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Objective: To determine the healing effect of topical becaplermin gel vs hydrogel dressing on hypertensive leg ulcers., Design: Randomized, double-blind, parallel-assignment, controlled study., Setting: Ambulatory or hospitalized patients from 17 dermatology departments., Patients: Among 64 consecutive randomized patients with 1 or more hypertensive leg ulcers who fulfilled all inclusion criteria, 59 received the allocated intervention, and findings were analyzed., Intervention: Becaplermin gel (human recombinant platelet-derived growth factor-BB, 0.1%, in hydrogel) or hydrogel dressing was applied, both in doses of 1 cm/cm(2), once daily for 8 weeks. Follow-up continued for 4 weeks beyond the final gel application., Main Outcome Measures: The primary end point was complete wound closure rate after 8 weeks of treatment. Secondary end points were percentages of patients with complete wound closure at week 12; changed ulcer area after treatment vs baseline; and changed ulcer-related pain and health-related quality of life during the study., Results: Complete wound closure rates were comparable after 8 weeks for becaplermin (5 of 28 patients) and hydrogel (3 of 31 patients) (8 percentage-point difference; 95% confidence interval, -10% to 26%). No statistically significant differences were observed between the 2 groups for percentages of complete closure at week 12, changed ulcer area at week 8, or changed ulcer-related pain and quality of life during the study (P > .05 for all comparisons)., Conclusions: Topical becaplermin gel is not superior to hydrogel dressing for hypertensive leg ulcer wound closure. Surgical management by grafting remains the most promising treatment strategy but requires further evaluation. Trial Registration clinicaltrials.gov Identifier: NCT00970697.

Background: The treatment of skin ulcers frequently presents a management challenge. Nonhealing wounds with poor response to conventional wound management therapy represent a significant cause of disability, affecting approximately 1% of the global population. Activated protein C is a serine protease with anticoagulant, angiogenic, and anti-inflammatory properties that has shown efficacy in patients for the treatment of severe sepsis. We report 4 cases of nonhealing lower limb skin ulcers that were treated with activated protein C., Observations: The study included 4 patients whose wounds were not improving despite standard wound treatment for 4 months or more. Activated protein C was applied topically to their wounds once weekly for 4 weeks. All 4 patients showed a rapid positive response to treatment that was maintained during a 4-month follow-up period. The treatment was well tolerated, with no remarkable adverse effects or complications., Conclusions: Activated protein C can stimulate wound healing in patients with skin ulcers that are refractory to conventional wound-healing therapies. The likely mechanism of action is its recognized ability to stimulate angiogenesis and reepithelialization and to inhibit inflammation. Activated protein C has potential as a therapeutic option for patients with chronic skin ulcers.

Background: Livedoid vasculopathy (LV) is an occlusive thrombotic disease that affects primarily the small blood vessels of the lower extremities and often is associated with recurrent painful ulcerations. The pathogenesis of LV is unclear, but the disease is largely attributed to a hypercoagulable state. Factor V Leiden mutation, heterozygous protein C deficiency, homozygous hyperhomocysteinemia, and other inherited thrombophilias have been associated with LV. Plasminogen activator inhibitor-1 (PAI-1) is an important inhibitor of the fibrinolytic system. Elevated levels of PAI-1 are found in some patients with thrombotic diseases. Some of these patients are homozygous for an allele of PAI-1 containing a stretch of 4 guanines at base -675 in the promoter region. This variant is associated with elevated PAI-1 protein levels, impaired fibrinolysis, and increased risk of thrombosis., Observations: A 33-year-old white woman had a 3-month history of painful enlarging ulcers on both ankles. Various therapies, including administration of oral antibiotic agents and prednisone up to 100 mg/d, to treat presumed vasculitis, were unsuccessful. Skin biopsy specimens revealed numerous thick-walled small blood vessels, many of which were filled with fibrin thrombi, in association with minimal perivascular inflammatory infiltrate, extensive epidermal necrosis, and focal ulceration. A diagnosis of thrombotic vasculopathy was made. Clinical workup revealed an elevated plasma level of PAI-1 (31 microM/mL; reference range, <25 microM/mL) and PAI-1 promoter 4G/4G homozygosity detected at DNA sequencing. Treatment with heparin sodium and tissue plasminogen activator dramatically improved the lesions, resulting in complete healing of the ulcerations. Continuation of anticoagulant therapy with warfarin sodium and episodic administration of tissue plasminogen activator was required for symptomatic control., Conclusions: Patients with LV may have elevated plasma PAI-1 levels. This may be associated with the PAI-1 promoter 4G/4G genotype, which has not previously been linked with LV. Further studies in patients with LV are warranted to determine how frequently this genotype is present because it may identify responsiveness to fibrinolytic therapy.

Background: Venous leg ulceration is a frequent and severe complication of lower limb venous insufficiency. Compression therapy is associated with a protracted course of healing and multiple recurrences. Minimally invasive surgery (subfascial endoscopic perforating surgery) is only possible in a subset of patients with leg ulcers. Low-cost and noninvasive therapeutic procedures are needed as alternative treatments., Objective: To evaluate the efficacy and safety of sclerosant in microfoam in treating venous leg ulceration., Design: A retrospective study of medical records, pretreatment and posttreatment color photographs, and echo Doppler in patients with venous leg ulceration. All patients were evaluated at 6 months after therapy, 70% were also evaluated at 2 years, 25% at 3 years, and 14% at 4 or more years after treatment. They were assessed for complete (100%) ulcer healing, time to wound closure, and recurrence., Setting: Private vascular surgery clinic in Granada and dermatology department at a hospital in Pamplona, Spain., Patients: Over 115 months, 116 consecutive patients (mean age [range], 57 [25-85] years) treated with ultrasound-guided injection of polidocanol microfoam (UIPM)., Interventions: To reduce venous hypertension, UIPM was used to selectively and progressively sclerose sources of incompetence. The number of sessions per patient varied between 1 and 17 (mean, 3.6)., Main Outcome Measures: Complete ulcer healing, defined as full reepithelialization of the wound with absence of drainage. Recurrence was defined as epithelial breakdown in the healed limb., Results: At 6-months' follow-up, treatment with UIPM achieved complete healing in 83% of patients (96/116), with median time to healing of 2.7 months; 7 patients were never cured, and 1 patient was lost to follow-up. There were recurrences in 10 patients., Conclusions: The use of UIPM to selectively and progressively sclerose incompetent veins produced by venous hypertension is highly effective to achieve a stable ulcer healing with minimal invasion, even in elderly patients. Recurrences are easily treatable with this approach. This technique may become a first-line treatment in the management of leg venous ulcers.

Objective: To determine whether oral zinc sulfate is an effective treatment for promoting healing of venous or arterial leg ulcers., Data Sources: The search strategy of the Cochrane Wounds Group was used. This includes searches of electronic databases, conference proceedings, relevant bibliographies, and hand searching of journals., Study Selection: Studies were included if they were randomized controlled trials of oral zinc sulfate in the treatment of chronic venous or arterial ulcers with objective measures of healing. Six of the 10 studies initially identified were included in the review., Data Extraction: The trial method, participants, interventions, outcomes, baseline comparability, adequate reporting of withdrawals, and blinding of assessment were extracted by 2 reviewers independently., Data Synthesis: No trial showed a statistically significant benefit of zinc sulfate for healing leg ulcers. There is limited evidence to suggest that zinc might increase healing in individuals with a low serum zinc level, but more evidence is needed., Conclusions: There is no evidence of benefit from the general use of zinc sulfate in patients with chronic leg ulcers. There is a need for further research to see if oral zinc sulfate is beneficial in the treatment of patients with leg ulcers who have a low serum zinc level. If it is demonstrated to be beneficial, further trials are required to establish dose and duration of treatment.

A 19-year-old woman presented with a 14-month history of multiple, factitially induced, full-thickness leg ulcers. Nocturnal polysomnography with video monitoring revealed a short sleep latency and frequent sleep stage changes. Rapid eye movement sleep was absent. All stages of non-rapid eye movement sleep were associated with leg rubbing. After treatment that included avoidance of daytime naps and administration of chlorpromazine at bedtime, affect, daytime behavior, nocturnal sleep, and the ulcers improved markedly. To our knowledge, there are no reports of factitial dermatosis associated with disordered sleep. Our findings suggest that abnormal sleep may play a role in initiating or perpetuating factitial dermatoses. This case illustrates that polysomnography and video monitoring may be indicated in the evaluation of patients with factitial dermatoses.

The quantitative bacteriology of 13 chronic leg ulcers was sequentially assessed by both swab and biopsy culture techniques, and the effect of either a 10% benzoyl peroxide lotion or placebo lotion was evaluated. There was good correlation between the swab and biopsy culture techniques in 12 of the 17 instances where simultaneous swabs and biopsies were done. Though the benzoyl peroxide did not favorably affect the bacterial flora, ulcer healing did appear to correlate with quantitative bacterial counts. THREE of five ulcers containing fewer than 10(5) organisms per gram of tissue or per centimeter of ulcer surface area healed, while none of eight ulcers containing more than 10(5) organisms healed. Quantitative bacteriological measurements can serve as useful tools in evaluating healing of leg ulcers.

Necrosis in chronic leg ulcers developed in all of the four patients who were treated topically with a fluocinolone acetonide-neomycin sulfate ointment. This was probably due to the vasoconstrictive properties of the steroid. A warning against the topical use of potent steroids in skin diseases with impaired circulation seems to be justified.