Lars Einar French

Background: Patients with immune‐mediated inflammatory diseases (IMIDs) of the skin face challenges beyond visible signs. Despite their significant psychosocial burden, the global impact of skin IMIDs on work productivity has not been systematically reviewed. Objective: To evaluate the global burden of skin IMIDs on work productivity. Methods: We conducted a systematic review and meta‐analysis. Eight electronic databases (PubMed, Web of Science Core Collection, Embase, SciELO, KCI Korean Journal Database, Global Index Medicus, Informit and Google Scholar) were searched from inception to June 2024. We included quantitative studies reporting work‐related outcomes in adults (≥18 years) with alopecia areata, atopic dermatitis, hidradenitis suppurativa, psoriasis or vitiligo. For the meta‐analysis, studies had to report Work Productivity and Activity Impairment (WPAI), Work Limitations Questionnaire (WLQ) or sick leave duration. Two reviewers independently screened and extracted data. Risk of bias was assessed using validated tools. Data were pooled using frequentist and Bayesian approaches to ensure estimations robustness across heterogeneous designs and sample sizes. Results: Across 100 studies with a cumulative sample of 306,619 participants worldwide, skin IMIDs were consistently associated with impaired work functioning. Notably, the mean WPAI overall work impairment was 28.96 (95% CI 25.61; 32.31), and participants averaged 16.74 days of sick leave per year (95% CI 7.39; 26.1). Findings suggest that occupational impairment was influenced by psychosocial factors, thereby highlighting broader societal and economic consequences. Conclusion: Skin IMIDs substantially reduce work functioning and productivity worldwide, representing an underrecognized burden on individuals, employers and health systems. Better multidisciplinary strategies are needed to prevent occupational disadvantage and mitigate the economic and social impact of these chronic conditions.

Demodex mites inhabit the pilosebaceous unit despite harsh environmental conditions including UV radiation, variable salinity, and cosmetics. Their recently characterized endobacterium may contribute to this resilience. This study aimed to elucidate mechanisms of the microbe–host interaction that help mites withstand environmental stress. The genome of Corynebacterium kroppenstedtii subsp. demodicis was sequenced using PacBio technology and annotated via MicroScope. Metabolic and symbiotic traits were analyzed using KEGG and compared with the Demodex folliculorum secretome from published transcriptome data. The complete 2,456,075 bp genome contains 2034 coding sequences and exhibits reduced variable genes compared to other Corynebacterium species. Primary metabolism comprises an almost complete minimal gene set but lacks two tRNA synthetases and genes for phosphatidylethanolamine and NAD ⁺ biosynthesis. Carbohydrate pathways are incomplete and fatty acid synthase I is absent. Secondary metabolism includes complete mevalonate and β‐carotene biosynthetic pathways, while the methylerythritol phosphate pathway is missing. UV protection and oxidative stress tolerance are supported by β‐carotene, ClpB, RecN, MsrA, KatA, SodA, and manganese transporter SitB. The secretome contains hydrolases likely aiding mite digestion. These findings provide genomic insights into mite–bacterium symbiosis and follicular adaptation. All functional inferences are based on genomic data and in silico predictions; experimental validation remains to be established.

Background: Psoriasis affects at least 60 million people globally, but access to effective biologic treatments is limited, particularly in low- and middle-income countries. This study models the incremental global health and economic impact of the World Health Organization (WHO) decision to expand the Essential Medicines List (EML) to include adalimumab and ustekinumab biosimilars for psoriasis, as recommended by the 25th WHO Expert Committee on Selection and Use of Essential Medicines.Methods: An empirical decision-analytic health economic model was developed to estimate the incremental costs and quality-adjusted life-years (QALYs) over a five-year horizon, using a 3% discount rate. The model compared the hypothetical current status quo with an EML expansion scenario for a target population of 8.9 million adults with moderate-to-severe psoriasis refractory to conventional systemic therapies.Findings: EML expansion was simulated to generate an incremental 0.625 QALYs per patient at an additional cost of $13,973 USD over five years. Extrapolated to the global target population, this policy could deliver a total health gain of 5.56 million QALYs, with an associated incremental budget impact of $124.35 billion USD over five years. One-way and probabilistic sensitivity analyses confirmed the robustness of these findings: probabilistic analysis mean of 5.67 million QALYs (95% Credible Interval [CrI] 0.38 - 12.84 million).Interpretation: The recent expansion of the WHO EML for psoriasis to include biosimilars could yield over 5.5 million QALYs globally. The profound health and equity implications of the world-wide implementation of this EML expansion will require regional monitoring.

Summary: Erythroderma is an acute and potentially life-threatening inflammatory condition characterized by redness and scaling of > 90% of the skin. Its treatment is challenging because various underlying skin diseases can cause erythroderma and are difficult to distinguish. Here, we performed in-depth proteomics and transcriptomics analyses of skin from 96 patients with erythroderma caused by five different diseases, including pityriasis rubra pilaris, psoriasis, atopic dermatitis, cutaneous T-cell lymphoma, and drug-induced maculopapular rash. High-throughput workflows enabled in-depth molecular profiling, identifying over 9,300 proteins and 17,200 protein coding transcripts, revealing distinct molecular signatures for each disease. The proteome showed elevated expression of type 2 immunity associated Charcot-Leyden crystal in skin of atopic dermatitis, potentially contributing to NLRP3-driven chronic inflammation in this disease. Complementary transcriptomic analysis demonstrated selective upregulation of IL17C in pityriasis rubra pilaris, strongly correlating with increased IL1 family cytokine expression. Interestingly, only a subset of these patients expressed this IL17C-IL1 signature, suggesting treatment-relevant disease endotypes. Through multi-omics integration, we uncovered disease-specific molecular signatures consistently altered at both protein and transcript levels. In particular, we identified elevated expression of T-cell regulator RASAL3 in cutaneous T-cell lymphoma, which has not been explored in its pathogenesis so far. To translate these molecular profiles into clinical utility, we expanded our adaptive machine-learning algorithm (ADAPT-Mx) for tissue based-disease classification. This achieved 76.6% diagnostic accuracy, substantially outperforming combined conventional clinical and histopathological methods (59.5%). This study provides a template for precision diagnostics in erythroderma and demonstrates the clinical potential of multi-omic profiling in severe inflammatory skin diseases.