International Journal of Dermatology

<jats:title>ABSTRACT</jats:title><jats:p>Although dermatologic conditions primarily manifest on the skin, an increasing amount of evidence demonstrates that these inflammatory conditions can have a deeper impact on our systemic health. The use of epigenetics to measure biological age, instead of chronological age, can give us insight into the systemic burden of these diseases on aging. We aimed to understand the degree to which each dermatological condition affects biological aging. A systematic review was performed of PubMed, Embase, and Web of Science to identify all publications that measured biological age in dermatological patients using epigenetic clocks. Six articles involved the following conditions: atopic dermatitis (AD) (1), hidradenitis suppurativa (HS) (1), and psoriasis (PsO) (4). Notably, patients with psoriatic arthritis, but not psoriasis alone, demonstrated significantly increased epigenetic aging compared to controls. Pediatric AD patients had an increase in the rate of biological aging as measured by the Horvath, Skin and Blood, PhenoAge, and GrimAge clocks. HS patients were found to have an increased biological age when assessing tissue from affected skin. Further research is needed to investigate correlations between disease severity and epigenetic aging, and for expansion into other dermatological diseases. Additionally, epigenetic clocks need to be developed that utilize different subsets of inflammation more broadly and skin biomarkers to provide a more accurate estimation for chronic inflammatory dermatological conditions.</jats:p>

publication_history

received

accepted

published

Risk of Myocardial Infarction in Patients With Psoriasis

JAMA

Psoriasis: A Possible Risk Factor for Development of Coronary Artery Calcification

British Journal of Dermatology

Management of Psoriasis as a Systemic Disease: What Is the Evidence?

DNA Methylation Analysis

Methods in Molecular Biology

Association Between Lifestyle Factors and CpG Island Methylation in a Cancer‐Free Population

Cancer Epidemiology, Biomarkers & Prevention

UV Radiation and Its Relation to DNA Methylation in Epidermal Cells: A Review

Epigenomes

Exercise Training and DNA Methylation in Humans

Acta Physiologica (Oxford)

Sleep Deprivation and the Epigenome

Frontiers in Neural Circuits

Filaggrin Mutations Associated With Skin and Allergic Diseases

New England Journal of Medicine

Genomic, Epigenomic, Transcriptomic, Proteomic and Metabolomic Approaches in Atopic Dermatitis

Current Issues in Molecular Biology

How Epigenetics Impacts on Human Diseases

European Journal of Internal Medicine

Epigenetic Clock: A Promising Biomarker and Practical Tool in Aging

Ageing Research Reviews

Epigenetic Biomarkers of Ageing Are Predictive of Mortality Risk in a Longitudinal Clinical Cohort of Individuals Diagnosed With Oropharyngeal Cancer

Clinical Epigenetics

The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews

A Case‐Control Study: Epigenetic Age Acceleration in Psoriasis

Archives of Dermatological Research

Aging in Psoriasis Vulgaris: Female Patients Are Epigenetically Older Than Healthy Controls

Immunity & Ageing

DNA Methylation Age Is Not Affected in Psoriatic Skin Tissue

Dysregulation of Epigenetic, Biological and Mitotic Age in the Context of Biologic Drug Treatment and Phototherapy in Plaque Psoriasis Patients

Journal of the European Academy of Dermatology and Venereology

Increased Epigenetic Age Acceleration in the Hidradenitis Suppurativa Skin

Epigenetic and Biological Age Acceleration in Children With Atopic Dermatitis

Journal of Allergy and Clinical Immunology: Global

An Epigenetic Biomarker of Aging for Lifespan and Healthspan

Aging (Albany NY)

Cutaneous and Systemic Psoriasis: Classifications and Classification for the Distinction

Frontier Medicine (Lausanne)

DNA Methylation GrimAge Strongly Predicts Lifespan and Healthspan

Genetic and Epigenetic Aspects of Atopic Dermatitis

International Journal of Molecular Sciences

The Aging of the Immune System

Transplant International

Role of Oestrogens on Oxidative Stress and Inflammation in Ageing

Hormone Molecular Biology and Clinical Investigation

Hidradenitis Suppurativa: Epidemiology, Clinical Presentation, and Pathogenesis

Journal of the American Academy of Dermatology

Epigenetic Regulation of Cellular Functions in Wound Healing

Experimental Dermatology

The Gut and Skin Microbiome and Its Association With Aging Clocks

Prolonging Fixation Time of an Alternative Fixative to Formalin for Dermatological Samples Using Standard Laboratory Protocols

Journal of Clinical Pathology

Although dermatologic conditions primarily manifest on the skin, an increasing amount of evidence demonstrates that these inflammatory conditions can have a deeper impact on our systemic health. The use of epigenetics to measure biological age, instead of chronological age, can give us insight into the systemic burden of these diseases on aging. We aimed to understand the degree to which each dermatological condition affects biological aging. A systematic review was performed of PubMed, Embase, and Web of Science to identify all publications that measured biological age in dermatological patients using epigenetic clocks. Six articles involved the following conditions: atopic dermatitis (AD) (1), hidradenitis suppurativa (HS) (1), and psoriasis (PsO) (4). Notably, patients with psoriatic arthritis, but not psoriasis alone, demonstrated significantly increased epigenetic aging compared to controls. Pediatric AD patients had an increase in the rate of biological aging as measured by the Horvath, Skin and Blood, PhenoAge, and GrimAge clocks. HS patients were found to have an increased biological age when assessing tissue from affected skin. Further research is needed to investigate correlations between disease severity and epigenetic aging, and for expansion into other dermatological diseases. Additionally, epigenetic clocks need to be developed that utilize different subsets of inflammation more broadly and skin biomarkers to provide a more accurate estimation for chronic inflammatory dermatological conditions.

Systematic Review of Accelerated Epigenetic Aging in Chronic Inflammatory Dermatology Conditions.

Systematic Review of Accelerated Epigenetic Aging in Chronic Inflammatory Dermatology Conditions

JAMA Dermatology

<jats:sec><jats:title>Importance</jats:title><jats:p>Psoriasis affects up to 3% of the population, with 30% of patients with psoriasis developing psoriatic arthritis (PsA), yet the transition between psoriasis and PsA has yet to be fully understood. Subclinical synovitis is a hallmark of PsA and is thought to precede psoriatic arthritis; its detection among patients with psoriasis without musculoskeletal (MSK) involvement through medical imaging modalities could offer valuable insights into the transition from psoriasis to PsA.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To evaluate the prevalence of synovitis on ultrasonograms and magnetic resonance imaging (MRI) among patients with psoriasis without MSK involvement compared with healthy controls and patients with PsA.</jats:p></jats:sec><jats:sec><jats:title>Data Sources</jats:title><jats:p>A comprehensive literature search was conducted in MEDLINE, Embase, Scopus, and Web of Science from inception to October 2024 using keywords related to psoriasis, synovitis, and medical imaging. A PROSPERO protocol was registered (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.crd.york.ac.uk/PROSPERO/view/CRD42024571308">CRD42024571308</jats:ext-link>).</jats:p></jats:sec><jats:sec><jats:title>Study Selection</jats:title><jats:p>Studies were eligible if they included patients with psoriasis without MSK involvement and assessed synovitis using imaging. Two reviewers independently screened studies and extracted data. Discrepancies were resolved by consensus. Twelve of 5132 initially identified studies met inclusion criteria.</jats:p></jats:sec><jats:sec><jats:title>Data Extraction and Synthesis</jats:title><jats:p>Data were extracted per PRISMA guidelines. Risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects model was used to pool risk ratios (RRs) for synovitis prevalence across comparison groups. Heterogeneity was assessed using the <jats:italic>I</jats:italic><jats:sup>2</jats:sup> statistic.</jats:p></jats:sec><jats:sec><jats:title>Main Outcomes and Measures</jats:title><jats:p>The primary outcome was the presence of imaging-detected synovitis among patients with psoriasis without MSK involvement compared with healthy controls and patients with PsA.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Twelve studies (N = 2606 patients) were included comprising 1593 patients with psoriasis (mean [SD] age, 46.4 [7.5] years; 982 men [61.6%]), 327 patients with PsA (mean [SD] age, 50.2 [7.1] years; 210 men [64.2%]), and 686 healthy controls (mean [SD] age, 45.7 [6.9] years; 281 of 576 men [48.8%]). Synovitis was 2.5 times more likely among patients with psoriasis than controls (RR, 2.55; 95% CI, 1.18-5.52). Detection rates were higher with MRI (RR, 6.40; 95% CI, 1.87-21.95) than ultrasonography (RR, 2.50; 95% CI, 1.10-5.67). Synovitis was more frequent among patients with PsA than those with psoriasis, but the difference was not statistically significant (RR, 0.50; 95% CI, 0.13-1.87).</jats:p></jats:sec><jats:sec><jats:title>Conclusions and Relevance</jats:title><jats:p>This systematic review and meta-analysis found that subclinical synovitis is significantly more prevalent among patients with psoriasis without MSK involvement compared with healthy controls. This finding suggests that imaging may aid in identifying individuals at risk for progression to psoriatic arthritis.</jats:p></jats:sec>

Subclinical joint inflammation in patients with psoriasis without concomitant psoriatic arthritis: a cross-sectional and longitudinal analysis.

Ann Rheum Dis

Magnetic resonance imaging (MRI) of feet demonstrates subclinical inflammatory joint disease in cutaneous psoriasis patients without clinical arthritis.

Clin Rheumatol

Pediatric psoriasis with or without arthritis: does it make a difference?

J Clin Med

Subclinical psoriatic arthritis and disease interception—where are we in 2024?

Rheumatology

The role of ultrasound in screening subclinical psoriatic arthritis in patients with moderate to severe psoriasis.

Eur Radiol

Ultrasonography enthesitis and synovitis screening in psoriatic patients: a case control study.

Mediterr J Rheumatol

Cutaneous immunohistochemical expression of interleukin-23 receptor (IL-23R) in psoriasis and psoriatic arthritis patients: relation to musculoskeletal ultrasound findings.

Egypt Rheumatol

Nail affection as a central part of the entheseal organ in psoriasis patients for early detection of psoriatic arthritis.

Subclinical synovitis and enthesitis in psoriasis patients and controls by ultrasonography in Saudi Arabia; incidence of psoriatic arthritis during two years.

MR imaging features of foot involvement in patients with psoriasis.

Eur J Radiol

High prevalence of ultrasonographic synovitis and enthesopathy in patients with psoriasis without psoriatic arthritis: a prospective case-control study.

Rheumatology (Oxford)

Power Doppler ultrasound evaluation of peripheral joint, entheses, tendon, and bursa abnormalities in psoriatic patients: a clinical study.

J Rheumatol

Risk factors and early detection of joint damage in patients with psoriasis: a case-control study.

Int J Dermatol

Transition phase towards psoriatic arthritis: clinical and ultrasonographic characterisation of psoriatic arthralgia.

RMD Open

Ultrasonographic detection of subclinical enthesitis and synovitis: a possible stratification of psoriatic patients without clinical musculoskeletal involvement.

Clin Exp Rheumatol

Psoriasis affects up to 3% of the population, with 30% of patients with psoriasis developing psoriatic arthritis (PsA), yet the transition between psoriasis and PsA has yet to be fully understood. Subclinical synovitis is a hallmark of PsA and is thought to precede psoriatic arthritis; its detection among patients with psoriasis without musculoskeletal (MSK) involvement through medical imaging modalities could offer valuable insights into the transition from psoriasis to PsA.
To evaluate the prevalence of synovitis on ultrasonograms and magnetic resonance imaging (MRI) among patients with psoriasis without MSK involvement compared with healthy controls and patients with PsA.
A comprehensive literature search was conducted in MEDLINE, Embase, Scopus, and Web of Science from inception to October 2024 using keywords related to psoriasis, synovitis, and medical imaging. A PROSPERO protocol was registered (CRD42024571308).
Studies were eligible if they included patients with psoriasis without MSK involvement and assessed synovitis using imaging. Two reviewers independently screened studies and extracted data. Discrepancies were resolved by consensus. Twelve of 5132 initially identified studies met inclusion criteria.
Data were extracted per PRISMA guidelines. Risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects model was used to pool risk ratios (RRs) for synovitis prevalence across comparison groups. Heterogeneity was assessed using the I2 statistic.
The primary outcome was the presence of imaging-detected synovitis among patients with psoriasis without MSK involvement compared with healthy controls and patients with PsA.
Twelve studies (N = 2606 patients) were included comprising 1593 patients with psoriasis (mean [SD] age, 46.4 [7.5] years; 982 men [61.6%]), 327 patients with PsA (mean [SD] age, 50.2 [7.1] years; 210 men [64.2%]), and 686 healthy controls (mean [SD] age, 45.7 [6.9] years; 281 of 576 men [48.8%]). Synovitis was 2.5 times more likely among patients with psoriasis than controls (RR, 2.55; 95% CI, 1.18-5.52). Detection rates were higher with MRI (RR, 6.40; 95% CI, 1.87-21.95) than ultrasonography (RR, 2.50; 95% CI, 1.10-5.67). Synovitis was more frequent among patients with PsA than those with psoriasis, but the difference was not statistically significant (RR, 0.50; 95% CI, 0.13-1.87).
This systematic review and meta-analysis found that subclinical synovitis is significantly more prevalent among patients with psoriasis without MSK involvement compared with healthy controls. This finding suggests that imaging may aid in identifying individuals at risk for progression to psoriatic arthritis.

Subclinical Synovitis Among Patients With Psoriasis Without Musculoskeletal Involvement: A Systematic Review and Meta-Analysis.

Subclinical Synovitis Among Patients With Psoriasis Without Musculoskeletal Involvement

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Although stress is considered to be a negative factor for psoriasis, no convincing scientific evidence of this association exists, largely because of difficulties in measuring stress. Stress resilience is the ability to cope with and adapt to stressful events. Stress resilience can be measured in a standardized way and used as a marker for chronic stress.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>The objective of this study is to investigate whether low stress resilience in adolescence increases the risk for onset of psoriasis and psoriatic arthritis later in life.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A cohort of Swedish men (mean age 18.3 years), enrolled in compulsory military service between 1968 and 2005, was created using data from the Swedish Military Service Conscription Register (<jats:italic>n</jats:italic> = 1,669,422). Stress resilience at conscription was estimated using standardized semi‐structured interviews, and was divided into three categories: low, medium and high. The men were followed from conscription until new‐onset psoriasis or psoriatic arthritis, death or emigration or at the latest until 31 December 2019. Cox regression models adjusted for confounders at conscription were used to obtain hazard ratios (HRs) with 95% confidence intervals (CIs) for incident psoriasis and psoriatic arthritis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Men in the lowest stress resilience category had an increased risk of psoriasis and psoriatic arthritis (HR 1.31 (95% CI 1.26–1.36) and 1.23 (95% CI 1.15–1.32), respectively), compared with those in the highest stress resilience category. When including only hospitalized patients the HRs for psoriasis and psoriatic arthritis in the lowest stress resilience group were 1.79 (1.63–1.98) and 1.53 (1.32–1.77), respectively.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>This large, prospective register study suggests that low stress resilience in adolescence is associated with an increased risk of incident psoriasis among men. The results indicate that patients with psoriasis have an inherent psychological vulnerability, and highlight the importance of addressing psychological well‐being in the management of psoriasis.</jats:p></jats:sec>

Forskningsrådet om Hälsa, Arbetsliv och Välfärd

Göteborgs Läkaresällskap

Although stress is considered to be a negative factor for psoriasis, no convincing scientific evidence of this association exists, largely because of difficulties in measuring stress. Stress resilience is the ability to cope with and adapt to stressful events. Stress resilience can be measured in a standardized way and used as a marker for chronic stress.
The objective of this study is to investigate whether low stress resilience in adolescence increases the risk for onset of psoriasis and psoriatic arthritis later in life.
A cohort of Swedish men (mean age 18.3 years), enrolled in compulsory military service between 1968 and 2005, was created using data from the Swedish Military Service Conscription Register (n = 1,669,422). Stress resilience at conscription was estimated using standardized semi-structured interviews, and was divided into three categories: low, medium and high. The men were followed from conscription until new-onset psoriasis or psoriatic arthritis, death or emigration or at the latest until 31 December 2019. Cox regression models adjusted for confounders at conscription were used to obtain hazard ratios (HRs) with 95% confidence intervals (CIs) for incident psoriasis and psoriatic arthritis.
Men in the lowest stress resilience category had an increased risk of psoriasis and psoriatic arthritis (HR 1.31 (95% CI 1.26-1.36) and 1.23 (95% CI 1.15-1.32), respectively), compared with those in the highest stress resilience category. When including only hospitalized patients the HRs for psoriasis and psoriatic arthritis in the lowest stress resilience group were 1.79 (1.63-1.98) and 1.53 (1.32-1.77), respectively.
This large, prospective register study suggests that low stress resilience in adolescence is associated with an increased risk of incident psoriasis among men. The results indicate that patients with psoriasis have an inherent psychological vulnerability, and highlight the importance of addressing psychological well-being in the management of psoriasis.

Influence of stress resilience in adolescence on long-term risk of psoriasis and psoriatic arthritis among men: A prospective register-based cohort study in Sweden.

Influence of stress resilience in adolescence on long‐term risk of psoriasis and psoriatic arthritis among men: A prospective register‐based cohort study in Sweden

Papers