BACKGROUND:The Eastern Cape is an under-resourced province and the poorest in South Africa, where little is known about the epidemiology of skin diseases. OBJECTIVES:To examine the nature and prevalence of skin diseases in two neighbouring rural villages in the Eastern Cape, South Africa. METHODS:We conducted a cross-sectional point prevalence study of skin diseases of residents (adults and children) in Mtyholo Dlova and Mdolomba villages in December 2023. Through house-to-house visits, we collected data on the households, participant demographics and skin diagnoses following clinical skin examination by dermatologists. Point prevalence rates and 95% confidence intervals (CIs) were calculated for each skin condition. RESULTS:A total of 309 households were visited with 698 participants included of whom 99% were Xhosa people, 56% were female [mean (SD) age 37.4 (24.2) years], 39% were unemployed, 18% were retired, 60% did not smoke and 69% did not drink alcohol. Seventy-five per cent of households had an average monthly income < ZAR3000 South African Rand (128 GBP). In total, 439 people had at least one skin disease with a point prevalence of any skin disease of 62.9% (95% CI 59.3-66.5). The most prevalent diseases in children (aged < 18 years) were tinea capitis (16.4%), acne vulgaris (13.0%), pityriasis alba (10.6%), prurigo (4.8%), postinflammatory hyperpigmentation (3.9%), xerosis (3.9%), atopic dermatitis (3.4%) and scabies (3.4%). In adults, the most prevalent diseases were xerosis (7.8%), acne vulgaris (7.4%), melasma (6.2%), dermatosis papulosa nigra (5.6%), scarring alopecia (3.5%), nonscarring alopecia (3.1%) and tinea pedis (3.1%). Psoriasis was rare, with a prevalence of 0.3% in the study population. Generally, skin disease was more common in female than male participants (65.8% vs. 59.2%) with sex-specific differences in the prevalence of certain dermatoses; melasma, alopecia (scarring and nonscarring), seborrhoeic dermatitis, dermatosis papulosa nigra and irritant contact dermatitis were more prevalent in female participants, whereas there was a predominance of pseudofolliculitis barbae, atopic dermatitis, postinflammatory hyperpigmentation, acne vulgaris, pityriasis versicolor, scabies, tinea pedis and tinea capitis in male participants. CONCLUSIONS:Skin disease is common in the Eastern Cape, South Africa. These findings may help strengthen the provision of dermatology services and the distribution of resources in the region, and highlight training opportunities for healthcare workers.

People with plaque psoriasis are more likely to live with obesity relative to individuals without psoriasis, which can affect response to biologic treatment. This pooled analysis of the phase III reSURFACE 1 and reSURFACE 2 trials explored efficacy and safety of tildrakizumab 100 mg and 200 mg in patients with plaque psoriasis who were living with obesity for up to 244 weeks of treatment. Both doses of tildrakizumab were effective long-term, with comparable safety profiles in patients who were living with obesity and those who were not. Patients who were not living with obesity experienced more improvement with treatment than those with obesity, and those living with obesity had more long-term improvement after treatment with tildrakizumab 200 mg vs. tildrakizumab 100 mg.

Using a real-world psoriasis cohort, we established the pharmacokinetic-pharmacodynamic (PKPD) relationship for the biologic therapy adalimumab and evaluated the clinical utility and cost-effectiveness of a proactive therapeutic drug monitoring (TDM) strategy. A total of 543 patients on adalimumab monotherapy for psoriasis provided 946 pharmacokinetic samples and 1700 Psoriasis Area Severity Index (PASI) disease severity measurements. To describe the PASI change over time, a one-compartment linear PK model with first-order absorption and elimination was linked to a turnover mechanism of skin lesions. Based on the PKPD relationship and a predefined therapeutic range, real-time stochastic simulation was performed for a proactive TDM strategy, where trough levels guided dose escalation or reduction. Compared to the standard care, the TDM strategy improved PASI90 and PASI75 by 37.5% and 12.8%, respectively, with a 25.9% increase in drug costs. In the future, incorporating the PKPD model into a Bayesian therapeutic monitoring algorithm could facilitate individualized adalimumab dosing.

Psoriasis is typically managed via a ‘Staircase’ approach, slowly escalating treatment from topical treatments to biologics, often delaying effective intervention for several years. Recent evidence supports an ‘Elevator’ approach, advocating for early use of systemic therapies to improve long-term outcomes, prevent disease memory and reduce comorbidities. A paradigm shift from reactive disease-centred care may improve long-term outcomes of psoriasis patients.

BACKGROUND AND AIMS:Psoriasis is a chronic inflammatory skin condition that adversely affects quality of life. Given limited evidence to inform dietary recommendations for psoriasis prevention, this study used data from the UK Biobank to examine associations between diet quality and incident psoriasis, and whether genetic susceptibility moderates this relationship. METHODS:Participants without psoriasis at baseline who completed ≥2 Oxford WebQ 24-h dietary recalls were included. Psoriasis incidence was identified through self-report, primary care, and hospital records. Ten diet quality indices (DQIs) were computed: Low Carbohydrate Diet Score (LCDS), Alternative Mediterranean Diet (aMed) Score, Eatwell Score (EWS), Alternative Binary Eatwell Score (BEWS), Alternative Graded Eatwell Score (GEWS), Healthy Diet Index (HDI), Alternative Healthy Eating Index (aHEI), Dietary Approaches to Stop Hypertension Score (DASH), Dietary Inflammatory Index (DII), and Plant-Based Diet Index (PDI). A multivariable Cox proportional hazards regression model adjusted for sociodemographic, lifestyle, and clinical, estimated association between each DQI and psoriasis incidence. RESULTS:Among 121,299 participants followed up for a mean 11.4 years, 822 developed psoriasis (incidence 0.68 %). In fully adjusted models, higher PDI scores (Q4: 56-77) were associated with a 19 % lower risk of psoriasis (HR: 0.806, [95 % CI: 0.651-0.997]) compared to lower PDI scores (Q1: 26-47). This was driven by lower intake of unhealthy plants (HR: 1.036, [95 % CI: 1.015-1.057], PFDR-trend = 0.021) and meat components (HR: 1.027, [95 % CI: 1.002-1.052]). While there was no strong evidence of interaction between PDI and genetic risk, the protective effect of PDI was stronger among individuals with low genetic risk (HR: 0.965, [95 % CI: 0.939-0.991], P = 0.009). Mediation analyses suggested partial effects via lower adiposity. CONCLUSION:Individuals with the highest adherence to a plant-based dietary pattern were at lower risk of incident psoriasis in this large UK cohort, with no evidence that this association differed by genetic risk.

BACKGROUND:Current treatment pathways for moderate-to-severe psoriasis in the United Kingdom and the Republic of Ireland direct initiation of targeted biologic immunomodulators when conventional systemic drugs are ineffective or not tolerated. Starting biologics early in the treatment pathway may modify the disease course and improve short- and long-term outcomes. OBJECTIVE:To compare the effectiveness and risk of incident comorbid conditions over five years between initiating a biologic as the first systemic treatment and the standard-of-care (beginning with conventional non-biologic systemic therapy with possible subsequent switch to biologics). METHODS:This study applied the target trial emulation framework using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from September 2007 to December 2024. Adults (≥18 years) with moderate-to-severe psoriasis (baseline Psoriasis Area and Severity Index [PASI] ≥10) and no prior systemic therapy were included. Five-year trajectories of PASI and Dermatology Life Quality Index (DLQI) were modelled using mixed-effects repeated-measures models (MMRM). The probability of complete skin clearance (PASI = 0) and the risk of developing long-term comorbidities (cardiovascular, hepatic, neoplastic, metabolic, mental health, musculoskeletal disorder conditions, and incident psoriatic arthritis) were estimated using marginal structural models with stabilised inverse probability weighting to adjust for baseline and time-varying confounding. RESULTS:We included 3,702 patients, 3,368 followed standard-of-care, and 334 initiated a biologic as first-line systemic therapy. At 5 years, mean PASI from MMRM was 4.7 (95% confidence interval [CI] 4.0-5.4) for standard-of-care and 2.0 (1.2-2.7) for biologic initiators; DLQI was 5.6 (4.2-7.0) and 3.5 (1.3-5.7), respectively. Cumulative rate of achieving PASI 0 was 32.2% versus 58.6%, with higher likelihood of PASI 0 for biologic initiators (hazard ratio [HR] 2.85, 95% CI 2.34-3.47). The cumulative risk of chronic comorbidities was lower among biologic initiators (47.5% vs 54.3%; HR 0.72, 95% CI 0.58-0.89), with lower risks of mental disorders (HR 0.64, 95%CI 0.44-0.94) and hepatic disorders (HR 0.54, 95%CI 0.38-0.76). CONCLUSION:Initiating biologics as the first systemic therapy was associated with better clinical outcomes compared with standard stepwise approaches. These results support reconsideration of existing pathways to allow earlier use of biologics.

The introduction of biosimilars for the treatment of moderate-to-severe psoriasis has demonstrated efficacy and safety comparable to those of originator biologics, with the potential to improve cost-effectiveness. We explored the potential for biosimilars to improve access to biologics for psoriasis, especially in low- and middle-income countries, where costs often limit access to originators. The analysis was based on a systematic review conducted as part of the submission process to include adalimumab and ustekinumab in the World Health Organization Essential Medicines List for psoriasis. Among the 17 studies included in the systematic review, we focused on those that provided data evaluating the cost and/or cost-effectiveness of biosimilars versus originators in the treatment of psoriasis. Two studies met the inclusion criteria. The first was a cohort-based Markov model, which showed that biosimilar adalimumab was cost-effective compared with the originator adalimumab for moderate-to-severe psoriasis. The second, using a cost-per-responder model, found that the adalimumab biosimilar had the lowest cost-per PASI complete clearance (PASI100) responder among the anti-TNF therapies. Biosimilars have a key role in reducing costs and expanding treatment availability for patients with psoriasis. Further health economic studies focusing on psoriasis are required to demonstrate how biosimilars can improve access to biologics in this condition.

BACKGROUND:Lifestyle factors have the potential to enhance wellbeing and quality of life (QoL). OBJECTIVES:To identify lifestyle patterns among UK-based adults with psoriasis and examine associations with QoL. METHODS:This was a cross-sectional analysis of the Asking People with Psoriasis about Lifestyle and Eating (APPLE) study (n = 353). QoL, body mass index (BMI) and physical activity were assessed using the Dermatology Life Quality Index (DLQI), self-reported weight and height, and the International Physical Activity Questionnaire. RESULTS:Participant demography was: 82% women; mean (SD) age of all participants was 41 (13) years; and BMI was 27 (7) kg m-2. When fully adjusted for age, sex, smoking and alcohol use, compared with individuals in the highest BMI tertile [35 (5) kg m-2], those in the lowest tertile [21 (2) kg m-2] reported a 71% reduced likelihood of QoL impairments (odds ratio 0.29, 95% confidence interval 0.14-0.59; adjusted P < 0.01). Dairy-free, gluten-free and pescatarian diets were more frequently adopted by individuals reporting healthy BMIs (≈ 24 kg m-2; adjusted P < 0.05). Higher levels of physical activity [2932 (1509) metabolic equivalent of task min per week], and adequate sleep duration [7 (0) h daily] were associated with lower odds of QoL impairments, although attenuated by multiple testing. Participants affected by embarrassment or self--consciousness related to their psoriasis engaged in less vigorous-intensity and walking activities compared with those who were less affected (adjusted P < 0.05). CONCLUSIONS:Assessing weight status and physical activity in individuals reporting high DLQI scores may help identify modifiable behaviours contributing to poorer QoL and thereby shape interventions.

Nutrition in psoriasis management is an area of active research interest, but estimates of macronutrient intakes are lacking. The present study aimed to assess macronutrient intakes of people living with psoriasis in the UK and explore the relationship between their dietary sources and psoriasis severity. This was an online cross-sectional study collecting diet and psoriasis severity information from adults with psoriasis. Responses to a Food Frequency Questionnaire and the self-assessed Simplified Psoriasis Index were used to determine nutrient intakes and psoriasis severity. Relative to Dietary Reference Values, participants with psoriasis (n = 257) reported an overconsumption of

Half of patients with advanced melanoma fail to benefit from immune checkpoint blockade, and novel treatments are urgently required. Testing topical medications for anticancer activity in an immunotherapy-resistant murine melanoma model, we found that, counterintuitively, glucocorticoids (GCs) elicit rapid cytotoxic T lymphocyte (CTL)-dependent tumor control. Genetic ablation of the GC receptor in different cellular compartments revealed that GCs acted not on immune cells but directly on tumor cells to downregulate the expression of glycoprotein A repetitions predominant (GARP). This inhibited TGFβ signaling and unleashed CTL killing. In agreement, GCs stimulated tumor control in multiple cancer models but only if the tumors also responded to pharmacologic inhibition of TGFβ signaling. Furthermore, patients with melanoma with high GC receptor expression or signaling showed improved prognosis and lower TGFβ signaling in tumor-infiltrating CTLs. Additionally, elevated GARP expression correlated with reduced survival, including in immunotherapy-treated patients. Thus, the GARP/TGFβ axis emerges as a GC-sensitive cancer cell-intrinsic immune-evasive mechanism. SIGNIFICANCE:This study uncovers a surprising role for GCs in triggering CD8+ T cell-dependent tumor control through downregulation of GARP and thus TGFβ signaling. Analysis of samples from patients with melanoma suggested that GARP expression may serve as both a biomarker of poor antitumor immunity and a therapeutic target to improve the response to immunotherapy. See related commentary by Roest et al., p. 198.

Despite increased understanding of psoriasis pathogenesis, molecular classification of clinical phenotypes and disease severity is poorly defined. Knowledge gaps include whether molecular endotypes of psoriasis underlie distinct clinical phenotypes and the positive and negative molecular regulators of disease severity across tissue compartments. We performed comprehensive RNA sequencing of skin and blood (n = 718) from prospectively-recruited, deeply-phenotyped discovery and replication cohorts of 146 subjects with moderate-to-severe chronic plaque psoriasis initiating TNF-inhibitor (adalimumab) or IL-12/23-inhibitor (ustekinumab) therapy. Here we show, using two complementary dimensionality reduction methods, that co-expressed gene modules and factors within skin and blood are significantly associated with psoriasis phenotypes and disease severity. We identify a 14-gene signature negatively associated with BMI in nonlesional skin and with disease severity in lesional skin. Genotype integration reveals that HLA-DQA1*01 and HLA-DRB1*15 genotypes are positively associated with baseline psoriasis severity. Using explainable machine learning models, we define two disease severity-associated gene modules in lesional skin - one positive, one negatively-associated - and a 9-gene signature in lesional skin predictive of disease severity. Disease severity signatures in blood are only seen following adalimumab exposure, suggesting greater systemic impact of adalimumab compared to ustekinumab, in line with its side effect profile. In contrast, a gene signature in blood linked to HLA-C*06:02 status is independent of disease severity or drug. These findings delineate gene-environmental and genetic effects on the psoriasis transcriptome linked to disease severity. Psoriasis is a common and debilitating skin disease, linked to other inflammatory conditions. A lot is known about what causes psoriasis and the factors that influence it, but doctors still cannot offer personalised treatments. This is because it has been difficult to understand what makes psoriasis more or less severe, why people respond differently to treatment, or why some people develop related diseases. To help address this, we collected skin and blood samples and personal information from people with severe psoriasis across the United Kingdom. Using computer-based methods, we found shared biological processes that link the disease with obesity and help predict its severity. Rider, Grantham, Smith, Watson et al. integrate multiomic data from patients with psoriasis using dimensionality reduction and machine learning techniques. This approach identifies biological relationships between genetic background, clinical features and disease severity, providing insight into disease variability across individuals.

Psoriasis is linked to significant stigmatization. Prior research suggests that people with psoriasis demonstrate altered neurobiological responses to disgust. However, chronically affected patients may develop coping mechanisms to disgust-related social cues. We investigated whether the duration of psoriasis is associated with more attenuated responses to disgust. We used brain functional magnetic resonance imaging while conducting a covert facial recognition task, and a task involving emotionally stimulating pictures in patients with chronic psoriasis, patients with recent-onset psoriasis, and controls without skin disease. We found no differences in disgust processing between patients and healthy controls. Shorter duration of psoriasis was marginally associated with an attenuated brain response to disgust in the left fusiform gyrus within the inferior temporal cortex. An inverse relationship was observed between the age of onset and the hippocampus response when comparing the chronic psoriasis and recent-onset psoriasis patient groups. Our findings suggest that both the duration and the age of psoriasis onset may modulate disgust processing in patients, possibly reflecting evolved learned strategies and disease coping mechanisms. Timely pharmacological and psychosocial interventions for psoriasis may be beneficial for people diagnosed during life stages that may increase vulnerability to neurocognitive changes. Further studies are needed to replicate these results.

Background & aim Chronic inflammatory skin disorders (CISDs)—including acne, psoriasis, and atopic dermatitis—are linked to substantial psychological distress and social stigma, often resulting in comorbid mental health conditions and contributing to the global disease burden. Diet, as a modifiable factor, has drawn growing attention for its potential impact on both CISDs and mental health. This systematic scoping review aimed to evaluate the current evidence on the interrelationships among dietary factors, CISDs, and mental health conditions. Methods A comprehensive literature search was performed across six databases (from inception to April 2024): MEDLINE, CINAHL, Embase, Scopus, Cochrane CENTRAL, and PROSPERO. After duplicate removal, 1,739 unique records were identified. Titles, abstracts, and full texts were screened using predefined eligibility criteria. 22 studies met inclusion criteria and were included in the final synthesis. Data were extracted and synthesized according to study design, population characteristics, dietary factors, CISDs, and mental health conditions. Results Of the 22 included studies, 11 were cross-sectional. Among the three focal domains, acne (n=12) was the most frequently studied CISD; food consumption and frequency (n=8) were the most common dietary exposures; and depression (n=13) was the most frequently assessed mental health condition. Across studies, consistent associations were observed: beneficial dietary factors, including guideline-aligned dietary patterns, components, and behaviours characterised by nutrient-dense and health-promoting profiles, were positively linked to reduced risk or severity of both CISDs and mental health conditions. A strong positive correlation between CISDs and mental health outcomes was also evident. Two major gaps were identified in the current literature. First, the overall strength of evidence remains limited, with only three cohort studies and two randomized controlled trials among the 22 included. Second, few studies concurrently examined the interrelationships among diet, CISDs, and mental health. The most promising conceptual framework for future mediation analysis appears to be the pathway: Diet → CISDs (mediator) → Mental health outcomes. Conclusions Diet represents a modifiable and potentially cost-effective factor within the interconnected system linking dietary factors, CISDs, and mental health conditions. Current evidence supports associations across all three domains, highlighting the need for integrated research and intervention strategies that simultaneously address diet, skin health, and mental health. Future studies using large-scale and integrated data sources are needed to clarify these complex interrelationships.

On 24 May 2025, the Seventy-Eighth World Health Assembly (WHA78) adopted a resolution recognizing skin diseases as a global public health priority. This reflects a collective commitment from WHO member states to strengthen policies, secure resources and improve care for those affected by skin diseases. This milestone comes a decade after the launch of the Grand Challenges in Global Skin Health initiative (GSHi).

BACKGROUND:Psoriasis is a chronic inflammatory skin disease, and the risk of developing cancer has been postulated due to the presence of several plausible underlying mechanisms. Understanding the association between psoriasis and cancer is imperative to the provision of optimal psoriasis care. OBJECTIVES:To examine the risk of developing cancer in individuals with psoriasis. METHODS:Population-based cohort studies were conducted in Denmark, England, Israel and Taiwan through the use of linked electronic health records. Individuals aged at least 18 years with a diagnosis of psoriasis in the country-specific study period were matched with up to six comparators with no record of psoriasis prior to the index date. Country-specific hazard ratios for the risk of cancer development overall and for 26 site-specific cancers between individuals with and without psoriasis were calculated through Cox regression. Country-specific estimates were pooled using random effects modelling. RESULTS:We included 702 022 individuals with psoriasis and 4 185 342 matched comparators. In models implicitly controlled for age, sex and calendar time by matching, there was a small association between psoriasis and cancer overall [pooled HR (pHR) 1.08, 95% confidence interval (CI) 1.04-1.13; I2 = 92.4%]. Adjustment for potential confounding factors resulted in a slight attenuation of risk (pHR 1.05, 95% CI 1.01-1.09; I2 = 81.2%). When restricted to those with moderate-to-severe psoriasis, the risk of cancer overall was slightly higher (pHR 1.16, 95% CI 1.04-1.28; I2 = 92.8%) than in confounder-adjusted models (pHR 1.09, 95% CI 1.03-1.15; I2 = 60.6%). Associations with psoriasis were present for oral cavity (pHR 1.29, 95% CI 1.12-1.47; I2 = 55.4%), pharynx (pHR 1.30, 95% CI 1.07-1.58; I2 = 58.4%), oesophagus (pHR 1.17, 95% CI 1.03-1.33; I2 = 56.6%), liver (pHR 1.53, 95% CI 1.33-1.77; I2 = 75.1%), pancreas (pHR 1.09, 95% CI 1.02-1.17; I2 = 0.0%), kidney (pHR 1.19, 95% CI 1.11-1.27; I2 = 0.0%), bladder (pHR 1.13, 95% CI 1.06-1.20; I2 = 28.7%) and keratinocyte cancers (pHR 1.37, 95% CI 1.16-1.63; I2 = 97.5%), and Hodgkin lymphoma (pHR 1.56, 95% CI 1.16-2.11; I2 = 69.7%), non-Hodgkin lymphoma (pHR 1.16, 95% CI 1.07-1.26; I2 = 35.5%) and leukaemia (pHR 1.18, 95% CI 1.08-1.29; I2 = 41.9%). Site-specific associations generally persisted, with slight risk exacerbations and additional associations for lung and ovarian cancers, when limited to people with moderate-to-severe psoriasis. CONCLUSIONS:Psoriasis was associated with an increased risk of developing 14 of 26 investigated site-specific cancers, including cancers with a poor prognosis, such as liver, lung and oesophageal cancer. Our findings can be used to reinforce cancer prevention strategies in psoriasis care.

BACKGROUND:Dandruff features epidermal scaling but lacks overt signs of inflammation, such as erythema. Characterisation of its inflammatory profile may improve understanding of the underlying inflammatory mechanisms and therefore indicate alternative approaches for treatment. METHODS:Full-thickness scalp biopsies were sampled from healthy volunteers and those with dandruff. Immunohistochemistry for Ki67 and keratin 16 was used to examine keratinocyte proliferation and differentiation. Mass spectrometry lipidomics was applied to profile scalp skin barrier lipids and lipid mediators. The presence of immune cells and their cytokine production was examined by flow cytometry. Cytokine and chemokine levels in scalp skin were analysed by cytometric bead array. RESULTS:Increased keratinocyte proliferation and aberrant keratinocyte differentiation were observed in dandruff relative to healthy scalp; however, this epidermal dysregulation was not mirrored by alterations to barrier lipid levels. Decreased numbers of innate lymphoid cells and reduced expression of CD86 on antigen-presenting cells, were the few cellular alterations observed in dandruff scalp, suggesting dandruff only subtly changes major skin immune cell populations. Despite this, increased proportions of interleukin-17-producing T-cells and increased C-C Motif Chemokine Ligand 17 (CCL17) levels were observed in dandruff scalp, indicative of a low-grade, mixed Type-2/Type17 inflammatory response. Increased levels of N-acyl ethanolamines, including the endocannabinoid anandamide, as well as linoleoyl- and oleoyl-ethanolamine, were also observed in dandruff scalp which could be responsible for suppressing inflammation to sub-clinical levels. CONCLUSION:These findings indicate that, contrary to being a mere flaking disorder, dandruff involves an altered inflammatory environment consistent with low-grade inflammation.