A Case Series of TNF Inhibitor-Induced Psoriasis Successfully Treated With Upadacitinib.

Tumor necrosis factor-alpha inhibitors (TNF-i) are commonly used to treat immune-mediated diseases such as psoriasis, psoriatic arthritis (PsA), inflammatory bowel disease (IBD), spondyloarthritis (SpA) and rheumatoid arthritis (RA). However, paradoxical psoriasis induced by TNF-i has been described and is not uncommon, particularly with infliximab and etanercept. The presentation of TNF-i-induced psoriasis is most commonly plaque or palmoplantar morphology. Optimal treatment strategies for recalcitrant psoriatic disease are not well understood. In this case series, we report three patients with TNF-i-induced psoriasis who were treated with upadacitinib and experienced complete resolution of their psoriatic eruptions. The efficacy of Janus kinase inhibitors (JAK-i) is possibly explained by mechanisms involving uncontrolled production of type 1 IFNs as well as increases in IL-23 and T-helper 17 cells upstream of relevant JAK/STAT pathways. We also offer a proposed treatment algorithm that includes the use of JAK-i as a promising management option in patients with recalcitrant disease. However, larger studies are needed to confirm the efficacy and safety of JAK-i in this patient population. J Drugs Dermatol. 2024;23(2): doi:10.36849/JDD.7645.

Patient-Reported Outcome Measures for Health-Related Quality of Life in Patients With Psoriasis: A Systematic Review.

Importance: Multiple patient-reported outcome measures (PROMs) for health-related quality of life (HRQL) exist for patients with psoriasis. Evidence for the content validity and other measurement properties of these PROMs is critical to determine which HRQL PROMs could be recommended for use. Objective: To systematically review the validity of HRQL-focused PROMs used in patients with psoriasis. Evidence Review: Using PubMed and Embase, full-text articles published in English or Spanish on development or validation studies for psoriasis-specific, dermatology-specific, or generic HRQL PROMs were included. Development studies included original development studies, even if not studied in psoriasis patients per Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) recommendations. If a study included multiple diagnoses, more than 50% of patients had to have psoriasis or psoriasis-specific subgroup analyses available. Data extraction and analysis followed the COSMIN guidelines. Two independent reviewers extracted and analyzed the data, including PROM characteristics, quality of measurement properties (structural validity, internal consistency, cross-cultural validity, reliability, measurement error, criterion validity, construct validity, and responsiveness), and level of evidence. PROMs were classified into 3 levels of recommendations: (1) PROM recommended for use; (2) PROM requires further validation; and (3) PROM not recommended for use. Findings: Overall, 97 articles were identified for extraction. This included 19 psoriasis-specific, 8 skin-specific, and 6 generic PROMs. According to COSMIN standards, most measures identified received a B recommendation for use, indicating their potential but requiring further validation. Only the Rasch reduced version of the Impact of Psoriasis Questionnaire (IPSO-11 Rasch) received an A recommendation for use given that it had sufficient content validity, structural validity, and internal consistency. Conclusions and Relevance: This study identified a significant lack of information concerning the quality of HRQL measures in psoriasis. This gap in knowledge can be attributed to the fact that traditional measures were developed using validation criteria that differ from the current standards in use. Consequently, additional validation studies in accordance with contemporary standards will be useful in aiding researchers and clinicians in determining the most suitable measure for assessing HRQL in patients with psoriasis.

International Dermatology Outcome Measures (IDEOM) - Report from the 2022 Annual Meeting.

BACKGROUND: The International Dermatology Outcome Measures (IDEOM) is a non-profit organization dedicated to the advancement of evidence-based, consensus-driven outcome measures in dermatological diseases. Researchers and stakeholders from various backgrounds collaborate to develop these objective benchmark metrics to further advance treatment and management of dermatological conditions. SUMMARY: The 2022 IDEOM Annual Meeting was held on June 17-18, 2022. Leaders and stakeholders from the hidradenitis suppurativa, acne, vitiligo, actinic keratosis, alopecia areata, itch, cutaneous lymphoma, and psoriatic disease workgroups discussed the progress of their respective outcome-measures research. This report summarizes each workgroup's updates from 2022 and their next steps as established during the 2022 IDEOM Annual Meeting. J Drugs Dermatol. 2023;22(12):1153-1159 doi:10.36849/JDD.7615.

Interleukin (IL)-17 Versus IL-23 Inhibitors: Which Is Better to Treat Patients With Moderate-to-Severe Psoriasis and Mild Psoriatic Arthritis in Dermatology Clinics?

Interleukin (IL)-17 and IL-23 inhibitors are both approved for the treatment of moderate-to-severe plaque psoriasis (PsO), as well as psoriatic arthritis (PsA). In the absence of head-to-head studies, it is not clear which agent is better suited to treat patients with moderate-to-severe PsO and mild PsA. During the 2022 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) conference, Dr. April Armstrong and Dr. Joseph Merola debated which of these 2 biologic classes should be used in this patient population. Armstrong argued in favor of IL-17 inhibition, whereas Merola presented reasons for IL-23 inhibition. An overview of their main arguments is described in this manuscript.

Report of the Skin Research Workgroups From the IDEOM Breakout at the GRAPPA 2022 Annual Meeting.

The International Dermatology Outcome Measures (IDEOM) organization presented an update on its progress related to patient-centered outcome measures for psoriasis (PsO) and psoriatic arthritis (PsA) at the 2022 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). The Musculoskeletal (MSK) Symptoms working group presented an update on the development of the IDEOM Musculoskeletal Questionnaire (IDEOM MSK-Q). The IDEOM MSK-Q is a patient-reported outcome measure intended to capture MSK symptoms and describe their intensity and impact on health-related quality of life in patients with psoriatic disease. IDEOM also presented the progress of the integration of the Psoriasis Epidemiology Screening Tool (PEST) and Psoriatic Arthritis Impact of Disease (PsAID) questionnaires into the Epic electronic health record system. This will allow for automated PsA screening and symptom measurement in the hopes of improving disease detection and treat-to-target strategies. The Treatment Satisfaction working group discussed the development of the DermSat-7, a 7-item treatment satisfaction questionnaire specific for dermatological conditions. The DermSat-7 is currently being validated in a multicenter study of patients with PsO.

Dupilumab-Associated Arthritis: A Dermatology-Rheumatology Perspective.

Dupilumab is an interleukin (IL)-4/13 inhibitor approved by the US FDA for multiple atopic indications. It is well-known to have favorable efficacy and safety profiles; however, emerging reports of dupilumab-associated arthritis suggest an underrecognized potential adverse effect. In this article, we summarize the literature to date to better characterize this clinical phenomenon. Arthritic symptoms were most commonly peripheral, generalized, and symmetric. Onset was generally within 4 months following initiation of dupilumab, and most patients resolved fully after a matter of weeks following discontinuation. Mechanistic insights suggest that suppression of IL-4 may lead to increased activity of IL-17, a prominent cytokine in inflammatory arthritis. We propose a treatment algorithm that stratifies patients by severity, recommending that patients with more mild disease continue dupilumab and treat through symptoms, while patients with more severe disease discontinue dupilumab and consider switching to another class (e.g., Janus kinase inhibitors). Lastly, we discuss important ongoing questions that should be addressed in future studies.

Sleep Problems in Patients With Psoriatic Arthritis: A Systematic Literature Review and Metaanalysis.

OBJECTIVE: The aim of this systematic review and metaanalysis is to summarize evidence regarding the relationship between psoriatic arthritis (PsA) and sleep problems. METHODS: We identified 36 eligible studies-26 cross-sectional, 7 cohort, and 3 interventional studies-in PubMed and Embase. RESULTS: The prevalence of self-reported sleep problems in patients with PsA ranged from 30% to 85%. A metaanalysis of 6 studies that used the Pittsburgh Sleep Quality Index revealed a prevalence of poor sleep quality for patients with PsA of 72.9% (95% CI 63-81.8; I2 = 78%), which was statistically higher than in healthy controls (26.9%, 95% CI 11.7-45.4; I2 = 81%) but not significantly different than in patients with psoriasis (59.8%, 95% CI 46.9-72.1; I2 = 51%). Sleep disturbance was ranked in the top 4 health-related quality of life domains affected by PsA. One study suggested a bidirectional relationship between PsA and obstructive sleep apnea. Predictors of sleep problems included anxiety, pain, erythrocyte sedimentation rate, depression, fatigue, physical function, and tender or swollen joint count. Tumor necrosis factor inhibitors, guselkumab, and filgotinib (a Janus kinase inhibitor) were associated with improved sleep outcomes. CONCLUSION: Poor sleep quality is prevalent in patients with PsA. Objective sleep measures (ie, actigraphy and polysomnography) have not been used in PsA studies, and evidence on the validity of patient-reported sleep measures in PsA is lacking. Future studies should validate self-reported sleep measures in PsA, explore how sleep quality relates to PsA disease activity and symptoms using both objective and subjective sleep measures, assess the efficacy of strategies to manage sleep problems, and assess the effects of such management on symptoms and disease signs in patients with PsA.

Leveraging behavioral economics to promote treatment adherence: A primer for the practicing dermatologist.

The problem of suboptimal treatment adherence among patients with dermatologic or other diseases has not been adequately addressed in health care. Despite a wide range of efficacious therapies, nonadherence remains a primary driver of suboptimal clinical outcomes. Novel solutions to address this unmet need can be found in behavioral economics. By leveraging our understanding of human decision-making, we may better promote treatment adherence, thereby improving quality of life and decreasing economic burdens. Behavioral economics has been studied extensively in relation to topics such as health policy and health behaviors; however, there is a dearth of research applying this approach to chronic diseases and only a handful within dermatology. We conducted a scoping review in PubMed to identify articles that discuss behavioral economics and its application to treatment adherence in dermatologic patients, with a particular focus on psoriasis, followed by a summary of key ethical considerations. We found that such principles can be employed in cost-effective, scalable interventions that improve patient adherence to a range of medical therapies and lifestyle modifications.

Education Research: Online Alzheimer education for high school and college students: A randomized controlled trial.

OBJECTIVE: Alzheimer disease (AD) risk factors are present throughout the lifespan. This randomized controlled trial evaluated the effectiveness of various online education strategies concerning AD risk reduction and brain health in younger populations. METHOD: High school and college students were recruited via social media (Facebook and Instagram) to join AlzU.org, an evidence-based education portal, and were randomized to 1 of 4 courses: highly interactive webinar lessons narrated by actor Seth Rogen (celebrity webinar) or a physician (doctor webinar), minimally interactive video lessons with Seth Rogen (celebrity video), or minimally interactive video lessons (control). Surveys were administered at baseline and postcourse. The primary outcome was change in knowledge of AD risk reduction assessed by pre vs post lesson quiz scores. Secondary outcomes included change in awareness of AD research, hopefulness about AD, interest in pursuing health care, willingness to volunteer, and likelihood of recommending AlzU.org. RESULT: A total of 721 participants joined. A total of 281 (38.9%) completed the course. Among college students, quiz score improvements were greater in celebrity webinar and celebrity video vs doctor webinar and control. Among high school students, no differences were found in quiz scores. In both groups, celebrity webinar, celebrity video, and doctor webinar resulted in greater improvements in awareness that nutrition and exercise may reduce AD risk vs controls. Among college students, celebrity webinar and celebrity video group participants felt more hopeful about the future of AD and more likely to recommend AlzU.org vs doctor webinar and control participants. Among college students, celebrity webinar, celebrity video, and doctor webinar participants were more willing to volunteer for AD causes and pursue health care careers vs controls. CONCLUSION: Online education involving a celebrity may be an effective strategy for educating college students about AD risk reduction strategies. Further studies are warranted in high school students.

Orthopedic Manifestations of Lead Toxicity.

Given the recent news regarding the water supply in Flint, Michigan, lead toxicity has become an increasingly important topic in health care. Lead toxicity can have a widespread effect on the human body. Because lead has a significant effect on mineralized tissue such as bone, the purpose of this review was to identify and analyze the orthopedic manifestations of lead poisoning. The effects of lead at the cellular level, on the hematopoietic system, in osteoporosis, and in pediatric patients are discussed. Possible treatment options and recommendations for further monitoring are presented. [Orthopedics. 2020;43(4):e202-e207.].

Modelling fibrinolysis: 1D continuum models.

Fibrinolysis is the enzymatic degradation of the fibrin mesh that stabilizes blood clots. Experiments have shown that coarse clots made of thick fibres sometimes lyse more quickly than fine clots made of thin fibres, despite the fact that individual thick fibres lyse more slowly than individual thin fibres. This paper aims at using a 1D continuum reaction-diffusion model of fibrinolysis to elucidate the mechanism by which coarse clots lyse more quickly than fine clots. Reaction-diffusion models have been the standard tool for investigating fibrinolysis, and have been successful in capturing the wave-like behaviour of lysis seen in experiments. These previous models treat the distribution of fibrin within a clot as homogeneous, and therefore cannot be used directly to study the lysis of fine and coarse clots. In our model, we include a spatially heterogeneous fibrin concentration, as well as a more accurate description of the role of fibrin as a cofactor in the activation of the lytic enzyme. Our model predicts spatio-temporal protein distributions in reasonable quantitative agreement with experimental data. The model also predicts observed behaviour such as a front of lysis moving through the clot with an accumulation of lytic proteins at the front. In spite of the model improvements, however, we find that 1D continuum models are unable to accurately describe the observed differences in lysis behaviour between fine and coarse clots. Features of the problems that lead to the inaccuracy of 1D continuum models are discussed. We conclude that higher-dimensional, multiscale models are required to investigate the effect of clot structure on lysis behaviour.