Leg Ulceration in Sickle Cell Disease: An Early and Visible Sign of End‐Organ Disease

Abstract

Leg ulcers are a frequent and debilitating complication of sickle cell disease (SCD), particularly of the SS genotype. The prevalence of leg ulcers in patients with sickle cell disease (SCD) varies geographically ranging widely from 75% in Jamaica to as low as 1% in Saudi Arabia. The prevalence of leg ulcers in the Cooperative Study of Sickle Cell Disease (CSSCD) in the United States was 5% in SS genotype with the incidence increasing with age. As patients with SCD have increasingly improved survival, the prevalence of leg ulcers is likely to be higher. These ulcers are slow to heal, have a high rate of recurrence, and are associated with severe unremitting pain and depression, thus leading to high healthcare costs. Despite being a well‐recognized complication of SCD, there are no specifically designed evidence‐based guidelines to help clinicians manage these patients.Abstract Introduction: Leg ulcers are a frequent and debilitating complication of sickle cell disease (SCD), particularly of the SS genotype. The prevalence of leg ulcers in patients with sickle cell disease (SCD) varies geographically ranging widely from 75% in Jamaica to as low as 1% in Saudi Arabia. The prevalence of leg ulcers in the Cooperative Study of Sickle Cell Disease (CSSCD) in the United States was 5% in SS genotype with the incidence increasing with age. As patients with SCD have increasingly improved survival, the prevalence of leg ulcers is likely to be higher. These ulcers are slow to heal, have a high rate of recurrence, and are associated with severe unremitting pain and depression, thus leading to high healthcare costs. Despite being a well‐recognized complication of SCD, there are no specifically designed evidence‐based guidelines to help clinicians manage these patients. Methods: To prepare this manuscript, we searched PubMed using the search terms “sickle cell,” “ulcer,” “sickle cell,” and “wound.” We also appraised the references mentioned in the identified articles. Inclusion criteria included case reports, case series, retrospective reviews, clinical trials, randomized controlled trials, systematic reviews, and meta‐analyses from 1945 to 2016. We present our extensive personal observations and expert opinion, whenever there is a lack of reliable data. Conclusion: Our understanding of the pathophysiology of leg ulceration in sickle cell disease is improved, though still limited since the first described case in the English literature over 100 years ago. Moreover, there remains a paucity of good quality randomized clinical trials to test new and effective therapies. No evidence‐based guidelines for the management of these patients are available. Currently, a holistic multidisciplinary approach is recommended with adequate systemic control of SCD as well as aggressive local therapy, with a focus on targeting pathways involved in potentiating healing of these ulcers including novel approaches like topical nitric oxide donors. SCD patients with leg ulcers represent a cohort of patients who are at an increased risk of developing other vasculopathic complications that have a potentially common mechanism including pulmonary hypertension, renal and retinal disease, and priapism. Prospective trials are needed to better evaluate the natural history of these patients in the modern era and develop preventative and therapeutic strategies for the management of this serious complication.