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Leg ulcers in sickle cell patients at the center for research and control of sickle cell disease: clinical and therapeutic study
Yamoussa Karabinta
1,2, Sekou Kéné4, Diakalia Berthé4, Bakary Ntio Coulibaly1, Téné Karambé3, Chata Traoré1, Moussa Sagara4, Chaka Fomba1, Ousmae Sylla1, Chaka Koné1, Boubacar Karembé1, Aldiouma Guindo5
1Dermatology Teaching Hospital, Bamako, Mali, 2Faculty of Medicine and Dentistry, Bamako, Mali, 3Gabriel Toure Teaching Hospital, Bamako, Mali, 4Center for Research and Control of Sickle Cell Disease (CRLD), Mali, 5Referral Health Center, Commune III, Bamako District, Mali
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ABSTRACT
Background: Sickle cell disease (SCD) is the most common genetic disorder worldwide, particularly in sub-Saharan Africa. Leg ulcers (LUs) are one of its most frequent and disabling complications but remain poorly studied in Mali.
Objective: The objective was to describe the epidemiological, clinical, and therapeutic characteristics of leg ulcers in SCD patients at the Center for Research and Control of Sickle Cell Disease (CRLD) in Bamako, Mali.
Methods: We conducted a descriptive, cross-sectional study based on retrospective data collected from January 2021 to December 2023. We included medical records of SCD patients diagnosed with leg ulcers and treated at the CRLD. Data on sociodemographic features, clinical presentation, treatment, and outcomes was collected and analyzed.
Results: Out of 13,584 patients seen, 63 cases of leg ulcers were identified (0.46%), including 13 children (20.63%). The mean age was 28.25 ± 23.13 years, with a male predominance (76.56%, sex ratio 3.2). Most patients had the SS genotype (52.38%). The ulcers were painful in 70% of the cases and located predominantly at the medial malleolus. Single ulcers were most common (65.07%) with an average diameter over 7 cm. The mean hemoglobin level was 8.2 g/dL. All patients received local care (saline cleansing, debridement, topical antibiotics, skin grafts when necessary) and systemic treatment (antibiotics, analgesics, folic acid, vasopressors, transfusions). Tetanus vaccination was systematic. The average treatment duration was 4 ± 2.34 months, with a favorable outcome in 72.18% of cases.
Conclusion: Leg ulcers in SCD patients are a frequent, chronic complication requiring early and multidisciplinary care. Awareness, early detection, and adapted therapeutic strategies remain essential to improve patient outcomes in Mali.
Key words: Sickle Cell Disease, Leg Ulcers, Epidemiology, Clinical Features, Treatment, Mali
INTRODUCTION
The term sickle cell disease derives from the Greek word drepanon, meaning “sickle,” in reference to the distinctive shape of the red blood cells (RBCs) in affected patients. It is a genetic hemoglobin disorder that had long been considered rare and restricted to certain populations [1]. Today, it is recognized as the most common genetic disease worldwide, affecting more than 120 million people [2]. The RBCs of these patients are more fragile, less deformable, and prone to increased hemolysis [3].
In Africa, sickle cell disease is particularly prevalent in sub-Saharan regions, where the sickle cell trait affects over 30% of the population in some areas [4]. It represents a major public health concern in developing countries. In Mali, around 12% of the population carries the sickle cell trait, and between 5,000 and 6,000 children are born each year with a major sickle cell phenotype [5]. Patients with the homozygous form (SS) suffer from chronic hemolytic anemia due to the fragility of their RBCs, painful vaso-occlusive crises, and multiple vascular complications—among which leg ulcers (LUs) are particularly significant [3]. In fact, leg ulcers are the most common cutaneous manifestation of sickle cell disease, with prevalence ranging from 25% to 73% depending on the study [6–8].
A leg ulcer is defined as a chronic dermo-epidermal substance loss, most often localized at the medial or lateral malleoli. Its slow healing process negatively impacts quality of life, compromises the function of the affected limb, and causes significant aesthetic and psychological consequences [9]. It appears to be more frequent in patients over the age of 20 with the homozygous SS form [7]. The occurrence of leg ulcers in sickle cell patients remains poorly understood and appears unpredictable. To date, microvascular function has not been directly studied in relation to the presence or absence of ulcers. The few existing histological studies report endothelial activation, microthrombosis, inflammatory infiltration, and loss of the veno-arteriolar reflex [3], suggesting complex mechanisms involving vascular abnormalities, chronic inflammation, and hematologic alterations.
In Mali, there is a scarcity of research specifically dedicated to leg ulcers in sickle cell patients. It is in this context that we undertook the present study, which aimed to analyze the epidemiological, clinical, and therapeutic aspects of this frequent and disabling complication among patients followed at the Center for Research and Control of Sickle Cell Disease in Bamako.
MATERIALS AND METHODS
Study Design and Setting
This was a descriptive, cross-sectional study based on retrospective data collection. It was conducted at the Centre de Recherche et de Lutte contre la Drépanocytose (CRLD) in Bamako, Mali—a national reference center dedicated to the care of sickle cell disease patients. The study covered a three-year period from January 1, 2021, to December 31, 2023.
Study Population
We included all medical records of patients with sickle cell disease who were diagnosed with leg ulcers and received care at CRLD during the study period. Leg ulcers were defined as chronic dermo-epidermal skin loss located on the lower limb, particularly around the malleoli, and associated with delayed healing, functional discomfort, or aesthetic/psychological impact.
Inclusion and Exclusion Criteria
Included were complete records of patients meeting the diagnostic criteria for leg ulcers and followed at CRLD during the defined period. Patients with incomplete records, no history of leg ulcers, or those lost to follow-up were excluded.
Sampling and Data Collection
Exhaustive sampling was used. Data was extracted from archived medical records using a structured data collection form specifically developed for the study.
Variables
The collected data included:
Sociodemographic variables: age, sex, education, ethnicity, place of residence.
Clinical variables: reason for consultation, ulcer type and location, duration of evolution, treatments received, and outcome under treatment.
Data Processing and Analysis
Data entry and analysis were performed using SPSS, version 22. Quantitative variables were expressed as means ± standard deviations, and qualitative variables as frequencies and percentages.
Ethical Considerations
This study was retrospective and relied exclusively on anonymized medical records. No direct patient contact was involved, and no identifying data was used. Each patient was assigned a unique numerical code for confidentiality. The study was conducted in accordance with ethical standards, and its results will be shared with health authorities and may be published for scientific purposes.
RESULTS
Frequency
During the study period, we recorded 63 cases of leg ulcers out of a total of 13,584 patients seen, representing a frequency of 0.46%. Among these, 13 cases occurred in children, accounting for 20.63%.
Sociodemographic Data
The sex ratio was 3.2 (Fig. 1).
The mean age was 28.25 ± 23.13 years.
Among the sickle cell patients with leg ulcers, 55.33% were enrolled in school.
The Sarakolé, Peulh, and Sonrhaï ethnic groups accounted for 47.62%, 14.29%, and 11.11% of the cases, respectively.
Patients from Bamako and Kayes represented 50.67% and 15.29%, respectively.
Additionally, 76.19% of the patients were single.
More than 60% of the patients had a family history of the sickle cell trait.
A sickle cell ulcer occurred in 52.38% of the patients with the SS genotype (Table 1). Sickle cell ulcers were located in the malleolar region (medial or lateral) in the majority of the cases (Table 2)
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Table 1: Distribution of the patients according to the type of hemoglobin. |
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Table 2: Distribution of the patients according to ulcer location. |
Fig. 2 shows a histogram illustrating the painful character of the ulcers, with 70% reporting pain and 30% reporting no pain.
The majority of the patients had an ulcer with a diameter greater than 7 cm (Table 3).
More than half of the patients had a single ulcer (Table 4).
The ulcer border was regular in 60% of the cases. 55.35% of the patients had an ulcer duration between 1 and 2 years. The average hemoglobin level was 8.2 g/dL. 21% of the patients presented with osteitis.
All patients received both local and systemic treatment along with tetanus vaccination (Table 5). The average duration of treatment was 4 ± 2.34 months.
DISCUSSION
Methodology
This was a descriptive, cross-sectional study with retrospective data collection. It focused on the records of sickle cell patients with leg ulcers who were followed at the Sickle Cell Research and Control Center, in whom the diagnosis was established and who received care in the treatment unit of the center. The study period covered January 1, 2020, to December 31, 2024, spanning five years.
However, we faced several limitations and challenges: incomplete data (medical history, number of lesions, lesion dimensions, duration of lesion progression), poor treatment adherence due to financial constraints, and the fact that the study was conducted exclusively at the Sickle Cell Research and Control Center.
Nevertheless, this study allowed us to describe the epidemiological and clinical aspects, as well as the management of leg ulcers in sickle cell patients followed at the center, and to formulate recommendations.
Frequency
At the end of our study, we recorded 63 cases of sickle cell leg ulcers out of a total of 1,568 sickle cell patients consulted, representing a frequency of 4.01%. Among them, 13 cases involved children, accounting for 20.63% of all sickle cell ulcers. This result is slightly higher than that reported by Delaney et al. and close to that by N’Diaye, who reported frequencies of 1% and 3.4%, respectively [8,10]. Similarly, Baali et al. in Morocco reported a frequency of 3.3% of leg ulcers in sickle cell patients, underlining that this complication should not be underestimated [11].
The prevalence of leg ulcers within the sickle cell population remains poorly understood. Indeed, data from the available literature does not clearly establish its frequency or distribution. The highest frequency of sickle cell ulcers appears to be observed in Jamaica [12].
Socio-demographic Characteristics
Age
The mean age in our study was 28.25 ± 23.13 years, with a predominance in the 26–30 age group. This finding is consistent with that by Ngolet et al. in Congo and Mohan et al., who reported mean ages of 26.04 and 30.43 years, respectively. This supports the literature, which indicates that sickle cell ulcers are more frequent among young adults [9,13].
Sex
A male predominance was observed in our study, accounting for 76.56%, with a sex ratio of 3.2. This result aligns with the literature, which states that sickle cell ulcers are more frequent in men than in women [8,9]. This may be explained by the fact that men are more exposed to trauma.
Education
More than half of the patients were enrolled in school. This high frequency among students can be explained by the fact that the Sickle Cell Research and Control Center, where the study was conducted, is located in Bamako, the capital city.
Family history of sickle cell trait
A family history of the sickle cell trait was found in 80.79% of our patients. This result is comparable to that by Cumming in Jamaica and Ngolet in Congo, who reported a sickle cell trait in over 70% of cases [9,11].
Ethnicity
The Sarakolé, Peulh, and Sonrhaï ethnic groups were predominant in our study, representing 47.62%, 14.29%, and 11.11%, respectively. This predominance could be explained by the high frequency of consanguineous marriages within these ethnic groups.
Clinical Characteristics
Functional symptoms
In our study, pain was present in 67.87% of sickle cell ulcers (Fig. 2). This finding is consistent with previous studies, which also reported the painful nature of sickle cell ulcers [9,11,14].
Circumstances of occurrence
In our study, post-traumatic ulcers were the most common, representing 51.58%. This result is similar to that by N’Diaye in Senegal, who reported a frequency of 50% [8], but differs from that by Ngolet in Congo, who reported it to be 22% [9]. This predominance can be explained by the young age of the population, which is more prone to trauma.
Topography (Table 2)
The medial malleolar location was observed in 42.86% of the cases (Fig. 3a). This internal malleolar location has been reported in several previous studies [8,9,11,14].
Size of lesions (Table 3)
The average diameter of these ulcers was 8.2 cm, which is smaller than that reported by Delaney et al., who found an average diameter of 11.54 cm [10]. In Senegal, Diadie et al. reported a mean diameter of 9.6 cm, which is also higher than in our findings [15]. These results suggest that, in our series, sickle cell ulcers tend to be relatively less extensive than those described in Western populations.
Number of ulcers
In our study, single ulcers predominated at 65.07%. This predominance of single ulcers has been confirmed by several studies, notably those by N’Diaye, Ngolet, and Cumming [8,9,11].
Duration of ulcer progression
55.35% of the patients had an ulcer that had been evolving for 1 to 2 years (Fig. 3b). This finding confirms the chronic nature of sickle cell ulcers, as reported in several studies [8,11,14].
Relationship between ulcer and hemoglobin level
The average hemoglobin level among our patients was 8.2 g/dL. This result is similar to those reported by N’Diaye et al., Ngolet et al., and Mohan et al., who found average hemoglobin levels of 7.2 g/dL, 7.53 g/dL, and 6.56 g/dL, respectively [8 9,13]. This reduction in hemoglobin level can be explained by the chronic nature of the ulcer, which leads to continuous blood loss.
Relationship between ulcer and hemoglobin phenotype
Sickle cell ulcers occurred more frequently in patients with homozygous SS sickle cell disease (80% of cases). This predominance has been reported in most studies, particularly in Senegal [8], North America [13], and Niger [16]. It may be explained by chronic hemolysis, more severe anemia, vaso-occlusive phenomena, and the resulting tissue hypoxia and ischemia due to vascular obstruction.
Treatment and outcome
The majority of our patients, following strict bed rest, received local treatment consisting of care with saline solution, debridement, application of topical antibiotics, and in some cases, skin grafting (Table 5).
Systemic treatment was also initiated, including antibiotics, analgesics, and folic acid. Additionally, 22 patients required the administration of vasopressors, and 28 received blood transfusions.
The evolution of the ulcers was favorable in 72.18% of patients who could be followed up. This improvement was achieved through appropriate local care, proper hospitalization, and guided wound healing.
CONCLUSION
Leg ulcers remain a frequent and debilitating complication in sickle cell patients. This study highlighted their prevalence, clinical characteristics, and the challenges associated with their management. Local factors such as infections, trauma, and poor living conditions play a significant role in their occurrence. Early and multidisciplinary management, along with better patient support, are essential to limit complications and improve quality of life. Strengthening awareness, early screening, and research on therapeutic strategies adapted to our context is crucial.
Statement of Human and Animal Rights
All the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the 2008 revision of the Declaration of Helsinki of 1975.
Statement of Informed Consent
Informed consent for participation in this study was obtained from all patients.
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Notes
Conflict of Interest: The authors have no conflict of interest to declare. Yes (The authors have no conflict of interest to declare.)
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