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This article discusses a study that examines the relationship between sun exposure, skin aging, and basal cell carcinoma (BCC). The study used DNA methylation data from sun-exposed and sun-protected skin samples, as well as BCC samples, to analyze epigenetic and biological age, and telomere length. The results show that sun-exposed skin has a slower epigenetic and biological aging process and shorter telomeres compared to sun-protected skin. These effects were more common in older individuals and females. The study suggests that these age dysregulation patterns may indicate an increased risk of skin cancer after prolonged sun exposure. The study was funded by various sources and the authors have no conflicts of interest. [Extracted from the article]

Introduction Currently approved dosing regimens of upadacitinib (UPA) for moderate-to-severe atopic dermatitis (AD) are 15 mg (UPA15) once daily (QD) and 30 mg (UPA30) QD based on clinical trial data. However, dose alterations may be required in the context of inadequate efficacy, adverse events (AEs), and patient preference. Objectives Our multicenter retrospective study evaluated the effect of upadacitinib dose alterations on real-world effectiveness and safety outcomes in patients with AD at three practices in Canada. Methods Among 119 patients with AD initiated on UPA with > 23-week follow-up, we identified patients undergoing dose alteration (escalation or reduction). Reasons for dose alteration were collected along with effects of dose alteration on effectiveness outcomes including Investigator Global Assessment (IGA), mean Eczema Area and Severity Index (EASI), body surface area (BSA), Dermatology Life Quality Index (DLQI)/Children's DLQI (CDLQI), and IGAxBSA. Impact of dose alteration on incidence and outcomes of AEs was additionally analyzed. Results From 119 total patients with AD initiated on UPA (> 23-week follow-up), 26.9% (32/119) underwent dose alteration: 40.6% (13/32) with dose escalation and 59.4% (19/32) with dose reduction. The mean age of patients who underwent dose alteration was 44.8 (range: 12-79) years; 62.5% (20/32) were female and 15.6% (5/32) were adolescents. Initial doses were UPA15 (43.8%, 14/32) and UPA30 (56.3%, 18/32). The mean time from UPA initiation to dose alteration was 228.3 (range: 9-520) days. Thirteen patients underwent dose escalation: 69.2% (9/13) from UPA15 QD to UPA30 QD and 30.8% (4/13) from UPA30 QD to 45 mg (UPA45) QD. At the time of dose escalation: mean EASI score was 2.8 (mean EASI improvement from baseline: 57.4%), with 53.8% (7/13) and 7.7% (1/13) having achieved 75% and 90% improvements in baseline EASI scores (EASI75 and EASI90), respectively, while IGA scores were 1 (n=5) and 2 (n=8). At follow-up (mean duration: 83.3 days) after dose escalation: mean EASI score was 1.6 (mean EASI improvement: 84.4% [from baseline] and 54% [from date of dose escalation]), with 69.2% (9/13), 61.5% (8/13), 38.5% (5/13), and 61.5% (8/13) of patients achieving EASI75, EASI90, 100% improvement in EASI (EASI100), and IGA 0/1, respectively. Two patients (15.4%) discontinued UPA due to lack of efficacy despite dose escalation. Only 2 AEs were noted with dose escalation: transaminitis (n=1) and elevated creatine phosphokinase (n=1); the patient with transaminitis subsequently discontinued UPA. Nineteen patients underwent dose reduction: UPA30 QD to UPA15 QD (63.1%, 12/19), UPA30 QD to UPA30 every other day (QOD) (10.5%, 2/19), and UPA15 QD to UPA15 QOD (26.3%, 7/19). Reasons for dose reduction included AEs (57.9%, 11/19) and patient preference following clearance or near-clearance (42.1%, 8/19). EASI/IGA responses were maintained in 78.9% (15/19) patients. Following dose reduction, 21.1% (4/19) of patients flared and required re-escalation (mean duration: 147.3 days). AEs requiring dose reduction included acne (36.4%, 4/11), herpes simplex (18.2%, 2/11), transaminitis (18.2%, 2/11), folliculitis (9.1%, 1/11), and recurrent respiratory tract infections (18.2%, 2/11). AEs improved in 54.5% (6/11) patients with dose reduction (mean follow-up: 164.1 days). Conclusions Our real-world data suggests dose escalation from UPA15 to UPA30 and UPA30 to UPA45 (off-label) can result in higher skin clearance without any short-term safety concerns. Comparable to a Japanese real-world study (n=23), we noted incremental benefits with dose escalation, including comparable and superior achievement of EASI75 (69.2% vs. 66.7%) and EASI90 (61.5% vs. 38.1%), respectively. Furthermore, we identified AEs at higher UPA doses can improve through dose reduction with majority of patients (78.9%) maintaining initial effectiveness response. Study limitations include its small sample size and retrospective nature. [ABSTRACT FROM AUTHOR]

Introduction While clinical trial data demonstrates the efficacy and safety of upadacitinib (UPA), an oral Janus kinase inhibitor (JAKi) for atopic dermatitis (AD), long-term real-world evidence remains limited. Objectives Our study evaluated the real-world effectiveness and safety of UPA for AD at week 52±6. Methods We conducted a multicenter retrospective review of 3 practices in Canada. Effectiveness endpoints were evaluated at weeks 52±6 and including the following: Investigator Global Assessment (IGA) score of clear or almost clear (IGA 0/1) as well as improvements in Eczema Area and Severity Index (EASI), body surface area (BSA), IGAxBSA, and Dermatology Life Quality Index (DLQI)/Children's DLQI (CDLQI). Safety was determined via incidence of treatment-related adverse events (AEs). Results A total of 102 patients with AD were included in the analysis; mean age was 44.2 (range: 12-79) years and 52.9% (54/102) were female. Initial UPA doses were 15 mg (UPA15: 41.2%, 42/102) or 30 mg (UPA30: 58.8%, 60/102) once daily. Previous systemic therapies included conventional non-biologics (72.5%), biologics (30.4%), and JAKi (2.9%). At week 52±6: 78.4% (80/102) of patients achieved Investigator Global Assessment (IGA) 0/1; 87.5% (49/56), 78.6% (44/56), and 50.0% (28/56) achieved Eczema Area and Severity Index (EASI) improvements of 75% (EASI75), 90% (EASI90), and 100% (EASI100), respectively; 75.0% (42/56) achieved EASI90 + IGA 0/1; mean EASI was reduced from 12.9 to 0.8 (mean EASI improvement = 91.4%); 91.9% (52/56), 92.9% (52/56), 82.1% (46/56), and 75.0% (42/56) achieved absolute EASI scores < 7, < 5, < 3, and < 1, respectively; mean body surface area (BSA) was reduced from 17.0% to 0.6% (mean BSA improvement=87.8%); mean IGAxBSA was reduced from 52.1 to 0.8 (mean IGAxBSA improvement=90.7%); and mean Dermatology Life Quality Index (DLQI)/Children's DLQI was reduced from 13 to 1.8 (mean DLQI/CDLQI improvement=86%), with 66.0% (33/50) of patients achieving DLQI/CDLQI 0/1. For patients not achieving IGA 0/1, EASI75, EASI90, and EASI100 at weeks 8-20, these responses were subsequently achieved in 60.0% (6/10), 88.9% (8/9), 84.6% (11/13), and 38.1% (8/21) of patients at week 52±6. Dose alterations occurred in 13 patients (12.7%) (escalation: 6.9%, 7/102; reduction: 5.9%, 6/102). Concomitant systemic therapies were used in 1.0% (1/102) of patients. We noted higher statistically significant achievement of endpoints for systemic biologic/JAKi-naïve vs -experienced patients (EASI75; EASI < 7; EASI < 5; DLQI/CDLQI > 4-point improvement). No significant differences in outcomes were identified between dosing regimens. Frequent AEs included: acne (19.6%, 20/102), hypertriglyceridemia (17.6%, 18/102), elevated creatine phosphokinase (13.7%, 14/102), neutropenia (7.8%, 8/102), and transaminitis (7.8%, 8/102). Seven patients (6.8%) discontinued UPA owing to treatment-related AEs, including one case of venous thromboembolism; four patients (3.9%) discontinued UPA due to patient preference, and one patient (1%) discontinued UPA due to lack of efficacy. No serious infections, tuberculosis, major adverse cardiovascular events, gastrointestinal perforation, malignancy, or deaths were observed in 102.5 patient-years of follow-up. Conclusions In contrast to 52-week data from the Measure Up 1/2 and AD Up clinical trials, our results were superior for several outcome parameters (IGA 0/1, EASI90, EASI100, and DLQI 0/1), possibly owing to a patient population with less extensive baseline disease severity. Additionally, we noted similar achievement of these endpoints versus comparable long-term real-world studies. Safety was consistent with existing data, highlighting acne as a common AE (5.3%-20.3% versus 19.6%). Study limitations include its sample size and retrospective nature. [ABSTRACT FROM AUTHOR]

Introduction While clinical trial data demonstrates the efficacy and safety of upadacitinib (UPA), a selective oral Janus kinase inhibitor (JAKi) for atopic dermatitis (AD), there is still a lack of real-world evidence. Objectives Our study evaluated the real-world effectiveness and safety of UPA for AD at weeks 20-32. Methods We conducted a multicenter retrospective review at three practices in Canada. Effectiveness endpoints evaluated at weeks 20-32 included Investigator Global Assessment (IGA) score of clear or almost clear (IGA 0/1) as well as improvements in Eczema Area and Severity Index (EASI), body surface area (BSA), IGAxBSA, and Dermatology Life Quality Index (DLQI)/Children's DLQI (CDLQI). Safety was -determined via incidence of treatment-related adverse events (AEs). Results A total of 131 patients were included in the analysis. Mean age was 44.3 ± 17.5 (range: 12-78) years; 53.4% (70/131) were female. UPA doses were 15 mg (43.5%, 57/131) or 30 mg (56.5%, 74/131) once daily. Previous treatments included: topical therapy (100%, 131/131), phototherapy (29%, 38/131), systemic non-biologic therapy (75.6%, 99/131), and systemic biologic/JAKi therapy (38.9%, 51/131). At weeks 20-32: 85.5% (112/131) of patients achieved IGA 0/1; 84.3% (59/70), 75.7% (53/70), and 62.9% (44/70) of patients achieved EASI improvements of 75% (EASI75), 90% (EASI90), and 100% (EASI100), respectively; mean EASI was reduced from 12.7 to 0.7 (p=0.0001; mean EASI improvement = 88.8%); 94.3% (66/70), 92.9% (65/70), 90% (63/70), and 77.1% (54/70) of patients achieved absolute EASI scores < 7, 5, < 3, and < 1, respectively; mean BSA was reduced from 16.4% to 0.9% (p=0.0001; mean BSA improvement=92.5%); mean IGAxBSA was reduced from 53.5 to 1.6 (p=0.0001; mean IGAxBSA improvement=95.7%); and mean DLQI/CDLQI was reduced from 13 to 1.2 (p=0.0001; mean DLQI/CDLQI improvement=90.5%), with 84.6% (55/65) of patients achieving DLQI/CDLQI 0/1. UPA monotherapy was utilized in 38.9% (51/131) of cases. Common concomitant therapies included topical corticosteroids (56.5%, 74/131), systemic corticosteroids (5.3%, 7/131), and topical calcineurin inhibitors (3.8%, 5/131). Frequent AEs included: acne (18.3%, 24/131), hypertriglyceridemia (18.3%, 24/131), elevated creatine phosphokinase (12.2%, 16/131), herpes simplex (5.3%, 7/131), and transaminitis (5.3%, 7/131). Five patients (3.8%) discontinued UPA due to treatment-related AEs (myalgia/arthralgia [n=2]; gastrointestinal discomfort [n=1]; venous thromboembolism [n=1]; folliculitis [n=1]). No serious infections, tuberculosis, major adverse cardiovascular events, gastrointestinal perforation, or malignancy were observed in 67.4 patient-years of safety follow-up. Conclusions Our real-world study shows that UPA is an effective and safe therapy for AD, with high levels of skin clearance and a favorable safety profile between weeks 20-32. These results indicate that UPA may perform better in the real-world versus clinical trial setting, as compared to the Heads Up and Rising Up studies at week 24, specifically for IGA 0/1 and EASI75/EASI90/EASI100 achievement. This may be explained by less severe baseline disease severity in our study. Limitations of this study include its sample size and retrospective nature. [ABSTRACT FROM AUTHOR]

Introduction Upadacitinib (UPA), an oral, selective Janus kinase inhibitor (JAKi), is approved for moderate-to-severe atopic dermatitis (AD). While its efficacy and safety are supported by clinical trial data1-3, real-world evidence is limited. Objectives Our study evaluated the real-world effectiveness and safety of UPA for AD between weeks 8-20. Methods We conducted a multicenter retrospective review at three practices in Canada. Effectiveness endpoints measured between weeks 8-20 included: Investigator Global Assessment (IGA) score of clear or almost clear (IGA 0/1) and improvements in Eczema Area and Severity Index (EASI), body surface area (BSA), IGAxBSA, and Dermatology Life Quality Index (DLQI)/Children's DLQI (CDLQI) improvements. Safety was assessed via treatment-related adverse events (AEs). Results A total of 179 patients were included in the analysis.. The mean age was 44.6 ± 17.5 (range: 12-79) years; 53.6% (96/179) were female. Previous treatments included: topicals (100%, 179/179), light (29.1%, 52/179), systemic non-biologics (74.9%, 134/179), and systemic biologics/JAKi (37.4%, 67/179). Initial UPA doses were 15 mg (44.7%, 80/179) or 30 mg (55.3%, 99/179) once daily. At weeks 8-20: 87.2% (156/179) of patients achieved IGA 0/1; 83.3% (85/102), 74.5% (76/102), and 57.8% (59/102) of patients achieved EASI improvements from baseline of 75% (EASI75), 90% (EASI90), and 100% (EASI100), respectively; mean EASI was reduced from 13.4 to 1.0 (p=0.0001; mean EASI improvement = 88.5%); 98% (100/102), 96.1% (98/102), 88.2% (90/102), and 70.6% (72/102) of patients achieved absolute EASI scores < 7, < 5, < 3, and < 1, respectively; mean BSA was reduced from 18.2% to 1.1% (p=0.0001; mean BSA improvement=92.2%); mean IGAxBSA was reduced from 60.9 to 2.1 (p=0.0001; mean IGAxBSA improvement=94.7%); and mean DLQI/CDLQI was reduced from 13.6 to 1.4 (p=0.0001; mean DLQI/CDLQI improvement=87.1%), with 75.9% (63/83) of patients achieving DLQI/CDLQI 0/1. UPA monotherapy was utilized in 39.7% (71/179) of cases. Common concomitant therapies included topical corticosteroids (55.3%, 99/179), topical calcineurin inhibitors (6.7%, 12/179), and intramuscular triamcinolone acetonide (2.2%, 4/179). Statistically significantly higher achievement of endpoints was noted for patients using concomitant therapies (EASI75; EASI90; EASI < 1) and systemic biologic/JAKi-naïve patients (EASI75; EASI < 5; IGA 0/1; DLQI/CDLQI > 4-point improvement). Outcomes were not significantly different between dosing regimens. Frequent AEs included: acne (16.2%, 29/179), hypertriglyceridemia (14%, 25/179), elevated creatinine phosphokinase (10.1%, 18/179), herpes simplex virus (6.7%, 12/179), and transaminitis (4.5%, 8/179). Three patients (1.7%) discontinued treatment (myalgia/arthralgia [n=2]; gastrointestinal discomfort [n=1]). No serious infections, tuberculosis, venous thromboembolism, major adverse cardiovascular events, gastrointestinal perforation, or malignancy were observed in 44.7 patient-years of safety follow-up for the treatment period being analyzed. Conclusions Our study included 75.4% (135/179) of patients with follow-up at weeks ≥12 to ≤16. Interestingly, we found more favourable results than Measure Up 1/2 and AD Up clinical trials at week 16 for IGA 0/1, EASI75, EASI90, EASI100, and DLQI 0/1, likely owing to a patient population with less extensive baseline disease severity, while the safety profile was commensurate. Additionally, we noted higher achievement of IGA 0/1, EASI75, and EASI90 endpoints versus similar real-world studies. Study limitations include its retrospective nature and short follow-up duration. Nonetheless, our results support clinical trial findings suggesting UPA is effective and safe for AD. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a rare, chronic skin disease, characterized by widespread pustules and erythema, often accompanied with systemic signs and symptoms. GPP flares occur episodically but may be protracted. Left untreated, GPP can be life‐threatening. Despite being first reported over 100 years ago, definitions and diagnostic criteria for GPP have been inconsistent and varied due, in part, to its rarity and a limited understanding of its pathogenesis. As such, many patients with GPP face delays in diagnosis and subsequent treatment. This manuscript aims to increase the recognition of GPP and provide foundational considerations to aid in the definition and diagnosis of this disease. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor discussing the development of immune checkpoint inhibitors (ICIs) and their association with cutaneous granulomatous reactions (GD). The authors conducted a systematic review of reports on ICI-associated GD to better understand the clinical implications. They found that GDs observed in patients treated with ICIs included sarcoid-like granulomas, interstitial granulomatous dermatitis, granuloma annulare, granulomatous panniculitis, and foreign-body granuloma. The review also highlighted the importance of timely biopsy to confirm the etiology of radiological findings and offered management considerations for dermatologists and dermatopathologists. [Extracted from the article]

This document is a letter to the editor discussing the real-world effectiveness and safety of risankizumab in adult patients with plaque psoriasis. The authors conducted a 16-week international multicenter retrospective cohort study to evaluate the outcomes of risankizumab treatment. The study included 388 patients, and after 16 weeks of treatment, 75% of patients achieved a 90% improvement in the Psoriasis Area and Severity Index (PASI90) score or a Physician Global Assessment (PGA) score of 0 or 1. Adverse events were infrequent, and treatment discontinuation events were uncommon. The study suggests that the effectiveness of risankizumab in real-world patients is comparable to the efficacy observed in phase III randomized controlled trials. However, further studies with control populations are needed to confirm these findings. [Extracted from the article]

This document is a letter to the editor published in the Journal of Cutaneous Medicine & Surgery. The letter discusses the connection between psoriasis and human papillomavirus (HPV) and aims to provide a comprehensive review of the relationship between the two conditions. The authors conducted a systematic review of existing literature and found that the occurrence of HPV in patients with psoriasis varies in different studies. They suggest that a dysregulation in immune response may be a key factor linking the two conditions. The authors also discuss potential treatment implications and call for further research to better understand the immune connections between HPV and psoriasis. [Extracted from the article]

This document is a letter to the editor discussing the seasonal fluctuations in atopic dermatitis (AD) on a global scale using Google Trends data. The authors conducted a time series analysis using search terms related to AD in 42 countries. The results showed that Google searches for AD peaked from January to May compared to July to October and December. The authors suggest that physicians should be aware of this seasonality and that increased searches may indicate a need for additional support and management for patients. However, the study has limitations, such as only using data from the northern hemisphere and not accounting for other factors like temperature and humidity. Further research is needed to investigate additional countries and search terms. [Extracted from the article]

This document is a letter to the editor titled "Association of Proton Pump Inhibitors on Psoriasis Treatment and Development: A Systematic Review." The authors conducted a systematic review to examine the evidence regarding the association between proton pump inhibitors (PPIs) and psoriasis treatment and development. They found that while the relationship between psoriasis and PPI use remains unclear, certain patient subsets may experience improvement in psoriasis symptoms with PPI use. However, further research is needed to understand this relationship and determine appropriate monitoring. The authors disclosed potential conflicts of interest and received no financial support for the research. [Extracted from the article]

This document is a letter to the editor of the Journal of Cutaneous Medicine & Surgery. It provides an evidence-based review of the use of Janus kinase inhibitors (JAKi) for the treatment of cicatricial alopecias (CAs), a group of immune-mediated scarring hair conditions. The review analyzed 16 articles published between 2018 and 2024, which included 91 patients and 98 treatments. The results showed that JAKi therapy, including topical and oral formulations, led to complete or partial resolution of CAs in various subtypes, such as lichen planopilaris/frontal fibrosing alopecia, folliculitis decalvans, and lupus-associated CA. The use of JAKi was generally well-tolerated, with some patients experiencing mild adverse events. The authors suggest the need for further large-scale studies to evaluate the effectiveness of JAKi for CAs. [Extracted from the article]