Local treatment of chronic cutaneous leg ulcers with recombinant human granulocyte-macrophage colony-stimulating factor

AIM: To test the efficacy and safety of recombinant granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) in the treatment of chronic cutaneous leg ulcers. METHODS: Five patients with chronic cutaneous leg ulcers were recruited for this 4-month study using only rHuGM-CSF to treat the ulcers. One patient had a neuropathic-diabetic ulcer, and four had long-standing vascular leg ulcers. RESULTS: The patient with the neuropathic diabetic ulcer showed complete healing after 1 month of treatment. The other four patients with vascular leg ulcers with a long history of ulceration had a poor prognosis for healing. The first, with three venous ulcerative lesions, presented complete resolution of one ulcer and stabilization of the other two; the second and third patients, with large vascular ulcers, improved with more then 50% reduction of the mean diameter of the ulcers; the fourth patient, with one large venous ulcer, did not show any improvement. CONCLUSIONS: Pathogenesis, size and duration of the ulcers seemed to be the most important parameters regarding wound repairing capability of rHuGM-CSF. None of the ulcers increased in size and none of the patients developed clinical side-effects or peripheral blood cell count abnormalities during the treatment. All the results described were stable after 6 months of follow up. The absence of peripheral leucocyte count variation and the size-dependent therapeutic effect indicate that the drug exercises local rather than systemic actions.     

Leg ulcers and hydroxyurea: report of three cases with essential thrombocythemia

CASE 1: A 65-year-old woman with essential thrombocythemia (ET) had been taking oral hydroxyurea (HU), 1,000 mg daily, for 7 years. Six months ago, she developed an ulcer on the outer part of her left ankle, which healed spontaneously within 2 months. She presented with a new, tender, shallow ulcer, 2 cm x 2 cm in size, at the same site. Doppler examination revealed thrombosis of the left common femoral vein and a calcified atheroma plaque of the left common femoral artery. The dosage of HU was decreased to 500 mg daily when the platelet counts were found to be within normal levels. The ulcer completely healed within 2 months with occlusive wound dressings, and has not recurred within the follow-up period of 1 year. CASE 2: A 56-year-old women presented with multiple, painful, leg ulcers of 1 year duration. She had been diagnosed as having ET and had been on HU therapy, 1,500 mg/day, for the past 5 years. Interferon-alpha-2b was started 3 months ago, in addition to HU, which was tapered to 1,000 mg daily. She had suffered from hypertension for 20 years treated with nifedipine and enalapril, and had recently been diagnosed with diabetes mellitus which was controlled by diet. Examination revealed three ulcers located on the lateral aspects of both ankles and right distal toe. Arterial and venous Doppler examinations were within normal limits. Histopathology of the ulcer revealed nonspecific changes with a mixed inflammatory cell infiltrate around dermal vessels. The ulcers completely healed within 10 weeks with topical hydrocolloid dressings. After healing, she was lost to follow-up. A year later, it was learned that she had developed a new ulcer at her right heel, 3 months after her last visit (by phone call). This ulcer persisted for 8 months until HU was withdrawn. CASE 3: A 64-year-old woman with ET presented with a painful leg ulcer of 6 months' duration. She had been taking oral HU for 5 years. She had a 20-year history of hypertension treated with lisinopril. Examination revealed a punched-out ulcer of 2 cm x 2 cm over the right lateral malleolus. Doppler examination of the veins revealed insufficiency of the right greater saphenous and femoral veins. Angiography showed multiple stenoses of the right popliteal and femoral arteries. As her platelet count remained high, HU was continued. During the follow-up period of 13 months, the ulcer showed only partial improvement with local wound care.     

Foot Ulcer Due to Arteriovenous Malformation: Report of a Case

A 41-year-old woman had erosive eruptions surrounded by irregularly shaped pigmentation on the lateral aspect of her right foot, where she had noted gradually increasing warmth and pain for 10 years. The eruptions waxed and waned without complete healing, and an ulcer which had formed one year previously did not respond to topical treatments. Arteriography performed on the right lower extremity disclosed multiple diffuse arteriovenous malformations in the right lower leg and foot. The ulcer was treated by bed rest, surgical debridement, and topical application of bucladesine sodium ointment. After three months, the ulcer healed, leaving a shallow scar and pigmentation.     

Calf muscle pump impairment and delayed healing of venous leg ulcers: air plethysmographic findings

There is a need for a diagnostic tool to predict clinical outcome of venous leg ulcer patients, as the prognosis of healing based on clinical data alone has not appeared to be satisfactory. Air plethysmographic assessment of calf muscle pump was performed in the supine and upright position in 129 patients with active ulcers on their legs. All patients were managed in a specialized leg ulcer clinic. Results of air plethysmography were compared to clinical data and time of healing of ulcers. Muscle pump failure was found in 42.6% of extremities (supine position, 33.3%; upright, 22.5%; both, 12.4%). Patients with insufficient pump were older, and their ulcers were larger. Failure of pump was found more often in patients who began the treatment after long, unsuccessful, non-specialized care. Healing time of ulcers was prolonged in cases with insufficient pump. Regarding the subgroups with good clinical prognosis (patients with small ulcers or with a short history of ulceration), it was found that insufficiency of muscle pump correlated with delayed healing. It could be summarized that venous leg ulcers associated with calf muscle failure were larger, long-standing, and that their healing even after specialized treatment was delayed. Impaired muscle pump function revealed in plethysmographic examination can be a prognostic factor of delayed healing of leg ulcer. Ulcers with poor prognosis according to plethysmographic findings, and no quick recovery after standard management, should be considered for advanced therapies.     

OUTPATIENT TREATMENT OF CHRONIC VENOUS ULCERS IN A SPECIALIZED CLINIC

Chronic leg ulcers have many different causes and therefore need an accurate diagnosis in order to give the most effective treatment. A specialized clinic was set up in Fremantle Hospital in July 1988 with the aims of performing a thorough clinical and laboratory assessment to establish the cause of ulceration in every patient, and treating patients according to the cause of ulceration. Patients with arterial, neoplastic or dermatological conditions were treated as appropriate for their diagnosis and patients with other chronic ulcers were managed as outpatients where possible. Patients were seen between July 1988 and July 1989. Only 43% had purely venous ulcers, 32.6% had a venous component plus some other abnormality, and 5.2% were purely arterial. Using an outpatient treatment regimen, 67% of all ulcerated limbs and 73.7% of limbs with purely venous ulcers were healed within 6 months. Only 11 patients with venous ulceration (15 limbs) failed on this therapy and required admission during the observation period. The initial ulcer size was shown to influence the time to total healing of the limb. The healing rates achieved compare favourably with studies from other specialized centres and suggest that the majority of patients with chronic leg ulcers can be treated successfully using ambulatory outpatient dressing techniques.     

A multicentre study of percentage change in venous leg ulcer area as a prognostic index of healing at 24 weeks

Venous leg ulcers, which may take months to heal, account for 40-70% of all lower extremity chronic wounds. New treatment options for venous leg ulcers have recently been proposed, and therefore deciding which patients are candidates for these novel-and often expensive-treatments is an important task. Moreover, researchers conducting clinical trials often wish to enroll patients who are unlikely to heal in order to minimize sample sizes needed and research costs. Our purpose was to assess the use of percentage change in venous leg ulcer area over the first few weeks of treatment as a prognostic indicator of healing or non-healing at 24 weeks. We conducted a cohort study based on an existing data set from a multicentre randomized clinical trial that enrolled 104 patients. Wounds were measured using digital planimetry for 4 consecutive weeks following the inception of good wound care. Utilizing the Wilcoxon rank sum (Mann-Whitney) test, we found that percentage change in area over time distinguished between those who healed and those who failed to heal after 24 weeks of good wound care (P < 0.05). The rate of healing, or area healed per week, did not differentiate between those who healed at 24 weeks and those who did not, as all patients had similar rates of healing over the first 4 weeks of treatment. Percentage change in area from baseline to week 4 provided the best combination of positive and negative predictive values (68.2%, 74.7%) and the largest area under the receiver operating characteristic curve (0.75). Thus, percentage change in area over the first 4 weeks of treatment represents a practical and predictive measure of complete wound healing by 24 weeks.     

Differential diagnosis of leg ulcers

In Germany about 0.7 % of the adult population have a chronic leg ulcer. Although chronic venous insufficiency accounts for at least 80 % of all chronic leg ulcers, knowledge of the relevant differential diagnostic considerations is of crucial importance, in particular for patients who are refractory to therapy. In addition to vascular disease, other causes include neuropathic, metabolic, hematologic and exogenous factors as well as neoplasias, infections, drugs, genetic defects and some primary skin disorders. For the long‐term successful treatment of patients with chronic leg ulcers, it is necessary to identify all relevant factors, in order to enable a pathogenesis‐oriented, interdisciplinary therapeutic approach.     

Leg and foot ulcers. Nursing care in Malm?, Sweden.

Questionnaires concerning nursing care of leg and foot ulcer patients in three major care-giving sectors of the national health service, namely the Department of Dermatology, general hospital wards/clinics, and primary care, have been analysed. The overall response rate was 88% (primary care: 100%). Forms regarding 193 patients with leg ulcers and 64 patients with foot ulcers were analysed. Substantial differences in nursing care were noted between the three sectors. In 55% of the leg ulcers and 45% of the foot ulcers fibrin slough was present in the ulcer. Black, necrotic tissue was present in 8% of the leg ulcers and 22% of the foot ulcers. Profuse ulcer-exudation was most commonly reported for leg ulcer patients treated at the Department of Dermatology, while the majority of foot ulcers had only a mild exudation. Frequency of dressing changes varied between 1.4 times/week for leg ulcers at the Department of Dermatology and 9.2 times/week (foot ulcers 11.6) at general hospital clinics. Local wound dressings were exclusively chosen by physicians at the Department of Dermatology, mainly by physicians at general hospital clinics, and equally often by physicians and nurses in primary care. Time since last evaluation of the ulcer by a physician varied. At the general hospital clinics, 89% of the patients with leg ulcers had been seen by a physician within the last 2-month period. At the Department of Dermatology, 89% and in primary care 61% of the patients were examined within this period. 11% of the patients in primary care had never consulted a physician for their ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contact allergy in chronic leg ulcers: results of a multicentre study carried out in 423 patients and proposal for an updated series of patch tests

Background:  There is a lack of prospective studies investigating contact sensitization in patients with chronic leg ulcers.
Objectives:  To determine the frequency of contact sensitization in patients with chronic leg ulcers using a special series of patch tests and to determine whether the number of sensitizations was correlated with the duration of the chronic leg ulcers.
Patients/methods:  Multicentre study carried out in patients with chronic leg ulcers; patch tests with the European baseline series and with an additional 34 individual allergens or mixes and 3 commercial products.
Results:  Of the 423 patients (301 women, 122 men, mean age 68.5 years) with chronic leg ulcers, 308 (73%) had at least one positive patch test with 3.65 positive patch tests per patient. The main allergens were Myroxylon pereirae (41%), fragrance mix I (26.5%), antiseptics (20%), and corticosteroids (8%). The number of positive tests per patient was not correlated with the cause of ulcer but was increased with the duration of the ulcer with a statistical difference between the group of the <1 year compared with the group >10 years duration.
Conclusions:  From this large prospective multicentre study, polysensitization is frequent in patients with chronic leg ulcers, increasing with the duration of the ulcer. We propose avoidance of topical antiseptics and ointments containing perfumes in patients with chronic leg ulcers and an updated patch test series for investigating these patients.     

Cytokine and protease levels in healing and non-healing chronic venous leg ulcers

Abstract Leg ulcers present a common and recurring problem in older people creating discomfort and distress for the patient and a great cost to the health care services. Cultured keratinocyte grafts have been used by many investigators to stimulate healing of chronic venous ulcers. It has been proposed that they may do this by producing cytokines which modulate the healing process. However, the types and levels of cytokines in the leg ulcer fluid before and during healing arc not known. Wound fluid was collected from venous leg ulcers in 18 patients beneath occlusive Tega-derm? dressing for 4 to 6 h. The leg ulcers were divided on clinical criteria into ‘healing’ and ‘non-healing’. PDGF-AB, GM-CSE IL-1α, IL-1β. IL-6 and bFGF were measured by ELISA and the levels of IL-1α, IL-1β. and IL-6 were also measured using biological assays. The effect of leg ulcer wound fluid on fibroblast and keratinocyte proliferation was measured indirectly by ³H-thymidine incorporation and MTT assay. Total protein, albumin levels, fibronectin degrading activity and collagenase activity, both active and latent were measured. No statistically significant differences in the levels of cytokines or collagenase were identified between healing and non-healing leg ulcers in the sample of leg ulcers studied. However, this study does give valuable information concerning the levels of cytokines and collagenase in chronic leg ulcer wound fluid.     

The lived experience of recurrence prevention in patients with venous leg ulcers: An interpretative phenomenological study

Aim of the studyTo explore patient understanding of why they develop a venous leg ulcer and how they can prevent recurrence.MethodThe methodological framework of the hermeneutic phenomenological approach was used. Semi-structured interviews were conducted with seventeen participants living with a venous leg ulcer from May 2017 to November 2018. Data were analysed using Smith's interpretative hermeneutic analysis.ResultsThe results are categorised into three main themes: “Trauma due to accident” (initial venous leg ulcer) and “Prevention of ulcer recurrence” (compression); “Trauma due to compression therapy” (venous leg ulcer recurrence). The findings demonstrate active venous leg ulcers are often caused by acute incidents while carrying out an activity in people with underlying chronic venous insufficiency. After a complete healing, preventive measures, such a compression stockings are initiated by the patient or health care provider. Trauma due to adherence to compression stockings caused skin breakdown beneath compression that caused subsequent ulcer recurrence.ConclusionThis study contributes to understanding the lived experience of patients with venous leg ulcers who develop a venous leg ulcer and their understanding of how they can prevent recurrence. Patients with VLUs would benefit from early preventive strategies, such as such a compression stockings fitting and application, integrated into daily care plan of primary care and community settings.     

Successful treatment of a leg ulcer occurring in a rheumatoid arthritis patient under leflunomide therapy

Objective We report the case of a leg ulcer in a rheumatoid arthritis (RA) patient under treatment with leflunomide, discuss the influence of the drug on the aetiopathogenesis of the ulcer and describe its successful treatment. Case summary A 68‐year‐old woman with a 12‐year history of RA developed a leg ulcer after 4 months of leflunomide treatment. Other ulcerogenic factors were ruled out. There were some clinical hints for rheumatoid vasculitis. The ulcer was resistant to ambulant conservative phase adapted wound bed preparation and a split skin transplantation failed. After omission of leflunomide and washout procedure with cholestyramine a second split skin transplantation resulted in complete healing. Discussion Leflunomide inhibits the division of activated T cells and thus inhibits among others the production of proinflammatory cytokines and the adhesion of cells to the endothelium. These mechanisms may partly explain the possible influence of leflunomide on the perpetuation of the ulcer. Until now, occurrence of vasculitis and leg ulcers has been described in one case each for the novel immunomodulator leflunomide. No successful treatment of a leg ulcer under leflunomide has been described yet. Omission of leflunomide and a washout treatment in our case led to a complete healing. This may indicate a critical role of leflunomide in the maintenance of this slow healing ulcer. Conclusions An association between leflunomide intake, occurrence of leg ulcers in RA patients and delayed wound healing should be considered.     

Changes in quality of life for patients with chronic venous insufficiency,present or healed leg ulcers

Background: Patients with chronic leg ulcers are handicapped in daily life, both by physical complaints and social problems. The aim of our study was not only to assess a possible impairment of quality of life (QOL) of leg ulcer patients but also to evaluate if there is a real improvement of QOL after healing of the ulcer. Patients with chronic venous insufficiency served as the control group. We further analyzed if there were significant differences in the response between patients who were and were not performing compression therapy. Patients and method: We interviewed three groups of patients (active venous leg ulcer, healed venous leg ulcer and patients with chronic venous insufficiency using the ?Freiburger Life Quality Assessment für Venenerkrankungen“ (FLQAv). Results: Physical problems, daily handicaps and social problems all increased with age. Contrary to our expectations, healing of a leg ulcer did not lead to a significant increase in QOL. Instead, patients with active ulcers did not regard their QOL as lower than those in the other groups. Compression therapy also did not impair QOL in the three groups. Conclusion: Even though ulcer healing is an admirable goal, it does not necessarily lead to an improved QOL, probably because of the numerous comorbidi‐ties in this patient group. Nonetheless, it is important to control problems associated directly with the wound to allow ulcer patients to participate actively in everyday life and minimize social problems.     

Infiltrating basal cell carcinoma in the setting of a venous ulcer

A 77-year-old man was referred with a 5-year history of an intermittently painful, nonhealing right medial ankle ulcer. The ulcer had not responded to multiple treatment modalities, including Unna boots, compression therapy, sclerotherapy, and split-thickness skin grafting. The past medical history was significant for a deep venous thrombosis in the right leg 30 years earlier (treated with warfarin for 3 months) and a history of greater saphenous vein harvesting for coronary bypass grafting 28 years previously. After the vein stripping, the patient had suffered from increasing right leg edema and stasis changes in the right leg. His history was also remarkable for coronary artery disease, dyslipidemia, and lymphoma treated with chemotherapy 8 years before presentation, with no evidence of recurrence. He had stopped smoking approximately 20 years earlier. Medications included atenolol, simvastatin, nicardipine, nitroglycerin, and aspirin. Skin examination revealed a 3.0 x 3.5-cm ulcer adjacent to the medial malleolus. The edges of the ulcer appeared raised and rolled (Fig. 1). Centrally, there was granulation tissue, which appeared healthy. There were surrounding dermatitic changes. Dorsalis pedis and the posterior tibial pulses were normal. Noninvasive vascular studies revealed severe venous incompetence of the right popliteal and superficial veins. Arterial studies and transcutaneous oximetry were normal. Computed tomographic scan of the pelvis did not reveal any adenopathy, and radiographic imaging did not reveal any bony changes suggestive of osteomyelitis. Biopsy of the ulcer edge and base showed infiltrating basal cell carcinoma (Fig. 2). Mohs' micrographic surgery required three layers; the final extent of the ulcer was 7.8 x 6.9 cm. A split-thickness skin graft was placed.     

Pinch grafting of chronic leg ulcers in primary care: fourteen years' experience

Pinch grafting for treatment of chronic leg ulcers has been evaluated mainly in hospitalized and immobilized patients. This study describes the results of 199 pinch graft operations of 126 chronic leg and foot ulcers in 85 patients in primary care between 1987 and 2001. The aetiology of the ulcers was venous insufficiency in 43% and multi-factorial in 25% (77% with venous insufficiency as the main determinant). The mean ulcer size was 13.5 cm2 and the mean ulcer duration was 15.9 months. The overall healing rate within 3 months was 33%, ranging from 19% for multi-factorial or combined venous and arterial ulcers to 48% for venous ulcers. Within 12 months the overall healing rate was 60%, with 67% healed venous ulcers. The results from our study suggest that pinch grafting is suitable for treating chronic leg ulcers, especially venous ulcers, in primary care.     

Allergic contact dermatitis in venous leg ulcer patients

Our aim was to determine the frequency and nature of contact sensitivity in venous leg ulcer patients in Lanarkshire. We performed patch testing with the European standard series, antimicrobials and medicaments on 200 patients referred to our leg ulcer clinics. Positive patch tests were found in 136 (68%) patients. Multiple allergies occurred in 102 (51%). The most frequent allergen groups were fragrances (30.5%), antimicrobials (19.5%), topical excipients (19.5%), rubber accelerators (13.5%) and topical corticosteroids (8%). We also found a high prevalence of positive patch tests to Intrasite gel (9.5%) and Hioxyl cream (8.5%), medicaments which are commonly used to treat leg ulcers in our area. Contact sensitivity is common in venous leg ulcer patients and has important implications for patient management. The allergens involved vary depending on local nursing practice. We suggest that all venous leg ulcer patients be patch tested with a locally relevant patch test series.     

Genese des Ulcus cruris

The etiology of chronic leg ulcers is very heterogeneous. The primary aim of our investigation was to analyze the etiology of leg ulcers in patients treated in our wound care center over a period of 5 years. In this open retrospective study, data of 354 patients was analyzed. We found a venous leg ulcer in 203 (57%), and in 52 (15%) patients a combined arterio-venous induced leg ulcer. The third most common cause was leg ulcers due to different types of vasculitis in 47 (13%) patients. An exclusively arterial induced leg ulcer was diagnosed in 13 (3.7%) patients. Overall 16 different etiologies were identified. In contrast to the few comparable other investigations, we found a higher incidence of immunologic und infectious causes for leg ulcers in our patients. Even if our results do not allow a representative overview about the prevalence of leg ulcer in Germany, they demonstrate the wide spectrum of leg ulcer causes in a dermatologic wound care centre.     

Development of spinocellular carcinoma in a long‐lasting and therapy resistant venous ulcer – two case studies

Background: While squamous cell carcinoma can primarily cause a leg ulcer, the malignant transformation of a primary venous leg ulcer to squamous cell carcinoma is rarer. Patients: Two women with longstanding venous legs ulcer are presented. Both had diverse conservative, interventional and surgical therapies for both chronic venous insufficiency and their ulcers. These led to shortterm or intermittent closure of the ulcer with recurrence. In view of the only short intervals between the last surgical treatment and the again fulminant and fast progressive relapse, biopsies were taken from the ulcer base and border, revealing squamous cell carcinoma.After conservative surgical measures failed, both women required amputation. Conclusions: In long‐standing venous ulcers, malignant transformation should be considered especially in a fulminant or rapidly relapsing course after a surgical treatment. Biopsies should be taken to verify diagnosis and lead to correct therapy.