Interleukin antagonists for atopic dermatitis: a new era of therapy.

INTRODUCTION: Over the last decade, increasing understanding of the immunopathogenesis of atopic dermatitis (AD) enabled the recognition of multiple therapeutic targets and subsequently the development of novel, highly effective systemic treatments, including interleukin (IL)-antagonists. To date, the IL-4Ra-inhibitor dupilumab, and the IL-13 inhibitor tralokinumab, have gained regulatory approval in Europe for the treatment of moderate-to-severe AD, while more than 70 new therapeutics are currently in development. AREAS COVERED: In this review, we address the role of ILs in the pathogenesis of AD and provide an overview of the novel and investigational IL-antagonists, as regards their efficacy and safety on moderate-to-severe AD. EXPERT OPINION: Current data have established IL-4 and IL-13 inhibitors as effective and safe for the treatment of moderate-to-severe AD, as regards the rapid control of flares as well as the long-term remission of the disease. Data regarding the efficacy and safety of other IL-inhibitors, including those targeting IL-31, IL-22, IL-33, IL-36 and IL-18, are accumulating. There is still an unmet need for real-world-evidence studies and head-to-head studies for both currently available and future agents in AD treatment. Establishing predictive biomarkers of treatment response in a disorder of such considerable heterogenicity might help physicians pursue a patient-tailored therapeutic response.

Editorial for the Special Issue "Skin and Cutaneous Adnexal Tumors: Diagnosis and Management".

We are delighted to present the Special Issue on "Skin and Cutaneous Adnexal Tumors: Diagnosis and Management" in Diagnostics [...].

Color Analysis of Merkel Cell Carcinoma: A Comparative Study with Cherry Angiomas, Hemangiomas, Basal Cell Carcinomas, and Squamous Cell Carcinomas.

Merkel cell carcinoma (MCC) is recognized as one of the most malignant skin tumors. Its rarity might explain the limited exploration of digital color studies in this area. The objective of this study was to delineate color alterations in MCCs compared to benign lesions resembling MCC, such as cherry angiomas and hemangiomas, along with other non-melanoma skin cancer lesions like basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), utilizing computer-aided digital color analysis. This was a retrospective study where clinical images of the color of the lesion and adjacent normal skin from 11 patients with primary MCC, 11 patients with cherry angiomas, 12 patients with hemangiomas, and 12 patients with BCC/SCC (totaling 46 patients) were analyzed using the RGB (red, green, and blue) and the CIE Lab color system. The Lab color system aided in estimating the Individual Typology Angle (ITA) change in the skin, and these results are documented in this study. It was demonstrated that the estimation of color components can assist in the differential diagnosis of these types of lesions because there were significant differences in color parameters between MCC and other categories of skin lesions such as hemangiomas, common skin carcinomas, and cherry hemangiomas. Significant differences in values were observed in the blue color of RGB (p = 0.003) and the b* parameter of Lab color (p < 0.0001) of MCC versus cherry angiomas. Similarly, the mean a* value of Merkel cell carcinoma (MCC) compared to basal cell carcinoma and squamous cell carcinoma showed a statistically significant difference (p < 0.0001). Larger prospective studies are warranted to further validate the clinical application of these findings.

Resorcinol 10% as a Promising Therapeutic Option for Mild Hidradenitis Suppurativa: A Prospective, Randomized, Open Study.

Introduction: Treatment of hidradenitis suppurativa (HS) is challenging, and in Hurley stage I, it is based on topical measures. Our aim was to compare the efficacy and safety of topical resorcinol 10% with topical clindamycin 1% and no therapy, in Hurley stage I HS. Methods: In this open, prospective, randomized trial, we studied 60 Hurley stage I patients with IHS4 ≤10. Group A was treated with topical resorcinol 10%; group B with clindamycin lotion 1%; and group C received no treatment. Patients were evaluated by total lesion count, the International Hidradenitis Suppurativa Severity Score System (IHS4) and the Dermatology Life Quality Index (DLQI) at baseline, 12 and 24 weeks. Self-reported number of flares and adverse events (AEs) were recorded. Results: A significant reduction in the mean total lesion count and DLQI scores were observed in group A, compared to group B at week 12 (p = 0.036, p < 0.001, respectively), and in the mean total lesion count, IHS4, and DLQI scores at week 24 (p = 0.034, p = 0.017, p < 0.001, respectively). Resorcinol 10% was well-tolerated with only mild AEs. Conclusion: Resorcinol 10% may represent a useful alternative for the long-term treatment of mild HS, which is superior to topical clindamycin and has a favorable safety profile.

Real-Life Utility of Basophil Activation Test in the Diagnosis of Immediate Hypersensitivity Drug Reactions.

INTRODUCTION: The basophil activation test (BAT) is a flow cytometry laboratory technique that assesses the level of activation indicators expressed on the surface of basophils. We conducted a real-life study in a prospective cohort of patients with reported drug hypersensitivity reactions to determine the true relevance of BAT as a diagnostic tool for assessing immediate hypersensitivity reactions to medicines. METHODS: We prospectively assessed individuals with clinical suspicion of immediate hypersensitivity reactions to drugs over a 2-year period. The allergological evaluation was carried out in accordance with European Academy of Allergy and Clinical Immunology (EAACI) guidance. All patients underwent BAT using the activation marker CD63. RESULTS: In total 13 patients with 54 reported immediate drug hypersensitivity reactions to medications were included in this study. Twelve were female (92.3%) and one was male (7.70%). The mean ± SD age of the patients was 47.31 ± 19.94 years. Antibiotics were tested in 35.2% (19/54) of patients, corticosteroids in 24.1% (13/54), iodinated contrast medium in 14.8% (8/54), and NSAIDs in 5.6% (3/54). There was no correlation between the BAT results and the age of patients, gender, type of medication, or time interval between the allergic reaction and BAT procedure. The sensitivity of BAT 5% CD63+ basophils to drugs was 97.6%, specificity was 96% for drug allergies, positive predictive value (PPV) was 94.3%, and negative predictive value (NPV) was 95.2%. CONCLUSIONS: The sensitivity of BAT for drug allergies is limited, but it can nevertheless be very helpful before contemplating provocation testing in cases of life-threatening drug allergies where patients cannot be rechallenged or in cases of medications for which no other tests are available or their results are ambiguous.

A narrative review of management of wounds in palliative care setting.

BACKGROUND AND OBJECTIVE: A chronic wound is one that is physiologically compromised as a result of a disturbance of the wound-healing cycle brought on by, among other parameters, poor angiogenesis, innervation, or cellular migration. Given the high frequency and incidence rates of different wound categories in clinical practice in the setting of chronically ill patients, wound management is becoming an increasingly important component and pillar of the overall care of patients with terminal illnesses. The purpose of this narrative review is to provide an overview and evaluation of the assessment methods and management of chronic wounds in the clinical practice of palliative care. METHODS: Papers on the management of wounds in palliative care have been retrieved using PubMed to July 2023. The search terms used included "wounds", "ulcers", "palliative care", "palliative management", and "end of life". KEY CONTENT AND FINDINGS: The review highlights the importance of early palliative care referral and total pain management in the management of wounds. Patients with wounds often report multiple symptoms, and pain is one of the most common and distressing among them. Despite the availability of multiple guidelines about treatment to relieve pain, almost half of all cancer patients still receive inappropriate care for pain. The review also discusses the etiology of pain and provides strategies for managing the painful wound once it has been identified. The greatest need today in the treatment of chronic wounds is consensus-based knowledge vetted by practical experience and backed up by scientific evidence, which is easily communicated and available to all wound care practitioners. CONCLUSIONS: High-quality research together with wound care practice that leads to the best outcomes might include pain reduction, exudate management, odor management, and/or other quality-of-life benefits to wound care. There is a need for specialized palliative care teams to manage expectations throughout the process while maintaining hope.

Biomechanical explanation of W-plasty effectiveness using a finite element method approach.

The finite element method has often been used to assist analyzing local flaps in terms of deformation and stress measurements as it takes into account complex skin properties. We, herein, present an isotropic two-dimensional finite element skin model applied to the W-plasty method to demonstrate that the good outcomes of W-plasty should be attributed to the geometry itself, as it generates lower stresses. The skin was modeled as a two-dimensional (2D) planar geometry. The model was created and solved as a plane stress problem. The model was based on simulation of the loading and stitching of W-plasties of various angles. Each central triangular flap was segmented in nine triangular elements. The stitching was modeled with one suture at the top of each triangular flap with the center of the opposite corner. X- and Y-axis stresses and shearing stresses Txy in the elements involved in the broken stitching line, show lower stresses than the elements behind the stitching line. Interestingly, in the triangular flaps, the stresses were clearly lower than those of their neighboring areas. The maximum compressive stresses in the 2D model we used, correspond to the dog ears. We conclude that the effectiveness of W-plasty should be attributed not only to the scar orientation in relation to the relaxed tension skin lines but also to the special design of the triangular flaps used. This finding assists the general understanding of the method and should be taken into account by the clinician during flap designing.

Responsiveness and Minimal Clinically Important Difference of the Infants and Toddlers Dermatology Quality of Life Questionnaire.

BACKGROUND: The Infants and Toddlers Dermatology Quality of Life (InToDermQoL) is the dermatology-specific proxy health-related quality of life (HRQoL) instrument for children from birth to 4 years. The aim of the present study was to confirm the responsiveness and establish minimal clinically important difference (MCID) for the InToDermQoL. METHODS: Parents of children with skin diseases were asked to fill in the InToDermQoL at the initial visit (T1) and subsequent consultation (T2). We hypothesized that correlations between change scores of the InToDermQoL and change scores of global assessment of clinical severity by dermatologists and by patients' parents should be above 0.3. The receiver operating characteristic (ROC) curves method was also used for confirmation of responsiveness and determination of MCIDs of the InToDermQoL. The area under the ROC curve (AUC) was used as an indicator of responsiveness. RESULTS: Results of 442 patients were included. Correlations between change scores of age-specific versions of the InToDermQoL and change scores of global assessment of clinical severity by dermatologists and by patients' parents were above 0.3 (0.46-0.74). AUCs for age-specific versions of the InToDermQoL were acceptable (above 0.7) or excellent (above 0.8). Estimated MCIDs for the InToDermQoL were as follows: 3 points of total score change for 0-11 months, 5 for 1-2 years and 3 or 4 for 3-4 years version. Estimated MCIDs for the InToDermQoL version for 1-2-year-old children was higher than MCIDs for the 3-4-year-old version despite the higher number of items in the latter. Therefore a MCID of 5 was recommended for both these versions. CONCLUSIONS: Responsiveness for all age-specific versions of the InToDermQoL questionnaire was confirmed. MCIDs for the InToDermQoL are proposed as follows: 3-point change of the total score for age version 0-11 months and 5-point for the age versions 1-2 years and 3-4 years.

Eccrine Porocarcinoma: A Review of the Literature.

Eccrine porocarcinoma (EPC) constitutes a rare malignant adnexal tumor, which accounts for about 0.005-0.01% of all cutaneous malignancies. It may develop de novo or arise from an eccrine poroma, after a latency period of years or even decades. Accumulating data suggest that specific oncogenic drivers and signaling pathways may be implicated in its tumorigenesis, while recent data have demonstrated a high overall mutation rate attributed to UV exposure. Diagnosis may be challenging and should rely on the combination of clinical, dermoscopical, histopathological and immunohistochemical findings. The literature is controversial regarding tumor behavior and prognosis and, therefore, there is no consensus on its surgical management, utility of lymph-node biopsy and further adjuvant or systemic treatment. However, recent advances in tumorigenesis of EPC may aid in the development of novel treatment strategies, which could improve survival of advanced or metastatic disease, such as immunotherapy. This review presents an update of the epidemiology, pathogenesis and clinical presentation of EPC and summarizes current data on diagnostic evaluation and management of this rare cutaneous malignancy.

Cutaneous body image in patients with hidradenitis suppurativa: a hospital-based cross-sectional study.

Hidradenitis suppurativa (HS) has been linked with body image (BI) impairment and reduced quality of life (QoL). We sought to evaluate the associations between Cutaneous Body Image Scale (CBIS) and disease severity in HS patients.Between July 2020 and January 2022, a cross-sectional study was carried out including consecutive HS patients above the age of 16 who attended a Tertiary Referral Hospital in Greece. Disease Severity was graded with the Hurley stage, HS-Physician's Global Assessment (HS-PGA) scale, and the Modified Sartorius scale (MSS). Patients completed at their first visit ten survey instruments including Patients' Severity of disease, pain and pruritus scale, CBIS, Multidimensional Body-Self Relations Questionnaire (MBSRQ) including 5 subscales: Appearance Evaluation (AE), Appearance Orientation (AO), Body Areas Satisfaction Scale (BASS), Overweight Preoccupation (OWP), and Self Classified Weight (SCW) , Dermatology Quality of Life Index (DLQI), Skindex-16, EQ5D 5L, EQ- visual analogue scale (VAS), PHQ9, and GAD7. In total, 70 HS patients above 16 years old participated, mean [SD] age, 34.44 [11.64] years; 49/70 (70%) males and 21/70 (30%) females. Mean ± SD CBI, DLQI, Skindex-16 total, EQ-5D-5L, EQ VAS, PHQ9 and GAD7 were 5.59 ± 1.58, 11.70 ± 8.88, 52.90 ± 27.75, 0.75 ± 0.21, 62.48 ± 21.12, 7.64 ± 5.56, 7.87 ± 5.23 respectively. Moderate to severe CBI dissatisfaction was reported by 36/70 (51.42%) patients. CBI was correlated with appearance evaluation (AE) (p < 0.01, r = 0.544), body areas satisfaction (BASS) (p < 0.01, r = 0.481), and overweight preoccupation subscale (OWPS) (p < 0.01, r = - 0.267), and Skindex-16 (p < 0.01, r = - 0.288). HS patients with affected genital areas scored higher in disease patient's severity score (p = 0.015), and male patients scored higher in Skindex-16 than females(p < 0.01). Our study found that the mean of CBI in HS patients was 5.59 ± SD 1.58. Predictors for CBI dissatisfaction were low scores of MBSRQ Appearance Evaluation (AE) and Body Areas Satisfaction Subscale (BASS).

A Six-Year Retrospective Study of Microbiological Characteristics and Antimicrobial Resistance in Specimens from a Tertiary Hospital's Surgical Ward.

Surgery has revolutionized the practice of medicine by allowing the treatment of conditions amenable to conservative medical management with some of them pathophysiologically involving the prevalence of pathogenic microorganisms. On the other hand, infections such as surgical site infections or urinary tract infections may complicate patients hospitalized in surgical wards leading to considerable morbidity, mortality, and increased healthcare-associated costs. The aim of this study was to present the microbiological characteristics and antimicrobial resistance of all isolates identified in microbiological specimens from a surgical ward of a tertiary hospital in Greece during a six-year period. Only specimens that yielded at least one microorganism were included in the analysis. In total, 1459 strains in 789 positive cultures were isolated. The most common sample sent to the microbiology department was pus from surgical wounds. The most common pathogens among all 1459 strains isolated were Enterobacterales at 33% (n = 482), however, the most common genus was Enterococcus at 22.3% (n = 326). Antimicrobial resistance against third-generation cephalosporins was 23% (n = 111/482) among Enterobacterales, while, the rate of vancomycin-resistant enterococci (VRE) was 18.5% (n = 60/324) among Enterococcus species and was increasing in the last years of the study. Antimicrobial resistance of Acinetobacter baumannii to carbapenems was 68.8% (n = 11/16), which was lower than the corresponding rate in other wards in Greece. The antimicrobial resistance rates noted herein raise questions regarding the appropriateness of currently suggested antimicrobials in guidelines and imply that a revision could be required. Practicing clinicians should always be aware of local microbiological data that allow the selection of appropriate antimicrobials for the management of infections. Finally, the increasing rates of VRE noted herein mandate further actions from the point of infection control and antimicrobial stewardship.

Pruritogenic Mediators and New Antipruritic Drugs in Atopic Dermatitis.

Atopic dermatitis (AD) is a common highly pruritic chronic inflammatory skin disorder affecting 5-20% of children worldwide, while the prevalence in adults varies from 7 to 10%. Patients with AD experience intense pruritus that could lead to sleep disturbance and impaired quality of life. Here, we analyze the pathophysiology of itchiness in AD. We extensively review the histamine-dependent and histamine-independent pruritogens. Several receptors, substance P, secreted molecules, chemokines, and cytokines are involved as mediators in chronic itch. We also, summarize the new emerging antipruritic drugs in atopic dermatitis.

Sensitivity to treatment and score bands of the Infants and Toddlers Dermatology Quality of Life questionnaire.

Background: The Infants and Toddlers Dermatology Quality of Life (InToDermQoL) questionnaire is the first dermatology-specific proxy health related QoL instrument for children from birth to 4 years. Score meaning bands and the sensitivity to successful therapeutic intervention are important to interpret the clinical meaning of an instrument. Objective: The aim of the present study was to check the sensitivity to successful therapeutic intervention and establish score bands of the InToDermQoL questionnaire. Methods: Parents or grandparents of 424 children with skin diseases from Spain, Malta, Croatia, Romania, Greece, and Ukraine filled in national language versions of the InToDermQoL questionnaire. Disease severity of children with atopic dermatitis was assessed by SCORAD (Scoring atopic dermatitis). Cohen's d was used to assess the responsiveness of the instrument. Results: The mean total InToDermQoL scores significantly decreased after treatment. Severity grading of the SCORAD scores gave stratification of the InToDermQoL severity grades based on 95% confidence intervals. Scores below a calculated minimal important difference of 2 corresponded to no effect on patient's health related QoL. Limitations: Score banding may be slightly different across patient population and study context. Conclusion: All 3 age-specific versions of the InToDermQoL questionnaire showed sensitivity to treatment. Score bands for the InToDermQoL questionnaire have been established.