The Differential Diagnosis of Leg Ulcers.

BACKGROUND: Chronic wounds on the leg (below the knee) are called leg ulcers. They have many causes, and thus patients with leg ulcers are treated by many different kinds of medical specialist. Appproximately 80% of sufferers have chronic venous insufficiency (CVI) and/or peripheral arterial occlusive disease (PAOD). Knowledge of the relevant differential diagnoses is important for appropriate treatment, particularly for patients with atypical findings or an intractable course. METHODS: This article is based on publications retrieved by a selective search in PubMed, including current guidelines and expert recommendations. RESULTS: The diagnostic evaluation of a leg ulcer can be structured according to the ABCDE rule. This involves individualized, targeted history-taking (anamnesis); bacteriological testing; clinical examination; ancillary testing, particularly for perfusion (defective vascular system); and extras, such as biopsies. Specifically, we present in this article the main aspects of the complex diagnostic evaluation of venous leg ulcers, arterial leg ulcers, vasculitis, vasculopathy, calciphylaxis, pyoderma gangrenosum, necrobiosis lipoidica, ecthyma, and squamous cell carcinoma. There remain many unsolved problems, including interactions between the various areas of clinical treatment and the relative paucity of relevant high-quality research. CONCLUSION: A timely differential-diagnostic evaluation for the many diseases that can cause leg ulcers, which require treatment from representatives of many different medical specialties and health professions, is a prerequisite for their effective individualized treatment.

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.

Non-Skin Related Symptoms Are Common in Chronic Spontaneous Urticaria and Linked to Active and Uncontrolled Disease: Results From the Chronic Urticaria Registry.

BACKGROUND: Chronic spontaneous urticaria (CSU) can present with non-skin related symptoms (NSRS), including recurrent unexplained fever, joint, bone, or muscle pain (JBMP), and malaise, which also occur in other conditions that manifest with wheals (eg, urticarial vasculitis or autoinflammatory disorders) or without wheals (eg, infection). OBJECTIVE: We sought to determine the rate of patients with CSU affected by fever, JBMP, and malaise, their trigger factors, links with clinical and laboratory characteristics, and their impact on everyday life and treatment responses. METHODS: We analyzed baseline data from the Chronic Urticaria Registry of 2,521 patients with CSU who were aged 16 years or older. RESULTS: One third of CSU patients (31.2%; 786 of 2,521) had one or more NSRS, including recurrent fever (5.3%), JBMP (19.1%), and/or malaise (18.6%). In a multivariable analysis, having one or more of these NSRS correlated with food and infection as trigger factors of urticaria (adjusted odds ratio [aOR] = 1.7 and 1.5), wheals of 24 hours or greater duration (aOR = 2.5), sleep disturbance (aOR = 2.4), anxiety (aOR = 2.8), comorbid atopic dermatitis (aOR = 2.1), gastrointestinal disease (aOR = 1.8), elevated leukocytes (aOR = 1.7) and erythrocyte sedimentation rate (aOR = 1.5). In a bivariate analysis, these NSRS were additionally associated with higher disease activity (weekly Urticaria Activity Score, median: 21 vs 14; P = .009), longer disease duration (years, median: 2 vs 1; P = .001), the presence of angioedema (74.6% vs 58.7%; P < .001), worse quality of life (Chronic Urticaria Quality of Life Questionnaire, median: 42 vs 29; P < .001) and more frequent poor control of CSU (78% vs 69%; P < .001). CONCLUSIONS: The presence of NSRS in a subpopulation of patients with CSU points to the need for better control of the disease, exclusion of comorbid conditions, and/or exclusion of urticarial vasculitis and urticarial autoinflammatory diseases.

Comparison of visual diagnostic accuracy of dermatologists practicing in Germany in patients with light skin and skin of color.

Visual clinical diagnosis of dermatoses in people of color (PoC) is a considerable challenge in daily clinical practice and a potential cause of misdiagnosis in this patient cohort. The study aimed to determine the difference in visual diagnostic skills of dermatologists practicing in Germany in patients with light skin (Ls) and patients with skin of color (SoC) to identify a potential need for further education. From April to June 2023, German dermatologists were invited to complete an online survey with 24 patient photographs depicting 12 skin diseases on both Ls and SoC. The study's primary outcomes were the number of correctly rated photographs and the participants' self-assessed certainty about the suspected visual diagnosis in Ls compared to SoC. The final analysis included surveys from a total of 129 dermatologists (47.8% female, mean age: 39.5 years). Participants were significantly more likely to correctly identify skin diseases by visual diagnostics in patients with Ls than in patients with SoC (72.1% vs. 52.8%, p ≤ 0.001, OR 2.28). Additionally, they expressed higher confidence in their diagnoses for Ls than for SoC (73.9 vs. 61.7, p ≤ 0.001). Therefore, further specialized training seems necessary to improve clinical care of dermatologic patients with SoC.

M.O.I.S.T. Concept for the Local Therapy of Chronic Wounds: An International Update.

Chronic wounds remain a significant clinical challenge both for those affected and for healthcare systems. The treatment is often comprised and complex. All patients should receive wound care that is integrated into a holistic approach involving local management that addresses the underlying etiology and provides for gold standard therapy to support healing, avoid complications and be more cost effective. There have been significant advances in medicine over the last few decades. The development of new technologies and therapeutics for the local treatment of wounds is also constantly increasing. To help standardize clinical practice with regard to the multitude of wound products, the M.O.I.S.T. concept was developed by a multidisciplinary expert group. The M stands for moisture balance, O for oxygen balance, I for infection control, S for supporting strategies, and T for tissue management. Since the M.O.I.S.T. concept, which originated in the German-speaking countries, is now intended to provide healthcare professionals with an adapted instrument to be used in clinical practice, and a recent update to the concept has been undertaken by a group of interdisciplinary experts to align it with international standards. The M.O.I.S.T. concept can now be used internationally both as an educational tool and for the practical implementation of modern local treatment concepts for patients with chronic wounds and can also be used in routine clinical practice.

How effective is simple mechanical wound debridement in reducing bacterial colonisation? Results of a prospective clinical study.

BACKGROUND AND AIMS: Bacteria in wounds can lead to stagnation of wound healing as well as to local or even systemic wound infections up to potentially lethal sepsis. Consequently, the bacterial load should be reduced as part of wound treatment. Therefore, the efficacy of simple mechanical wound debridement should be investigated in terms of reducing bacterial colonisation. PATIENTS AND METHODS: Patients with acute or chronic wounds were assessed for bacterial colonisation with a fluorescence camera before and after mechanical wound debridement with sterile cotton pads. If bacterial colonisation persisted, a second, targeted wound debridement was performed. RESULTS: A total of 151 patients, 68 (45.0%) men and 83 (55.0%) women were included in this study. The male mean age was 71.0 years and the female 65.1 years. By establishing a new analysis method for the image files, we could document that the bacterial colonised areas were distributed 21.9% on the wound surfaces, 60.5% on the wound edges (up to 0.5 cm) and 17.6% on the wound surroundings (up to 1.5 cm). One mechanical debridement achieved a significant reduction of bacterial colonised areas by an average of 29.6% in the wounds, 18.9% in the wound edges and 11.8% in the wound surroundings and was increased by performing it a second time. CONCLUSIONS: It has been shown that even a simple mechanical debridement with cotton pads can significantly reduce bacterial colonisation without relevant side effects. In particular, the wound edges were the areas that were often most contaminated with bacteria and should be included in the debridement with special attention. Since bacteria remain in wounds after mechanical debridement, it cannot replace antimicrobial therapy strategies, but offer a complementary strategy to improve wound care. Thus, it could be shown that simple mechanical debridement is effective in reducing bacterial load and should be integrated into a therapeutic approach to wounds whenever appropriate.

[Acquisition, status and transfer of knowledge in compression therapy : Cross-sectional study in healthcare professions using phlebological compression therapy]. / Wissenserwerb, Wissensstand und Wissenstransfer in der Kompressionstherapie : Querschnittsstudie in Gesundheitsberufen, die phlebologische Kompressionsversorgungen anwenden.

BACKGROUND: Due to scientific progress, healthcare professionals should regularly undergo appropriate continuing education. For this, knowledge transfer is essential. Therefore, the aim of this cross-sectional study was to investigate the acquisition, status and transfer of knowledge of professional groups applying phlebological compression therapy in Germany. MATERIALS AND METHODS: Healthcare professionals (physicians, nurses and medical assistants) received a questionnaire developed for this study, which queried different aspects of acquisition, status and transfer of knowledge. RESULTS: Responses from 522 participants were analysed. The topic of compression therapy was not taught in the nursing or medical education of 43.3%. Specialist journals that address compression therapy were read regularly (at least 6 times/year) by 16.1% of the participants; 63.0% had no specialist books on this subject. Only 6.7% were aware of AWMF ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften") guidelines on the topic and 16.3% of the corresponding DNQP ("Deutsches Netzwerk für Qualitätsentwicklung in der Pflege") expert standard. In all, 41.2% participated in at least one internal training on compression therapy per year, 72.0% in external training and 19.2% in online training. A total of 30.7% stated that they did not use any information sources to acquire knowledge. CONCLUSIONS: Possible sources of knowledge about compression therapy in Germany are insufficiently known within the investigated healthcare professional groups studied or are not regularly used. The result is a considerable knowledge deficit with a discrepancy between the current state of science and practice.

[Compression therapy for inflammatory dermatoses of the legs]. / Kompressionstherapie bei entzündlichen Dermatosen der Beine.

In addition to venous and lymphatic diseases, there is increasing scientific evidence that inflammatory dermatoses of the legs are also indications for compression therapy. Specifically, diseases such as pyoderma gangrenosum, livedoid vasculopathy, cutaneous vasculitides, necrobiosis lipoidica, psoriasis, or erysipelas are conditions for which adjunctive compression therapy may be used when manifestations occur on the lower extremities. When inflammatory dermatoses are accompanied by edema, compression therapy is not an off-label use. Especially because of the often problematic pain symptoms, compression therapy can be performed with low resting pressures around 20 mmHg, especially in inflammatory dermatoses.In this review article, the current scientific aspects of compression therapy in inflammatory dermatoses of the legs and the corresponding limitations are presented in a differentiated manner.

A core domain set for pyoderma gangrenosum trial outcomes: an international eDelphi and consensus study from the UPGRADE initiative.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare ulcerative skin condition with no current standardized outcomes or outcome measures. With a rich investigational therapeutic pipeline, standardization of outcomes and improvement of data quality and interpretability will promote the appropriate and consistent evaluation of potential new therapies. Core outcome sets (COS) are agreed, standardized sets of outcomes that represent the minimum that should be measured and reported in all clinical trials of a specific condition. OBJECTIVES: To identify and reach a consensus on which domains (what to be measured) should be included in the Understanding Pyoderma Gangrenosum: Review and Analysis of Disease Effects (UPGRADE) core domain set for clinical trials in PG. METHODS: Collaborative discussions between patients and PG experts, and a systematic review of the literature identified items and prospective domains. A three-round international eDelphi exercise was performed to prioritize the domains and refine the provisional items (consensus: ≥ 70% of participants rating a domain as 'extremely important' and < 15% of participants voting 'not important'), followed by an international meeting to reach consensus on the core domain set (consensus: < 30% disagreement). Item-generation discussions and consensus meetings were hosted via online videoconferences. The eDelphi exercise and consensus voting were performed using Qualtrics survey software. Participants were adults with PG, healthcare professionals, researchers and industry representatives. RESULTS: Collaborative discussions and systematic reviews yielded 115 items, which were distilled into 15 prospective domains. The eDelphi exercise removed the three lowest-priority domains ('laboratory tests', 'treatment costs' and 'disease impact on family') and ranked 'pain', 'quality of life' and 'physical symptoms' as the highest-priority prospective domains. Consensus was reached on the domains of 'pain', 'quality of life' and 'clinical signs'. The domain of 'disease course/disease progression' narrowly failed to reach consensus for inclusion in the core set (32% of participants voted 'no'). Refinement of this domain definition will be required and presented for consideration at future consensus meetings. CONCLUSIONS: The UPGRADE core domain set for clinical trials in PG has been agreed by international multistakeholder consensus. Future work will develop and/or select outcome measurement instruments for these domains to establish a COS.

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.

Minimum data set for treatment effectiveness in pyoderma gangrenosum (MIDSTEP): an international protocol of an e-Delphi study to develop a clinical physician-driven treatment effectiveness registry on behalf of the UPGRADE initiative.

Pyoderma gangrenosum (PG) is a rare inflammatory condition with an immense disease burden that remains understudied. With limited approved treatments and low-quality clinical evidence, PG continues to have poor patient outcomes. Unfortunately, improvement in PG treatments and patient care is based on additional research endeavors that can only be developed from existing high-quality data. The following protocol outlines the development of the Minimum Data Set for Treatment Effectiveness in Pyoderma gangrenosum (MIDSTEP), a core set of domains and domain items for the Pyoderma Gangrenosum Treatment Effectiveness (PyGaTE) international registry. The outcomes and benefits are focused on providing real-world data for physicians to improve their clinical decisions on PG treatment and inform clinical trial design, promoting clinical research among the international scientific community. MIDSTEP is a multi-phase project. The first phase will produce a domain item list from a literature review to take into the second phase which would finalize the core data set by an e-Delphi exercise. There will be a single stakeholder group participating together in the e-Delphi consisting of PG experts (healthcare providers, researchers, methodologists, industry representatives, and regulators), ulcerative PG patients, and PG patient advocates. The methodology outlined in the protocol is a systematic method based on several guidelines through COMET and established dermatologic registries and outcome sets with systematic methodologies of their own. The third phase will identify the instruments for the items, the 'when to measure' the items, and the platform for the registry. The last phase is the implementation and continued maintenance of the international registry PyGaTE. By solidifying a consensus on standardized outcomes and collecting information on PG treatment effectiveness in a centralized database, existing treatments can be compared more systematically and analyzed with increased evidence. MIDSTEP and the PyGaTE international registry will have the ambitious goal to generate and disseminate real-world data that can be used by all stakeholders to improve health outcomes for PG patients. Future potential for the outcome of this project includes the development of a gold-standard PG treatment.

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.

Patients With Chronic Spontaneous Urticaria Who Have Wheals, Angioedema, or Both, Differ Demographically, Clinically, and in Response to Treatment-Results From CURE.

BACKGROUND: Patients with chronic spontaneous urticaria (CSU) have spontaneous wheals (W), angioedema (AE), or both, for longer than 6 weeks. Clinical differences between patients with standalone W, standalone AE, and W and AE (W+AE) remain incompletely understood. OBJECTIVE: To compare W, AE, and W+AE CSU patients regarding demographics, disease characteristics, comorbidities, disease burden, and treatment response. METHODS: Baseline data from 3,698 CSU patients in the ongoing, prospective, international, multicenter, observational Chronic Urticaria REgistry (CURE) were analyzed (data cut: September 2022). RESULTS: Across all CSU patients, 59%, 36%, and 5% had W+AE, W, and AE, respectively. The W+AE patients, compared with W and AE patients, showed the lowest male-to-female ratio (0.33), higher rates of concomitant psychiatric disease (17% vs 11% vs 6%, respectively), autoimmune disease (13% vs 7% vs 9%, respectively), and nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity (9% vs 5% vs 2%, respectively) and the highest disease impact. The W patients, compared with W+AE and AE patients, showed the lowest rates of concomitant hypertension (15% vs 21% vs 40%, respectively) and obesity (11% vs 16% vs 17%, respectively), the highest rate of concomitant inducible urticaria (24% vs 22% vs 6%, respectively), and shorter W duration. The AE patients, compared with W+AE and W patients, were older at disease onset, showed longer AE duration, and the best response to increased doses of H1-antihistamines (58% vs 24% vs 31%, respectively) and omalizumab (92% vs 67% vs 60%, respectively). CONCLUSIONS: Our findings provide a better understanding of CSU phenotypes and may guide patient care and research efforts that aim to link them to pathogenic drivers.