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

MRSA eradication in dermatologic outpatients theory and practice

Background: The dissemination of methicillin resistant staphylococcus aureus (MRSA) is an increasing challenge in medical care. Apart from hospital acquired MRSA, there has also been an increase in community acquired and livestock associated MRSA. While the risks of MRSA (e. g. wound infections) and consequences (e. g. rejection of patients) are well known, there are little data on the effectiveness of eradication procedures. Patients and methods: 32 patients with proven MRSA colonization were monitored during eradication for the following aspects: (1) localization of MRSA (swabs from hairline, anterior nares, throat, axillae, groins, perineum, and wounds, if present), (2) presence of eradication-impairing factors, (3) length of time needed for eradication, (4) cost of eradication, (5) molecular fingerprint and risk assessment (spa-types). Results: We describe the successful eradication of MRSA in all 32 patients. Most positive nasal swabs were obtained from the anterior nares and the throat and only rarely from the hairline or axillae. The greater the number of positive swabs, the more time was needed for eradication. In most patients (37.5 %), eradication with topical antiseptics was successful. The average time for eradication was 12.97 (+/- 7.6) days. Twelve patients required systemic antibiotic therapy. Treatment costs associated with the use of systemic antibiotics were significantly higher. The most frequent spa types were t032 and t003. Conclusions: We report successful MRSA eradication in outpatients. Systemic antibiotics are unnecessary in the majority of patients. A combined anti-MRSA strategy for inpatients and outpatients is recommended

Proteinase-activated receptor-2 agonist activates anti-influenza mechanisms and modulates IFNγ induced antiviral pathways in human neutrophils

Proteinase-activated receptor-2 (PAR2) is expressed by human leukocytes and participates in the development of inflammatory diseases. Recent studies demonstrated an ability of PAR2 agonist to enhance IFNγ-induced antiviral responses of human leukocytes. However, the precise cellular antiviral defense mechanisms triggered in leukocytes after stimulation with IFNγ and/or PAR2 agonist remain elusive. Therefore, we aimed to identify neutrophil defense mechanisms involved in antiviral resistance. Here we demonstrated that PAR2 agonist enhanced IFNγ-related reduction of influenza A virus (IAV) replication in human neutrophils. PAR2-mediated decrease in IAV replication was associated with reduced NS-1 transcription. Moreover, PAR2-dependent neutrophil activation resulted in enhanced myeloperoxidase degranulation and extracellular myeloperoxidase disrupted IAV. The production of ROS was elevated in response to PAR2 activation. Interestingly, IFNγ did not influence both effects: PAR2 agonist-triggered myeloperoxidase (MPO) release and reactive oxygen species (ROS) production, which are known to limit IAV infections. In contrast, orthomyxovirus resistance gene A (MxA) protein expression was synergistically elevated through PAR2 agonist and IFNγ in neutrophils. Altogether, these findings emphasize two PAR2-controlled antiviral mechanisms that are independent of or modulated by IFNγ

Modern wound care - practical aspects of non-interventional topical treatment of patients with chronic wounds

The treatment of patients with chronic wounds is becoming increasingly complex. It was therefore the aim of the members of the working group for wound healing (AGW) of the German Society of Dermatology (DDG) to report on the currently relevant aspects of non-interventional, topical wound treatment for daily practice. Beside necessary procedures, such as wound cleansing and debridement, we describe commonly used wound dressings, their indications and practical use. Modern antiseptics, which are currently used in wound therapy, usually contain polyhexanide or octenidine. Physical methods, such as negative-pressure treatment, are also interesting options. It is always important to objectify and adequately treat pain symptoms which often affect these patients. Modern moist wound therapy may promote healing, reduce complications, and improve the quality of life in patients with chronic wounds. Together with the improvement of the underlying causes, modern wound therapy is an important aspect in the overall treatment regime for patients with chronic wounds

Integrin-independent role of CalDAG-GEFI in neutrophil chemotaxis

Chemotaxis and integrin activation are essential processes for neutrophil transmigration in response to injury. CalDAG-GEFI plays a key role in the activation of β1, β2, and β3 integrins in platelets and neutrophils by exchanging a GDP for a GTP on Rap1. Here, we explored the role of CalDAG-GEFI and Rap1b in integrin-independent neutrophil chemotaxis. In a transwell assay, CalDAG-GEFI−/− neutrophils had a 46% reduction in transmigration compared with WT in response to a low concentration of LTB4. Visualization of migrating neutrophils in the presence of 10 mM EDTA revealed that CalDAG-GEFI−/− neutrophils had abnormal chemotactic behavior compared with WT neutrophils, including reduced speed and directionality. Interestingly, Rap1b−/− neutrophils had a similar phenotype in this assay, suggesting that CalDAG-GEFI may be acting through Rap1b. We investigated whether the deficit in integrin-independent chemotaxis in CalDAG-GEFI−/− neutrophils could be explained by defective cytoskeleton rearrangement. Indeed, we found that CalDAG-GEFI−/− neutrophils had reduced formation of F-actin pseudopodia after LTB4 stimulation, suggesting that they have a defect in polarization. Overall, our studies show that CalDAG-GEFI helps regulate neutrophil chemotaxis, independent of its established role in integrin activation, through a mechanism that involves actin cytoskeleton and cellular polarization