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The pathophysiology of SCD leg ulcers is not well defined. Known risk factors include male gender, poor social conditions, malnutrition and a lack of compression therapy when oedema occurs. Leg ulcers typically start with spontaneous pain, followed by induration, hyperpigmentation, blister formation and destruction of the epidermis. SCD is characterized by chronic haemolysis, increased oxidative stress and decreased nitric oxide bioavailability, which promote ischaemia and inflammation and consequently impair vascular function in the skin. This cutaneous vasculopathy, coupled with venostasis around the ankle, creates an ideal environment for local vaso\u2010occlusive crises, which can result in the development of leg ulcers that resemble arterial ulcers. Following the development of the ulcer, healing is hindered as a result of factors commonly observed in venous ulceration, including venous insufficiency, oedema and impaired angiogenesis. All of these factors are modulated by genetic factors. However, our current understanding of these genetic factors remains limited and does not yet enable us to accurately predict ulceration susceptibility.<\/jats:p>","DOI":"10.1111\/bjh.19584","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T02:41:45Z","timestamp":1718246505000},"page":"61-70","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Controversies in the pathophysiology of leg ulcers in sickle cell disease"],"prefix":"10.1111","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8028-6827","authenticated-orcid":false,"given":"Judith","family":"Catella","sequence":"first","affiliation":[{"name":"Service de M\u00e9decine Interne et Vasculaire, H\u00f4pital Edouard Herriot Hospices Civils de Lyon  Lyon France"},{"name":"Laboratoire d'Excellence du Globule Rouge (Labex GR\u2010Ex) Sorbonne  Paris France"},{"name":"Laboratoire Interuniversitaire de Biologie de la 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