Dermoscopic characteristics of Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous tumour with high mortality and frequently delayed diagnosis. Clinically, it often manifests as a rapidly growing erythematous to purple nodule usually located on the lower extremities or face and scalp of elderly patients. There is limited available data on the dermoscopic findings of MCC, and there are no specific features that can be used to definitively diagnose MCC. AIM OF THE STUDY: Here, we aimed to summarize existing published literature on dermatoscopic and reflectance confocal microscopy (RCM) features of MCC. MATERIALS AND METHODS: To find relevant studies, we searched the PubMed and Scopus databases from inception to April 12, 2023. Our goal was to identify all pertinent research that had been written in English. The following search strategy was employed: (" dermoscopy" OR " dermatoscopy" OR " videodermoscopy" OR " videodermatoscopy" OR " reflectance confocal microscopy") AND " Merkel cell carcinoma". Two dermatologists, DK and GE, evaluated the titles and abstracts separately for eligibility. For inclusion, only works written in English were taken into account. RESULTS: In total 16 articles were retrieved (68 cases). The main dermoscopic findings of MCC are a polymorphous vascular pattern including linear irregular, arborizing, glomerular, and dotted vessels on a milky red background, with shiny or non-shiny white areas. Pigmentation was lacking in all cases. The RCM images showed a thin and disarranged epidermis, and small hypo-reflective cells that resembled lymphocytes arranged in solid aggregates outlined by fibrous tissue in the dermis. Additionally, there were larger polymorphic hyper-reflective cells that likely represented highly proliferative cells. CONCLUSION: Dermoscopic findings of MCC may play a valuable role in evaluating MCC, aiding in the early detection and differentiation from other skin lesions. Further prospective case-control studies are needed to validate these results.

Five-Membered Nitrogen Heterocycles Angiotensin-Converting Enzyme (ACE) Inhibitors Induced Angioedema: An Underdiagnosed Condition.

Angiotensin-converting enzyme (ACE) inhibitors are used primarily in the treatment of hypertension, heart failure, and in the acute phase of myocardial infarction. Lisinopril [N2-[(1S)-1-car-boxy-3-phenylpropyl]-L-lysyl-L-proline], enalapril [(S)-1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline] and ramipril [2-aza-bicyclo-[3.3.0]-octane-3-carboxylic acid] are all five-membered heterocycles and three of the most prevalent ACE inhibitors in clinical use worldwide. ACE inhibitor-induced angioedema (AE) is clinically characterized by self-limited edema of the dermis and subcutaneous lipid tissue, localized on face skin, oral mucosa and tongue in most cases. However, severe episodes of intestinal AE misdiagnosed as acute appendicitis and laryngeal AE requiring incubation have been reported. The pathophysiology of ACE inhibitor-induced angioedema is attributed to the accumulation of bradykinin, which is a potent vasodilator with proinflammatory activity that is normally degraded by angiotensin-converting enzyme (ACE) and aminopeptidase P; however, a small proportion of treated patients is affected. Given that patients do not respond to anti-H1 antihistamines and steroids, early clinical recognition and discontinuation of the ACE inhibitors are the treatments of choice for the long-term management of ACE inhibitor- induced angioedema. The search period of the present review was set up until November 2023, and its aim is to shed light on the broader context of ACE inhibitor-induced angioedema, exploring aspects such as clinical presentation, pathophysiology, and therapeutic considerations in this potentially life-threatening condition. The exploration of alternative drug options such as angiotensin II receptor blockers, the potential association of coadministration of DPP-4 inhibitors with ACE inhibitors, the presentation of angioedema and the significant clinical importance of this condition are also discussed. By focusing on the chemical structure of ACE inhibitors, specifically their nitrogen-based heterocycles-an attribute shared by over 880 drugs approved by the FDA within the pharmaceutical industry-this review emphasizes the pivotal role of nitrogen scaffolds in drug design and underscores their relevance in ACE inhibitor pharmacology.

Tinea Incognito: Challenges in Diagnosis and Management.

Tinea incognito is a dermatophyte infection with atypical features, due to the use of topical or systemic steroids or other immunosuppressive medications. Delayed diagnosis, spread of the infection to critical body surfaces, resistance to antifungal drugs, and increased costs due to prolonged hospitalization and multiple treatment regimens often complicate tinea incognito. It can affect individuals of all ages and genders, but it is more common in children. Atypical clinical appearance often necessitates differentiation from other diseases such as eczema, seborrheic dermatitis, lupus erythematosus, psoriasis, or other non-fungal skin conditions. The treatment of tinea incognito usually involves discontinuation of topical steroids or other immunosuppressive medications. Preventive measures and management of the underlying fungal infection are necessary and can be achieved with antifungal drugs. Patients should wear loose cotton clothes, use boiling water for laundry, and iron their clothing before wearing them. Additionally, they should avoid sharing bed linens, towels, clothes, and shoes. This review aims to raise awareness of tinea incognito among health practitioners, provide tips for detecting the disorder, include it in the differentials, and evaluate the available diagnostic procedures.

Evaluation of Delayed Contact Hypersensitivity in Patients with Rosacea.

Introduction: Rosacea is a common chronic inflammatory dermatosis characterized by erythema, telangiectasia, papules, and pustules on the central face. The frequency of contact sensitization complicating rosacea and its therapy is unknown, with only few studies published in the literature. In the present study, we aimed to evaluate contact sensitivity in patients with rosacea. Methods: A total of 50 rosacea patients and 50 age- and sex-matched healthy controls were enrolled. Both groups were patch tested with the European Baseline Series. Results: A positive reaction to at least one allergen of the European Baseline Series was observed in 15 (30%) of rosacea patients and 10 (20%) of the healthy controls. Although the rate of positive reaction in the rosacea group was higher than in the controls, no statistically significant difference was documented. In addition, the total number of positive reactions to allergens in the rosacea group was higher than the control group, namely, 26 versus 17. Conclusion: Contact hypersensitivity may coexist with rosacea. Its identification holds significant clinical relevance, influencing the long-term management and justifying the application of patch testing in rosacea patients.

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.

Translation and validation of patient-oriented eczema measure in the Greek language.

Translating and validating the Greek version of the Patient Oriented Eczema Measure (POEM) was our goal. A parallel backtranslation process was used to translate POEM. A total of fifty-nine adult atopic dermatitis patients were enlisted to assess validity and reliability. Through patient interviews with physicians, a questionnaire comprising demographics, POEM, and the dermatology life quality index (DLQI) was filled out. 3-7 days after the first visit, a second POEM completion was conducted. The POEM items conducted with study participants demonstrated a good level of internal consistency (Cronbach's alpha = 0.88), and no overall floor and ceiling effects were found. There was a significant correlation between the DLQI and POEM scores (Spearman rho =0.71; p<0.001). The POEM score between interviews showed an average intraclass correlation coefficient (95% confidence interval) of 0.89 (0.80, 0.94), indicating good to excellent test-retest reliability. Patient-reported outcome measures are becoming more and more common in Greece, so it's critical to have access to Greek translations of validated instruments that are frequently used in literature.

Insights into Early Systemic Treatment in Atopic Dermatitis: Scientific Facts and Practical Considerations.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized clinically by pruritus, and pathophysiologically by immune dysregulation, and compromised skin barrier function. While topical therapies are currently the cornerstone of AD management, especially in mild disease, recent advancements in systemic treatments and a deeper understanding of similar skin diseases, such as psoriasis, have highlighted the importance of early intervention. In this commentary, we explore the potential benefits of early systemic intervention in AD, with pruritus determining such a decision. Building on this concept, we assume that, through the timely systemic treatment that targets the immune dysregulation present in AD, the progression of the disease could be modified, improving overall patient outcomes. Early systemic intervention may minimize systemic inflammation, halting the "atopic march" and disrupting the "itch-scratch" cycle. Managing pruritus at its root could prevent secondary complications and reduce the psychosocial burden of the disease. This paradigm shift fosters a collaborative healthcare approach that empowers patients with long-term disease control strategies. In conclusion, the safety and efficacy of novel systemic treatments offer a compelling scenario for early intervention in atopic dermatitis care.

Antimicrobial Resistance Trends in Hidradenitis Suppurativa Lesions.

Background/Objectives: Antibiotic (AB) therapy is the first step in managing hidradenitis suppurativa (HS). Knowledge of the local patterns of antimicrobial resistance is paramount for the appropriate selection of antimicrobials. This study aimed to assess the occurrence of antibiotic resistance in patients with HS. Methods: A cross-sectional study was conducted on 103 patients with HS seen at the Dermatology Department at the University Hospital of Heraklion, Heraklion, Crete, Greece, from January 2019 to December 2023, who were not on any antibiotics in the last three months. Results: A total of 103 patients with HS participated in this study. Purulent material from 139 skin lesions of these patients was swabbed, and 79.86% (111/139) tested positive for bacteria. Gram-positive isolates accounted for 73%, whereas Gram-negative isolates comprised 27%. Among the isolates, 85.1% were aerobes, and 14.9% were anaerobic. The most common bacterial families isolated were Staphylococcaceae (48.27%), Enterobacteriaceae (14.94%), and Streptococcaceae (6.89%). The antibiogram profiles of bacterial cultures revealed a 57.1% resistance to levofloxacin and a 53.3% resistance to penicillin in Staphylococcus lugdunensis, whereas Staphylococcus aureus showed a 76.9% resistance to penicillin and a 58.3% resistance to fusidic acid. High resistance rates of 63.5% for tigecycline, 63.3% for ampicillin, and 40.5% for colistin were observed for Gram-negative isolates. Resistances of 62.5%, 61.5%, and 53.8% to erythromycin, clindamycin, and penicillin, respectively, were observed in the anaerobes. Conclusions: Patients with HS displayed considerable resistance to bacterial proliferation. The revised therapeutic guidelines for HS should incorporate the latest insights into bacterial antibiotic resistance.

Clinical Significance and Microbiological Characteristics of Staphylococcus lugdunensis in Cutaneous Infections.

Background/Objectives:Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) commonly found on human skin. Unlike other CoNS, S. lugdunensis has a notable potential to cause severe infections comparable to Staphylococcus aureus. This study aimed to characterize the clinical and microbiological profile of patients with S. lugdunensis skin infections at a single center. Methods: We conducted a retrospective analysis of patient records from the Dermatology Department of the University Hospital of Heraklion, Greece, covering the period from January 2014 to January 2024. Patients' clinical presentations, demographics, infection sites, comorbidities, prior infections, antimicrobial treatments, and therapeutic responses were examined. Specimens were collected, transported, and processed according to standardized microbiological protocols. Bacterial identification and antibiotic susceptibility testing were performed using the Vitek 2 automated system and MALDI-TOF MS, with results interpreted according to Clinical and Laboratory Standards Institute (CLSI) criteria. Results: A total of 123 skin specimens positive for S. lugdunensis were analyzed. The cohort comprised 62 males (50.4%) and 61 females (49.6%), with a mean age of 40.24 ± 20.14 years. Most specimens were collected from pus (84%), primarily from below the waist (66.7%). Hidradenitis suppurativa (26%) was the most common condition associated with S. lugdunensis, followed by folliculitis, abscesses, ulcers, cellulitis, and acne. Co-infections with other bacteria were noted in 49.6% of cases, and 25.2% of infections were nosocomially acquired. The majority of patients (65%) received systemic antibiotics, predominantly amoxicillin/clavulanic acid, cefuroxime axetil, and doxycycline, with a cure rate of 100%. All isolates were susceptible to several antibiotics, though resistance to penicillin (28.5%) and clindamycin (36%) was observed. Conclusions:S. lugdunensis is a significant pathogen in skin infections, capable of causing severe disease. The high cure rate demonstrates the effectiveness of appropriate antibiotic therapy. Continued monitoring and antimicrobial stewardship are essential to manage resistance and ensure effective treatment.

Italian S3-Guideline on the treatment of Atopic Eczema - Part 1: Systemic therapy, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA).

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for pediatric, adolescent, pregnant and breastfeeding patients.

Italian S3-Guideline on the treatment of Atopic Eczema - First Update, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Occupational Dermatology (SIDAPA).

The evidence- and consensus-based guideline on atopic eczema, published in JEADV on 18 August 2022 (part 1) and 3 September 2022 (part 2) was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. To reflect the most recent evidence on novel systemic medications, an update was published in October 2022. According to the purpose of the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA) to adapt the EuroGuiDerm guideline on the treatment of atopic eczema into the Italian Healthcare setting, the original update has been supplemented by inserting notes, well highlighted by the original text, to emphasize the laws, rules, procedures and suggestions of the Italian Ministry of Health and regional Health authorities.

Italian S3-Guideline on the treatment of Atopic Eczema - Part 2: non-systemic treatments and treatment recommendations for special AE patient populations, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Occupational Dermatology (SIDAPA).

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for pediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

Switching between JAK Inhibitors in Patients with Atopic Dermatitis: Unanswered Questions in Daily Clinical Practice.

Data on switching between agents in patients with atopic dermatitis (AD) are scarce (1-3). We report the case of a patient with severe AD and inadequate response to upadacitinib who showed a complete response after switching to abrocitinib. A 23-year-old male patient with severe AD was enrolled in the Measure Up double-blind, placebo-controlled, phase 3 randomized clinical trial. At baseline, the Eczema Area Severity Index (EASI) was 50.6, the Investigator's Global Assessment (IGA) was 4, the affected Body Surface Area (BSA) was 80%, and the Worst Pruritus-Numeric Rating Scale (WP-NRS) was 10/10 (Figure 1). At week 124, the patient discontinued participation in the trial, while EASI was 9.2, IGA 3, BSA 20%, and WP-NRS 5/10 at the time. After one month off treatment, and while expecting unblinding, the patient again presented with exacerbation of AD, since EASI was 45.6, IGA 4, BSA 80%, and WP-NRS 10/10. At that point of time, access to both dupilumab and tralokinumab was not available in Greece, while upadacitinib was avoided due to inadequate patient satisfaction, partly due to recurrent ocular herpes simplex infections during the previous upadacitinib treatment. The patient was prescribed abrocitinib 200 mg daily. One month after initiation of therapy, the patient achieved complete control of the disease (EASI 0.0, IGA 0, BSA 0%, and WP-NRS 0/10) (Figure 2). This has been maintained with no reported adverse events after 12 months of continuous treatment. After unblinding, the patient was confirmed to have received 15 mg of upadacitinib daily during his participation in the clinical trial. When to switch agents in the treatment of patients with severe AD if the response is not adequate, and what agent to switch to, is an issue that is not clearly defined. Data available from the JADE EXTEND study concluded that patients failing to achieve efficacy outcomes with dupilumab can benefit from switching to both doses of abrocitinib (1). However, a number of patients in this study did not achieve efficacy outcomes even after treatment with 200 mg of abrocitinib. Furthermore, sub-population analysis of the JADE EXTEND study, evaluating difficult-to-achieve patient-oriented outcomes such as Patient Oriented Eczema Measure (POEM) ≤2 and Dermatology Life Quality Index (DLQI) ≤1, further emphasized that switching might be beneficial for a significant number of patients, but unmet need was still evident for some of them (4). The literature lacks data on switching between Janus kinase (JAK) inhibitors in AD. Treat-to-target might be different for early control of the disease, as baricitinib and upadacitinib were assessed at 16 weeks, while abrocitinib was assessed at 12 weeks in the pivotal studies. Regarding the present case, the different clinical response obtained cannot be clearly defined since abrocitinib and upadacitinib are both selective JAK1 inhibitors. Consequently, the targeted inflammatory pathways and the expected regulation of immune functionality could be similar. We may assume that the high dose of abrocitinib vs. the low dose of upadacitinib could have accounted for the improved response. However, it is impossible to assess whether clinical outcomes would have been comparable with the administration of the full dose of upadacitinib 30 mg daily or whether usage of a half-dose of abrocitinib 100 mg daily would have also resulted in inadequate response in the same patient. Switching within the same class of treatment agents has also been a heavily-debated issue for psoriasis for many years; however, recent data suggest that switching between interleukin (IL)-17A antagonists may be of benefit to some patients, although the underlying mechanism of action is still under investigation (5,6). Treatment modification in inadequate response could include: up-dosing, adding classical treatments like methotrexate to the JAK inhibitor, switching to monoclonals, or switching to another JAK inhibitor, taking into account published metanalyses of the efficacy of novel agents. Consequently, there is an unmet need to determine an algorithmic step-by-step approach of treat-to-target and switching or adding treatment in the current landscape of AD therapy. Different policies of reimbursement in different countries, along with a lack of comparative studies, may complicate adding such recommendations to existing treatment guidelines.