Prevalence and characteristics of pain in patients with lower-extremity ulcers-A cross-sectional study.

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.

Basal cell carcinoma arising from a nonhealing lower extremity ulcer: a case report.

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.

Lanolin.

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.

Factors Associated with Leg Ulcers in Adults with Sickle Cell Disease in Brazil.

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 Sß0-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.

Contribution of fetal microchimeric cells to maternal wound healing in sickle cell ulcers.

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.

Cutaneous manifestations of sickle cell disease: an updated review.

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.

Clinical Vignettes Part I.

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.

Risk factors for the recurrence of venous leg ulcers in adults: A systematic review protocol.

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.

[Treatment of acute and chronic ulcers].

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.

A Description of the Hemolytic Component in Sickle Leg Ulcer: The Role of Circulating miR-199a-5p, miR-144, and miR-126.

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.

Obstinate leg ulceration secondary to prolidase deficiency, treated with 5% topical proline.

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.

Leg Ulcers: A Report in Patients with Hemoglobin E Beta Thalassemia and Review of the Literature in Severe Beta Thalassemia.

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.

Treatment dilemmas: strategies for priapism, chronic leg ulcer disease, and pulmonary hypertension in sickle cell disease.

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.

Patients who experience systemic lupus erythematosus and leg ulcer: phenomenological approach.

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.

The presence of anemia in patients with leg ulcer: laboratory test.

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.

Cost-effectiveness analysis of domiciliary topical sevoflurane for painful leg ulcers.

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.

Management and Outcomes of Patients with Isolated Superficial Vein Thrombosis under Real Life Conditions (INSIGHTS-SVT).

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/m2). 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.