Diagnosis and treatment of venous leg ulcers: S2k Guideline of the German Society of Phlebology and Lymphology (DGPL) e.V.

This S2k guideline on venous leg ulcers was created on the initiative and under the leadership of the German Society of Phlebology and Lymphology (DGPL). The guideline group also consisted of representatives from the German Society for Phlebology and Lymphology, German Dermatological Society, German Society for General Medicine, German Society for Angiology, German Society for Vascular Surgery and Vascular Medicine, German Society for Surgery, German Society for Dermatosurgery, German Society for Wound Healing and Wound Treatment, Professional Association of Phlebologists and Lymphologists and Initiative Chronische Wunden. The aim of this guideline is to combine the different approaches and levels of knowledge of the respective professional groups on the basis of consensus, so that a basic concept for the best possible treatment of patients with venous leg ulcers can be provided. A total of 70 specific recommendations were formulated and agreed upon, divided into the subject areas of diagnostics, therapy, prevention of recurrences, and everyday challenges. The guideline thus reflects the current state of scientific knowledge and is intended to be widely used as the best available document for the treatment of patients with venous leg ulcers in everyday clinical practice.

Intravenous Immunoglobulin Therapy in Livedoid Vasculopathy: Retrospective Observation of Clinical Outcome and Patient's Activity Level.

BACKGROUND: Livedoid vasculopathy (LV) is a rare disease characterized by livedo racemosa, atrophie blanche, ulcerations, and severe pain. Low molecular weight heparins and rivaroxaban can be used in LV-patients. In addition, intravenous immunoglobulins (IVIG) have been described as treatment-option. OBJECTIVES: Objective was to investigate the therapeutic effect of IVIG on ulcer, pain and restrictions in daily life. METHODS: Thirty-two LV-patients who received IVIG at the Department of Dermatology Tübingen between 01/2014 and 06/2019 were identified. Twenty-five of these patients were available for further follow up and were included in the study. Patients were interviewed using a questionnaire focusing on the course of the disease, symptoms, and subjective response to IVIG-treatment. RESULTS: Twenty-five patients were included in the study (mean follow up: 28.9 months). Patients received an average of 6.8 cycles (range 1-45) of IVIG during the observed period.Significant improvements were seen regarding skin findings, pain, and limitation of daily activities. Complete remission of symptoms was observed in 68% of patients. Good tolerability of IVIG was shown in 92%. CONCLUSIONS: A good therapy response regarding ulceration, pain, and daily life restrictions with good tolerability was demonstrated for IVIG (2 g/kg bodyweight over 5 days).

Squamous cell carcinomas in chronic venous leg ulcers. Data of the German Marjolin Registry and review.

BACKGROUND: Secondary squamous cell carcinoma (SCC) is a rare complication of chronic venous leg ulcers. So far, little is known about its pathophysiology and clinical behavior. Initiated by the working group "Wound Healing" (AGW) of the German Society of Dermatology (DDG), it is the objective of the current Marjolin registry to collect cases of SCC arising in venous ulcers, in order to evaluate diagnostic characteristics. PATIENTS AND METHODS: All members of the AGW received questionnaires inquiring about basic patient data, ulcer characteristics, and therapy conducted. RESULTS: From 2010 to 2013, 30 patients (20 women, 10 men) from six tertiary wound care centers were registered. Mean age was 76.17 years. The average duration of venous leg ulcers prior to SCC diagnosis was 15.93 years. Suspicious wound characteristics primarily included: pain (n = 3), therapy resistance (n = 27), and fetor (n = 12) as well as clinical appearance (n = 10) with atypical morphology, nodular wound bed, and hypergranulation. CONCLUSIONS: Atypical morphology or changes in appearance as well as therapy resistance despite optimal care (6-12 weeks) should prompt physicians to take spindle-shaped, if necessary multiple and serial, biopsies. Primary risk factors for malignant transformation include patient age and ulcer duration.

Multicentre prospective observational study on professional wound care using honey (Medihoney™).

In recent years, the treatment of wounds with honey has received an increasing amount of attention from healthcare professionals in Germany and Austria. We conducted a prospective observational multicentre study using Medihoney™ dressings in 10 hospitals - nine in Germany and one in Austria. Wound-associated parameters were monitored systematically at least three times in all patients. Data derived from the treatment of 121 wounds of various aetiologies over a period of 2 years were analysed. Almost half of the patients were younger than 18 years old, and 32% of the study population was oncology patients. Overall, wound size decreased significantly during the study period and many wounds healed after relatively short time periods. Similarly, perceived pain levels decreased significantly, and the wounds showed noticeably less slough/necrosis. In general, our findings show honey to be an effective and feasible treatment option for professional wound care. In addition, our study showed a relationship between pain and slough/necrosis at the time of recruitment and during wound healing. Future comparative trials are still needed to evaluate the extent to which the positive observations made in this and other studies can definitely be attributed to the effects of honey in wound care.

Concomitant thrombosis in patients with cellulitis as incidental finding.

BACKGROUND: Although inflammation and thrombosis are tightly connected, only 45% of patients with lower leg cellulitis receive anticoagulant therapy. Available data about the prevalence of concomitant deep venous thrombosis (DVT) in patients with cellulitis of the lower extremity is scarce and general guidelines regarding diagnosis and prevention of venous thromboembolism are missing. OBJECTIVE: We sought to determine how frequently DVT occurs as an incidental finding in patients with cellulitis and to provide recommendations for diagnostics and anticoagulant therapy. METHODS: Patients' records were analysed and 192 consecutive patients with cellulitis were included in this study. The prevalence of concomitant DVT was examined by duplex ultrasound, as well as comorbidities and risk factors. RESULTS: We detected thrombosis in 12.0% of the patients with lower leg cellulitis, of which 43.5% were located in a proximal vein and 52.2% in the veins of the calf. CONCLUSIONS: Our results clearly indicate that cellulitis is not only a differential diagnosis, but should be considered a risk factor for venous thrombosis. Therefore, prophylactic anticoagulation should be considered in patients suffering from cellulitis and a systematic screening for venous thrombosis in patients with cellulitis should be performed.

Influence of controlled vascular training on the pain free walking distance and plasmaviscosity in patients suffering from peripheral arterial occlusive disease.

Does controlled vascular training influence plasmaviscosity and the pain free walking distance in patients with peripheral arterial occlusive disease (paod) Fontaine stage II?37 patients, 24 men and 13 women with a mean age of 64.5 years SD 8.5 took part in ambulant vascular training over a period of 12 months.Before, after 6 months and after 12 months, pain free (pfwd) and maximum walking distance (mwd) was measured using a standardized treadmill program. Also ankle-brachials systolic pressure index (a-bspi), transcutaneous oxygen tension (tcPO2) and plasmaviscosity (pv) were measured.Pfwd increased from 212 SD 143 m to 371 SD 249 m (p<0.02). TcPO2 increased during training, but without statistically significance. A-bspi increased between the first 6 months of training statistically significant. Before training pv was 1.31 mPa s SD 0.10, after training period of 6 months it was 1.27 mPa s SD 0.11 (p=0.06) and 12 months later it was 1.28 SD 0.11 mPa s (p=0.35). The improvement of pfwd and the decrease of pv correlates (r=-0.39, p=0.05).In most patients, arterial vascular training improves pfwd and mwd. Simultaneously to the increase of the walking distances plasmaviscosity decreases and crurobrachial indexes increases. We found a coupling between improvement of pfwd and pv. Pv seems to participate in improvement of leg hemodynamics in patients with paod.

Changes in acral blood flux under local application of ropivacaine and lidocaine with and without an adrenaline additive: a double-blind, randomized, placebo-controlled study.

Vascular effects of local anesthetics are especially important in dermatological surgery. In particular, adequate perfusion must be ensured in order to offset surgical manipulations during surgical interventions at the acra. However, the use of adrenaline additives appears fraught with problems when anesthesia affects the terminal vascular system, particularly during interventions at the fingers, toes, penis, outer ears, and tip of the nose. We studied skin blood flux at the fingerpads via laser Doppler flowmetry over the course of 24 hours in a prospective, double-blind, randomized, placebo-controlled study with 20 vascularly healthy test persons following Oberst's-method anesthetic blocks. In each case, 6 ml ropivacaine (7.5 mg/ml) (A), lidocaine 1% without an additive (B), and lidocaine 1% with an adrenaline additive (1:200,000) (C) was used respectively as a verum. Isotonic saline solution was injected as a placebo (D). Measurements were carried out with the aid of a computer simultaneously at D II and D IV on both hands. Administration of (A) led to increased blood flux (+155.2%); of (B) initially to a decrease of 27%; of (C) to a reduction of 55% which was reversible after 40 minutes and of (D) to no change.(A) resulted in sustained vasodilatation which was still demonstrable after 24 h. (B) had notably less vasodilative effect, although comparison with (D) clearly showed that (B) is indeed vasodilative. (C) resulted in only a passing decrease in perfusion; this was no longer measurable when checked after 6 and 24 h. This transient inadequacy of blood flux also appeared after administration of (D). These tests show that adrenaline additive in local anesthesia does not decrease blood flow more than 55% for a period of 16 min. Following these results an adrenaline additive can be safely used for anesthetic blocks at the acra in healthy persons.

Mobilization versus immobilization in the treatment of acute proximal deep venous thrombosis: a prospective, randomized, open, multicentre trial.

OBJECTIVE: The aim of prescribing strict bed rest for acute deep venous thrombosis is to reduce the risk of pulmonary embolism and pain in the legs, as well as swelling. This study was performed in order to compare outcome of mobilization against 5 days of strict bed rest in patients with acute proximal deep venous thrombosis (DVT). METHODS: 103 in-patients with proximal DVT or patients admitted to the hospital because of proximal DVT were recruited to a randomized study. All patients were treated in hospital and given a lower leg and thigh compression bandage as well as therapeutic doses of the low molecular weight heparin, dalteparin-sodium (Fragmin). RESULTS: Seven of 52 patients (13.5%) in the mobile group versus 14 of 50 patients (28.0%) in the immobile group suffered at least one of the outcomes defined under the combined primary endpoint (clinically relevant pulmonary embolisms, pulmonary embolisms detectable by scintigraphy or computer tomography, progression of thrombosis or new thrombosis, nosocomial infections and/or serious adverse events) (p = 0.088), whereby serious adverse events occurred once in the mobile group and three times in the immobile group. New pulmonary embolisms over the course were seen in 10 of 50 patients (20%) with a perfusion disorder at baseline scintigraphy, while such was ascertained only in one of 52 patients (1.9%) without a perfusion disorder at baseline scintigraphy. Leg pain was reduced from 54.1 (+/-30.4) to 20.7 (+/-19.2) in the mobilized group and from 41.0 (+/-26.8) to 14.0 (+/-11.1) in the immobilized patients. Leg pain was assessed using the visual analogue scale (0 = no pain, 100 = maximum pain). More immobilized patients complained of increasing back pain (23% versus 6%) and disturbed micturition (10% versus 2%) as well as defecation (13% versus 6%) on day 5. More patients in the mobile group reported increased stress from the thrombosis and its treatment (15% versus 6%). CONCLUSIONS: No benefit of prescribing bed rest in patients with deep venous thrombosis could be detected in this study. Based on data available, strict bed rest for at least 5 days is not justified if adequate therapy with low molecular weight heparin and adequate compression is assured. It remains open whether patients with initial signs of pulmonary embolism might profit from a brief immobilization.

Anticoagulation with rivaroxaban for livedoid vasculopathy (RILIVA): a multicentre, single-arm, open-label, phase 2a, proof-of-concept trial.

BACKGROUND: Livedoid vasculopathy is a thrombotic skin disease characterised by recurrent occlusion of the cutaneous microcirculation in lower extremities, which results in skin infarctions with painful ulcerations and irreversible scar formation. Rivaroxaban is a direct factor Xa inhibitor that prevents thrombus formation. We investigated whether rivaroxaban is effective for the treatment of livedoid vasculopathy. METHODS: We did this single-arm, open-label, multicenter, phase 2a, proof-of concept trial at three university hospitals in Germany. Patients with livedoid vasculopathy and a minimum pain score of 40 on the visual analogue scale were eligible to participate. Patients received oral rivaroxaban tablets for 12 weeks at an initial dose of 10 mg twice per day, which was reduced to once per day if a reduction of pain by 50% on the visual analogue scale was achieved. Subcutaneous enoxaparin at 1 mg per kg bodyweight once or twice per day was allowed as a backup treatment in case of insufficient efficacy and increased pain. The primary endpoint was change in pain on the visual analogue scale from baseline to 12 weeks. Efficacy was assessed in the intention-to-treat population and safety was assessed in all patients who received at least one dose of study drug. This trial is registered with the EU Clinical Trials Register, EudraCT number 2012-000108-13-DE, and is closed to new participants. FINDINGS: Between Dec 28, 2012, and April 24, 2014, 36 patients were screened, 28 patients were recruited for the study, and 25 patients received treatment. During treatment, five patients dropped out of the study because of withdrawal of consent (one patient), lack of compliance (one patient), violation of inclusion criteria (two patients), and a serious adverse event (one patient). Median pain on the visual analogue scale decreased from 65·0 (IQR 52·0-78·0) at baseline to 6·0 (1·0-14·0) after 12 weeks of treatment (p<0·0001). Six of the 20 patients required additional treatment with enoxaparin. Eight treatment-related adverse events were recorded in six (24%) of the 25 patients: five cases of menorrhagia including one classified as both menorrhagia and dysmenorrhoea, one case of dyspnoea, and one case of gingival bleeding. The only serious adverse reaction to rivaroxaban during the study was one case of menorrhagia in a patient with concomitant endometriosis, which resulted in study discontinuation. INTERPRETATION: Rivaroxaban seems to effectively reduce pain in livedoid vasculopathy. Therefore we suggest that rivaroxaban with enoxaparin as a backup treatment is a suitable treatment option for patients with livedoid vasculopathy. FUNDING: Deutsche Forschungsgemeinschaft and Bayer Vital.

Associated factors and comorbidities in patients with pyoderma gangrenosum in Germany: a retrospective multicentric analysis in 259 patients.

BACKGROUND: Pyoderma gangrenosum (PG) is a rarely diagnosed ulcerative neutrophilic dermatosis with unknown origin that has been poorly characterized in clinical studies so far. Consequently there have been significant discussions about its associated factors and comorbidities. The aim of our multicenter study was to analyze current data from patients in dermatologic wound care centers in Germany in order to describe associated factors and comorbidities in patients with PG. METHODS: Retrospective clinical investigation of patients with PG from dermatologic wound care centers in Germany. RESULTS: We received data from 259 patients with PG from 20 different dermatologic wound care centers in Germany. Of these 142 (54.8%) patients were female, 117 (45.2%) were male; with an age range of 21 to 95 years, and a mean of 58 years. In our patient population we found 45.6% with anemia, 44.8% with endocrine diseases, 12.4% with internal malignancies, 9.3% with chronic inflammatory bowel diseases and 4.3% with elevated creatinine levels. Moreover 25.5% of all patients had a diabetes mellitus with some aspects of potential association with the metabolic syndrome. CONCLUSIONS: Our study describes one of the world's largest populations with PG. Beside the well-known association with chronic bowel diseases and neoplasms, a potentially relevant new aspect is an association with endocrine diseases, in particular the metabolic syndrome, thyroid dysfunctions and renal disorders. Our findings represent clinically relevant new aspects. This may help to describe the patients' characteristics and help to understand the underlying pathophysiology in these often misdiagnosed patients.

Wavelet analysis of Laser Doppler Flux time series of tumor and inflammatory associated neoangiogenesis. Differences in rhythmical behavior.

We use continuous wavelet analysis (WA) of Laser Doppler Flux (LDF) time series measured in basal cell carcinomas (BCC) and plaque psoriasis (PP) in order to investigate the rhythmical behavior of blood flow in tumor or inflammatory associated neoangiogenesis.A total of 68 patients with primary BCCs and 40 patients with PP were included in the study. LDF time series were separated in four scaling levels corresponding to the influences of sympathetic activity (SL1), myogenic activity in the vessel wall (SL2), respiration (SL3) and heart beat (SL4).In BCC, SL1 decreased compared to healthy skin. In all other scaling levels, we found a statistically significant increase of the SLs compared to healthy skin. These increases were not found in PP.Rhythmical behavior of blood flow in malignant tumors is totally different from that in regions with inflammation. In BCCs, thermoregulatory processes, ascribed to sympathetic activity, decrease statistically significant. In contrast, inflammatory processes in PP do not substantially change sympathetic activity. WA of tumor perfusion could open a new noninvasive monitor system for controlling tumor therapy.

Wavelet analysis of skin perfusion in healthy volunteers.

OBJECTIVE: Rhythmical changes in microvascular perfusion of the skin depend on various influences, which appear continuously but not in a predictable manner. For identifying and quantifying different physiological influences the authors used wavelet transformation, analyzing continuously and simultaneously measured data. METHODS: A total of 34 healthy volunteers were included in the study. At the dorsum of the left hand, skin perfusion was measured by laser Doppler fluxmetry (LDF) and skin temperature was measured. Simultaneously, the electrocardiogram and the respiration were recorded. The recorded time series were analyzed with wavelet transformation and scale correlation (S-correlation). RESULTS: Semilinear analysis with wavelet transformation allowed a visualization of temporal changes in LDF frequency and amplitude in a color-coded quasi three-dimensional diagram. The authors found that tissue perfusion over an observation period of 327.68 s is governed by 6 closely connected, overlying waves with different degrees of freedom. The major determinants are low frequencies in LDF, which correlates with changes in skin temperature, responsible for 68.5% of the influence. Surprisingly, though indispensable for blood flow, respiration and heartbeat contributed to less then 2.5% of the rhythmic changes. CONCLUSIONS: When wavelet transformation is used in analyzing LDF time series, the different rhythms of cutaneous blood flow are made visible and quantifiable and can be assigned to different physiological origins. The application of this novel analysis method allows identifying mechanisms regulating skin perfusion, which will greatly facilitate the diagnosis of a variety of important vascular diseases, such as chronic venous insufficiency, diabetes, or neurotrophic disorders.