Clinical Validation of Digitally Acquired Clinical Data and Machine Learning Models for Remote Measurement of Psoriasis and Psoriatic Arthritis: A Proof-of-Concept Study.

OBJECTIVE: Psoriatic disease remains underdiagnosed and undertreated. We developed and validated a suite of novel, sensor-based smartphone assessments (Psorcast app) that can be self-administered to measure cutaneous and musculoskeletal signs and symptoms of psoriatic disease. METHODS: Participants with psoriasis (PsO) or psoriatic arthritis (PsA) and healthy controls were recruited between June 5, 2019, and November 10, 2021, at 2 academic medical centers. Concordance and accuracy of digital measures and image-based machine learning models were compared to their analogous clinical measures from trained rheumatologists and dermatologists. RESULTS: Of 104 study participants, 51 (49%) were female and 53 (51%) were male, with a mean age of 42.3 years (SD 12.6). Seventy-nine (76%) participants had PsA, 16 (15.4%) had PsO, and 9 (8.7%) were healthy controls. Digital patient assessment of percent body surface area (BSA) affected with PsO demonstrated very strong concordance (Lin concordance correlation coefficient [CCC] 0.94 [95% CI 0.91-0.96]) with physician-assessed BSA. The in-clinic and remote target plaque physician global assessments showed fair-to-moderate concordance (CCCerythema 0.72 [0.59-0.85]; CCCinduration 0.72 [0.62-0.82]; CCCscaling 0.60 [0.48-0.72]). Machine learning models of hand photos taken by patients accurately identified clinically diagnosed nail PsO with an accuracy of 0.76. The Digital Jar Open assessment categorized physician-assessed upper extremity involvement, considering joint tenderness or enthesitis (AUROC 0.68 [0.47-0.85]). CONCLUSION: The Psorcast digital assessments achieved significant clinical validity, although they require further validation in larger cohorts before use in evidence-based medicine or clinical trial settings. The smartphone software and analysis pipelines from the Psorcast suite are open source and freely available.

Racial and ethnic determinants of psoriatic arthritis phenotypes and disease activity.

OBJECTIVE: Individuals of racially and ethnically diverse backgrounds are underrepresented in psoriatic arthritis (PsA) research/clinical trials, despite evidence that their disease presentation, severity and course may be distinct. Here we aim to describe how race, ethnicity and other socioeconomic factors inform disease characteristics in PsA. METHODS: 817 consecutive patients with PsA from a large, diverse metropolitan area, were enrolled in an observational, longitudinal registry. Demographics, medical history, medication use, and psoriatic disease phenotype and activity were all recorded and analyzed. RESULTS: The population was 77.4% non-Hispanic White, 2.2% Black, 7.1% Asian, and 9.9% identified as other races or multiracial, and 11.8% identified as Hispanic. Hispanic and non-White individuals had higher tender joint counts (p= 0.033) with similar swollen joint counts (p= 0.308) and medication use (p= 0.171). They also had high rates of radiographic axial disease. Hispanic individuals were significantly more likely to have higher tender joint counts (p= 0.029), higher RAPID3 scores (p= 0.004), and moderate-severe psoriasis (p= 0.010) compared with non-Hispanic White individuals. CONCLUSION: In this diverse cohort, 22.6% of patients identified as underrepresented racial and/or ethnic groups, mostly Asian or Hispanic. Despite similar swollen joint counts and medication use, non-white individuals have higher tender joint counts compared with white individuals. Phenotypically, they also were more likely to have radiographic axial involvement. These findings may reflect differences in PsA presentation, experience and outcomes in individuals of various racial and ethnic groups, which need to be taken into consideration in clinical care and research design.

Alterations in the cutaneous microbiome of patients with psoriasis and psoriatic arthritis reveal similarities between non-lesional and lesional skin.

OBJECTIVES: To investigate the cutaneous microbiome spanning the entire psoriatic disease spectrum, and to evaluate distinguishing features of psoriasis (PsO) and psoriatic arthritis (PsA). METHODS: Skin swabs were collected from upper and lower extremities of healthy individuals and patients with PsO and PsA. Psoriatic patients contributed both lesional (L) and contralateral non-lesional (NL) samples. Microbiota were analysed using 16S rRNA sequencing. RESULTS: Compared with healthy skin, alpha diversity in psoriatic NL and L skin was significantly reduced (p<0.05) and samples clustered separately in plots of beta diversity (p<0.05). Kocuria and Cutibacterium were enriched in healthy subjects, while Staphylococcus was enriched in psoriatic disease. Microbe-microbe association networks revealed a higher degree of similarity between psoriatic NL and L skin compared with healthy skin despite the absence of clinically evident inflammation. Moreover, the relative abundance of Corynebacterium was higher in NL PsA samples compared with NL PsO samples (p<0.05), potentially serving as a biomarker for disease progression. CONCLUSIONS: These findings show differences in diversity, bacterial composition and microbe-microbe interactions between healthy and psoriatic skin, both L and NL. We further identified bacterial biomarkers that differentiate disease phenotypes, which could potentially aid in predicting the transition from PsO to PsA.

Paradoxical Effects of Depression on Psoriatic Arthritis Outcomes in a Combined Psoriasis-Psoriatic Arthritis Center.

Backgroud: Psoriatic arthritis (PsA) is a chronic, inflammatory arthritis that, when left untreated, can lead to erosions, deformities and decrease in quality of life. PsA is known to be associated with multiple comorbidities, including cardiovascular, metabolic and mental health syndromes, all of which can increase its overall morbidity and mortality. Objective: To characterize a cohort of patients with PsA and understand the impact of depression on PsA outcome measures. Methods: 527 consecutive patients with PsA were enrolled in an observational, longitudinal registry that followed them prospectively at standard of care visits. Demographics, medical history, medication use, and clinical exam were all recorded. Results: Depression was reported in 22.8% of the population, anxiety in 18%, and attention deficit hyperactivity disorder in 4%. Depression was more common in female participants (P < .001). At baseline, individuals with PsA and concomitant depression had similar tender and swollen joint counts and RAPID3 compared to those without depression, and had lower body surface area affected by psoriasis (P = .04). At year one, all patients had improvement in clinical outcomes. However, patients with depression had a significantly higher tender joint count compared to those without depression (P = .001), despite similar swollen joint count and body surface area. Conclusion: In patients with depression, there is a discrepancy between improvement in physician assessed measures and patient reported outcomes. These observations underscore the importance of addressing depression and psychological distress as part of PsA treatment outcomes and points towards the need to address residual pain through co-adjuvant approaches.

Efficacy of guselkumab, a selective IL-23 inhibitor, in Preventing Arthritis in a Multicentre Psoriasis At-Risk cohort (PAMPA): protocol of a randomised, double-blind, placebo controlled multicentre trial.

INTRODUCTION: Psoriatic arthritis (PsA) is a complex, immune-mediated disease associated with skin psoriasis that, if left untreated, can lead to joint destruction. Up to 30% of patients with psoriasis progress to PsA. In most cases, psoriasis precedes synovio-entheseal inflammation by an average of 5-7 years, providing a unique opportunity for early and potentially preventive intervention in a susceptible and identifiable population. Guselkumab is an effective IL-23p19 inhibitor Food and Drug Administration (FDA-approved for treatment of moderate-to-severe psoriasis and PsA. The Preventing Arthritis in a Multicentre Psoriasis At-Risk cohort (PAMPA) study aims to evaluate the efficacy of guselkumab in preventing PsA and decreasing musculoskeletal power Doppler ultrasound (PDUS) abnormalities in a population of patients with psoriasis who are at-increased risk for PsA progression. METHODS AND ANALYSIS: The PAMPA study is a multicentre, randomised, double-blind, placebo-controlled, interventional, preventive trial comparing PDUS involvement and conversion to PsA in patients with psoriasis at-increased risk for progression treated with guselkumab compared with non-biological standard of care. The study includes a screening period, a double-blind treatment period (24 weeks) and an open-label follow-up period (72 weeks). At baseline, 200 subjects will be randomised (1:1) to receive either guselkumab 100 mg (arm 1) or placebo switching to guselkumab 100 mg starting at week 24 (arm 2). Arm 3 will follow 150 at-risk psoriasis patients who decline biological therapy and randomisation. Changes from baseline in the PDUS score at week 24 and the difference in proportion of patients transitioning to PsA at 96 weeks will be examined as the coprimary endpoints. ETHICS AND DISSEMINATION: Ethics approval for this study was granted by the coordinating centre's (NYU School of Medicine) Institutional Review Board (IRB). Each participating site received approval through their own IRBs. The findings will be shared in peer-reviewed articles and scientific conference presentations. TRIAL REGISTRATION NUMBER: NCT05004727.

CCL20 in psoriasis: A potential biomarker of disease severity, inflammation, and impaired vascular health.

BACKGROUND: Psoriasis is associated with increased cardiovascular risk that is not captured by traditional proinflammatory biomarkers. OBJECTIVE: To investigate the relationship between Psoriasis Area and Severity Index, circulating proinflammatory biomarkers, and vascular health in psoriasis. METHODS: In patients with psoriasis and in age and sex-matched controls, 273 proteins were analyzed with the Proseek Multiplex Cardiovascular disease reagents kit and Inflammatory reagents kit (Olink Bioscience), whereas vascular endothelial inflammation and health were measured via direct transcriptomic analysis of brachial vein endothelial cells. RESULTS: In psoriasis, chemokine ligand 20 (CCL20), interleukin (IL) 6, and IL-17A were the top 3 circulating proinflammatory cytokines. Vascular endothelial inflammation correlated with CCL20 (r = 0.55; P < .001) and less so with IL-6 (r = 0.36; P = .04) and IL-17A (r = 0.29; P = .12). After adjustment for potential confounders, the association between CCL20 and vascular endothelial inflammation remained significant (ß = 1.71; P = .02). In nested models, CCL20 added value (χ2 = 79.22; P < .001) to a model already incorporating the Psoriasis Area and Severity Index, Framingham risk, high-sensitivity C-reactive protein, Il-17A, and IL-6 (χ2 = 48.18; P < .001) in predicting vascular endothelial inflammation. LIMITATIONS: Our study was observational and did not allow for causal inference in the relationship between CCL20 and cardiovascular risk. CONCLUSION: We demonstrate that CCL20 expression has a strong association with vascular endothelial inflammation, reflects systemic inflammation, and may serve as a potential biomarker of impaired vascular health in psoriasis.

Interleukin-17 Inhibition in Spondyloarthritis Is Associated With Subclinical Gut Microbiome Perturbations and a Distinctive Interleukin-25-Driven Intestinal Inflammation.

OBJECTIVE: To characterize the ecological effects of biologic therapies on the gut bacterial and fungal microbiome in psoriatic arthritis (PsA)/spondyloarthritis (SpA) patients. METHODS: Fecal samples from PsA/SpA patients pre- and posttreatment with tumor necrosis factor inhibitors (TNFi; n = 15) or an anti-interleukin-17A monoclonal antibody inhibitor (IL-17i; n = 14) underwent sequencing (16S ribosomal RNA, internal transcribed spacer and shotgun metagenomics) and computational microbiome analysis. Fecal levels of fatty acid metabolites and cytokines/proteins implicated in PsA/SpA pathogenesis or intestinal inflammation were correlated with sequence data. Additionally, ileal biopsies obtained from SpA patients who developed clinically overt Crohn's disease (CD) after treatment with IL-17i (n = 5) were analyzed for expression of IL-23/Th17-related cytokines, IL-25/IL-17E-producing cells, and type 2 innate lymphoid cells (ILC2s). RESULTS: There were significant shifts in abundance of specific taxa after treatment with IL-17i compared to TNFi, particularly Clostridiales (P = 0.016) and Candida albicans (P = 0.041). These subclinical alterations correlated with changes in bacterial community co-occurrence, metabolic pathways, IL-23/Th17-related cytokines, and various fatty acids. Ileal biopsies showed that clinically overt CD was associated with expansion of IL-25/IL-17E-producing tuft cells and ILC2s (P < 0.05), compared to pre-IL-17i treatment levels. CONCLUSION: In a subgroup of SpA patients, the initiation of IL-17A blockade correlated with features of subclinical gut inflammation and intestinal dysbiosis of certain bacterial and fungal taxa, most notably C albicans. Further, IL-17i-related CD was associated with overexpression of IL-25/IL-17E-producing tuft cells and ILC2s. These results may help to explain the potential link between inhibition of a specific IL-17 pathway and the (sub)clinical gut inflammation observed in SpA.

Early Recognition and Treatment Heralds Optimal Outcomes: the Benefits of Combined Rheumatology-Dermatology Clinics and Integrative Care of Psoriasis and Psoriatic Arthritis Patients.

PURPOSE OF REVIEW: Diagnosis and treatment of psoriatic arthritis (PsA) can be challenging and require a multidisciplinary approach. This review provides an overview of combined dermatology-rheumatology clinics. RECENT FINDINGS: Combined dermatology-rheumatology clinics have emerged to optimize integrated care for patients with psoriasis and PsA. There are over 20 such clinics across the USA. These clinics facilitate multidisciplinary care for patients with psoriasis and PsA and have been found to improve outcomes and enhance both patient and physician satisfaction and knowledge. Challenges presented by these clinics include appropriate scheduling for both dermatologists and rheumatologists and proving the benefits of the clinics to obtain institutional support. Combined dermatology-rheumatology clinics are a novel model of care for patients with psoriasis and PsA. They improve outcomes, patient and physician satisfaction, and efficiency. As more of these clinics are established, we must further understand their impact on outcomes and care processes.

Vesicular erythema migrans: an atypical and easily misdiagnosed form of Lyme disease.

Erythema migrans is the initial sign in the majority of patients infected with Borrelia, the genus of spirochetes that causes Lyme disease. Early identification and treatment decrease the risk of progression to later stages of disease. Although a "bull's eye" appearance owing to lesional clearing is considered classic for erythema migrans, this feature is surprisingly often lacking among patients in the United States. Furthermore, cutaneous Lyme disease can exhibit a wide range of morphologic variability in a minority of patients. Herein, we describe the case of a patient with Lyme disease in which the presence of atypical vesicular features, in conjunction with the initial absence of clearing, resulted in multiple misdiagnoses and delayed treatment. We also review the literature on the epidemiology and management of erythema migrans for cases in which the diagnosis may pose a challenge.

Patients with severe psoriasis are at increased risk of cardiovascular mortality: cohort study using the General Practice Research Database.

AIMS: Psoriasis is a common chronic inflammatory T-helper cell-1/17 mediated skin disease. Recent studies suggest that psoriasis, particularly if severe, may be an independent risk factor for atherosclerosis, myocardial infarction (MI), and stroke. We conducted a cohort study using the General Practice Research Database to determine if severe psoriasis patients have an increased risk of cardiovascular (CV) mortality. METHODS AND RESULTS: Severe psoriasis was defined as patients who received a psoriasis diagnosis and systemic therapy consistent with severe psoriasis (n = 3603). Up to four unexposed patients without psoriasis were selected from the same practices and start dates for each psoriasis patient (n = 14 330). For every death, the cause was determined by review of the electronic medical record. Severe psoriasis was an independent risk factor for CV mortality (HR 1.57; 95% CI 1.26, 1.96) when adjusting for age, sex, smoking, diabetes, hypertension, and hyperlipidaemia. Overall, severe psoriasis patients experienced one extra CV death per 283 patients per year, even when adjusting for major CV risk factors. The relative risk of CV mortality was modified by age. For example, the RR of CV death for a 40-year-old and 60-year-old with severe psoriasis was 2.69 (1.45, 4.99) and 1.92 (1.41, 2.62), respectively. The findings were robust to multiple sensitivity analyses. CONCLUSION: Patients with severe psoriasis have an increased risk of CV mortality that is independent of traditional CV risk factors. Additional studies are needed to determine the mechanism of this association and the impact that control of psoriasis has on CV risk.

Epstein-Barr virus and human herpesvirus type 6 infection in patients with psoriasis.

The association of psoriasis with latent human herpesvirus infection has not been well described. To better understand the relationship between severe psoriasis and its treatment with latent human herpesvirus infection, we performed a cross-sectional study to determine if patients with severe psoriasis and psoriasis patients treated with immunosuppressive therapies have higher rates of Epstein-Barr virus and human herpesvirus 6 replication compared to healthy controls. The prevalence of Epstein-Barr virus and human herpesvirus 6 replication was measured in white blood cells by quantitative polymerase chain reaction. We found no evidence of active viral replication in white blood cells of healthy controls (0/10; 95% confidence interval 0-0.26), patients with severe psoriasis (0/25; 95% confidence interval 0-0.11) or severe psoriasis patients on immunosuppressive treatment (0/26; 95% confidence interval 0-0.11). The results of this study suggest that neither severe psoriasis alone, nor in combination with immunosuppressive therapy, is associated with an increase in Epstein-Barr virus or human herpesvirus 6 replication in white blood cells.

Prevalence of cardiovascular risk factors in patients with psoriasis.

BACKGROUND: Previous studies suggest that patients hospitalized for psoriasis have an increased frequency of a variety of cardiovascular comorbidities. Limited population-based data exist on this association, and few studies have determined which factors are independently associated with psoriasis. OBJECTIVE: We sought to determine whether the prevalence of the major cardiovascular risk factors was higher in mild and severe psoriasis than in patients without psoriasis. METHODS: We conducted a population-based study in the United Kingdom using the General Practice Research Database. Patients were classified as having severe psoriasis if they received a code for psoriasis as well as systemic therapy. Patients were defined as having mild psoriasis if they ever received a psoriasis code but no systemic therapy. Control subjects were selected from the same practices and start dates as psoriasis patients. Patients were classified as having risk factors if they received codes for diabetes, hypertension, hyperlipidemia, obesity, or smoking. Analyses were performed by using conditional logistic regression, and adjustments were made considering age, gender, person-years, and all cardiovascular risk factors. RESULTS: We identified 127,706 patients with mild psoriasis and 3854 with severe psoriasis. Respective prevalence rates of risk factors in those with severe psoriasis, mild psoriasis, and in controls were as follows: diabetes (7.1%, 4.4%, 3.3%), hypertension (20%, 14.7%, 11.9%), hyperlipidemia (6%, 4.7%, 3.3%), obesity (20.7%, 15.8%, 13.2%), and smoking (30.1%, 28%, 21.3%). Patients with mild psoriasis had a higher adjusted odds of diabetes (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.08-1.18]), hypertension (OR, 1.03; 95% CI, 1.01-1.06), hyperlipidemia (OR, 1.16; 95% CI, 1.12-1.21), obesity (OR, 1.27; 95% CI, 1.24-1.31), and smoking (OR, 1.31; 95% CI, 1.29-1.34) than controls. Patients with severe psoriasis had a higher adjusted odds of diabetes (OR, 1.62; 95% CI, 1.3-2.01), obesity (OR, 1.79; 95% CI, 1.55-2.05), and smoking (OR, 1.31; 95% CI, 1.17-1.47) than controls. Additionally, diabetes (OR, 1.39; 95% CI, 1.22-1.58) and obesity (OR, 1.47; 95% CI, 1.32-1.63) were more prevalent in those with severe psoriasis than with mild psoriasis. LIMITATIONS: The study was cross-sectional and therefore the directionality of the associations could not be determined. CONCLUSION: Multiple cardiovascular risk factors are associated with psoriasis. Cardiovascular risk factors that are key components of the metabolic syndrome are more strongly associated with severe psoriasis than with mild psoriasis.

Risk of myocardial infarction in patients with psoriasis.

CONTEXT: Psoriasis is the most common T-helper cell type 1 (T(H)1) immunological disease. Evidence has linked T(H)1 diseases to myocardial infarction (MI). Psoriasis has been associated with cardiovascular diseases, but has only been investigated in hospital-based studies that did not control for major cardiovascular risk factors. OBJECTIVE: To determine if within a population-based cohort psoriasis is an independent risk factor for MI when controlling for major cardiovascular risk factors. DESIGN, SETTING, AND PATIENTS: A prospective, population-based cohort study in the United Kingdom of patients with psoriasis aged 20 to 90 years, comparing outcomes among patients with and without a diagnosis of psoriasis. Data were collected by general practitioners as part of the patient's medical record and stored in the General Practice Research Database between 1987 and 2002, with a mean follow-up of 5.4 years. Adjustments were made for hypertension, diabetes, history of myocardial infarction, hyperlipidemia, age, sex, smoking, and body mass index. Patients with psoriasis were classified as severe if they ever received a systemic therapy. Up to 5 controls without psoriasis were randomly selected from the same practices and start dates as the patients with psoriasis. A total of 556,995 control patients and patients with mild (n = 127,139) and severe psoriasis (n = 3837) were identified. MAIN OUTCOME MEASURE: Incident MI. RESULTS: There were 11,194 MIs (2.0%) within the control population and 2319 (1.8%) and 112 (2.9%) MIs within the mild and severe psoriasis groups, respectively. The incidences per 1000 person-years for control patients and patients with mild and severe psoriasis were 3.58 (95% confidence interval [CI], 3.52-3.65), 4.04 (95% CI, 3.88-4.21), and 5.13 (95% CI, 4.22-6.17), respectively. Patients with psoriasis had an increased adjusted relative risk (RR) for MI that varied by age. For example, for a 30-year-old patient with mild or severe psoriasis, the adjusted RR of having an MI is 1.29 (95% CI, 1.14-1.46) and 3.10 (95% CI, 1.98-4.86), respectively. For a 60-year-old patient with mild or severe psoriasis, the adjusted RR of having an MI is 1.08 (95% CI, 1.03-1.13) and 1.36 (95% CI, 1.13-1.64), respectively. CONCLUSIONS: Psoriasis may confer an independent risk of MI. The RR was greatest in young patients with severe psoriasis.

The risk of lymphoma in patients with psoriasis.

Psoriasis is a common, chronic, inflammatory disease. Psoriasis has been hypothesized to be associated with an increased risk of lymphoma due to its pathophysiology, its treatments, or a combination of these factors. We performed a large population-based cohort study of the risk of lymphoma in psoriasis patients using the General Practice Research Database. We identified 153,197 patients with psoriasis and 765,950 corresponding subjects without psoriasis. Psoriasis patients who received a systemic treatment consistent with extensive disease were classified as severe (N=3,994) and those who did not receive systemic therapies were classified as mild (N=149,203). The analyses were adjusted for age, gender, and person-time using a Cox proportional hazards model. For mild and severe psoriasis patients, the respective adjusted relative risks for lymphoma and its subtypes were as follows: all lymphoma 1.34 (1.16, 1.54) and 1.59 (0.88, 2.89); non-Hodgkin's lymphoma 1.15 (0.97, 1.37) and 0.73 (0.28, 1.96); Hodgkin's lymphoma (HL) 1.42 (1.00, 2.02) and 3.18 (1.01, 9.97); cutaneous T-cell lymphoma (TCL) 4.10 (2.70, 6.23) and 10.75 (3.89, 29.76). Psoriasis is associated with an increased risk of lymphoma. The association is strongest for HL and CTCL. The excess risk of lymphoma attributed to psoriasis was 7.9/100,000 psoriasis patients per year. Although patients with psoriasis have an increased relative risk of lymphoma, the absolute risk attributable to psoriasis is low given that lymphoma is a rare disease and the magnitude of association is modest.