BACKGROUND:Chronic hand eczema (CHE) is a chronic inflammatory skin condition that affects the hands and wrists causing itching, dryness, cracking, and pain. It often affects people with atopic dermatitis (AD) and can interfere with work and daily life. Topical therapies may have limited utility from ineffectiveness, poor adherence, or poor tolerability. Here, we evaluate oral upadacitinib (UPA) as a potential therapeutic alternative for patients with AD and refractory CHE. METHODS:This narrative review analyzed studies from PubMed, SCOPUS, and EMBASE evaluating CHE treatments. Eligible studies utilized the Hand Eczema Severity Index (HECSI), a validated clinician-reported outcome measure assessing CHE severity. HECSI-75 is the proportion of patients achieving at least a 75% improvement in clinical severity. Cases of three CHE patients from diverse demographics are presented. RESULTS:In two phase 3 randomized controlled trials of UPA for moderate-to-severe AD, 94.8% (803/847) and 92.6% (774/836) of patients had CHE with HECSI assessments at baseline. Rapid improvement in CHE was observed in patients who received either dose of UPA (15 mg or 30 mg) as early as week 1 (P≤0.001 vs placebo). By week 8, up to 83% of UPA-treated patients achieved a statistically significant improvement in CHE (HECSI 75; P≤0.001 vs placebo). These benefits were sustained through week 16. Real-world clinical cases showed CHE patients experienced marked symptom relief within days of initiating UPA. CONCLUSION:UPA-treated patients experienced rapid and sustained relief from CHE lesions, making it a promising therapeutic option for CHE patients for whom topical therapies are ineffective.

BACKGROUND:Atopic dermatitis (AD) is a chronic inflammatory skin condition associated with risk of cardiovascular disease (CVD), potentially mediated by persistent systemic inflammation. Upadacitinib (UPA), a selective Janus kinase 1 (JAK1) inhibitor, effectively reduces AD-related inflammation and may confer additional cardioprotective and thromboprotective benefits. OBJECTIVE:This review evaluates the incidence of major adverse cardiovascular events (MACE) in patients with AD, comparing background rates reported in the literature to long-term MACE rates observed in clinical trials of UPA. METHODS:A literature review was conducted across PubMed, SCOPUS, and EMBASE to identify studies reporting MACE and venous thromboembolism (VTE) rates in moderate-to-severe AD populations. Long-term (5-year) incidence rates in UPA-treated patients were extracted from clinical trials. Reported background incidence rates in AD populations were included. RESULTS:MACE rates in the background AD populations ranged from 0.3 to 1.2 per 100 patient-years (PY), whereas UPA-treated patients exhibited lower rates (15 mg: 0.2, 30 mg: <0.1). VTE rates in AD populations ranged from 0.1 to 0.3, while UPA-treated patients showed lower rates at 0.1 for both 15 mg and 30 mg doses. CONCLUSIONS:The observed lower MACE and VTE rates in UPA-treated patients suggests potential cardiovascular and thrombotic benefits. While these findings are hypothesis-generating, further studies are needed to confirm the impact of UPA on CVD and thrombosis and explore the mechanistic basis of JAK1 inhibition in cardiovascular health. CITATION:Alani O, Wang D, Wahood S, et al. Is upadacitinib cardioprotective in chronic inflammatory diseases? A review of major adverse cardiovascular events and venous thromboembolism in atopic dermatitis. J Drugs Dermatol. 2025;24(5):doi:10.36849/JDD.9049.

Erosive pustular dermatosis (EPD) of the scalp is an inflammatory condition that is characterized by skin atrophy, erosions, and keratotic crusts and primarily affects elderly patients. The lesions of EPD develop over time and can lead to scarring alopecia. There are no established clinical guidelines or consensus on treatment for EPD, but some authors report success with photodynamic therapy using aminolevulinic acid as the sensitizer (ALA-PDT). This report presents 2 cases of male patients, 91 and 86 years of age, with EPD that did not resolve despite prior treatment with topical steroids or retinoids but was successfully treated using ALA-PDT. In both patients, ALA-PDT resulted in improvement of EPD of the scalp after 2 sessions, with visible progress by 6 weeks after the second ALA-PDT session. The ALA-PDT treatments were well tolerated. The cases presented here demonstrate that ALA-PDT can be a potential therapeutic option for EPD of the scalp.

Background: Fluoroquinolones, available in topical and oral formulations, are used to manage bacterial skin and soft tissue infections, including Pseudomonas aeruginosa, atypical mycobacteria, and select multidrug-resistant Gram-negative organisms. Their excellent tissue penetration, bactericidal activity, and convenient dosing make them effective for certain skin and soft tissue infections. However, their use is limited by potential safety concerns, including tendinopathy (odds ratio up to 9.1 in corticosteroid users), QT interval prolongation with risk of torsades de pointes, phototoxicity, and rising antimicrobial resistance. Methods: A literature search of PubMed, Scopus, and Web of Science was conducted for articles from January 1985 to April 2025 with the search terms (quinolone OR fluoroquinolone) AND (dermatology OR “skin and soft tissue infection” OR “skin structure infection”). Abstracts and presentations were excluded. A Google search used the same terms for articles from government regulatory agencies. Results: This review provides practical guidance on the clinical use of topical and oral fluoroquinolones in dermatology. Delafloxacin demonstrated over 90% cure rates in trials for complicated skin infections. However, serious safety concerns remain, including a ninefold increase in tendinopathy risk among older adults on corticosteroids and corrected QT intervals exceeding 500 milliseconds in high-risk patients. Phototoxicity varies, with agents like sparfloxacin linked to heightened ultraviolet sensitivity. Resistance to ciprofloxacin exceeds 20 percent in Escherichia coli and P. aeruginosa in some populations. Culture-based prescribing, shorter treatment courses, and preference for topical treatments can reduce risk and preserve efficacy. Conclusions: Fluoroquinolones remain clinically useful in dermatology when prescribed selectively. Their appropriate use requires careful attention to patient risk factors along with their evolving resistance patterns and ongoing stewardship efforts.

To the Editor: Social media has an increasingly important role in life. Healthcare-related topics make up an important aspect of social posts because approximately 25% of social media users follow friends health updates online and approximately 10% post about their own health.(1) The impact of social media on our actual health cannot be underestimated. Indeed, Facebook and other social media have been shown to have a positive impact on patients with chronic conditions.(1) Moreover, recent studies have shown that patients with chronic conditions, particularly adolescents, tend to spend more time online during flare-ups.(2) Although this suggests a potential role for social media in helping patients with chronic conditions, little is known about how chronic conditions affect social media posting. We created a survey questionnaire to investigate how psoriasis affects social media posting habits and the general attitude of psoriasis patients toward social media.

Abstract Introduction/Background Atopic dermatitis (AD) is a chronic, recurrent, immune-mediated inflammatory disease associated with burdensome symptoms including itch, skin pain, sleep disruption, as well as reduced quality of life (QoL).1 It is therefore important to consider signs, symptoms, and QoL impairments when evaluating long-term benefits of AD treatments. Upadacitinib is an oral selective Janus kinase inhibitor approved to treat moderate-to-severe AD.2 Objective To evaluate the effects of upadacitinib monotherapy on skin and patient-reported outcomes (PROs) in patients with moderate-to-severe AD over 140 weeks. Methods Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) were replicate, multicenter, phase 3 studies evaluating once-daily oral upadacitinib monotherapy for adolescents (aged 12–17 years) and adults (aged ≥ 18 years) with moderate-to-severe AD.3,4 At baseline, patients were randomized 1:1:1 to upadacitinib 15 mg, upadacitinib 30 mg, or placebo. In this analysis, data for patients who were randomized to upadacitinib 15 mg or upadacitinib 30 mg at baseline in Measure Up 1 and Measure Up 2 were integrated and reported based on observed cases from week 16 (the end of the double-blind period) through week 140 of the blinded extension period; week 16 data for patients randomized to placebo were also reported. Assessments included itch (Worst Pruritus Numerical Rating Scale [WP-NRS]); Eczema Area and Severity Index (EASI); skin pain (AD Symptom Scale [ADerm-SS] Skin Pain); skin symptoms (ADerm-SS 7-item Total Symptom Score [TSS-7]); skin symptom severity (Patient-Oriented Eczema Measure [POEM]); QoL (Dermatology Life Quality Index [DLQI; patients aged ≥ 16 years], and Children’s DLQI [CDLQI; patients aged < 16 years]); and sleep, daily activities, and emotional state (AD Impact Scale [ADerm-IS]). Assessed outcomes included achievement of (1) minimal clinically important differences vs baseline (WP-NRS, ADerm-SS Skin Pain, and POEM improvement ≥ 4; ADerm-SS TSS-7 improvement ≥ 28; ADerm-IS Sleep, Daily Activities, and Emotional State improvements ≥ 12, ≥ 14, and ≥ 11, respectively), (2) no/minimal disease burden or impact (WP-NRS 0/1, ≥ 90% improvement from baseline in EASI [EASI 90], DLQI 0/1,and CDLQI 0/1), and (3) simultaneous achievement of EASI 90 and WP-NRS 0/1, an endpoint that aligns with the recently proposed minimal disease activity concept.5 Results Data for 1213 patients (upadacitinib 15 mg, n = 603; upadacitinib 30 mg, n = 610), including 241 adolescents (19.9%) and 972 adults (80.1%), from Measure Up 1 and Measure Up 2 were analyzed. At week 16, over 50% of patients receiving either dose of upadacitinib reported clinically meaningful improvements in PROs; among patients receiving upadacitinib 15 mg and upadacitinib 30 mg, 36.7% and 53.1% achieved WP-NRS 0/1, while 29.0% and 44.1% achieved DLQI 0/1, and 23.5% and 50.0% achieved CDLQI 0/1, respectively. Response rates at week 16 were sustained or improved further through week 140. At week 140, the proportion of patients treated with upadacitinib 15 mg and upadacitinib 30 mg from baseline who achieved clinically meaningful improvements were 64.8% and 70.9% for itch, 74.6% and 81.5% for skin pain, 67.6% and 75.4% for skin symptoms, 89.0% and 94.2% for skin symptom severity, 76.5% and 84.0% for sleep, 79.2% and 84.0% for daily activities, and 78.6% and 82.7% for emotional state, respectively. At week 140, achievement rates with upadacitinib 15 mg and upadacitinib 30 mg were 45.1% and 51.4% for WP-NRS 0/1, 67.3% and 75.6% for EASI 90, 40.5% and 47.1% for simultaneous EASI 90 and WP-NRS 0/1 achievement, 40.2% and 48.5% for DLQI 0/1, and 35.7% and 65.0% for CDLQI 0/1, respectively. Conclusions Patients with moderate-to-severe AD experienced sustained improvements in skin signs/symptoms through 140 weeks while receiving upadacitinib. Rates of long-term PRO improvements were numerically higher with upadacitinib 30 mg compared with upadacitinib 15 mg.

Abstract Introduction/Background Patients with atopic dermatitis (AD) may be at an increased risk for a range of malignancies, including lymphoma.1 However, real-world data characterizing malignancy risk among US patients with AD remain limited. Objective To evaluate the risk of malignancy excluding non-melanoma skin cancer (NMSC) in patients with AD compared to individuals without AD and to those with rheumatoid arthritis (RA). Additionally, these analyses were repeated in a subgroup of patients with moderate-to-severe disease to evaluate the effect of disease activity on cancer risk. Methods This retrospective observational claims-based study utilized the Optum Clinformatics Data Mart. Eligible patients were aged ≥18 years with a diagnosis of AD or RA during the study period (March 2017–December 2019). Diagnosis was determined using International Classification of Diseases (ICD)-9 or ICD-10 codes for AD (≥2 claims for AD or ≥1 claim for AD with asthma and/or hay fever, food allergies, allergic rhinitis, or eczema) and RA (≥2 claims ≥ 7 days apart and filled by a rheumatologist). Receipt of advanced systemic therapy during the follow-up period was used as a proxy for disease severity in patients with AD (dupilumab only) and RA. Patients with AD were matched 1:1 with non-AD controls based on age (±1 year), sex, and cohort entry date. Follow-up occurred until study end, disenrollment, death, or occurrence of an adverse event of interest. Malignancies excluding NMSC were identified based on 2 separate ICD diagnosis codes ≥30 days apart in an inpatient or outpatient setting. For each comparative analysis, the risk of malignancy excluding NMSC was calculated using a multivariable-adjusted Cox proportional hazards model with results reported as an adjusted hazard ratio (aHR). Results This analysis included 391,753 patients with AD (7136 with moderate-to-severe AD) and 97,455 patients with RA (35,846 with moderate-to-severe RA). The matched non-AD cohort included 381,221 patients and the matched non-AD cohort for moderate-to-severe disease included 7134 patients. The mean (SD) age at cohort entry date was lower for patients in the AD and matched non-AD controls than those in the RA cohort (58.0 [18.8] years for AD, 58.1 [18.8] years for non-AD controls, and 67.0 [13.6] years for RA). Median (IQR) follow-up was 1093 (490–1492) days for AD, 995 (357–1552) days for non-AD controls, and 1190 (484–1773) days for RA. The incidence of malignancies excluding NMSC per 100 patient-years (95% CI) was 2.18 (2.15, 2.21) for AD, 2.38 (2.35, 2.41) for non-AD controls, 3.32 (3.25, 3.38) for RA, 2.43 (2.18, 2.69) for moderate-to-severe AD, and 2.57 (2.47, 2.67) for moderate-to-severe RA. The risk of malignancies excluding NMSC (aHR [95% CI]) was lower for AD vs matched non-AD controls (0.92 [0.90, 0.93]; P<.001) and for moderate-to-severe AD vs their matched non-AD controls (0.76 [0.63, 0.91]; P<.01). Although the risk of malignancies excluding NMSC (aHR [95% CI]) was lower in patients with AD vs RA (0.97 [0.94, 0.99]; P=.03), there was no significant difference in risk for patients with moderate-to-severe AD vs moderate-to-severe RA (1.06 [0.95, 1.18]; P=.28). Among patients with AD, the risk of malignancies excluding NMSC (aHR [95% CI]) was greater among patients who were older (1.04 [1.04, 1.04]; P<.001) and those with a history of any type of malignancy excluding NMSC and including recurrence (12.76 [12.32, 13.22]; P<.001), cardiovascular disease (1.12 [1.07, 1.17]; P<.01), smoking (1.15 [1.11, 1.19]; P<.01), asthma (1.05 [1.01, 1.08]; P<.01), or chronic liver disease (1.16 [1.10, 1.22]); P<.01). Conclusions Patients with AD demonstrated a lower risk of malignancy excluding NSMC vs matched controls without AD. This lower risk was also observed in patients with moderate-to-severe AD vs their matched non-AD controls and in patients with AD vs RA.

Introduction: Lichen nitidus is a rare chronic inflammatory condition that presents as shiny, flat-topped papules. The pathophysiology of lichen nitidus is not well understood but has been theorized to stem from allergens that cause antigen presenting cells to activate, thus causing a cell-mediated response that ultimately creates the distinct inflammatory papules1. Cytokines produced by this cell-mediated response may cause an increase in T-helper 2 cells which have the potential to produce the superficial dermal granulomas seen in lichen nitidus2. Currently, no FDA approved treatments for lichen nitidus exist. Due to the inflammatory nature of the disease, off-label therapies may include topical corticosteroids, topical calcineurin inhibitors and UV light1. Lichen nitidus can be a chronic condition and in cases where long term topical corticosteroid use is required, has been associated with hypopigmentation in African Americans. Roflumilast cream 0.3% is a highly selective, non-steroidal and potent topical phosphodiesterase 4 (PDE4) inhibitor approved in 2022 by the FDA for the treatment of psoriasis, including intertriginous disease. Here, we report the case of a 51-year-old African American patient with lichen nitidus that is pruritic and refractory to typical off-label treatments including emollients, triamcinolone and clobetasol. The patient was started on roflumilast cream 0.3% daily with complete resolution of lesions and pruritus in 4 weeks. Case Report: We report the case of a 51-year-old African American patient presenting to the clinic with a history of firm, pruritic, white colored papules on both of his hands that made it hard for him to drive. These lesions had been present for 2 years and did not respond to previous treatment with emollients and topical corticosteroids including triamcinolone cream 0.1% and clobetasol ointment 0.05% both twice daily. A biopsy was performed and demonstrated lymphocytic infiltrate in the upper dermis and the classic “claw and ball” configuration consistent with lichen nitidus. The patient was subsequently started on topical roflumilast 0.3% daily which resulted in complete resolution of lesions and pruritus within 4 weeks. Conclusion: We reported a case of a 51-year-old African American papules on both hands that were consistent with lichen nitidus. In this case, the patient’s lichen nitidus was refractory to topical corticosteroids and emollients. Long term corticosteroid use is also associated with hypopigmentation in this population. After starting topical roflumilast 0.3% daily, the patient reported complete resolution of the lesions and puritus. This report suggests reduction of inflammation with roflumilast cream 0.3%, can offer a treatment option for patients with lichen nitidus.

Supplemental Fig. S4. (A) Effect of engineered KRAS expression on response to CDK2 inhibition by seliciclib. KRAS mutation sensitized lung cancer cells towards seliciclib-mediated CDK2 inhibition of growth as compared to control-ED-1 cells. (B) Cells transfected with the plasmid expressing HA-tagged human CP110 were used for detection of CP110 using an anti-CP110 antibody (1:1000) and an anti-HA antibody (1:1000), respectively. The upper band detected by the anti-CP110 antibody specifically recognizes CP110. (C) Respective CP110 and RAS protein expression profile in murine lung cancer cell lines is shown. (D) Effect of KRAS knockdown at 48 hours (left panel) and 72 hours (right panel) on CP110 expression in the 344P cell line. (E) Effect of KRAS knockdown at 72 hours (left panel) and 96 hours (right panel) on CP110 expression in the Hop62 cell line.

PDF file, 90K, Repression of UBP43 mRNA levels reduces cyclin D1 protein, but not mRNA expression.

Supplemental File S1. The siRNA sequences and real-time qPCR primer sequences.

PDF file, 76K, Reduction of UBP43 induces apoptosis and decreases cyclin D1 levels in ED-1L lung cancer cells.

<p>Supplemental Fig. S3. (A) Schematic diagram showing the relationship between CDK2, CP110, activated KRAS and anaphase catastrophe. (B) Engineered overexpression of CP110 was detected in A549, Hop62, H522 and H460 cells (versus control transfectants) using anti-HA antibody after 24 and 48 hours of transfection. A representative immunoblot for each cell line is displayed.</p>

Supplementary Fig. S1 from UBE1L causes lung cancer growth suppression by targeting cyclin D1

Perspective on This Article from Bexarotene Plus Erlotinib Suppress Lung Carcinogenesis Independent of KRAS Mutations in Two Clinical Trials and Transgenic Models

Supplementary Figure S1 from Bexarotene Plus Erlotinib Suppress Lung Carcinogenesis Independent of KRAS Mutations in Two Clinical Trials and Transgenic Models

Supplementary Data from Targeting the Cyclin E-Cdk-2 Complex Represses Lung Cancer Growth by Triggering Anaphase Catastrophe