Interventions for treating leg ulcers in people with sickle cell disease

Facultad de Ciencias de la Salud Eugenio Espejo, Universidad Tecnológica Equinoccial, Quito, Ecuador.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 11/2012; 11(11):CD008394. DOI: 10.1002/14651858.CD008394.pub2
Source: PubMed


BACKGROUND: The frequency of skin ulceration makes it an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease. OBJECTIVES: To assess the clinical effectiveness and safety of interventions for treating leg ulcers in people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.We searched LILACS (1982 to August 2012), the African Index Medicus (up to August 2012), ISI Web of Knowledge (1985 to August 2012), and the Clinical Trials Search Portal of the World Health Organization (August 2012). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area.Date of the last search of the Group's Haemoglobinopathies Trials Register: 25 May 2012. SELECTION CRITERIA: Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data. MAIN RESULTS: Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl(®) cream, RGD peptide dressing, topical antibiotics). Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, RGD peptide matrix significantly reduced ulcer size compared with a control group, mean reduction 6.60cm(2) (95% CI 5.51 to 7.69). Three trials reported on the incidence of complete closure (isoxsuprine, arginine butyrate, RGD peptide matrix). None reported a significant effect. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; or incidence of amputation. There was no reported information on the safety of these interventions. AUTHORS' CONCLUSIONS: There is evidence that a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants compared to controls. This evidence of efficacy is limited by the generally high risk of bias associated with these reports.We planned to analyse results according to general groups: pharmaceutical interventions (systemic and topical); and non-pharmaceutical interventions (surgical and non-surgical). However, we were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the unit of randomisation and the unit of analysis. This heterogeneity, along with a paucity of identified trials, prevented us performing any meta-analyses.This Cochrane review provides some evidence for the effectiveness of one topical intervention - RGD peptide matrix. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having a high risk of bias. We recommend that readers interpret the trial results with caution. The safety profile of the all interventions was inconclusive.

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    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.
    Hemoglobin 04/2013; 37(4). DOI:10.3109/03630269.2013.789968 · 0.79 Impact Factor
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    ABSTRACT: Abstract A 35-year-old African Brazilian patient had sickle cell anemia complicated with recurrent vasoocclusive (VOC) crises and refractory painful leg ulcers for 16 years. The ulcers started over both medial malleoli and expanded gradually. The ulcer on the left leg spread from the foot to the knee circumferentially and was refractory to all forms of therapy within the frame work of multi-disciplinary care. The patient agreed to a below the knee amputation of the left leg. He felt much better after the amputation but developed severe neuropathic phantom pain that was well controlled medically. He could differentiate the sickle cell anemia and ulcer pain from the neuropathic pain. About 6 months after the amputation he had dengue fever with fatal outcome. This is the first report of treatment of refractory sickle cell anemia leg ulcer with amputation and probably the first report of a Brazilian patient with sickle cell anemia and dengue fever.
    Hemoglobin 01/2014; 38(2). DOI:10.3109/03630269.2013.875476 · 0.79 Impact Factor
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    ABSTRACT: Background There is a need for well-tolerated, effective therapies for chronic leg ulcers in sickle cell anemia (SCA). Methods We recruited 18 adults with SCA with leg ulcers persisting at least 4 weeks to a safety and tolerability trial of topical sodium nitrite, an innovative nitric oxide donor with biological activities that make it an attractive therapeutic candidate for wound healing. Escalating concentrations of sodium nitrite cream (0•5% - 2%) were applied twice weekly for 4 weeks to one ulcer per patient at 5 dose levels. The primary endpoints were safety and tolerability with secondary endpoints of blood flow, wound healing, and pain relief. Endpoints were analyzed over time for the whole study population and according to dose level. Findings Tolerability was excellent, with no grade 3-4 adverse events, no serious adverse events, and no dose-limiting side effects. Systemic absorption was minimal. Application of topical sodium nitrite was associated with significant increase in peri-wound cutaneous blood flow measured by laser speckle contrast imaging (p=0•03), corroborated by increases in infrared thermography (p<0•01). We observed a dose-dependent decrease in leg ulcer size (p<0•0001) and pain (p<0•0001). Ulcers healed completely in three patients at the highest concentrations. Brief Pain Inventory scores improved in pain severity (p<0•01) and pain interference (p<0•001). Interpretation Our results indicate that topical sodium nitrite 2% cream is suitable for additional clinical trials in adults with SCA to promote healing of leg ulcers. Funding This study was supported by the National Heart, Lung and Blood Institute Division of Intramural Research.
    12/2014; 1(2). DOI:10.1016/S2352-3026(14)00019-2
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