Effects of eczema calming lotion on the stratum corneum in atopic dermatitis: Corneodesmosin and intercellular lipid lamellae.

OBJECTIVE: Atopic dermatitis (AD) is characterized by compositional and structural changes to the skin at lesional sites. Alteration to the levels and organization of both protein and lipid components are associated with disease status and lead to impaired barrier and hydration. Corneodesmosin (CDSN) and the arrangement and length of the intercellular lipid lamellae (ICLL) are altered in disrupted skin states. The aim of this research was to profile the distribution of CDSN and the ICLL in the stratum corneum (SC) at lesional and non-lesional sites in AD-prone skin and to investigate the impact of an eczema calming lotion containing petroleum jelly, fatty acids, and colloidal oatmeal. METHODS: An IRB-approved study was conducted with participants with active AD. From a small subset of participants, tape strips were collected from lesional and non-lesional sites on the arm, prior to and after twice daily application, over 4 weeks of an eczema calming lotion containing petroleum jelly, fatty acids, and colloidal oatmeal. Fluorescent antibody staining was used to investigate the distribution of CDSN. Transmission electron microscopy (TEM) was used to characterize the ICLL. RESULTS: The distribution/coverage of CDSN was similar between lesional and non-lesional sites at baseline; application of the lotion resulted in a more defined honeycomb/peripheral distribution. Normalized ICLL (nICLL) was lower in baseline samples from lesional sites relative to non-lesional sites. Application of the lotion increased this parameter by the end of the study at all sites. CONCLUSION: The eczema calming lotion containing petroleum jelly, fatty acids and colloidal oatmeal provided changes in corneodesmosomal proteins distribution and ICLL, consistent with improvements in corneocyte maturation and improved barrier function in the skin of individuals with atopic dermatitis.

OBJECTIF: La dermatite atopique (DA) est caractérisée par des modifications de la composition et de la structure de la peau au niveau des sites lésionnels. L'altération des taux et de l'organisation des composants protéiques et lipidiques est associée au statut de la maladie, et entraîne une altération de la barrière et de l'hydratation. La cornéodesmosine (CDSN), et la disposition et la longueur des lamelles lipidiques intercellulaires (LLIC) sont altérées dans les états cutanés perturbés. L'objectif de cette étude était d'établir le profil de la distribution de la CDSN et des LLIC dans la couche cornée (CC) au niveau des sites lésionnels et non lésionnels dans la peau sujette à la DA, et d'étudier l'impact d'une lotion apaisante contre l'eczéma contenant de la vaseline, des acides gras et de l'avoine colloïdale. MÉTHODES: Une étude approuvée par un CPP a été menée auprès de participants atteints de DA active. Dans un petit sous­ensemble de participants, des bandes adhésives ont été prélevées sur des sites lésionnels et non lésionnels du bras, avant et après l'application deux fois par jour pendant 4 semaines d'une lotion apaisante contre l'eczéma contenant de la vaseline, des acides gras et de l'avoine colloïdale. Une coloration par anticorps fluorescents a été utilisée pour étudier la distribution de la CDSN. La microscopie électronique en transmission (MET) a été utilisée pour caractériser les LLIC. RÉSULTATS: La distribution/couverture de la CDSN était similaire entre les sites lésionnels et non lésionnels à l'entrée dans l'étude; l'application de la lotion a entraîné une distribution en nid d'abeille/périphérique plus définie. Le taux normalisé de LLIC (LLICn) était plus faible dans les échantillons prélevés à l'entrée dans l'étude au niveau des sites lésionnels par rapport aux sites non lésionnels. L'application de la lotion a augmenté ce paramètre à la fin de l'étude pour tous les sites. CONCLUSIONS: La lotion apaisante contre l'eczéma contenant de la vaseline, des acides gras et de l'avoine colloïdale a entraîné des changements dans la distribution des protéines cornéodesmosomales et des LLIC, ce qui correspond à des améliorations de la maturation des cornéocytes et de la fonction de barrière de la peau des personnes atteintes de dermatite atopique.

Topical anti-inflammatory treatments for eczema: network meta-analysis.

BACKGROUND: Eczema (atopic dermatitis) is the most burdensome skin condition worldwide and cannot currently be prevented or cured. Topical anti-inflammatory treatments are used to control eczema symptoms, but there is uncertainty about the relative effectiveness and safety of different topical anti-inflammatory treatments. OBJECTIVES: To compare and rank the efficacy and safety of topical anti-inflammatory treatments for people with eczema using a network meta-analysis. SEARCH METHODS: We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries on 29 June 2023, and checked the reference lists of included studies. SELECTION CRITERIA: We included within-participant or between-participant randomised controlled trials (RCTs) in people of any age with eczema of any severity, but excluded trials in clinically infected eczema, seborrhoeic eczema, contact eczema, or hand eczema. We included topical anti-inflammatory treatments used for at least one week, compared with another anti-inflammatory treatment, no treatment, or vehicle/placebo. Vehicle is a 'carrier system' for an active pharmaceutical substance, which may also be used on its own as an emollient for dry skin. We excluded trials of topical antibiotics used alone, complementary therapies, emollients used alone, phototherapy, wet wraps, and systemic treatments. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Primary outcomes were patient-reported eczema symptoms, clinician-reported eczema signs and investigator global assessment. Secondary outcomes were health-related quality of life, long-term control of eczema, withdrawal from treatment/study, and local adverse effects (application-site reactions, pigmentation changes and skin thinning/atrophy were identified as important concerns through patient and public involvement). We used CINeMA to quantify our confidence in the evidence for each outcome. MAIN RESULTS: We included 291 studies involving 45,846 participants with the full spectrum of eczema severity, mainly conducted in high-income countries in secondary care settings. Most studies included adults, with only 31 studies limited to children aged < 12 years. Studies usually included male and female participants, multiple ethnic groups but predominantly white populations. Most studies were industry-funded (68%) or did not report their funding sources/details. Treatment duration and trial participation were a median of 21 and 28 days (ranging from 7 days to 5 years), respectively. Interventions used were topical corticosteroids (TCS) (172), topical calcineurin inhibitors (TCI) (134), phosphodiesterase-4 (PDE-4) inhibitors (55), janus kinase (JAK) inhibitors (30), aryl hydrocarbon receptor activators (10), or other topical agents (21). Comparators included vehicle (170) or other anti-inflammatory treatments. The risk of bias was high in 242 of the 272 (89.0%) trials contributing to data analyses, most commonly due to concerns about selective reporting. Network meta-analysis (NMA) was only possible for short-term outcomes. Patient-reported symptoms NMA of 40 trials (6482 participants) reporting patient-reported symptoms as a binary outcome ranked tacrolimus 0.1% (OR 6.27, 95% CI 1.19 to 32.98), potent TCS (OR 5.99, 95% CI 2.83 to 12.69), and ruxolitinib 1.5% (OR 5.64, 95% CI 1.26 to 25.25) as the most effective, all with low confidence. Mild TCS, roflumilast 0.15%, and crisaborole 2% were the least effective. Class-level sensitivity analysis found potent/very potent TCS had similar effectiveness to potent TCI and was more effective than mild TCI and PDE-4 inhibitors. NMA of 29 trials (3839 participants) reporting patient-reported symptoms as a continuous outcome ranked very potent TCS (SMD -1.99, 95% CI -3.25 to -0.73; low confidence) and tacrolimus 0.03% (SMD -1.57, 95% CI -2.42 to -0.72; moderate confidence) the highest. Direct information for tacrolimus 0.03% was based on one trial of 60 participants at high risk of bias. Roflumilast 0.15%, delgocitinib 0.25% or 0.5%, and tapinarof 1% were the least effective. Class-level sensitivity analysis found potent/very potent TCS had similar effectiveness to potent TCI and JAK inhibitors and mild/moderate TCS was less effective than mild TCI. A further 50 trials (9636 participants) reported patient-reported symptoms as a continuous outcome but could not be included in NMA. Clinician-reported signs NMA of 32 trials (4121 participants) reported clinician signs as a binary outcome and ranked potent TCS (OR 8.15, 95% CI 4.99, 13.57), tacrolimus 0.1% (OR 8.06, 95% CI 3.30, 19.67), ruxolitinib 1.5% (OR 7.72, 95% CI 4.92, 12.10), and delgocitinib 0.5% (OR 7.61, 95% CI 3.72, 15.58) as most effective, all with moderate confidence. Mild TCS, roflumilast 0.15%, crisaborole 2%, and tapinarof 1% were the least effective. Class-level sensitivity analysis found potent/very potent TCS more effective than potent TCI, mild TCI, JAK inhibitors, PDE-4 inhibitors; and mild TCS and PDE-4 inhibitors had similar effectiveness. NMA of 49 trials (5261 participants) reported clinician signs as a continuous outcome and ranked tacrolimus 0.03% (SMD -2.69, 95% CI -3.36, -2.02) and very potent TCS (SMD -1.87, 95% CI -2.69, -1.05) as most effective, both with moderate confidence; roflumilast 0.15%, difamilast 0.3% and tapinarof 1% were ranked as least effective. Direct information for tacrolimus 0.03% was based on one trial in 60 participants with a high risk of bias. For some sensitivity analyses, potent TCS, tacrolimus 0.1%, ruxolitinib 1.5%, delgocitinib 0.5% and delgocitinib 0.25% became some of the most effective treatments. Class-level analysis found potent/very potent TCS had similar effectiveness to potent TCI and JAK inhibitors, and moderate/mild TCS was more effective than mild TCI. A further 100 trials (22,814 participants) reported clinician signs as a continuous outcome but could not be included in NMA. Investigator Global Assessment NMA of 140 trials (23,383 participants) reported IGA as a binary outcome and ranked ruxolitinib 1.5% (OR 9.34, 95% CI 4.8, 18.18), delgocitinib 0.5% (OR 10.08, 95% CI 2.65, 38.37), delgocitinib 0.25% (OR 6.87, 95% CI 1.79, 26.33), very potent TCS (OR 8.34, 95% CI 4.73, 14.67), potent TCS (OR 5.00, 95% CI 3.80, 6.58), and tacrolimus 0.1% (OR 5.06, 95% CI 3.59, 7.13) as most effective, all with moderate confidence. Mild TCS, crisaborole 2%, pimecrolimus 1%, roflumilast 0.15%, difamilast 0.3% and 1%, and tacrolimus 0.03% were the least effective. In a sensitivity analysis of low risk of bias information (12 trials, 1639 participants), potent TCS, delgocitinib 0.5% and delgocitinib 0.25% were most effective, and pimecrolimus 1%, roflumilast 0.15%, difamilast 1% and difamilast 0.3% least effective. Class-level sensitivity analysis found potent/very potent TCS had similar effectiveness to potent TCI and JAK inhibitors and were more effective than PDE-4 inhibitors; mild/moderate TCS were less effective than potent TCI and had similar effectiveness to mild TCI. Longer-term outcomes over 6 to 12 months showed a possible increase in effectiveness for pimecrolimus 1% versus vehicle (4 trials, 2218 participants) in a pairwise meta-analysis, and greater treatment success with mild/moderate TCS than pimecrolimus 1% (based on 1 trial of 2045 participants). Local adverse effects NMA of 83 trials (18,992 participants, 2424 events) reporting application-site reactions ranked tacrolimus 0.1% (OR 2.2, 95% CI 1.53, 3.17; moderate confidence), crisaborole 2% (OR 2.12, 95% CI 1.18, 3.81; high confidence), tacrolimus 0.03% (OR 1.51, 95%CI 1.10, 2.09; low confidence), and pimecrolimus 1% (OR 1.44, 95% CI 1.01, 2.04; low confidence) as most likely to cause site reactions. Very potent, potent, moderate, and mild TCS were least likely to cause site reactions. NMA of eight trials (1786 participants, 3 events) reporting pigmentation changes found no evidence for increased pigmentation changes with TCS and crisaborole 2%, with low confidence for mild, moderate or potent TCS and moderate confidence for crisaborole 2%. NMA of 25 trials (3691 participants, 36 events) reporting skin thinning found no evidence for increased skin thinning with short-term (median 3 weeks, range 1-16 weeks) use of mild TCS (OR 0.72, 95% CI 0.12, 4.31), moderate TCS (OR 0.91, 95% CI 0.16, 5.33), potent TCS (OR 0.96, 95% CI 0.21, 4.43) or very potent TCS (OR 0.88, 95% CI 0.31, 2.49), all with low confidence. Longer-term outcomes over 6 to 60 months showed increased skin thinning with mild to potent TCS versus TCI (3 trials, 4069 participants, 6 events with TCS). AUTHORS' CONCLUSIONS: Potent TCS, JAK inhibitors and tacrolimus 0.1% were consistently ranked as amongst the most effective topical anti-inflammatory treatments for eczema and PDE-4 inhibitors as amongst the least effective. Mild TCS and tapinarof 1% were ranked amongst the least effective treatments in three of five efficacy networks. TCI and crisaborole 2% were ranked most likely to cause local application-site reactions and TCS least likely. We found no evidence for increased skin thinning with short-term TCS but an increase with longer-term TCS.

Case report: Psoriasiform eczema with immune-mediated comorbidities treated with upadacitinib.

Immune-mediated comorbidities in patients with psoriasiform eczema are common. It can be challenging to manage multiple immune-mediated diseases, especially considering that biologic treatments are prone to causing paradoxical effects. The aim of this retrospective observational case series was to describe the course of both psoriasiform eczema and immune-mediated comorbidities in five patients treated with upadacitinib for psoriasiform dermatitis. Five patients, all male, were included. All the patients suffered from psoriasiform eczema. Moreover, two of the patients suffered from alopecia areata, two from vitiligo, one from ulcerative colitis and one from hidradenitis suppurativa. In all cases, the treatment with upadacitinib was rapidly effective on the eczema. The effectiveness on alopecia areata was good in both cases, while the results on vitiligo were only partial. The only case of ulcerative colitis achieved complete remission, while the case of hidradenitis suppurativa experience partial improvement. In conclusion, upadacitinib was effective in treating not only psoriasiform eczema, but also several immune mediated comorbidities. Additional studies are necessary to determine the efficacy of upadacitinib in alopecia areata, vitiligo and hidradenitis suppurativa.

Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 1 and DELTA 2): results from multicentre, randomised, controlled, double-blind, phase 3 trials.

BACKGROUND: Chronic hand eczema is a fluctuating, inflammatory, pruritic, often painful disease of hands and wrists that strongly impacts quality of life and occupational capabilities of patients. The aim of phase 3 DELTA 1 and DELTA 2 was to assess the efficacy and safety of twice-daily applications of the topical pan-Janus kinase inhibitor delgocitinib cream 20 mg/g versus cream vehicle in adults with moderate to severe chronic hand eczema. METHODS: Both trials were randomised, double-blinded, and vehicle-controlled, with DELTA 1 being conducted at 53 trial centres in Canada, France, Germany, Italy, Poland, and the UK and DELTA 2 at 50 trial centres in Belgium, Canada, Denmark, Germany, the Netherlands, Poland, and Spain. Adults (aged ≥18 years) with moderate to severe chronic hand eczema were randomly assigned 2:1 to twice-daily delgocitinib cream 20 mg/g or cream vehicle for 16 weeks. The primary endpoint was Investigator's Global Assessment for Chronic Hand Eczema (IGA-CHE) treatment success at week 16, defined as IGA-CHE score of 0 (clear) or 1 (almost clear, defined as only barely perceptible erythema). Efficacy and safety were assessed in all patients who were exposed to trial treatment. These trials are registered with ClinicalTrials.gov, NCT04871711 and NCT04872101. FINDINGS: Between May 10, 2021, and Oct 31, 2022, 487 patients (181 male and 306 female) were enrolled in DELTA 1; between May 25, 2021, and Jan 6, 2023, 473 patients (161 male and 312 female) were enrolled in DELTA 2. 325 patients in DELTA 1 and 314 in DELTA 2 were assigned to delgocitinib cream; 162 patients in DELTA 1 and 159 in DELTA 2 were assigned to cream vehicle. At week 16, a greater proportion of delgocitinib-treated patients versus cream vehicle patients had IGA-CHE treatment success (64 [20%] of 325 vs 16 [10%] of 162 in DELTA 1 and 91 [29%] of 313 vs 11 [7%] of 159 in DELTA 2; both trials p≤0·0055). The proportion of patients who reported adverse events was similar with delgocitinib (147 [45%] of 325 in DELTA 1 and 143 [46%] of 313 in DELTA 2) and the cream vehicle (82 [51%] of 162 in DELTA 1 and 71 [45%] of 159 in DELTA 2). Most frequent adverse events occurring in at least 2% of patients were similar in both treatment groups and included COVID-19 and nasopharyngitis. INTERPRETATION: Overall, delgocitinib cream showed superior efficacy versus cream vehicle and was well tolerated over 16 weeks. These results support the clinical benefit of delgocitinib cream as a potential treatment option for patients with moderate to severe chronic hand eczema, who are unable to adequately control their disease with basic skin care practices and topical corticosteroids. FUNDING: LEO Pharma.

Flavonoids as Potential Natural Compounds for the Prevention and Treatment of Eczema.

Eczema is a systemic autoimmune disease characterized by inflammation and skin manifestation with a range of comorbidities that include physical and psychological disorders. Despite recent advancements in understanding the mechanisms involved in atopic dermatitis, current marketed products have shown varying results with more side effects. The present objective of the research studies is to develop new agents for eczema that cut down the cost of the novel drugs available and also improve the efficacy with the least adverse effects. Natural compounds and medicinal plants have been traditionally used since ancient civilizations. Nowadays, research in the herbal field is at its peak. One such natural compound, flavonoid, was found to be beneficial for the treatment of eczema. This review describes the use of certain flavonoid products to prepare preparations suitable for the treatment of prophylaxis or eczema. This is especially true for prophylaxis or atopic eczema treatment. These compounds exhibit anti-inflammatory, anti-inflammatory, anti-inflammatory, and anti-inflammatory properties and are, therefore, used in treatments to prevent allergies, inflammation, and irritation to the skin. We also dock the flavonoid derivatives used with the protein associated with the inhibition of eczema for better lead optimization. These preparations appear to be used for cosmetic, dermatological, or herbal remedies as a local application.

Antihypertensive Medications and Eczematous Dermatitis in Older Adults.

Importance: Rates of physician-diagnosed eczema have been increasing among older adults, but little is known regarding the pathophysiologic processes and best treatments in this subgroup. Preliminary data suggest that medications-antihypertensive medications in particular-may contribute to eczematous dermatitis; however, there are limited population-based data on the proportion of eczematous dermatitis diagnoses among older adults that may be attributed to antihypertensive drugs. Objectives: To determine whether antihypertensive drug use is associated with eczematous dermatitis in older adults. Design, Settings, and Participants: This was a longitudinal cohort study of a population-based sample of individuals 60 years and older without a diagnosis of eczematous dermatitis at baseline. It was conducted at primary care practices participating in The Health Improvement Network in the United Kingdom from January 1, 1994, to January 1, 2015. Data analyses were performed from January 6, 2020, to February 6, 2024. Exposure: Exposure date by first prescription for an antihypertensive drug within each drug class. Main outcome measures: Newly active eczematous dermatitis was based on the first date for 1 of the 5 most common eczema codes used in a previously validated algorithm. Results: Among the total study sample of 1 561 358 older adults (mean [SD] age, 67 [9] years; 54% female), the overall prevalence of eczematous dermatitis was 6.7% during a median (IQR) follow-up duration of 6 (3-11) years. Eczematous dermatitis incidence was higher among participants receiving antihypertensive drugs than those who did not (12 vs 9 of 1000 person-years of follow-up). Adjusted Cox proportional hazard models found that participants who received any antihypertensive drugs had a 29% increased hazard rate of any eczematous dermatitis (hazard ratio [HR], 1.29; 95% CI, 1.26-1.31). When assessing each antihypertensive drug class individually, the largest effect size was observed for diuretic drugs (HR, 1.21; 95% CI, 1.19-1.24) and calcium channel blockers (HR, 1.16; 95% CI, 1.14-1.18), and the smallest effect sizes were for angiotensin-converting enzyme inhibitors (HR, 1.02; 95% CI, 1.00-1.04) and ß-blockers (HR, 1.04; 95% CI, 1.02-1.06). Conclusions and Relevance: This cohort study found that antihypertensive drugs were associated with a small increased rate of eczematous dermatitis, with effect sizes largest for calcium channel blockers and diuretic drugs, and smallest for angiotensin-converting enzyme inhibitors and ß-blockers. Although additional research is needed to understand the mechanisms underlying the association, these data could be helpful to clinicians to guide management when a patient presents with eczematous dermatitis in older age.

Recent Advances in Phytochemical-Based Topical Applications for the Management of Eczema: A Review.

Eczema (atopic dermatitis, AD) is a skin disease characterized by skin barrier dysfunction due to various factors, including genetics, immune system abnormalities, and environmental triggers. Application of emollients and topical drugs such as corticosteroids and calcineurin inhibitors form the mainstay of treatments for this challenging condition. This review aims to summarize the recent advances made in phytochemical-based topical applications to treat AD and the different carriers that are being used. In this review, the clinical efficacy of several plant extracts and bioactive phytochemical compounds in treating AD are discussed. The anti-atopic effects of the herbs are evident through improvements in the Scoring Atopic Dermatitis (SCORAD) index, reduced epidermal thickness, decreased transepidermal water loss, and alleviated itching and dryness in individuals affected by AD as well as in AD mouse models. Histopathological studies and serum analyses conducted in AD mouse models demonstrated a reduction in key inflammatory factors, including thymic stromal lymphopoietin (TSLP), serum immunoglobulin E (IgE), and interleukins (IL). Additionally, there was an observed upregulation of the filaggrin (FLG) gene, which regulates the proteins constituting the stratum corneum, the outermost layer of the epidermis. Carriers play a crucial role in topical drug applications, influencing dose delivery, retention, and bioavailability. This discussion delves into the efficacy of various nanocarriers, including liposomes, ethosomes, nanoemulsions, micelles, nanocrystals, solid-lipid nanoparticles, and polymeric nanoparticles. Consequently, the potential long-term side effects such as atrophy, eruptions, lymphoma, pain, and allergic reactions that are associated with current topical treatments, including emollients, topical corticosteroids, topical calcineurin inhibitors, and crisaborole, can potentially be mitigated through the use of phytochemical-based natural topical treatments.

Network Pharmacology Combined with Molecular Docking Approach to Investigate the Mechanism of ChuShiWeiLing Decoction against Perianal Eczema.

BACKGROUND: ChuShiWeiLing Decoction (CSWLD) is a famous classical Chinese prescription for the treatment of eczema with desirable effect in clinical practice. It has gradually exerted good curative effects on perianal eczema (PE) in recent years, but its specific mechanism is not elucidated yet. OBJECTIVE: This research explores the underlying pharmacological mechanism of CSWLD in addressing PE through network pharmacology combined with molecular docking strategy. METHODS: The key chemical compounds and potential target genes of CSWLD were screened by bioinformatics. The major targets of CSWLD were discovered using network modules. Functional annotation of Gene Ontology (GO) was undertaken, as well as pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Molecular docking of core protein-ligand interactions was modeled using AutoDock software. Pymol software was used to perform a molecular dynamics simulation for the ideal core protein-ligand that was discovered by molecular docking. RESULTS: A total of 2,853 active compounds and 922 targets of CSWLD were collected. The target with a higher degree was identified through the PPI network, namely TNF, IL6, ALB, STAT3, EGFR, TLR4, CXCL8 and PTPRC. GO and KEGG analyses suggested that CSWLD treatment of PE mainly involves cellular activation, activation of leukocytes, and adhesion among leukocytes. The molecular docking results showed that wogonin, hederagenin and quercetin of CSWLD could bind to IL-6 and TNF, respectively. CONCLUSION: Our results indicated that the bioactives, potential targets, and molecular mechanism of CSWLD against PE.

Immunologic Profiling of Immune-Related Cutaneous Adverse Events with Checkpoint Inhibitors Reveals Polarized Actionable Pathways.

PURPOSE: Immune-related cutaneous adverse events (ircAE) occur in ≥50% of patients treated with checkpoint inhibitors, but the underlying mechanisms for ircAEs are poorly understood. EXPERIMENTAL DESIGN: Phenotyping/biomarker analyses were conducted in 200 patients on checkpoint inhibitors [139 with ircAEs and 61 without (control group)] to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies, skin tape strip extracts, and plasma using real-time PCR and Meso Scale Discovery multiplex cytokine assays. RESULTS: Eight ircAE phenotypes were identified: pruritus (26%), maculopapular rash (MPR; 21%), eczema (19%), lichenoid (11%), urticaria (8%), psoriasiform (6%), vitiligo (5%), and bullous dermatitis (4%). All phenotypes showed skin lymphocyte and eosinophil infiltrates. Skin biopsy PCR revealed the highest increase in IFNγ mRNA in patients with lichenoid (P < 0.0001) and psoriasiform dermatitis (P < 0.01) as compared with patients without ircAEs, whereas the highest IL13 mRNA levels were detected in patients with eczema (P < 0.0001, compared with control). IL17A mRNA was selectively increased in psoriasiform (P < 0.001), lichenoid (P < 0.0001), bullous dermatitis (P < 0.05), and MPR (P < 0.001) compared with control. Distinct cytokine profiles were confirmed in skin tape strip and plasma. Analysis determined increased skin/plasma IL4 cytokine in pruritus, skin IL13 in eczema, plasma IL5 and IL31 in eczema and urticaria, and mixed-cytokine pathways in MPR. Broad inhibition via corticosteroids or type 2 cytokine-targeted inhibition resulted in clinical benefit in these ircAEs. In contrast, significant skin upregulation of type 1/type 17 pathways was found in psoriasiform, lichenoid, bullous dermatitis, and type 1 activation in vitiligo. CONCLUSIONS: Distinct immunologic ircAE endotypes suggest actionable targets for precision medicine-based interventions.

Validation of the Investigator Global Assessment of Chronic Hand Eczema (IGA-CHE): a new clinician reported outcome measure of CHE severity.

The Investigator Global Assessment of Chronic Hand Eczema (IGA-CHE) is a novel Clinician-Reported Outcome measure that allows investigators to assess cross-sectional CHE global disease severity using clinical characteristics of erythema, scaling, lichenification/hyperkeratosis, vesiculation, oedema, and fissures as guidelines for overall severity assessment. This study aimed to evaluate the psychometric properties of the IGA-CHE for use as an outcome measure in CHE clinical trials and clinical practice. Psychometric analyses were performed using data from a sample of 280 patients with moderate to severe CHE from a phase 3 trial of delgocitinib cream, pooled across treatment groups. Test-retest reliability results were moderate to strong with kappa coefficients ranging from 0.63 to 0.76. Correlations with measures assessing related concepts were moderate or strong (range 0.65-0.72) and exceeded a priori hypotheses, providing evidence of convergent validity. Known-groups validity was supported by statistically significant differences between severity groups (< 0.001). Within-group effect sizes were consistently larger for improved groups compared to stable groups, providing evidence of ability to detect change. Anchor-based analyses generated within-subject meaningful change estimates ranging from - 0.8 to - 2.3. A correlation weighted average suggested a single value of - 1.7 in change from baseline. These findings provide evidence the IGA-CHE scale has strong reliability, construct validity, and ability to detect change, supporting its use as an endpoint in CHE clinical trials and clinical practice. Based on the evidence, 2-level changes in IGA-CHE score are considered a conservative meaningful change threshold; however, findings also indicate 1-level change in IGA-CHE scores reflects a clinically meaningful improvement for patients.Clinical trial registration: NCT04871711.

Efficacy and safety of crisaborole ointment, 2%, in participants aged ≥45 years with stasis dermatitis: Results from a fully decentralized, randomized, proof-of-concept phase 2a study.

BACKGROUND: Crisaborole ointment, 2%, is a nonsteroidal topical phosphodiesterase 4 inhibitor approved for the treatment of mild-to-moderate atopic dermatitis. OBJECTIVE: To evaluate the efficacy and safety of crisaborole in stasis dermatitis (SD). METHODS: In this randomized, double-blind, vehicle-controlled, decentralized phase 2a study (NCT04091087), 65 participants aged ≥45 years with SD without active ulceration received crisaborole or vehicle (1:1) twice-daily for 6 weeks. The primary end point was percentage change from baseline in total sign score at week 6 based on in-person assessment. RESULTS: Crisaborole-treated participants had significantly reduced total sign score from baseline versus vehicle based on in-person (nondermatologist) assessment (-32.4% vs -18.1%, P = .0299) and central reader (dermatologists) assessment of photographs (-52.5% vs -10.3%, P = .0004). Efficacy according to success and improvement per Investigator's Global Assessment score and lesional percentage body surface area reached statistical significance based on central reader but not in-person assessments. Skin and subcutaneous tissue disorders were common all-causality treatment-emergent adverse events with crisaborole. LIMITATIONS: Small sample size and short treatment duration were key limitations. In-person assessment was not conducted by dermatologists. CONCLUSION: Crisaborole improved signs and symptoms of SD and was well tolerated. Central reader assessment represents a promising approach for siteless clinical research.

Topical steroid withdrawal: a survey of UK dermatologists' attitudes.

The term topical steroid withdrawal (TSW) refers to a condition widely discussed on social media, but rarely mentioned in the medical literature. It typically involves a patient with chronic eczema who abruptly discontinues topical corticosteroids (TCS) believing they are ineffective and damaging. Symptoms include an acute eruption, worse than the previous eczema, of painful erythema followed by oozing, crusting, desquamation and sometimes prolonged systemic weakness. Patients self-diagnose and often avoid healthcare professionals who dismiss the diagnosis and persist in offering TCS, leaving them unsupported. We analysed 121 responses to a survey of UK dermatologists' attitudes to TSW. Views on aetiology included relapsed eczema, erythroderma and a social construct. A total of 88.4% (107/121) agreed that TSW needs better understanding and more research. Respondents earlier in their careers are more cautious than senior respondents about prescribing TCS long term because of TSW, suggesting a trend that might lead to better understanding, communication and management.

Comparison of the effect of topical triamcinolone 0.1% cream with sulfur 2.0% cream in the treatment of patients with hand eczema: A randomized controlled trial.

BACKGROUND: Hand eczema (HE) is a common and heterogeneous condition. It has a wide range of etiologies and clinical manifestations. In this study the efficacy of triamcinolone 0.1% cream and sulfur 2% creams was compared in treating patients with HE. METHODS: This randomized, triple-blind clinical trial was performed on 70 patients with HE (including 70 right and 70 left hands). In this study, two creams were used including triamcinolone 0.1% and sulfur 2.0%. Patients were treated with these creams twice a day (once in every 12 h) for 4 weeks. Follow-up was 4 weeks after treatment. Hand Eczema Severity Index (HECSI), itching, dryness, burning sensation, and erythema scores were collected three times during the study and compared between treatment regimens. RESULTS: Findings showed that both triamcinolone (0.1%) and sulfur (2.0%) creams could significantly reduce the scores of HECSI, itching, dryness, burning sensation, and erythema, and the therapeutic effects lasted for at least 4 weeks after cessation of topical treatment. CONCLUSION: Topical sulfur cream (2.0%) is as effective as triamcinolone (0.1%) cream in treatment of HE without any prominent adverse reactions.