Leg Ulcers in Sickle Cell Disease: Current Patterns and Practices

Abstract

Leg ulcers are a debilitating complication of patients with sickle cell disease, and their frequency in North America was reported to be 2.5% by the Cooperative Study of Sickle Cell Disease more than 20 years ago. We sought to determine if the frequency of leg ulcers in sickle cell patients in the United States had declined and to assess which treatments providers use most commonly. We sent an e-mail survey to health professionals belonging to the national Sickle Cell Adult Provider Network. Responses were obtained from 31 of them (26.0%). Most of them (96.0%) reported having some patients with leg ulcers. Providers reported a total of 185 patients with active leg ulcers and 224 in the previous 5 years, for a total of 409 patients. Hb SS (homozygous sickle cell anemia) was the most common genotype of affected individuals, followed by Hb SC (double heterozygote for Hb S [β6(A3)Glu→Val, GAG>GTG; HBB: c.20A>T] and Hb C [β6(A3)Glu→Lys, GAG>AAG; HBB: c.19G>A]). Males showed a 2:1 predominance. Two-thirds of patients were treated with either hydroxyurea (HU) or transfusion therapy and most used compression stockings and topical therapies as directed by wound care services. We conclude that leg ulcers continue to be a debilitating complication of young adults with sickle cell disease, despite improved supportive care and the widespread use of disease modifying agents such HU and transfusion. While some providers offer office-based ulcer care, the majority prefer specialty consultation including podiatry, plastic surgery and dermatology. Despite their frequency, there is no clear consensus among providers as to the best treatment.

Critical Reviews: How we treat sickle cell patients with leg ulcers

“…These patients are often tall but asthenic, have poor appetite, are very anemic with evidence of high hemolytic rate, have nephropathy, are rarely hospitalized for vaso-occlusive crisis, have trouble with employment, have limited social interaction, are depressed; eventually they and their caregivers may feel that an amputation is better than "living with the current reminder" of their illness. As in our patient, a recent survey of practitioners in the US confirmed that none of them had recommended amputation to their patients [10].…”

“…At this time, the approach to the patient with sickle cell, or other hematologic disorder, and leg ulcer is fragmented and inadequate, involves specialized wound care specialists only in about half of the cases in North America [10], often working in isolation from the primary care team and the hematologist. Access to care and quality of care varies widely within the US and abroad.…”

“…Moreover, interpretation of available studies is complicated by lack of clear separation between prior history of leg ulcers and active ulcer. A recent survey of North American hematologists specializing in SCD, estimated that 1% SCD patients have active ulcers [10], while in the Bethesda Cohort of more than 500 SCD patients, 22% of HbSS and 9% of HbSC patients reported "history of ulcer" [5]. Regardless, leg ulcers occur ten times more frequently in SCD than the general population and begin at a younger age [11].…”

Key endothelial cell angiogenic mechanisms are stimulated by the circulating milieu in sickle cell disease and attenuated by hydroxyurea

“…While hydroxyurea therapy could be beneficial for clinical manifestations in which unregulated neovascularization participates, mechanisms for which angiogenesis may be important, such as wound healing and vascularization of infarcted tissues, may be hindered by this molecule. Although simultaneous improvements in vaso-occlusive mechanisms may outweigh the effects of hydroxyurea on angiogenic processes, there is some evidence to suggest that hydroxyurea therapy may complicate leg ulcer healing in SCD and myeloproliferative diseases 45,46 and further studies to explore the anti-angiogenic effects of hydroxyurea may be warranted.…”

Orphan drugs for sickle vaso-occlusion: dawn of a new era of targeted treatment

“…70 The role of venous stasis or other vascular factors remains controversial. 71 Avascular necrosis in the vertebral column, shoulder, or hips, from vascular compromise of the cortical bone and/or bone marrow circulations can be a source of acute pain as well as chronic pain in adolescent and young adult patients.…”