Sickle Cell Leg Ulcers Research Articles

Psychosocial impact of leg ulcers on the quality of life of adults living with sickle cell disease in Ghana

BackgroundSickle cell disease-related persistent chronic manifestations, such as leg ulcers, continue to raise clinical and psychosocial concerns. The Quality of Life (QoL) issues have not been adequately defined in sickle cell disease (SCD) management. This study examined the psychosocial effects of leg ulcers in people living with SCD in Ghana.MethodsA total of 95 adult SCD patients aged 18–65 participated in the cross-sectional study, with 41 having chronic leg ulcers and 54 without leg ulcers. Participants were administered the Sickle Cell Illness Impact Measurement Scale (SIMS) to assess five main domains of QoL: general health perception, physical functioning, social functioning, emotional well-being, and quality of care. The Analysis of Covariance (ANCOVA) test was used to determine the differences in the quality of life between the groups while controlling for the effect of genotype, gender, and age. The multivariate logistic regression was conducted to identify the clinical and demographic predictors of QoL among adult SCD by examining the relationships between multiple independent variables and a binary QoL outcome.ResultsGenerally, SCD patients without leg ulcers had an overall good QoL (p = 0.017), functioned better socially (p < 0.001) and had good general health perception (p = 0.012) than their counterparts with leg ulcers. Patient’s age at registration at clinic [aOR = 1.062 (95%CI 1.01, 1.12) p = 0.022], having a Sickle Cell Leg Ulcer (SCLU) [aOR = 3.716 (95%CI 1.44, 9.62) p = 0.007] predicted poorer QoL of the SCD population.ConclusionThese findings have significant clinical implications. Integrating early, enhanced and targeted interventions into the clinical management of SCD patients, especially those with sickle cell leg ulcers, is crucial to improving their quality of life.

WHOQOL-BREF in Measuring Quality of Life Among Sickle Cell Disease Patients with Leg Ulcers.

Sickle cell disease (SCD) presents complex clinical manifestations influenced by genetic, social, environmental, and healthcare access factors as well as socioeconomic status. In this context, sickle cell leg ulcers (SLUs) are a debilitating complication of SCD. We aimed to describe sociodemographic data and evaluate the quality of life (QoL) of SCD patients with and without SLUs. We conducted a cross-sectional study including 13 SCD patients with SLUs and 42 without LUs. Clinical data were obtained by reviewing the medical records, and QoL was assessed with the WHOQOL-BREF questionnaire. Our cohort of patients had a mean age of 34.9 years, with 52.8% male, 52.8% identifying as black, and 41.7% identifying as brown. Most had low income, incomplete education, and high unemployment rates. The social habits and relationships of SCD patients showed varying levels of friendship and family closeness, and the majority of SLU+ patients did not practice sports. We failed to find statistical differences in the WHOQOL-BREF domains between SLU+ and SLU- patients. However, higher income and employment status were associated with improved WHOQOL-BREF domain scores in SCD patients, while vaso-occlusive episodes and female gender were linked to lower scores. Our data reinforce the sociodemographic characteristics of SCD. The physical domain was associated with income, occupation, and vaso-occlusion. The psychological domain was associated with income and occupation. The social relationship domain was associated with occupation and female gender. The environmental domain was associated with vaso-occlusion. The WHOQOL-BREF is a reliable tool to measure QoL in SCD.

Thrombomodulin and Lactate Dehydrogenase as Potential Predictors of Leg Ulcers in Sickle Cell Disease

Abstract Background: Endothelial dysfunction, hypercoagulability, hemolysis, and vasculopathy are involved in the pathogenesis of sickle cell leg ulcers (SCLUs). Understanding these processes is crucial for developing effective strategies to manage and prevent SCLU. Objectives: To evaluate the plasma levels of thrombomodulin (TM) in patients with SCLU, determine if TM levels have any association with SCLU and its severity, and determine if TM has any association with markers of hemolysis. Materials and Methods: This was a cross-sectional analytical study carried out among patients with SCLU and their age-matched sickle cell disease (SCD) patients without leg ulcers. Venous blood samples were collected for the determination of TM and lactate dehydrogenase (LDH) levels. Statistical significance across means was determined using independent t tests and the one-way analysis of variance (ANOVA). Pearson’s correlation and linear regression analysis were used to determine the relationship between variables. Results: Of the 82 patients with SCD, 41 had SCLU (test group), and 41 had no SCLU (control group). Their mean age was 33.3 ± 9.0 and 33.0 ± 8.5 (P = 0.30), respectively. There was no significant statistical difference between plasma levels of TM and number (P = 0.191) and severity (P = 0.148) of SCLU. Seventy-three (89%) SCD patients had LDH concentration above the reference limit of normal, and 9 (11%) were within normal limits (P = 0.002). None of the test (SCLU) group patients had normal LDH values. Conclusion: SCLU is associated with higher levels of LDH, whereas plasma TM levels showed no association with the occurrence and severity of SCLU.

Genetic Modifiers in Sickle Cell Disease Leg Ulcers: Unveiling the Pathways associated with the development and, or progression of Leg Ulcers - A Scoping Review Protocol.

This scoping review aims to assess the literature on genetic modifiers of leg ulcers in sickle cell disease, evaluating available evidence, methodologies, and research gaps. A major morbidity in sickle cell disease is the development of leg ulcers. This clinical syndrome of SCD leg ulcers (SLU) has continued to be an enigma due to its multifactorial evolution, dearth of promising guidelines on treatment, and generally unsatisfactory response to treatment. Underlying genetic susceptibilities for SLU may impact counselling, prognostication, risk of development, severity as well as response to interventions. Hence the need for this scoping review. This scoping review will collate and assess studies in English on genetic markers of SLU among all SCD age groups, genders, races, and regions. Genetic or molecular markers to be assessed among patients with sickle cell leg ulcers included, genetic markers of Inflammation, vasculopathy, tissue damage, oxidative stress, coagulopathy as well as genetic predispositions that have been studied in relation to SLUs across all countries. This includes most common biomarkers that promote development of SLU, the single nucleotide polymorphic markers (SNPs) that work through the MAPK and SMAD signaling pathway. A PubMed search of all fields for literature published in English using the strategy (sickle cell) AND (leg ulcer), and (sickle cell) AND (leg ulcer genetics) from 1998 to 2023 (last 25 years) will be undertaken. This will be modified, according to the inclusion criteria, as appropriate across other databases. The other databases will include Google Scholar, web of Knowledge, Scopus, New Zealand Science, Silver chair, Taylor and Francis+NEJM, and journals.lww.com.

"SCULP" study: The benefits of skin graft pellets on the pain of sickle cell leg ulcers (SCLU).

"SCULP" study: The benefits of skin graft pellets on the pain of sickle cell leg ulcers (SCLU).

Sickle Cell Leg Ulcer Extending to the Achilles Tendon

Sickle Cell Leg Ulcer Extending to the Achilles Tendon

Gender Differences in the Complications of Sickle Cell Anemia

Background: The clinical severity of sickle cell anemia (SCA) varies from one individual to another. Several factors, including genetic predisposition, environmental and social factors, are known to modify the clinical presentation and complications of SCA but not much is known about the influence of gender. Objective: This study aims at determining the gender differences in the pattern of SCA complications in Enugu, Nigeria. Materials and Methods: This is a retrospective analysis of clinical and laboratory data from the folders of patients with SCA at the University of Nigeria Teaching Hospital Enugu, Nigeria between February 2008 and February 2014. A total of 248 folders comprising 151 males and 97 females were retrieved. Data on the age, sex, hematological parameters, number of complications, and frequency of SCA crises were extracted and analyzed. Only the case files of adult patients with SCA were investigated. Results: The median age of the participants was 25 (IQR = 22–30) years. The male to female ratio was 1.5:1. A total of 182 out of 248 (73.4%) cases reviewed had one form of complication or the other. Sickle cell leg ulcer was the most common complication seen among the cases (50/182 [27.5%]), followed by avascular necrosis (AVN) (28/182 [15.4%]). The mean frequency of crises was not different between the male and female genders (15.00 ± 9.01 vs. 9.8 ± 6.97; P = 0.293). However, the male gender had more complications than the female gender (116/151 [73.9%] vs. 116/151 [73.9%]; odds ratio [OR] = 2.13; 95% confidence interval [CI] = 1.2–3.7; P = 0.007). Conclusion: The male gender is twice more likely to develop complications of SCA and, thus, are more likely to have more morbidity from this condition.

Interventions for treating leg ulcers in people with sickle cell disease.

The frequency of skin ulceration makes an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease. This is an update of a previously published Cochrane Review. To assess the clinical effectiveness and harms of interventions for treating leg ulcers in people with sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. We searched LILACS (1982 to January 2020), ISI Web of Knowledge (1985 to January 2020), and the Clinical Trials Search Portal of the World Health Organization (January 2020). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area. Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 13 January 2020; date of the last search of the Cochrane Wounds Group Trials Register: 17 February 2017. Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment. Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data. We used GRADE to assess the quality of the evidence. Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl® cream, arginine-glycine-aspartic acid (RGD) peptide dressing and topical antibiotics). No trials on non-pharmaceutical interventions were included in the review. All trials had an overall unclear or high risk of bias, and drug companies sponsored four of them. We were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the units of randomisation and analysis. Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, only arginine butyrate showed a reduction of ulcer size compared with a control group, mean reduction -5.10 cm² (95% CI -9.65 to -0.55), but we are uncertain whether this reduces ulcer size compared to standard care alone as the certainty of the evidence has been assessed as very low. Three trials reported on complete leg ulcer closure (isoxsuprine, arginine butyrate, RGD peptide matrix; very low quality of evidence). None reported a clinical benefit. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; incidence of amputation or harms. Given the very low quality of the evidence identified in this updated Cochrane Review we are uncertain whether any of the assessed pharmaceutical interventions reduce ulcer size or result in leg ulcer closure in treated participants compared to controls. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having an unclear or high risk of bias. The harm profile of the all interventions remains inconclusive.

Evaluation Of Some Markers Of Haemolysis – Endothelial Dysfunction And Haematological Parameters In People With Sickle Cell Disease Leg Ulcers

Abstract Introduction/Objective Sickle cell leg ulcer (SCLU) is one of the commonest cutaneous manifestation of the sickle cell anaemia (SCA). This study was designed to evaluate the haematological parameters and contribution of haemolysis to leg ulcers in persons with sickle cell anaemia Methods A comparative cross-sectional study of 73 participants (24 sickle cell leg ulcer-SCLU, 24 sickle cell without leg ulcer-SCWLU and 25 healthy controls). Physical examination was conducted to grade the SCLU. ELISA kits were used to analyse Nitric oxide, while FBC, Reticulocyte count, liver function test (AST and ALT), total Bilirubin (unconjugated and conjugated) were determined using standard methods. ANOVA was used to compare the association between sickle cell leg ulcers and markers of haemolysis-endothelial dysfunction among the three groups. Probability score of less than 5% (p-values&amp;lt;0.05) was considered statistically significant Results There was no statistically significant difference in the age distribution of the participants in this study. Those with SCLU were diagnosed at an older age and majority (52.2%) had clinical stage 2 leg ulcer. Among the markers for haemolysis-endothelial dysfunction (HED); Reticulocyte production index (PRI) was lower in SCLU (1.87 + 0.72) compared to SCWLU, (2.04 + 0.78) p= 0.01. Total and unconjugated bilirubin (µmol/L) level was higher for SCLU (53.0 + 17) in comparison to SCWLU (42.2 + 8.2) with statistical significance of p=0.00. Aspartate and alanine transaminases (AST and ALT) (U/L) were higher in SCLU in comparison with SCWLU, (60.1 + 21.5, 43.8 + 15.8 and 30.1 + 13, 29.8 + 11.7) respectively, and was statistically significant p= 0.00. However Nitric oxide was not statistically different between SCLU and SCWLU mean ± SD (49.57 + 12 and 46.19 + 9) respectively. p = 0.35 Conclusion Markers of haemolysis were higher in participants with sickle cell leg ulcer (SCLU) when compared to those without leg ulcer (SCWLU). However, no statistically significant difference was obtained for Nitric oxide (NO) between the two groups. Therefore, markers of haemolysis cannot be used as an effective predictor for risk of developing SCLU but early diagnosis of SCA can prevent SCLU.

Leg ulcers in sickle cell disease patients.

Leg ulcers are the most common cutaneous complication of sickle cell disease. These lesions occur mainly in homozygous forms, are slow to heal and often relapse, causing negative physical, emotional, and economic impacts. In this paper, we discuss the clinical presentation, diagnosis, and pathophysiology of sickle cell leg ulcers and their implications for treatment.

609 Production of clinical grade temporary epidermal substitute obtained from hESC derived keratinocytes for the treatment of sickle cell leg ulcers: a challenge for regenerative medicine

609 Production of clinical grade temporary epidermal substitute obtained from hESC derived keratinocytes for the treatment of sickle cell leg ulcers: a challenge for regenerative medicine

Leg Ulcers in Sickle-Cell Disease: Treatment Update.

Significance: Sickle-cell leg ulcers (SCLUs) are a severe, chronic, and recurrent complication of sickle-cell disease (SCD). There are no official recommendations for treatment. Recent Advances: Only a few studies with a high level of evidence have been conducted to evaluate treatment of SCLUs. However, several studies have been conducted with a high level of evidence to evaluate the efficacy of treatments in venous leg ulcers, and SCLUs could benefit from these treatments, especially when a venous incompetence or an edema is associated. Pathophysiology of SCLUs includes a vasculopathy related to chronic hemolysis and an endothelial dysfunction, which could be therapeutic approaches to SCLU treatment. Critical Issues: Therapeutic approaches to SCLUs can target SCD on the one hand and skin healing and associated aggravating factors on the other. A review of the literature found only case series and six randomized controlled trials; some offered encouraging results, but most had serious biases. Clinical trials specifically targeting SCLUs are difficult to realize because of the small number of affected patients, in comparison with patients with leg ulcers from other causes. Future Direction: Treating SCLUs remains a challenge. Data in the literature are currently insufficient to offer clear treatment guidelines because of several biases in controlled studies. New studies are under way to assess the efficacy of topical treatments and describe the microbiome of SCLUs. Prevention of SCLU recurrence should be assessed in future clinical trials because the high risk of recurrence is an unsolved critical issue.

Efficacy of Lidocaine Patch in Relieving Severe Sickle Cell Leg Ulcer Pain

Efficacy of Lidocaine Patch in Relieving Severe Sickle Cell Leg Ulcer Pain

A treatment algorithm to identify therapeutic approaches for leg ulcers in patients with sickle cell disease.

Sickle cell leg ulcers (SCLUs) are a common complication of sickle cell disease (SCD). Patients who develop ulcers appear to have a more severe haemolysis-associated vasculopathy than individuals who do not develop them, and manifest other complications such as priapism and pulmonary hypertension. SCLUs are slow to heal and often recur, affecting both the emotional and physical well-being of patients. Here we summarise what is known about the pathophysiology of SCLUs, describe available treatment options and propose a treatment algorithm.

Interventions for treating leg ulcers in people with sickle cell disease.

The frequency of skin ulceration makes it an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease. To assess the clinical effectiveness and safety of interventions for treating leg ulcers in people with sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.We searched LILACS (1982 to August 2012), the African Index Medicus (up to August 2012), ISI Web of Knowledge (1985 to August 2012), and the Clinical Trials Search Portal of the World Health Organization (August 2012). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 21 July 2014; date of the last search of the Cochrane Wounds Group Trials Register: 18 September 2014. Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment. Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data. Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl(®) cream, RGD peptide dressing, topical antibiotics). Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, RGD peptide matrix significantly reduced ulcer size compared with a control group, mean reduction 6.60cm(2) (95% CI 5.51 to 7.69; very low quality of evidence). Three trials reported on the incidence of complete closure (isoxsuprine, arginine butyrate, RGD peptide matrix; ranging between low and very low quality of evidence). None reported a significant effect. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; or incidence of amputation. There was no reported information on the safety of these interventions. There is evidence that a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants compared to controls. This evidence of efficacy is limited by the generally high risk of bias associated with these reports.We planned to analyse results according to general groups: pharmaceutical interventions (systemic and topical); and non-pharmaceutical interventions (surgical and non-surgical). However, we were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the unit of randomisation and the unit of analysis. This heterogeneity, along with a paucity of identified trials, prevented us performing any meta-analyses.This Cochrane review provides some evidence for the effectiveness of one topical intervention - RGD peptide matrix. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having a high risk of bias. We recommend that readers interpret the trial results with caution. The safety profile of the all interventions was inconclusive.

Nitric oxide-based treatment for sickle cell leg ulcers?

Nitric oxide-based treatment for sickle cell leg ulcers?

Refractory sickle cell leg ulcer: is heparan sulphate a new hope?

Patients with sickle cell disease are known to have recurrent lower extremity ulcers that have a high pain score and are resistant to conventional means of wound therapy. This study reports the successful use of synthetic heparan sulphate (Cacipliq20(®) , OTR3, Paris, France) in the treatment of a sickle cell ulcer that had failed to respond to several other means of treatment. Therapeutic success was assessed by complete wound coverage and vast improvement in pain score. This is the first study to report use of heparan sulphate in sickle cell ulcers.

Blood Flow Is Increased in Wounds and Peri-Wound Area by Laser Speckle Contrast Imaging and Infrared Thermography in Adults with Sickle Cell Leg Ulcers

Blood Flow Is Increased in Wounds and Peri-Wound Area by Laser Speckle Contrast Imaging and Infrared Thermography in Adults with Sickle Cell Leg Ulcers

Sickle Cell Disease and Leg Ulcers

Sickle Cell Disease and Leg Ulcers

Experience with the use of vacuum-assisted closure therapy in the management of sickle cell leg ulcers

Leg ulcers are the commonest cutaneous manifestation of sickle cell disease, typically running an indolent course. They commonly occur around the distal third of the leg, an area notorious for difficult-to-heal wounds. The vacuum-assisted closure (VAC) device has been found efficacious in the management of chronic ulcers of varying aetiologies. However, reports on its use in the management of sickle cell ulcers are at best scanty. The purpose of this study was to determine the usefulness of VAC therapy in the management of sickle cell ulcers. Over an 18-month period, consecutive patients presenting at the plastic surgery centre of the Imo State University Teaching Hospital were managed using VAC therapy and subsequent skin grafting for extensive ulcers. Data were extracted from the case records after completion of wound care and analysed using descriptive statistics. There were seven males and two females aged 14–34 years with 15 ulcers affecting the distal third of the leg. Ulcer duration before commencement of VAC care ranged from 2.5 to 84 months. All wounds showed remarkable reduction in size, had healthy granulation tissue and were ready for skin grafting within 6–10 days of VAC care. Graft take was 98% to 100%. Use of the VAC device is valuable in the management of sickle cell ulcers. This device rapidly improves the vascularity of the wound bed and permits early successful coverage of sickle cell ulcers.