(a) levels have been reported in patients with LV and may have an important role in the pathogenesis of LV., Objectives: To investigate Lp(a) expression in skin lesions and circulating serum Lp(a) levels in patients with LV., Methods: Skin biopsy samples from 38 patients (27 women and 11 men) with active lesions diagnosed as LV and 9 samples of normal skin (5 women and 4 men) from control patients without LV were evaluated for skin expression of Lp(a) by immunohistochemistry. Plasma levels of Lp(a) were analyzed by immunoturbidimetry., Results: We found that lesional skin in patients with LV expressed 10-fold higher Lp(a) immunostaining than controls. High plasma levels of Lp(a) were observed in LV patients. We did not find a correlation (P = .02) between expression of Lp(a) in the skin and plasma levels of Lp(a) in patients with LV., Conclusions: Increased Lp(a) expression in lesional skin of LV patients suggests the role of Lp(a) in the thrombo-occlusive vasculopathy observed in this disease., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Chronic leg ulcers persist for > 6 weeks and show no tendency to heal after 3 or more months. They can be distressing to patients, both directly through physical symptoms caused by the disease and indirectly through limitations on work capacity, social activity, and personal hygiene. The quality of life (QoL) of patients with leg ulcers can be impaired by a complex set of aspects. Restrictions in their ability to perform paid employment, handle household duties, and engage in personal hygiene adversely affect patients' QoL. Patients with chronic leg ulcers frequently experience negative emotions such as shame, embarrassment, and loneliness, and they present higher levels of depression and anxiety compared with healthy individuals. When the expected healing results do not occur, these patients feel as if they have no control over their condition; this ongoing frustration leads them to feel depressed. The ulcers contribute to anxiety and psychological stress, creating a vicious, difficult-to-manage circle. This review aims to describe the negative psychosocial impacts on patients with chronic leg ulcers and emphasize their impaired QoL.