Differential diagnosis of leg ulcers

Over the last years the treatment of chronic leg ulcers has developed from a merely symptomatic to a differentiated therapy. Although more than 90% of the ulcers are of vascular origin, many other causes are possible. A survey of the various triggers of chronic ulcers of the lower limb is given. Vascular, hematological, neuropathic, infectious, malignant and chemico-physical causes are discussed. New findings regarding hemostatic defects as the basis of thrombophilia and ulcers are presented.     

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.     

Differential diagnosis of leg ulcers

There are various types of leg ulcers. The lesions may result from interference with venous outflow or from marked impairment of cutaneous arterial blood flow, or they may be associated with metabolic, hematologie, neoplastic, drug-induced, or with a miscellaneous group of conditions. The initiating factor is frequently trauma, although some of the ulcers may occur spontaneously.

In determining the cause of a given leg ulcer, a knowledge of the relative frequency of the different types of ulcers, careful consideration of certain salient features of the patient's history and clinical examination, and proper use of the laboratory are diagnostically important.     

Differential diagnosis and therapy of leg ulcers

A leg ulcer is a symptom and the treating physician needs to find out its origin by differential diagnostic approaches and procedures. The correct diagnosis leads to a specific therapy that ideally accelerates the healing of the ulceration. Identifying the pathogenesis of a leg ulcer is the first and main step towards healing. Although vascular diseases are the major causes of leg ulcers, one needs to consider, in addition to venous and arterial disorders, autoimmune, infectious, metabolic and neoplastic causes. The simple truth that one can only make a diagnosis that was considered holds particularly true in leg ulcers. The differential diagnostic considerations presented here appear in the daily routine of a dermatologist and the article provides help in diagnostic approaches and therapeutic decisions.     

Treatment of chronic venous leg ulcers by platelet gel

ABSTRACT:  Chronic venous leg ulcers (CVLU) are chronic wounds, associated with long-standing venous hypertension, which have a poor prognosis for healing. In the process of wound healing the first step is represented by platelet aggregation and subsequent release of growth factors and other mediators, which play a key role in the repair response. Platelet gel (PG), a hemocomponent obtained by mixing platelets, thrombin, and calcium, is able, when applied topically, to release platelet mediators that likely favor CVLU healing. However, unstandardized protocols have been described in studies utilizing PG for the regeneration of a number of tissues, including CVLU; the relative clinical outcomes were hence highly variable. In our experience the topical use of PG, together with the strict adherence to the principles of good wound care, quickly promoted increased granulation tissue, followed by a complete CVLU epithelization. Although further studies and trials are needed to establish the major outcome affecting rules for optimal indications, preparation, and use of PG for CVLU treatment, PG can be undoubtedly considered a useful tool, able to improve the management of CVLU.     

Bacteriology of chronic leg ulcers.

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.     

Current therapeutic options of chronic leg ulcers

Wound treatment is continually becoming more complex and difficult. In the following review, we focus on the different options of wound debridement, stimulation of granulation tissue, different wound dressings, and therapeutic strategies in hard‐to‐heal‐wounds. We also present some future treatment options for chronic wounds.     

Mast cell tryptase and chymase in chronic leg ulcers: chymase is potentially destructive to epithelium and is controlled by proteinase inhibitors

BACKGROUND: Numerous mast cells are present in chronic leg ulcers. Tryptase and chymase are the major mediators of mast cells, but their significance is mostly dependent on their activity. In addition, the proteinases may affect ulcer epithelialization. OBJECTIVES: To study levels and activity of tryptase and chymase in wash samples and biopsies from chronic leg ulcers and the possible effect of these proteinases on keratinocyte growth and adherence. METHODS: Wash samples were taken from 16 patients and a superficial shave biopsy was taken in eight of these patients; a second biopsy series was obtained from the edge of chronic venous leg ulcers (n = 6). RESULTS: Significant levels of soluble tryptase activity and histamine, but low levels of chymase activity, were measured in wash samples from chronic ulcers. No tryptase-inhibiting activity, but clear chymase-inhibiting activity, was detected in the wash samples. In superficial wound bed biopsies, relatively marked levels of chymase activity together with histamine and tryptase activity were detected. In the second biopsy series, about 80% of the mast cells belonged to the MC(TC) type (tryptase- and chymase-immunopositive). However, about 55-61% of the chymase-immunopositive cells displayed chymase activity and 64 +/- 17% of the tryptase-positive cells revealed immunoreactivity of alpha(1)-antichymotrypsin. As the activity of chymase and tryptase was detected in the ulcer base in a ratio of 1:8, a preparation containing both chymase and tryptase was partially purified from human skin yielding a similar activity ratio of 1:11-13. Treatment of fibronectin-coated plastic surfaces with this preparation decreased the adherence of cultured human keratinocytes, this effect being attributable mainly to chymase. In 2-day cultures using growth factor/serum-deficient low- or high-calcium medium, the tryptase-chymase preparation inhibited the slow growth and at higher concentrations it even induced detachment of keratinocytes. This effect was attributed to chymase, and it was partially regulated by heparin and histamine. CONCLUSIONS: Even though chymase is partially inactivated in chronic leg ulcers, accumulated mast cells in the close proximity of the epithelium edge and their chymase may impair keratinocyte adherence and migration.     

Autologous suction blister grafting for chronic leg ulcers

Background Non‐healing leg ulcers represent a treatment problem. Objective Investigate grafting of autologous suction blister roofs as treatment. Methods Twenty‐nine chronic, non‐healing leg ulcers of various aetiologies in 18 inpatients were treated by autologous epidermal grafting using the roofs of suction blisters. Results 55% of ulcers completely healed 2 to 6 weeks after grafting. A 50–90% reduction in size was documented in 34% and no change was observed in 11% of ulcers. Twelve weeks after grafting, 89% of ulcers were healed completely. In most ulcers, we observed a stimulation of reepithelialization from the wound edge (‘edge effect’) and an accelerated formation of healthy granulation tissue. During a follow‐up period of 12 months, 90% of the ulcers remained healed. Conclusion Grafting of autologous suction blister roofs is an effective treatment option for non‐healing leg ulcers. The advantages of the method are its lack of pain, low costs and immediate availability.     

Wound teleconsultation in patients with chronic leg ulcers

BACKGROUND: The treatment of chronic leg ulcers requires frequent assessments of local wound status and adjustment of therapy. The availability of reasonably priced photographic equipment and quick electronic transfer of high-quality digital images should make it possible that the assessment of wound status can be made by remote experts. OBJECTIVE: This study examines the feasibility of using teledermatology for wound assessment and therapeutic suggestions for patients with chronic leg ulcers. METHODS: One hundred ten chronic leg ulcers of different origins were examined in face-to-face consultations. The examining doctor assessed the wound, made therapeutic recommendations and took 1-4 photographs of the wound using a digital camera. The digital images and relevant clinical information were then transmitted via a web application to an expert in wound care, who provided an independent teledermatological assessment of wound status and therapeutic recommendations. RESULTS: In our study, a high accordance between direct consultations and electronic consultations was found in the assessment of chronic leg ulcers, especially for important features like slough (concordance: 84.6%), necrosis (concordance: 98.2%) and granulation tissue formation (concordance: 76.4%). Furthermore, the teledermatologist generally felt confident in recommending further treatment strategies and in planning further wound assessments via the internet. CONCLUSIONS: Our results suggest that teledermatology offers great potential for the future in chronic wound care. By reducing the need to travel long distances to the hospital or to consult a physician with expertise in wound care, wound teleconsultation might lower health care costs and improve the quality of life for patients with chronic wounds, while still maintaining a high quality of wound care.     

Systemic amyloidosis secondary to chronic leg ulcers.

Chronic leg ulcers due to any cause are almost invariably associated with an inflammatory process. As with any long-standing inflammation, leg ulcers may be complicated by systemic amyloidosis, which occurs in rheumatoid arthritis, cystic fibrosis, tuberculosis, and other disorders. There are, however, very few reports on the association between these two conditions. We report a patient with severe leg ulcers of twenty years' duration in whom reactive systemic amyloidosis presented as a nephrotic syndrome.     

Hepatocyte growth factor; expression, concentration and biological activity in chronic leg ulcers

BACKGROUND: Hepatocyte growth factor (HGF) is a multifunctional cytokine that is involved in recovery process after organ injuries. OBJECTIVE: We studied HGF and the membrane bound receptor, c-met locally in patients who suffered from chronic leg ulcers (> or =1 year) caused by venous insufficiency. METHODS: Skin biopsies from the edge of the ulcers were taken from patients (n=13) and studied by immunohistochemical staining for detection of HGF and c-met. Skin biopsies from healthy volunteers (n=10) were used as the control material. Ulcer secretion from chronic ulcers (n=11) was examined for the presence of HGF by ELISA and the concentration of HGF was compared with acute ulcers in healthy controls (n=10) and in patients operated for a non-invasive breast cancer (n=12). RESULTS: We observed that c-met expression in the ulcer area increased significantly in chronic ulcers compared to controls (p=0.005). Concentration of ulcer-HGF in the patients with chronic ulcer was significantly higher than acute ulcers (p<0.01). The biological activity of HGF in ulcer secret was assessed in-vitro in transferred, mouse skin epithelial cell monolayer. Enhanced migration and morphologic changes were seen after adding ulcer secret from acute ulcers (> 1 ng/mL) that was inhibited by anti-HGF antibodies. No biological activity was observed by adding ulcer secret from chronic ulcers irrespective HGF concentration. CONCLUSION: We conclude that in chronic skin ulcers decreased biological activity of endogenous HGF and overexpression of c-met is seen which might explain fibrosis and delayed recovery. Administration of exogenous active HGF might contribute to accelerated healing in these patients.