Current Developments in the Immunology of Psoriasis.

Psoriasis is a frequent inflammatory skin disease. Fundamental research on the pathogenesis of psoriasis has substantially increased our understanding of skin immunology, which has helped to introduce innovative and highly effective therapies. Psoriasis is a largely T lymphocyte-mediated disease in which activation of innate immune cells and pathogenic T cells result in skin inflammation and hyperproliferation of keratinocytes. B cells have thus far largely been neglected regarding their role for the pathogenesis of psoriasis. However, recent data shed light on their role in inflammatory skin diseases. Interestingly, interleukin (IL)-10-producing regulatory B cells have been assumed to ameliorate psoriasis. In this review, we will discuss the development of disease, pathogenicity, and current developments in therapeutic options. We describe different roles of T cells, B cells, and cytokines for the immunopathology and disease course of psoriasis.

Patient-Centered Chronic Wound Care Mobile Apps: Systematic Identification, Analysis, and Assessment.

Background: The prevalence of chronic wounds is predicted to increase within the aging populations in industrialized countries. Patients experience significant distress due to pain, wound secretions, and the resulting immobilization. As the number of wounds continues to rise, their adequate care becomes increasingly costly in terms of health care resources worldwide. eHealth support systems are being increasingly integrated into patient care. However, to date, no systematic analysis of such apps for chronic wounds has been published. Objective: The aims of this study were to systematically identify and subjectively assess publicly available German- or English-language mobile apps for patients with chronic wounds, with quality assessments performed by both patients and physicians. Methods: Two reviewers independently conducted a systematic search and assessment of German- or English-language mobile apps for patients with chronic wounds that were available in the Google Play Store and Apple App Store from April 2022 to May 2022. In total, 3 apps met the inclusion and exclusion criteria and were reviewed independently by 10 physicians using the German Mobile App Rating Scale (MARS) and the System Usability Scale (SUS). The app with the highest mean MARS score was subsequently reviewed by 11 patients with chronic wounds using the German user version of the MARS (uMARS) and the SUS. Additionally, Affinity for Technology Interaction (ATI) scale scores were collected from both patients and physicians. Results: This study assessed mobile apps for patients with chronic wounds that were selected from a pool of 118 identified apps. Of the 73 apps available in both app stores, 10 were patient oriented. After excluding apps with advertisements or costs, 3 apps were evaluated by 10 physicians. Mean MARS scores ranged from 2.64 (SD 0.65) to 3.88 (SD 0.65) out of 5, and mean SUS scores ranged from 50.75 (SD 27) to 80.5 (SD 17.7) out of 100. WUND APP received the highest mean MARS score (mean 3.88, SD 0.65 out of 5) among physicians. Hence, it was subsequently assessed by 11 patients and achieved a similar rating (uMARS score: mean 3.89, SD 0.4 out of 5). Technical affinity, as measured with the ATI scale, was slightly lower in patients (score: mean 3.62, SD 1.35 out of 6) compared to physicians (score: mean 3.88, SD 1.03 out 6). Conclusions: The quality ratings from physicians and patients were comparable and indicated mediocre app quality. Technical affinity, as assessed by using the ATI scale, was slightly lower for patients. Adequate apps for patients with chronic wounds remain limited, emphasizing the need for improved app development to meet patient needs. The ATI scale proved valuable for assessing technical affinity among different user groups.

Delayed-Type Heparin Allergy: Intravenous Tolerance Despite Inflammatory Skin Reaction After Subcutaneous Injection.

BACKGROUND: Heparin allergy most frequently manifests as delayed-type hypersensitivity (DTH) causing an itchy inflammatory skin reaction at the site of subcutaneous injection. An important differential diagnosis is circumscribed skin necrosis due to heparin-induced thrombocytopenia. OBJECTIVES: An inflammatory skin reaction to subcutaneously injected heparin generally entails the quest for alternative anticoagulation; concerns may particularly arise in an emergency situation requiring intravenous heparin administration. METHODS: All heparin DTH cases seen in our department over the last 17 years underwent standardized allergy diagnostics including challenge testing, that is, subcutaneous injection of fondaparinux and intravenous administration of unfractionated heparin (UFH). RESULTS: Of a total of 50 patients with confirmed heparin allergy, DTH was found in 48 (96.0%), and immediate-type, presumably IgE-mediated hypersensitivity was diagnosed in only 2 (4.0%). In the 48 DTH cases, intradermal testing revealed broad cross-reactivity between UFH and low-molecular-weight heparins (LMWH) including nadroparin, dalteparin, and enoxaparin. Cross-reactivity with (or concomitant sensitization to) fondaparinux was seen in only 3 (6.3%) cases. Intravenous administration of UFH was tolerated by all 45 patients challenged, despite DTH to UFH and LMWH as demonstrated by intradermal testing. CONCLUSIONS: If an inflammatory skin reaction at the site of subcutaneously injected heparin is observed or reported without any evidence of skin necrosis or thrombocytopenia, intravenous administration of UFH seems to be sufficiently safe and may be considered without allergy testing if urgently indicated in an emergency situation. Fondaparinux is the most suitable alternative for subcutaneous application.

Response to combined ipilimumab and nivolumab after development of a nephrotic syndrome related to PD-1 monotherapy.

BACKGROUND: High response rates of metastatic melanoma have been reported upon immune checkpoint inhibition by PD-1 blockade alone or in combination with CTLA-4 inhibitors. However, the majority of patients with a primary resistance to anti-PD-1 monotherapy is also refractory to a subsequent combined checkpoint inhibition. In BRAF wildtype patients with a primary resistance to PD-1 inhibitors, therapeutic options are therefore limited and immune-related adverse events (irAE) have to be taken into consideration when discussing a subsequent immunotherapy. CASE PRESENTATION: We report the case of a 68-year-old male patient with metastatic melanoma who experienced an acute renal failure with nephrotic syndrome due to a minimal change disease developing after a single dose of the anti-PD-1 antibody pembrolizumab. A kidney biopsy revealed a podocytopathy without signs of interstitial nephritis. Renal function recovered to almost normal creatinine and total urine protein levels upon treatment with oral steroids and diuretics. Unfortunately, a disease progression (PD, RECIST 1.1) was observed in a CT scan after resolution of the irAE. In a grand round, re-exposure to a PD-1-containing regime was recommended. Consensually, a combined immunotherapy with ipilimumab and nivolumab was initiated. Nephrotoxicity was tolerable during combined immunotherapy and a CT scan of chest and abdomen showed a deep partial remission (RECIST 1.1) after three doses of ipilimumab (3 mg/kg) and nivolumab (1 mg/kg). CONCLUSION: This case illustrates that a fulminant response to combined checkpoint inhibition is possible after progression after anti-PD-1 monotherapy and a severe irAE.

T Cells Control Chemokine Secretion by Keratinocytes.

The massive infiltration of lymphocytes into the skin is a hallmark of numerous human skin disorders. By co-culturing murine keratinocytes with splenic T cells we demonstrate here that T cells affect and control the synthesis and secretion of chemokines by keratinocytes. While pre-activated CD8+T cells induce the synthesis of CXCL9 and CXCL10 in keratinocytes and keep in check the synthesis of CXCL1, CXCL5, and CCL20, keratinocytes dampen the synthesis of CCL3 and CCL4 in pre-activated CD8+T cells. One key molecule is IFN-γ that is synthesized by CD8+T cells under the control of NFATc1 and NFATc2. CD8+T cells deficient for both NFAT factors are unable to induce CXCL9 and CXCL10 expression. In addition, CD8+T cells induced numerous type I IFN-inducible "defense genes" in keratinocytes encoding the PD1 and CD40 ligands, TNF-α and caspase-1. The enhanced expression of type I IFN-inducible genes resembles the gene expression pattern at the dermal/epidermal interface in lichen planus, an inflammatory T lymphocyte-driven skin disease, in which we detected the expression of CXCL10 in keratinocytes in close vicinity to the infiltration front of T cells. These data reflect the multifaceted interplay of lymphocytes with keratinocytes at the molecular level.