Dermatologische Proktologie: Eine Übersicht anhand des Pruritus ani

Zusammenfassung: Pruritus ani ist eines der häufigsten Symptome, die den Patienten in die proktologische Sprechstunde führen. Als Ursache können zahlreiche Krankheiten zugrunde liegen. Bei einem Großteil aller Patienten mit Pruritus ani finden sich dermatologische Ursachen. Fast jede Dermatose kann sich auch perianal manifestieren und zu Pruritus führen. Eine Blickdiagnose ist selten möglich, da die klinische Präsentation häufig atypisch ist. So sind für die Diagnosestellung neben ausführlicher Anamnese und körperlicher Untersuchung mit Ganzkörperhautstatus mikrobiologische und allergologische Abklärungen sowie eine Hautbiopsie wichtige diagnostische Maßnahmen. Begleitend zur Behandlung der Grundkrankheit empfiehlt sich als Basistherapie eine milde Reinigung mit seifenfreiem Wasser, anschließendem vorsichtigen Trocknen sowie die Anwendung von rückfettenden oder zinkhaltigen Extern

IL-31 expression by inflammatory cells is preferentially elevated in atopic dermatitis

Interleukin-31 (IL-31) is a recently discovered cytokine expressed in many human tissues, and predominantly by activated CD4+ T cells. IL-31 signals through a heterodimeric receptor consisting of IL-31 receptor alpha (IL-31RA) and oncostatin M receptor beta (OSMR). Earlier studies have shown involvement of IL-31 and its receptor components IL-31RA and OSMR in atopic dermatitis, pruritus and Th2-weighted inflammation at the mRNA level. The aim of this study was to investigate IL-31 protein expression in skin of such conditions. Immunohisto-chemical staining for IL-31, IL-31RA and OSMR was performed in formalin-fixed paraffin-embedded biopsy specimens. IL-31 expression was increased in the inflammatory infiltrates from skin biopsies taken from subjects with atopic dermatitis, compared with controls (p ≤ 0.05). IL-31, IL-31RA and OSMR protein immunoreactivity was not increased in biopsies from subjects with other Th2-weighted and pruritic skin diseases. Our results confirm, at the protein level, the relationship between IL-31 expression and atopic dermatitis. Our results do not support a general relationship between expression of IL-31/IL-31R and pruritic or Th2-mediated diseases

CARD14 Gain-of-Function Mutation Alone Is Sufficient to Drive IL-23/IL-17-Mediated Psoriasiform Skin Inflammation In Vivo.

Rare autosomal dominant mutations in the gene encoding the keratinocyte signaling molecule CARD14, have been associated with an increased susceptibility to psoriasis, but the physiological impact of CARD14 gain-of-function mutations remains to be fully determined in vivo. Here, we report that heterozygous mice harboring a CARD14 gain-of-function mutation (Card14ΔE138) spontaneously develop a chronic psoriatic phenotype with characteristic scaling skin lesions, epidermal thickening, keratinocyte hyperproliferation, hyperkeratosis, and immune cell infiltration. Affected skin of these mice is characterized by elevated expression of anti-microbial peptides, chemokines, and cytokines (including T helper type 17 cell-signature cytokines) and an immune infiltrate rich in neutrophils, myeloid cells, and T cells, reminiscent of human psoriatic skin. Disease pathogenesis was driven by the IL-23/IL-17 axis, and neutralization of IL-23p19, the key cytokine in maintaining T helper type 17 cell polarization, significantly reduced skin lesions and the expression of antimicrobial peptides and proinflammatory cytokines. Therefore, hyperactivation of CARD14 alone is sufficient to orchestrate the complex immunopathogenesis that drives T helper type 17-mediated psoriasis skin disease in vivo

Getting to implementation: Adaptation of an implementation playbook

IntroductionImplementation strategies supporting the translation of evidence into practice need to be tailored and adapted for maximum effectiveness, yet the field of adapting implementation strategies remains nascent. We aimed to adapt “Getting To Outcomes”® (GTO), a 10-step implementation playbook designed to help community-based organizations plan and evaluate behavioral health programs, into “Getting To Implementation” (GTI) to support the selection, tailoring, and use of implementation strategies in health care settings.MethodsOur embedded evaluation team partnered with operations, external facilitators, and site implementers to employ participatory methods to co-design and adapt GTO for Veterans Health Administration (VA) outpatient cirrhosis care improvement. The Framework for Reporting Adaptations and Modifications to Evidenced-based Implementation Strategies (FRAME-IS) guided documentation and analysis of changes made pre- and post-implementation of GTI at 12 VA medical centers. Data from multiple sources (interviews, observation, content analysis, and fidelity tracking) were triangulated and analyzed using rapid techniques over a 3-year period.ResultsAdaptations during pre-implementation were planned, proactive, and focused on context and content to improve acceptability, appropriateness, and feasibility of the GTI playbook. Modifications during and after implementation were unplanned and reactive, concentrating on adoption, fidelity, and sustainability. All changes were collaboratively developed, fidelity consistent at the level of the facilitator and/or implementer.ConclusionGTO was initially adapted to GTI to support health care teams' selection and use of implementation strategies for improving guideline-concordant medical care. GTI required ongoing modification, particularly in steps regarding team building, context assessment, strategy selection, and sustainability due to difficulties with step clarity and progression. This work also highlights the challenges in pragmatic approaches to collecting and synthesizing implementation, fidelity, and adaptation data.Trial registrationThis study was registered on ClinicalTrials.gov (Identifier: NCT04178096)

Identification of B Cell Epitopes of Alcohol Dehydrogenase Allergen of Curvularia lunata

BACKGROUND/OBJECTIVE: Epitope identification assists in developing molecules for clinical applications and is useful in defining molecular features of allergens for understanding structure/function relationship. The present study was aimed to identify the B cell epitopes of alcohol dehydrogenase (ADH) allergen from Curvularia lunata using in-silico methods and immunoassay. METHOD: B cell epitopes of ADH were predicted by sequence and structure based methods and protein-protein interaction tools while T cell epitopes by inhibitory concentration and binding score methods. The epitopes were superimposed on a three dimensional model of ADH generated by homology modeling and analyzed for antigenic characteristics. Peptides corresponding to predicted epitopes were synthesized and immunoreactivity assessed by ELISA using individual and pooled patients' sera. RESULT: The homology model showed GroES like catalytic domain joined to Rossmann superfamily domain by an alpha helix. Stereochemical quality was confirmed by Procheck which showed 90% residues in most favorable region of Ramachandran plot while Errat gave a quality score of 92.733%. Six B cell (P1-P6) and four T cell (P7-P10) epitopes were predicted by a combination of methods. Peptide P2 (epitope P2) showed E(X)(2)GGP(X)(3)KKI conserved pattern among allergens of pathogenesis related family. It was predicted as high affinity binder based on electronegativity and low hydrophobicity. The computational methods employed were validated using Bet v 1 and Der p 2 allergens where 67% and 60% of the epitope residues were predicted correctly. Among B cell epitopes, Peptide P2 showed maximum IgE binding with individual and pooled patients' sera (mean OD 0.604±0.059 and 0.506±0.0035, respectively) followed by P1, P4 and P3 epitopes. All T cell epitopes showed lower IgE binding. CONCLUSION: Four B cell epitopes of C. lunata ADH were identified. Peptide P2 can serve as a potential candidate for diagnosis of allergic diseases

Impact of Aspergillus fumigatus in allergic airway diseases

For decades, fungi have been recognized as associated with asthma and other reactive airway diseases. In contrast to type I-mediated allergies caused by pollen, fungi cause a large number of allergic diseases such as allergic bronchopulmonary mycoses, rhinitis, allergic sinusitis and hypersensitivity pneumonitis. Amongst the fungi, Aspergillus fumigatus is the most prevalent cause of severe pulmonary allergic disease, including allergic bronchopulmonary aspergillosis (ABPA), known to be associated with chronic lung injury and deterioration in pulmonary function in people with chronic asthma and cystic fibrosis (CF). The goal of this review is to discuss new understandings of host-pathogen interactions in the genesis of allergic airway diseases caused by A. fumigatus. Host and pathogen related factors that participate in triggering the inflammatory cycle leading to pulmonary exacerbations in ABPA are discussed

Identification of Critical Amino Acids in an Immunodominant IgE Epitope of Pen c 13, a Major Allergen from Penicillium citrinum

Background: Pen c 13, identified as a 33-kDa alkaline serine protease, is a major allergen secreted by Penicillium citrinum. Detailed knowledge about the epitopes responsible for IgE binding would help inform the diagnosis/prognosis of fungal allergy and facilitate the rational design of hypoallergenic candidate vaccines. The goal of the present study was to characterize the IgE epitopes of Pen c 13. Methodology/Principal Findings: Serum samples were collected from 10 patients with mold allergy and positive Pen c 13 skin test results. IgE-binding epitopes on rPen c 13 were mapped using an enzymatic digestion and chemical cleavage method, followed by dot-blotting and mass spectrometry. A B-cell epitope-predicting server and molecular modeling were used to predict the residues most likely involved in IgE binding. Theoretically predicted IgE-binding regions were further confirmed by site-directed mutagenesis assays. At least twelve different IgE-binding epitopes located throughout Pen c 13 were identified. Of these, peptides S16 (A 148 –E 166) and S22 (A 243 –K 274) were recognized by sera from 90 % and 100 % of the patients tested, and were further confirmed by inhibition assays. Peptide S22 was selected for further analysis of IgE-binding ability. The results of serum screening showed that the majority of IgE-binding ability resided in the C-terminus. One Pen c 13 mutant, G270A (T 261 –K 274), exhibited clearly enhanced IgE reactivity, whereas another, K274A, exhibited dramatically reduced IgE reactivity