Alexander J Stratigos’s research while affiliated with National and Kapodistrian University of Athens and other places

Comorbidities between atopic dermatitis (AD) and neuropsychiatric disorders are frequently reported, however the extent of shared genetic architecture remains unclear. Here, we performed a large-scale genome-wide pleiotropy approach to investigate the genetic correlations and causal associations between AD and five neuropsychiatric disorders, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BP), major depressive disorder (MDD), and schizophrenia (SCZ). Using genome-wide association (GWAS) data, we explored genetic overlaps, pleiotropic loci and assessed the capacity of pleiotropic associations to identify drug targets. We identified significant positive genetic correlations between AD and ADHD (rg=0.14, P-value=2e-4), MDD (rg=0.13, P-value=1.2e-3) and BP (rg=0.11, P-value=4e-3). Genome-wide pleiotropy scans identified 37 distinct pleiotropic loci between AD and neuropsychiatric traits, with gene-based analyses highlighting 86 unique genes participating in inflammatory pathways. Pleiotropy-informed target prioritization facilitated the identification of novel pathophysiological mechanisms for AD and putative drug targets, such as members of TNF and JAK-STAT3 signaling. Mendelian randomization provided evidence of a causal relationship between genetic liability to MDD and BP with an increased risk of AD, independent of sample overlap. Collectively, our findings elucidate shared molecular mechanisms between AD and neuropsychiatric disorders, emphasizing immune-related pathways as key contributors to both disease categories, with potential implications for therapeutic interventions targeting common inflammatory mechanisms.

Background: Moderate to severe (M2S) atopic dermatitis (AD) is a chronic condition impacting individuals, society, and healthcare systems. Considering the changing M2S-AD treatment landscape, this study assesses the M2S-AD burden in patients reaching referral centers in Greece. Methods: This was a multicenter, cross-sectional study. Patients aged 12 years or older with clinically diagnosed M2S-AD were enrolled. Data collected included clinical practice assessments and the following validated patient-reported instruments: Dermatology Life Quality Index (DLQI); EuroQol-5 Dimensions-3 Level scale (EQ-5D-3L); Patient Oriented Eczema Measure (POEM); Peak Pruritus Numerical Rating Scale (PP-NRS); and Work Productivity and Activity Impairment: General Health (WPAI:GH). A pain frequency/intensity/cause questionnaire and a sleep disturbance scale were also used. Results: Outcomes of 184 adults (51.1% female) with M2S-AD based on the Eczema Area and Severity Index (EASI) are presented (n = 117 moderate; n = 67 severe). Among the patients, 14.8% were obese, 59.2% had allergic comorbidities, and 88.0% were receiving AD-specific therapy (systemic: 38.6%). The median age, disease duration, body surface area, and total EASI scores were 38.8 years, 11.8 years, 30.0%, and 16.9, respectively. The median DLQI score was 12.0, with ‘symptoms/feelings’ being the most affected domain. EQ-5D dimensions ‘anxiety/depression’ and ‘pain/discomfort’ were also affected (65.2% and 64.1% reporting problems, respectively). The median POEM score was 17.0. Pain, severe pruritus (PP-NRS ≥ 7), and sleep disturbance were reported by 80.4%, 62.0%, and 88.5%, respectively. The median WPAI:GH ‘work productivity loss’ and ‘activity impairment’ scores were 23.8% and 30.0%, respectively. Conclusions: Both moderate and severe AD patients reaching Greek specialized centers experience significant symptom burden and impairments in quality of life, sleep, work, and daily activities.

Purpose of Review The integration of pharmacological insights into the treatment landscape of hand eczema (HE) is continuously evolving, driven by a deep understanding of immunological signaling pathways. This review aims to investigate the advancements in understanding and treating HE with small molecules and biologics. Specifically, we sought to answer how novel therapeutic targets and agents have influenced the management of HE. Recent Findings Recent research has identified promising treatments involving monoclonal antibodies, such as dupilumab, tralokinumab, lebrikizumab, targeting IL-4 and IL-13, which reduce HE severity and improve quality of life. Emerging selective JAK inhibitors, including delgocitinib, gusacitinib, tofacitinib, upadacitinib, and abrocitinib, have demonstrated promising efficacy, pruritus reduction and are actively researched. Furthermore, topical PDE4 inhibitors, such as crisaborole, roflumilast, and difamilast cream, remain potential options for chronic HE, offering alternatives to conventional treatments like topical steroids or calcineurin inhibitors, as is botulinum toxin for vesicular HE. Summary The examination revealed significant advancements in the treatment of HE with biologics and small molecules, suggesting a shift towards more personalized and precise dermatological strategies. Monoclonal antibodies and JAK inhibitors are emerging as effective options for HE management, offering improvements in symptom control and quality of life. Topical PDE4 inhibitors provide additional alternatives for chronic HE. These developments highlight the need for clinicians to stay updated on immunologic and therapeutic progress, as they can enhance management strategies and offer more comprehensive care options before considering systemic therapies. This evolving landscape may significantly impact future research and clinical practice in HE management.

Aim: To evaluate health-related quality of life (HRQoL) in cemiplimab-treated patients with locally advanced basal cell carcinoma (laBCC).Materials & methods: Eighty-four patients with laBCC received cemiplimab 350 mg every 3 weeks (up to 9 cycles). HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (QLQ-C30) and Skindex-16 questionnaires at baseline and each cycle. Mixed-effects repeated-measures models evaluated change from baseline across cycles.Results: Clinically meaningful improvement or maintenance was reported by 62-90% of patients on QLQ-C30 scales and by approximately 80% on Skindex-16 scales at Cycle 2, with consistent results at Cycle 9 except fatigue.Conclusion: Most cemiplimab-treated patients with laBCC reported improvement or maintenance of HRQoL with low symptom burden except fatigue.Clinical Trial Registration: ClinicalTrials.gov identifier NCT03132636, registered 28 April 2017.

Background A phase 2 cemiplimab study (NCT03132636) demonstrated a 24.1% objective response rate in patients diagnosed with metastatic basal cell carcinoma (mBCC) who were not candidates for continued hedgehog inhibitor (HHI) therapy due to intolerance to previous HHI therapy, disease progression while receiving HHI therapy, or having not better than stable disease on HHI therapy after 9 months. Here, health‐related quality of life (QoL) for this patient population is reported. Methods Adult patients with mBCC were treated with intravenous cemiplimab at a dose of 350 mg every 3 weeks for 5 treatment cycles of 9 weeks/cycle then 4 treatment cycles of 12 weeks/cycle. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life‐Core 30 (QLQ‐C30) and Skindex‐16 questionnaires at baseline and Day 1 of each cycle. Across Cycles 2 to 9, the overall change from baseline was analyzed using a mixed model with repeated measures. Responder analyses determined clinically meaningful improvement or deterioration (changes ≥10 points) or maintenance across all scales. Results Patients reported low symptom burden and moderate‐to‐high functioning at baseline. Maintenance for QLQ‐C30 global health status (GHS)/QoL and across all functioning and symptom scales was indicated by overall mean changes from baseline. Clinically meaningful improvement or maintenance was reported at Cycle 2 for GHS/QoL (77%), functioning scales (77% to 86%), and symptom scales (70% to 93%), with similar proportions of improvement or maintenance at Cycles 6 and 9, excluding fatigue. On the Skindex‐16, clinically meaningful improvement or maintenance was reported across the emotional, symptom, and functional subscales, in 76%–88% of patients at Cycle 2, which were generally maintained at Cycles 6 and 9. Overall mean changes from baseline showed maintenance across these subscales. Conclusions The majority of patients treated with cemiplimab reported improvement or maintenance in GHS/QoL and functioning while maintaining a low symptom burden.

Actinic keratoses (AK) are common skin lesions associated with chronic exposure to sun. They are believed to be precursors of malignancy as they potentially may progress to invasive squamous cell carcinomas. The goal of current therapies is to reduce the number of AK and to prevent future cancer development. This review aims at providing an overview of the hallmarks of AK and skin field cancerization. We discuss epidemiology trends, risk factors and the state of the art and evidence of the current treatments. We review key figures of AK prevalence from different countries with regard to skin cancer risk and the associated economic burden of AK. We discuss the mutational status in AK lesions and the difficulties encountered by clinicians in evaluating AK visible and invisible lesions, referring to the concept of field cancerization. Based on a systematic literature review, we further evaluate the available treatment options. The presence of subclinical skin alterations in the periphery of visible AK lesions has gained a particular attention as those non‐visible lesions are known to contain the same genetic changes as those found in the AK lesions themselves, prompting the concept of ‘field cancerization’. Therefore, AK treatment guidelines now recognize the importance of treating the field in patients with AK. A recent systematic literature review and network meta‐analysis showed that 5‐FU interventions were associated with the best efficacy and a satisfactory acceptability profile compared with other field‐directed therapies used in the treatment of AK. Although AK are considered quite common, they lack an accurate descriptive definition and conclusive epidemiologic data. Limited public awareness is a barrier to early and effective treatment, including prevention strategies. While different treatment options are available, there is still a limited understanding of long‐term outcomes of treatment as measured by recurrence of cancer prevention.