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.

Occlusive cutaneous vasculopathies as cause of chronic ulcers.

The term occluding vasculopathies covers a large number of different conditions. These often manifest as skin ulcers. Occluding vasculopathies should be considered in the differential diagnosis of leg ulcers. The term "occlusive vasculopathies" encompasses pathophysiologically related entities that share structural or thrombotic obliteration of small cutaneous vessels. In this article, we will focus on livedoid vasculopathy with and without antiphospholipid syndrome and calciphylaxis with differentiation from hypertonic leg ulcer as the most relevant differential diagnoses of leg ulcer. The term also includes vascular occlusion, for example due to oxalate or cholesterol embolism, and septic vasculopathy. This often leads to acral ulceration and is therefore not a differential diagnosis with classic leg ulcers. It will not be discussed in this article. Occlusive vasculopathy may be suspected in the presence of the typical livedo racemosa or (non-inflammatory) retiform purpura as a sign of reduced cutaneous perfusion in the wound area. Inflammatory dermatoses, especially vasculitides, must be differentiated. This is achieved by histopathological evaluation of a tissue sample of sufficient size and depth taken at the appropriate time. In addition, specific laboratory parameters, particularly coagulation parameters, can support the diagnosis.

Clinical characteristics and treatment modalities in uremic and non uremic calciphylaxis - a dermatological single-center experience.

Calciphylaxis (CP) is a serious, potentially life-threatening disease that presents with medial calcification of small-sized vessels and painful ischemic ulcerations. Although calciphylaxis is frequently seen in patients with end-stage kidney disease on dialysis (calcific uremic arteriolopathy, CUA), there are reported cases of nonuremic calciphylaxis (NUC), which often remain undiagnosed. We conducted a retrospective chart review at our dermatological hospital and evaluated data concerning the epidemiology, comorbidities, medication, laboratory abnormalities, and therapeutic approaches of 60 patients diagnosed with calciphylaxis between 01/2012 and 12/2022. We identified 21 patients diagnosed with NUC and 39 with kidney disease. The predilection sites of skin lesions were the lower legs in 88% (n = 53), followed by the thigh and gluteal regions in 7% (n = 4). Significant differences were identified in comorbidities, such as atrial fibrillation (p < 0.001) and hyperparathyroidism (p < 0.01) accounting for CUA patients. Medication with vitamin K antagonists (p < 0.001), phosphate binders (p < 0.001), and loop diuretics (p < 0.01) was found to be associated with the onset of calciphylaxis. Hyperphosphatemia (p < 0.001), increased parathyroid hormone (p < 0.01) and triglyceride levels (p < 0.01), hypoalbuminemia (p < 0.01) and decreased hemoglobin values (p < 0.001) in the CUA cohort were significantly different from those in the NUC group. All patients with CUA received systemic medication. In contrast, only 38% (n = 8) of patients with NUC received systemic treatment. Striking discrepancies in the treatment of both cohorts were detected. In particular, NUC remains a disease pattern that is still poorly understood and differs from CUA in several important parameters.

Design and Implementation of an ETL-Process to Transfer Wound-Related Data into a Standardized Common Data Model.

For observational studies, which are relevant especially for chronic conditions like chronic wounds, the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) offers a standardized database schema. In this study an ETL process for the transition of wound related data was developed. After understanding the data in general and mapping the relevant codes to concepts available in OMOP, the ETL process was implemented. In a first step, a generic algorithm to convert data to a csv format was implemented in Java. The resulting csv file was then processed within KNIME to be loaded into an OMOP CDM conformant database. During the whole ETL process, HL7 FHIR CodeSystem and ConceptMap resources were used for coding and mapping. First clinical test cases to retrieve data were successfully processed as an example to demonstrate the feasibility and usefulness. They concerned wound size at the first visit and the main issues of patients in the wound quality of life questionnaire (n = 24). In general, the ETL process worked well, yet some challenges arose, like post coordinated SNOMED codes or conditions, which might occur more than once.

Predilection sites of pyoderma gangrenosum: Retrospective study of 170 clearly diagnosed patients.

Pyoderma gangrenosum (PG) is a non-infectious, neutrophilic dermatosis that was difficult to diagnose in clinical practice. Today, the PARACELSUS score is a validated tool for diagnostics. Based on this score, patients with clearly diagnosed PG were examined with regard to predilection sites. In this retrospective study, the data of patients from the University Hospitals of Essen and Erlangen were analysed in whom the diagnosis of PG could be clearly confirmed using the PARACELSUS score. A total of 170 patients, 49 men (29%) and 121 women (71%) with an average age at first manifestation of 55.5 years, could be included in the analysis. The predilection sites were identified as the lower legs in 80.6% of the patients and the extensor sides in 75.2%. Other localisations of PG were the thighs in 14.1%, mammae and abdomen in 10.0% each, back and gluteal in 7.1% each, feet in 5.9%, arms in 4.7%, genital in 3.5% and head in 2.9%. This retrospective study is the first to identify a collective of PG patients with the highest data quality using the PARACELSUS score. It could be shown that PG can basically occur on the entire integument. However, the predilection sites of PG, which have now been reliably identified for the first time, are the lower legs and in particular the extensor sides.

Can Synthetic Images Improve CNN Performance in Wound Image Classification?

For artificial intelligence (AI) based systems to become clinically relevant, they must perform well. Machine Learning (ML) based AI systems require a large amount of labelled training data to achieve this level. In cases of a shortage of such large amounts, Generative Adversarial Networks (GAN) are a standard tool for synthesising artificial training images that can be used to augment the data set. We investigated the quality of synthetic wound images regarding two aspects: (i) improvement of wound-type classification by a Convolutional Neural Network (CNN) and (ii) how realistic such images look to clinical experts (n = 217). Concerning (i), results show a slight classification improvement. However, the connection between classification performance and the size of the artificial data set is still unclear. Regarding (ii), although the GAN could produce highly realistic images, the clinical experts took them for real in only 31% of the cases. It can be concluded that image quality may play a more significant role than data size in improving the CNN-based classification result.

Mobility range, level of pain and sleep quality of patients with venous leg ulcers.

This study aimed to compare mobility range, level of pain and sleep quality in patients with venous leg ulcers to age- and gender-matched controls without ulcers. Twenty patients with venous leg ulceration and 20 matched controls each answered a questionnaire, completed the short-physical performance battery, filled in a subject diary and wore a smartwatch for 1 week. The median daily step counts of the ulcer group (3622 steps/day) and the control group (5133 steps/day) were significantly different (P = .017). Significant correlations between total step count and age, duration of physical outdoor activities and scores in the short-physical performance battery were observed in the ulcer group. The scores in the short-physical performance battery were significantly different in both groups (P = .005), indicating weaker physical performance in the ulcer group. The greatest difference in the self-reported level of pain between the two groups was stated during movement. On average, the ulcer group slept shorter by 1 h 38 min (P = .002) and had 0.7 wake phases per night (P = .019) more than the control group. Assessing mobility in patients with venous leg ulcers can be used to develop preventive and interventional concepts to improve and individualise physical therapies.

Clinical Manifestation of Cutaneous Leishmaniasis Following a Mechanical Trauma.

Unusual skin ulcers frequently represent a diagnostic challenge. When the most common disease entities such as arterial, venous or diabetic ulcers have been excluded, the question of further differential diagnoses and procedures arises. Other possible causes include chronic inflammatory diseases, neoplasia, self-inflicted wounds, primary infectious diseases and physical/chemical damage to the skin. To narrow down the differential diagnoses, a detailed history of the patient is essential, which also needs to include events further back in time.

Clinical Experience Using a Monofilament Fiber Cleansing and Debriding Technology for Various Skin Conditions.

BACKGROUND: Gentle skin cleansing and exfoliation and the use of moisturizers as an adjunct to medical treatment should be part of the prevention, treatment, and maintenance of cutaneous conditions such as acne vulgaris (acne) psoriasis, and xerosis. A monofilament fiber debriding technology (MFDT) is used for effective, safe, and rapid skin cleansing and exfoliation and debris, slough, and biofilm removal. The current review addresses the clinical experience using MFDT for various cutaneous conditions that require cleansing or exfoliation or both and how to combine it with medical treatment. METHODS: A literature review explored clinical insights into the role of skin cleansing and exfoliation for patients with various dermatological conditions. The searches yielded 29 publications, 7 guidelines/algorithms, 13 reviews, 8 clinical studies, and one in vitro study. RESULTS: Mechanical cleansing using a device can be helpful; however, avoid injury of the skin as it may result in thickening of the epidermis leading to hyperkeratosis and disruption of the skin barrier. Clinical experience with MFDT for acne, psoriasis, atopic dermatitis, and xerosis is discussed. Additionally, MFDT was used to exfoliate hyperkeratosis, actinic keratosis, and traumatic skin tattoos. CONCLUSIONS: Mechanical cleansing using MFDT was shown to be safe and beneficial for skin cleansing and exfoliation of various cutaneous conditions; however, only anecdotal evidence or small studies are available to support its use for these conditions. J Drugs Dermatol. 2022;21(11):1173-1180. doi:10.36849/JDD.6261.

[Local therapeutic procedure for blisters of the skin: a position paper of the Initiative Chronic Wounds (ICW)]. / Lokaltherapeutisches Vorgehen bei Blasen der Haut: Ein Positionspapier der Initiative Chronische Wunden (ICW) e. V.

Blisters of the skin can be caused by very different diseases. Therefore, it is an interdisciplinary and interprofessionally relevant challenge. In the clinical routine different local therapeutic procedures are currently practiced. Either the blister is left in place or the blister is punctured and the blister roof is left in place; alternatively, the complete blister roof is ablated. Each of these approaches has potential advantages and disadvantages. A review of the current literature and consensus by the experts of the Initiative Chronische Wunde (ICW) e.V. was performed. The following approaches are recommended: uncomplicated blisters without pressure pain: leave blisters in place; pressure painful and palmar and plantar localized blisters: puncture blister and leave roof; ruptured blisters without clinical signs of infection: leave remnants of bladder roof; ruptured bladders with clinical signs of infection: remove remnants of the blister roof; blisters in burns of grade 2a or higher or in cases of unclear burn depth or chemical burn: remove blister roof. This is followed in each case by the application of a sterile wound dressing. There is no single correct local therapeutic procedure for blisters on the skin. When planning a therapeutic concept, the genesis of the blisters should be clarified and, if necessary, causal treatment should be given. Local therapy is then based on various individual factors. Thus, the approach chosen together with the patient can vary between individuals.

Automatic Wound Type Classification with Convolutional Neural Networks.

Chronic wounds are ulcerations of the skin that fail to heal because of an underlying condition such as diabetes mellitus or venous insufficiency. The timely identification of this condition is crucial for healing. However, this identification requires expert knowledge unavailable in some care situations. Here, artificial intelligence technology may support clinicians. In this study, we explore the performance of a deep convolutional neural network to classify diabetic foot and venous leg ulcers using wound images. We trained a convolutional neural network on 863 cropped wound images. Using a hold-out test set with 80 images, the model yielded an F1-score of 0.85 on the cropped and 0.70 on the full images. This study shows promising results. However, the model must be extended in terms of wound images and wound types for application in clinical practice.

An Image Based Object Recognition System for Wound Detection and Classification of Diabetic Foot and Venous Leg Ulcers.

Venous leg ulcers and diabetic foot ulcers are the most common chronic wounds. Their prevalence has been increasing significantly over the last years, consuming scarce care resources. This study aimed to explore the performance of detection and classification algorithms for these types of wounds in images. To this end, algorithms of the YoloV5 family of pre-trained models were applied to 885 images containing at least one of the two wound types. The YoloV5m6 model provided the highest precision (0.942) and a high recall value (0.837). Its mAP_0.5:0.95 was 0.642. While the latter value is comparable to the ones reported in the literature, precision and recall were considerably higher. In conclusion, our results on good wound detection and classification may reveal a path towards (semi-) automated entry of wound information in patient records. To strengthen the trust of clinicians, we are currently incorporating a dashboard where clinicians can check the validity of the predictions against their expertise.

Epidermotropie von Immunzellen unterscheidet Pyoderma gangraenosum vom Ulcus cruris venosum.

HINTERGRUND UND ZIELE: Pyoderma gangraenosum ist eine ulzerierende, autoinflammatorische Erkrankung. Es gibt keine eindeutigen histopathologischen Merkmale zur Differenzierung von anderen Ursachen chronischer Wunden wie dem Ulcus cruris venosum. Ziel dieser Studie war es, histopathologische Merkmale von Pyoderma gangraenosum und Unterschiede zu venösen Ulzerationen zu detektieren. PATIENTEN UND METHODIK: Acht Gewebeproben von Pyoderma gangraenosum, zwölf Proben von Ulcus cruris venosum und sechs Proben von gesunder Haut wurden einer immunhistologischen Multi-Antigen-Analyse unterzogen. Das Immuninfiltrat und seine räumliche Verteilung wurden anhand von Fluoreszenzbildern mit einer Gewebezytometriesoftware analysiert. ERGEBNISSE: Die dichte epidermale Präsenz von CD45RO+ -T-Gedächtnis-Zellen und die Rarefizierung von CD1a+ -Langerhans-Zellen in der Epidermis waren Marker für Pyoderma gangraenosum, welche auch auf eine epidermale Immunreaktion schließen lassen. Darüber hinaus konnte dermal eine hohe Anzahl CD11c+ CD68+ pro-inflammatorischer M1-Makrophagen nachgewiesen werden. Diese überstieg die Anzahl der in venösen Ulzerationen beobachteten Makrophagen deutlich. SCHLUSSFOLGERUNGEN: Die histopathologischen Unterschiede zwischen Pyoderma gangraenosum und Ulcus cruris venosum können zur Unterscheidung der beiden Erkrankungen herangezogen werden und somit eine wichtige Hilfe zur schnellen Einleitung einer adäquaten Therapie sein. Darüber hinaus deuten unsere Daten auf einen antigengesteuerten Prozess in der Epidermis hin, möglicherweise unter Beteiligung von CD1a+ Langerhans-Zellen.

Epidermotropism of inflammatory cells differentiates pyoderma gangrenosum from venous leg ulcers.

BACKGROUND AND OBJECTIVES: Pyoderma gangrenosum is an ulcerative autoinflammatory disease, lacking distinct histopathological characteristics to differentiate from other ulcerating conditions, like venous leg ulcers. The objective of this study was therefore to find histopathological characteristics of pyoderma gangrenosum in a head-to-head comparison to venous leg ulcers. PATIENTS AND METHODS: Eight tissue samples of pyoderma gangrenosum, twelve samples of venous leg ulcers and six samples of healthy skin were stained using an immunohistological multi antigen staining technology. The immune infiltrate and its spatial distribution were analyzed with contextual tissue cytometry software using fluorescence images. RESULTS: The dense epidermal presence of CD45RO+ memory T cells and the rarefication of CD1a+ Langerhans cells in the epidermis were defining markers for pyoderma gangrenosum, implicating an epidermal immune reaction. In addition, high numbers of CD11c+ CD68+ pro-inflammatory M1 macrophages were detected in the dermis, significantly extending the numbers seen in venous leg ulcers. CONCLUSIONS: The histopathological differences found between pyoderma gangrenosum and venous leg ulcer can be used to distinguish between the two diseases and thus provide an important aid for the rapid initiation of adequate therapy. In addition, our data hint at an antigen-driven process in the epidermis, possibly involving CD1a+ Langerhans cells.

[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.

Automatic Classification of Diabetic Foot Ulcer Images - A Transfer-Learning Approach to Detect Wound Maceration.

Diabetic foot ulcer (DFU) is a chronic wound and a common diabetic complication as 2% - 6% of diabetic patients witness the onset thereof. The DFU can lead to severe health threats such as infection and lower leg amputations, Coordination of interdisciplinary wound care requires well-written but time-consuming wound documentation. Artificial intelligence (AI) systems lend themselves to be tested to extract information from wound images, e.g. maceration, to fill the wound documentation. A convolutional neural network was therefore trained on 326 augmented DFU images to distinguish macerated from unmacerated wounds. The system was validated on 108 unaugmented images. The classification system achieved a recall of 0.69 and a precision of 0.67. The overall accuracy was 0.69. The results show that AI systems can classify DFU images for macerations and that those systems could support clinicians with data entry. However, the validation statistics should be further improved for use in real clinical settings. In summary, this paper can contribute to the development of methods to automatic wound documentation.

[Position paper of the Initiative Chronische Wunde (ICW) e. V. on the nomenclature of debridement in chronic wounds]. / Positionspapier der Initiative Chronische Wunde (ICW) e. V. zur Nomenklatur des Débridements chronischer Wunden.

The nomenclature used today in wound treatment varies widely across different disciplines and professions. Therefore, it is a mission of the professional association Initiative Chronische Wunde (ICW) e. V. to exactly and comprehensibly describe terms that were previously unclear. Therefore, the experts of the ICW defined in a consensus procedure debridement of chronic wounds as the removal of adherent, dead tissue, scabs or foreign bodies from wounds. There are various therapy options for this, which can be differentiated into autolytic, biosurgical, mechanical, osmotic, proteolytic/enzymatic and technical debridement. In the case of surgical debridement, a distinction is also made between sharp debridements that can usually be performed on an outpatient basis, such as minor surgical procedures, and surgical debridements with adequate anaesthesia in an operating theatre. Wound irrigation is defined by the ICW as the removal of non-adherent components on wounds with sterile solutions. Debridement and/or wound irrigation are often the first step in phase-appropriate modern wound treatment. Several methods are suitable for use in a combined or successive therapy. When deciding which therapeutic option to use, a number of individually different factors should be taken into account, depending on the patients to be treated but also on the therapists. The final individual decision for a method should be made together with the patient in each case and then adequately documented.

Allogeneic ABCB5+ mesenchymal stem cells for treatment-refractory chronic venous ulcers: a phase I/IIa clinical trial.

A significant number of chronic venous ulcers (CVUs) fail to heal despite of guideline-conform standard of care. Skin-derived ABCB5+ mesenchymal stem cells (MSCs) can dampen the sustained IL-1ß-driven inflammation present in chronic wounds. Based on their wound healing-facilitating effects in a mouse CVU model and an autologous first-in-human study, ABCB5+ MSCs have emerged as a potential candidate for cell-based advanced therapy of non-healing CVUs. In the present interventional, multicenter, single-arm, phase I/IIa clinical trial, subjects whose CVU had emerged as standard therapy-resistant received one or two topical applications of 1×106 allogeneic ABCB5+ MSCs/cm2 wound area in addition to standard treatment. Out of 83 treatment-emergent adverse events, only three were judged related to the cell product; they were mild or moderate and recovered without sequelae. Wound size markedly decreased from baseline to week 12, resulting in a median wound size reduction of 76% (full analysis set, N=31), 78% (per-protocol set, N=27) and 87% (subset of responders; n=21). In conclusion, the study treatment was well tolerated and safe. The treatment elicited a profound wound size reduction within 12 weeks, identifying ABCB5+ MSCs as a potential candidate for adjunctive therapy of otherwise incurable CVUs. These results justify the conduct of a larger, randomized, controlled trial to confirm clinical efficacy.

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.