Cheryl F. Rosen

Cardiovascular and other comorbidities in patients with psoriatic arthritis: A comparison with patients with psoriasis

To determine whether the presence of psoriatic arthritis (PsA) is associated with greater comorbidity, in particular cardiovascular morbidity, compared to psoriasis without arthritis.

Soluble biomarkers differentiate patients with psoriatic arthritis from those with psoriasis without arthritis

OBJECTIVE Biomarkers may be helpful in screening patients with psoriasis for PsA. Our purpose was to identify serum biomarkers for psoriasis and PsA. METHODS Fifty-two patients with psoriasis (26 satisfying CASPAR classification criteria for PsA) and 26 healthy controls were recruited for our study. Patients with psoriasis and PsA were group matched for age, sex and psoriasis duration, whereas controls were matched for age and sex. Blood samples were drawn at the time of assessment and serum was analysed for the following: IL-12, IL-12p40, IL-17, TNF super family member 14 (TNFSF14), MMP-3, RANK ligand (RANKL), osteoprotegerin (OPG), cartilage oligomeric matrix protein (COMP), C-propeptide of Type II collagen (CPII), collagen fragment neoepitopes Col2-3/4(long mono) (C2C) and Col2-3/4(short) (C1-2C) and highly sensitive CRP (hsCRP). Data were analysed using logistic regression and receiver operating characteristic curves were plotted. RESULTS Fifty-two patients with psoriatic disease had a mean age of 46 years and psoriasis duration of 16.8 years. Compared with controls, increased serum levels of RANKL, TNFSF14, MMP-3 and COMP independently associated with psoriatic disease (P < 0.05). Twenty-six PsA patients (mean swollen and/or tender joint count 16, swollen joint count 5) were then compared with 26 patients who had psoriasis alone. Increased levels of hsCRP, OPG, MMP-3 and the CPII : C2C ratio were independently associated with PsA (P < 0.03). CONCLUSION This pilot study indicates that hsCRP, OPG, MMP-3 and the CPII : C2C ratio are biomarkers for PsA in patients with psoriasis.

Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci.

Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genomewide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susceptibility loci. Here, we extend our previous meta-analysis of European ancestry by refined genotype calling and imputation and by the addition of 5,033 cases and 5,707 controls. The combined analysis, consisting of over 15,000 cases and 27,000 controls, identifies five new psoriasis susceptibility loci at genomewide significance (p < 5 × 10−8). The newly identified signals include two that reside in intergenic regions (1q31.1 and 5p13.1) and three residing near PLCL2 (3p24.3), NFKBIZ (3q12.3), and CAMK2G (10q22.2). We further demonstrate that NFKBIZ is a TRAF3IP2–dependent target of IL-17 signaling in human skin keratinocytes, thereby functionally linking two strong candidate genes. These results further integrate the genetics and immunology of psoriasis, suggesting new avenues for functional analysis and improved therapies.

IL13 gene polymorphism is a marker for psoriatic arthritis among psoriasis patients

Aim To study the association between smoking and IL13 gene polymorphisms with psoriatic arthritis (PsA) and psoriasis. Methods The authors genotyped three groups of Caucasians: those with PsA, those with psoriasis without arthritis (PsC) and healthy controls for the rs20541 and rs848 IL13 single nucleotide polymorphisms (SNPs). An additional SNP, rs1800925, was genotyped only in the PsA and PsC groups. The differences in allelic distributions were compared by χ2 test. The prevalence of smoking was compared between people with PsA and those with PsC. The combined effect of genotype and smoking was tested by comparing the frequencies of different combinations of rs1800925 genotype and smoking status in PsA and PsC. Results 555 PsA patients, 342 PsC patients and 217 healthy controls were included in the study. Smoking was less prevalent in patients with PsA compared with PsC (47.4% vs 59.4%, p<0.0006). rs20541*G and rs848*C alleles were associated with PsA compared with controls (OR 1.64, p=0.0005, OR 1.61, p=0.0007 respectively). The association between these alleles and PsC compared with controls was only of borderline significance (OR 1.33, p=0.06, OR 1.26, p=0.11 respectively). Two major alleles, rs1800925*C (OR 1.28, p=0.045) and rs848*C (OR 1.30, p=0.047) were increased in PsA compared with PsC. The combination of non-smoking and the genotype rs1800925*CC was associated with increased susceptibility to PsA compared with PsC. Among smokers, rs1800925*CC was not associated with PsA compared with PsC. Conclusions IL13 gene polymorphism is associated with increased susceptibility to PsA in psoriasis patients.

Is the Madrid Sonographic Enthesitis Index Useful for Differentiating Psoriatic Arthritis from Psoriasis Alone and Healthy Controls

Objective. To assess the usefulness of the MAdrid Sonographic Enthesitis Index (MASEI) in classifying patients as having psoriatic arthritis (PsA) and comparing entheseal abnormalities between patients with PsA, psoriasis alone (PsC), and healthy controls (HC). Methods. Patients with PsC were assessed to exclude inflammatory arthritis. The MASEI scoring system was used to quantify the extent of ultrasonographic (US) entheseal abnormalities. The total MASEI score was categorized into items that reflected inflammatory abnormalities (MASEI-inflammatory) and chronic damage (MASEI-damage). Nonparametric tests were used to compare MASEI scores across the groups. A cutoff point of MASEI ≥ 20 was used to calculate the sensitivity and specificity of the MASEI to classify patients as having PsA. Results. Patients with PsA (n = 50), PsC (n = 66), and HC (n = 60) were assessed. Total MASEI scores were higher in patients with PsA than in those with PsC, and both those groups were higher than HC (p < 0.0001). MASEI-inflammatory showed a similar trend (p < 0.0001). MASEI-damage was higher in patients with PsA compared to both patients with PsC and HC (p < 0.0001); however, no difference was observed between patients with PsC and HC. No significant difference in MASEI scores was found across the 3 groups in patients with a body mass index > 30. The sensitivity of the MASEI score to correctly classify patients as having PsA was 30% and the specificity was 95% when compared to HC and 89% when compared to PsC. Conclusion. The severity of US entheseal abnormalities is highest in patients with PsA followed by PsC and is lowest in healthy controls. MASEI can specifically classify patients as having PsA.

Evaluation of Sun-Protective Practices of Organ Transplant Recipients

The incidence, morbidity and mortality of skin cancer are markedly increased in organ transplant recipients. Efforts aimed at reducing sun exposure through sun avoidance, sunscreens and sun‐protective clothing are the most effective means to reduce the risk of skin cancer. We evaluated the sun‐protective behaviors of 205 transplant recipients. Twenty‐three percent of transplant patients continued to seek a tan. Thirty percent of patients did not use sunscreens, and of those patients who did, less than 5% were committed to using them daily. Thirty‐seven percent of patients frequently wore hats and 39% of patients frequently wore additional clothing to block the sun. When data were stratified according to patient age, gender or skin phototype, we identified preferences for specific sun‐protective methods. These data strongly suggest that many transplant recipients do not use adequate sun protection. Further study of strategies to encourage the use of sun protection among transplant patients is needed to reduce the incidence of skin cancer.

Point-of-care autofluorescence imaging for real-time sampling and treatment guidance of bioburden in chronic wounds: first-in-human results.

Background Traditionally, chronic wound infection is diagnosed by visual inspection under white light and microbiological sampling, which are subjective and suboptimal, respectively, thereby delaying diagnosis and treatment. To address this, we developed a novel handheld, fluorescence imaging device (PRODIGI) that enables non-contact, real-time, high-resolution visualization and differentiation of key pathogenic bacteria through their endogenous autofluorescence, as well as connective tissues in wounds. Methods and Findings This was a two-part Phase I, single center, non-randomized trial of chronic wound patients (male and female, ≥18 years; UHN REB #09-0015-A for part 1; UHN REB #12-5003 for part 2; clinicaltrials.gov Identifier: NCT01378728 for part 1 and NCT01651845 for part 2). Part 1 (28 patients; 54% diabetic foot ulcers, 46% non-diabetic wounds) established the feasibility of autofluorescence imaging to accurately guide wound sampling, validated against blinded, gold standard swab-based microbiology. Part 2 (12 patients; 83.3% diabetic foot ulcers, 16.7% non-diabetic wounds) established the feasibility of autofluorescence imaging to guide wound treatment and quantitatively assess treatment response. We showed that PRODIGI can be used to guide and improve microbiological sampling and debridement of wounds in situ, enabling diagnosis, treatment guidance and response assessment in patients with chronic wounds. PRODIGI is safe, easy to use and integrates into the clinical workflow. Clinically significant bacterial burden can be detected in seconds, quantitatively tracked over days-to-months and their biodistribution mapped within the wound bed, periphery, and other remote areas. Conclusions PRODIGI represents a technological advancement in wound sampling and treatment guidance for clinical wound care at the point-of-care. Trial Registration ClinicalTrials.gov NCT01651845; ClinicalTrials.gov NCT01378728

The Development of Psoriatic Arthritis in Patients With Psoriasis Is Preceded by a Period of Nonspecific Musculoskeletal Symptoms: A Prospective Cohort Study

To assess whether the presence of nonspecific musculoskeletal symptoms, their degree, and change over time predict the development of psoriatic arthritis (PsA) in a prospective cohort of psoriasis patients without arthritis at baseline.

Improved detection of clinically relevant wound bacteria using autofluorescence image-guided sampling in diabetic foot ulcers

Clinical wound assessment involves microbiological swabbing of wounds to identify and quantify bacterial species, and to determine microbial susceptibility to antibiotics. The Levine swabbing technique may be suboptimal because it samples only the wound bed, missing other diagnostically relevant areas of the wound, which may contain clinically significant bacteria. Thus, there is a clinical need to improve the reliability of microbiological wound sampling. To address this, a handheld portable autofluorescence (AF) imaging device that detects bacteria in real time, without contrast agents, was developed. Here, we report the results of a clinical study evaluating the use of real‐time AF imaging to visualise bacteria in and around the wound bed and to guide swabbing during the clinical assessment of diabetic foot ulcers, compared with the Levine technique. We investigated 33 diabetic foot ulcers (n = 31 patients) and found that AF imaging more accurately identified the presence of moderate and/or heavy bacterial load compared with the Levine technique (accuracy 78% versus 52%, P = 0·048; adjusted diagnostic odds ratio 7·67, P < 0·00022 versus 3·07, P = 0·066) and maximised the effectiveness of bacterial load sampling, with no significant impact on clinical workflow. AF imaging may help clinicians better identify the wound areas with clinically significant bacteria, and maximise sampling of treatment‐relevant pathogens.

Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network Consortium (PPACMAN) Survey: Benefits and Challenges of Combined Rheumatology-dermatology Clinics

Optimal management of patients with both psoriasis and psoriatic arthritis (PsA) necessitates collaboration among dermatologists and rheumatologists. In this manuscript, we discuss challenges and opportunities for dual care models for patients with psoriasis and PsA and the results of a survey of combined clinics based in North America.