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.

Eligibility Criteria for Active Ulcerative Pyoderma Gangrenosum in Clinical Trials: A Delphi Consensus on Behalf of the UPGRADE (Understanding Pyoderma Gangrenosum: Review and Assessment of Disease Effects) Group.

At present, there are no standardized guidelines for determining patient eligibility for pyoderma gangrenosum (PG) clinical trials. Thus, we aim to determine which clinical features, histopathological features, or laboratory features should be included in active ulcerative PG clinical trial eligibility criteria for treatment-naïve patients and patients already treated with immunomodulating medications (treatment-exposed patients). This study employed 4 rounds of the Delphi technique. Electronic surveys were administered to 21 international board-certified dermatologists and plastic surgeon PG experts (June 2022-December 2022). Our results demonstrated that for a patient to be eligible for a PG trial, they must meet the following criteria: (i) presence of ulcer(s) with erythematous/violaceous undermining wound borders, (ii) presence of a painful or tender ulcer, (iii) history/presence of rapidly progressing disease, (iv) exclusion of infection and other causes of cutaneous ulceration, (v) biopsy for H&E staining, and (vi) a presence/history of pathergy. These criteria vary in importance for treatment-naïve versus treatment-exposed patients. Given the international cohort, we were unable to facilitate live discussions between rounds. This Delphi consensus study provides a set of specific, standardized eligibility criteria for PG clinical trials, thus addressing one of the main issues hampering progress toward Food and Drug Administration approval of medications for PG.

Aquacel Ag Advantage/Ag+ Extra and Cutimed Sorbact in the management of hard-to-heal wounds: a cohort study.

OBJECTIVE: To compare Aquacel Ag Advantage/Ag+ Extra (Aquacel Ag+) (Convatec, UK) and Cutimed Sorbact (Sorbact) (Essity, US) dressings indicated for the treatment of patients with venous leg ulcers (VLUs), diabetes foot ulcers (DFUs) and pressure injuries (PIs) for clinical performance and outcomes using real-world evidence in Germany and the US. METHOD: This study was a chart audit review of patients who used either Aquacel Ag+ or Sorbact dressings in the 24 months prior to October 2022. Healthcare providers with access to electronic medical records and charts were asked to capture data via patient record forms. The quantitative data were analysed. RESULTS: Findings in Germany were comparable between Aquacel Ag+ and Sorbact with regards to wound description, management and treatment outcomes, including percent area reduction and wound closure. A difference was that a greater proportion of Sorbact patients required surgery (0% versus 11%; p=0.039). In the US, a greater proportion of wounds were worsening before dressing in the Aquacel Ag+ cohort (49% versus 34%; p=0.010). A multinomial logistic regression yielded the result that patients who received Aquacel Ag+ were 3.53 times more likely to have the wound completely healed (p=0.033). CONCLUSION: Both Aquacel Ag+ and Sorbact dressings are widely used in Germany and the US for patients with VLUs, DFUs and PIs. Our study found two important differences: patients who used Aquacel Ag+ were less likely to need further surgery in Germany; and in the US, there were significantly higher odds that wounds would completely heal with Aquacel Ag+ dressings compared to Sorbact.

Pyoderma Gangrenosum: Treatment Options.

Pyoderma gangrenosum is a rare neutrophilic dermatosis that leads to exceedingly painful ulcerations of the skin. Although the exact pathogenesis is not yet fully understood, various auto-inflammatory phenomena with increased neutrophil granulocyte activity have been demonstrated. Despite the limited understanding of the pathogenesis, it is no longer a diagnosis of exclusion, as it can now be made on the basis of validated scoring systems. However, therapy remains a major multidisciplinary challenge. Various immunosuppressive and immunomodulatory therapies are available for the treatment of affected patients. In addition, concomitant topical pharmacologic therapy, wound management and pain control should always be addressed. Corticosteroids and/or cyclosporine remain the systemic therapeutics of choice for most patients. However, in recent years, there has been an increasing number of studies on the positive effects of biologic therapies such as inhibitors of tumour necrosis factor-α; interleukin-1, interleukin-17, interleukin-23 or complement factor C5a. Biologics have now become the drug of choice in certain scenarios, particularly in patients with underlying inflammatory comorbidities, and are increasingly used at an early stage in the disease rather than in therapy refractory patients.

[Wound treatment without curative intention: position paper of the Initiative Chronische Wunden (ICW) e. V.] / Wundbehandlung ohne kurative Zielsetzung: Ein Positionspapier der Initiative Chronische Wunden (ICW) e. V.

Today, patients with chronic wounds are treated in many different fields of medicine. Despite this great interdisciplinary and interprofessional importance, there is still a lack of uniformly accepted definitions and classifications. Therefore, a group of experts from the professional society Initiative Chronische Wunden (ICW) e. V. translated and adapted the classification of chronic wounds into healable, maintenance and nonhealable wounds on the basis of the internationally published literature into German. This classification results in the aim of curative, limited respectively non-curative or palliative wound care, which are very important for everyday clinical practice. It thus becomes clear that complete wound closure is not always the central intention of wound treatment. For many patients with chronic wounds, other aspects such as the best possible quality of life and the promotion of health-related self-management as well as the avoidance of complications are important for treatment concepts. These therapy intentions should be differentiated and individually discussed with patients in order to facilitate shared decision making.

Comorbidity and Therapeutic Approaches in Patients with Necrobiosis Lipoidica.

BACKGROUND: Necrobiosis lipoidica (NL) is a rare granulomatous disorder of unknown aetiology. Randomized controlled studies are not available due to it being an orphan disease. OBJECTIVES: We evaluated patients in 2 dermatological centres to cluster data about epidemiology, the therapeutic approaches for NL, and their efficacy. MATERIALS AND METHODS: Comorbidity and the efficacy of the applied treatment was assessed for 98 patients. RESULTS: We identified 54% of patients with concomitant diabetes and 19% with thyroidal disorders. Topical steroids (85.7%) were predominantly used followed by calcineurin inhibitors (31%) and phototherapy (41.8%). Systemically, fumaric acid esters were more frequently applied (26.8%) than steroids (24.4%) and dapsone (24.4%). Steroids, compression therapy, calcineurin inhibitors, phototherapy, fumaric acid esters, and dapsone showed remarkable efficacy. CONCLUSION: Therapeutic options were chosen individually in accordance with the severity of NL and presence of ulceration. Topical calcineurin inhibitors, systemic application of fumaric acid esters, and dapsone represent effective alternatives to the use of steroids.

A Case of Critical Essential Thrombocythemia Complicated by Severe Lower-Extremity Arterial Disease.

BACKGROUND Atherosclerosis and malignancies are leading causes of morbidity and mortality worldwide. In lower-extremity arterial disease (LEAD), progressing or ruptured atherosclerotic plaques are the main culprit for limb ischemia and may cause claudication, chronic wounds, or necrotic lesions. In those cases, standard of care includes revascularization in addition to best medical therapy. Other sources for acute or chronic limb ischemia different from atherosclerosis are often overlooked, especially once atherosclerotic plaques have been detected. CASE REPORT We report the rare case of a patient presenting with painful necrotic ulcerations of the lower extremity due critical essential thrombocythemia that was complicated by an atherosclerotic disease. Based on the clinical presentation, 4 major differential diagnoses were initially considered: Martorell's ulcer, pyoderma gangrenosum, LEAD, and recurrent thromboembolic occlusions due to a malignant disease. Following a thorough, holistic diagnostic work-up, we identified the first diagnosis of critical essential thrombocythemia, which was aggravated by LEAD. CONCLUSIONS This case report highlights the importance of taking malignancies into consideration as a differential diagnosis in patients with repetitive arterial occlusions. With a broad variety of differential diagnoses to be considered for the presented ulcerations, this case report highlights the crucial importance of a rapid interdisciplinary approach to treat and relieve symptoms and prevent further arterial thrombotic events. The learning objective is to give a clear diagnostic work-up to navigate through the most important differential diagnoses of non-atherosclerotic conditions aggravating LEAD.

[Long-term healing of a therapy-refractory venous leg ulcer after crural fasciectomy and split skin graft transplantation]. / Langfristige Abheilung eines therapierefraktären Ulcus cruris venosum nach kruraler Fasziektomie und Spalthauttransplantation.

A 59-year-old obese woman had been suffering from a painful, chronic leg ulcer since 1986. We diagnosed a venous leg ulcer due to functional chronic venous insufficiency in the context of obesity per magna (dependency syndrome) and arthrogenic congestion syndrome due to immobility. Although a high ligation and stripping of the great saphenous vein and several so-called shave therapies with split skin transplantation after appropriate wound bed preparation had been previously performed, the wound persisted. In 2012, the patient wanted to amputate her leg because the course of wound healing was so refractory to therapy and she suffered from severe pain. As an alternative to amputation, we performed a crural fascietomy and, after a wound bed preparation with two cycles of negative pressure wound therapy, we covered the defect with a split skin graft using the mesh graft technique. The surgery could be performed without complications and the skin healed completely. At the current presentation 7 years after the intervention, complete healing of the previously therapy-refractory venous leg ulcer was shown despite the persistent obesity per magna and immobility. This case report shows that a crural fasciectomy should be considered, especially in the case of otherwise therapy-refractory courses of venous leg ulcers.

Pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that presents with rapidly developing, painful skin ulcers hallmarked by undermined borders and peripheral erythema. Epidemiological studies indicate that the average age of PG onset is in the mid-40s, with an incidence of a few cases per million person-years. PG is often associated with a variety of other immune-mediated diseases, most commonly inflammatory bowel disease and rheumatoid arthritis. The cause of PG is not well understood, but PG is generally considered an autoinflammatory disorder. Studies have focused on the role of T cells, especially at the wound margin; these cells may support the destructive autoinflammatory response by the innate immune system. PG is difficult to diagnose as several differential diagnoses are possible; in addition to clinical examination, laboratory tests of biopsied wound tissue are required for an accurate diagnosis, and new validated diagnostic criteria will facilitate the process. Treatment of PG typically starts with fast-acting immunosuppressive drugs (corticosteroids and/or cyclosporine) to reduce inflammation followed by the addition of more slowly acting immunosuppressive drugs with superior adverse event profiles, including biologics (in particular, anti-tumour necrosis factor (TNF) agents). Appropriate wound care is also essential. Future research should focus on PG-specific outcome measures and PG quality-of-life studies.

Re-evaluation of polihexanide use in wound antisepsis in order to clarify ambiguities of two animal studies.

OBJECTIVE: Due to classification of the agent polihexanide (PHMB) in category 2 'may cause cancer' by the Committee for Risk Assessment of the European Chemicals Agency in 2011, the users of wound antiseptics may be highly confused. In 2017, this statement was updated, defining PHMB up to 0.1% as a preservative safe in all cosmetic products. In the interest of patient safety, a scientific clarification of the potential carcinogenicity of PHMB is necessary. METHODS: A multidisciplinary team (MDT) of microbiologists, surgeons, dermatologists and biochemists conducted a benefit-risk assessment to clarify the hazard of antiseptic use of PHMB. RESULTS: In two animal studies, from which the assessment of a carcinogenic risk was derived, PHMB was administered orally over two years in extremely high concentrations far above the NO(A)EL (no-observed-(adverse-) effect level) in rats and mice. Feeding in the NO(A)EL range resulted in no abnormal effects. In one male in the highest dose group of 4000ppm PHMB, an adenocarcinoma was found, which the author attributed to chronic inflammation of the colon with systemic atypical exposure. The increasing incidence of hemangiosarcomas highly probably resulted from increased endothelial proliferation, triggered by the exceedingly high dosage fed, because PHMB is not genotoxic and there is no evidence for epigenetic effects. DISCUSSION: It is well known that PHMB is not absorbed when applied topically. Considering the absence of genotoxicity and epigenetic effects together with the interpretation of the animal studies, it is the consensus of the multidisciplinary experts that a carcinogenic risk from PHMB-use for wound antisepsis can be ruled out. CONCLUSION: On this basis and considering their effectiveness, tolerability and clinical evidence, the indications for PHMB based wound antiseptics are justified.

Health-related quality of life and patient burden in patients with split-thickness skin graft donor site wounds.

Split-thickness skin grafting is a common procedure to treat different kinds of wounds. This systematic, multicentre, observational, cross-sectional study of adult patients with split-thickness skin graft (STSG) donor site wounds was conducted to evaluate quality of life (QoL) impairments caused by donor site wounds following split-thickness skin grafting. Therefore, 112 patients from 12 wound centres in Germany were examined based on patient and physician questionnaires as well as a physical examination of the donor site wound. Most indications for skin grafting were postsurgical treatment (n = 51; 42.5%) and chronic wounds (n = 47; 39.2%). European QoL visual analoque scale (EQ VAS) averaged 64.7 ± 23.3, European QoL 5 dimensions (EQ-5D) averaged 77.4 ± 30.0. Wound-QoL (range: 0-4) was rated 0.8 ± 0.8 post-surgery and 0.4 ± 0.6 at the time of survey (on average 21 weeks between the time points). Compared to averaged Wound-QoL scores of chronic wounds donor site-related QoL impairments in split-thickness skin-graft patients were less pronounced. There were significant differences in patient burden immediately after surgery compared to the time of the survey, with medium effect sizes. This supports the hypothesis that faster healing of the donor site wound leads to more favourable patient-reported outcomes.

Oxygenation Status in Chronic Leg Ulcer After Topical Hemoglobin Application May Act as a Surrogate Marker to Find the Best Treatment Strategy and to Avoid Ineffective Conservative Long-term Therapy.

PURPOSE: Chronic leg ulcers can be a challenge to treat and long-term therapy a significant cost factor in western public health budgets. Objective wound assessment assays enabling selection of appropriate wound therapy regimes would be desirable. Oxygenation status in ulcer tissue has obtained increased attention as a relevant factor in wound healing. To increase oxygenation in wounds, a topical hemoglobin spray was developed. Although favorable results have been noted, the link between clinical efficacy and the mode of action has not been demonstrated. The aims were to determine if changes in tissue oxygenation can be measured after topical application of hemoglobin on chronic wounds and to evaluate the findings in terms of therapy strategies. PROCEDURES: Photoacoustic imaging was used to measure the local oxygen saturation (StO2) in leg ulcers before and after hemoglobin spray treatment. Sclerosis of the leg ulcers was histopathologically graded and the change in wound size was documented in a follow-up examination. RESULTS: Measuring 49 patients, an increase in StO2 after topical hemoglobin application from on average 66.1 to 71 % (p = 0.017) after 20 min was observed. Depending on the increase in StO2 (>10 % or <10 %) patients were stratified into a Responder and a Non-Responder group. Wound size significantly decreased in the Responder Group (p = 0.001), while no significant difference in the Non-Responder group (p = 0.950) was noted. CONCLUSION: Our findings suggest that the likelihood of wound healing under conservative therapy can be predicted by measuring changes in StO2 after topical hemoglobin application. This assay may reduce treatment time and costs by avoiding ineffective conservative long-term therapy. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00005993.