Leg Ulcers

Background
Leg ulcers are a common complication of SCD in general and SCA in particular. Leg ulceration was reported in all of the first four people with SCD described in the English literature. Data from the Cooperative Study of Sickle Cell Disease (CSSCD) in the United States found active leg ulcers at entry in 2.5 percent of 2,075 people aged 10 years or older and in none of 1,700 people less than 10 years old. Among those with active leg ulcers, about 22 percent were between the ages of 10 and 20.

Data on leg ulcers from the CSSCD3 identified five factors which could affect the person’s risk. Leg ulcers were more common in males and older people and less common in people with a,-gene deletion, high total Hb level, and high levels ofHbF. Trauma, infection, and severe anemia may predispose people to ulcer formation. Studies showing a positive association between leg ulcers and the severity of hemolysis and priapism are disputed. The ulcers occur most frequently on the medial or lateral surfaces of the ankles. Leg ulcers can range from mild and small to large and severe. Severity can be based on depth and duration. Osteomyelitis may complicate chronic leg ulcers, especially deeper ones. A bone scan or MRI and bone biopsy are used to assess this complication. Multidisciplinary teams including wound care specialists have been developed to provide support and consultation in the management of recurrent and recalcitrant leg ulcers.

Summary of the Evidence
Five RCTs, three observational studies, and a case series described various approaches to manage leg ulcers in people with SCD and evaluated topical and systemic agents. The methodological quality of the studies was fair, but the studies had small sample size, which led to imprecise estimates of treatment effect and weak inference. The overall quality of the supporting evidence was low to moderate.

The five RCTs included a total of 155 people and had follow up periods of 8 weeks to 6 months. Four studies compared different topical modalities, including arginylglycylaspartic acid (RGD) peptide; arginine butyrate; Duo Derm; solcoseryl; and an aerosolized preparation of neomycin, bacitracin, and polymyxin B to either standard care or placebo. One study331 compared oral propionyl-L-carnitine to placebo. Propionyl-L-carnitine was not shown to have any significant differences in healing effect. Of the topical preparations, RGD peptide and the arginine butyrate/standard care combination showed a significant improvement in healing rates. The aerosol solution trial showed significant reduction in ulcer size for ulcers with a positive bacterial swab test.

The studies also found severe intolerance to DuoDerm and good tolerance to solcoseryl without any significant differences in healing rates.

The three observational studies enrolled more than 70 people and reported no difference in healing between natural honey and eusol dressing (sodium hypochlorite disinfectant); higher healing rate with oral zinc sulfate compared to placebo; and favorable results with hydrocolloid dressing (DuoDerm). The case series335 reported improved healing after 6 weeks of treatment with subcutaneous heparin and human antithrombin concentrate. The quality of evidence of these observational data is low, thus limiting the ability to make inferences applicable to the general population.

Recommendations

Inspect the lower extremities during physical examination for active or healed ulcers, record their number, and measure their depth.
(Weak Recommendation, Low-Quality Evidence)
Treat leg ulcers inpatients with SCD with initial standard therapy (i.e.,debridement, wet to dry dressings, and topical agents).
(Moderate Recommendation, Low-Quality Evidence)
Evaluate People with chronic recalcitrant deep leg ulcers for osteomyelitis.
(Moderate Recommendation, Low-Quality Evidence)
Evaluate Possible etiologies of leg ulcers to include venous insufficiency and perform wound culture if infection is suspected or if the ulcers deteriorate.
(Moderate Recommendation, Low-Quality Evidence)
Treat with systemic or local antibiotics if leg ulcer sites suspicious for infection and wound culture is positive and organism susceptible.
(Moderate Recommendation, Low-Quality Evidence)
Consult or refer to a wound care specialist or multidisciplinary wound team for persistent or recalcitrant leg ulcers. (Consensus-Panel Expertise)

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