Increased histological severity and chronicity of interface inflammation in anti-MDA5 dermatomyositis-A comparative dermatopathological analysis.

Anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis is characterized by serological detection of anti-MDA5 antibody and rapidly progressive interstitial lung disease. In this study, the largest cohort of skin biopsies to date of anti-MDA5 dermatomyositis was reviewed and compared with cases of dermatomyositis with negative serology. Findings contribute to the histological diagnosis and evaluation of the severity of cutaneous inflammation in anti-MDA5 dermatomyositis. Skin biopsies collected over a 7-year period from individuals with clinically and histologically confirmed dermatomyositis with anti-MDA5 serology were reviewed. A total of 46 cases with 17 anti-MDA5 positive cases were retrieved. Patients with positive antibody were younger (53.7 vs. 60.6 years, p = .013). No differences in epidermal changes (p > .05) were observed. Pertaining to interface changes, anti-MDA5 dermatomyositis showed a higher degree of pigmentary incontinence (p = .014), suggesting increased and sustained cutaneous inflammation. Periodic acid-Schiff (PAS) stain demonstrated a greater degree of basement membrane thickening (p = .045). Other parameters, including dermal inflammation, dermal mucin deposition and vasculitic/vasculopathic features did not show statistical difference between anti-MDA5 positive and negative dermatomyositis (p > .05). Findings suggest increased cutaneous inflammation for anti-MDA5 dermatomyositis. In skin biopsies, marked pigmentary incontinence or basement membrane thickening should raise suspicion of anti-MDA5 dermatomyositis.

Diagnostic work-up and treatment in patients with pyoderma gangrenosum: retrospective analysis of US insurance claims-based data.

Pyoderma gangrenosum (PG) is a rare, and often challenging to diagnose, inflammatory disorder with relatively high rates of morbidity and mortality. Central to the diagnosis of PG is histologic evaluation and exclusion of other entities. Large-scale studies investigating the proportion of patients receiving a thorough diagnostic work-up, as well as prevalence studies regarding comorbidities and systemic treatment in PG using claims-based data, are sparse. Our objective was to identify patients diagnosed with PG and describe the diagnostic work-up and prevalence of common comorbidities and therapies in this population using claims-based data in a retrospective cohort study. In order to better understand practices of diagnostic work-up, we captured rates of skin biopsy, tissue culture, and/or surgical debridement prior to initial diagnosis. We also identified the prevalence of PG-associated comorbidities and initial immunosuppressive therapy given for PG. Of the 565 patients diagnosed with PG, 9.4% underwent skin biopsy, 8% tissue culture, and 1.4% both skin biopsy AND tissue culture prior to diagnosis. Inflammatory bowel disease was the most prevalent comorbidity (16.3%). The most common treatment administered was systemic corticosteroids (17%). Although practice guidelines explicitly delineate histology and exclusion of infection as important diagnostic criteria, only a minority of patients in this study underwent skin biopsy and/or tissue culture prior to receiving a diagnosis of PG, suggesting that patients may receive a diagnosis of PG without having tissue evaluation. Such discordance between practice guidelines and "real-world" practice inevitably increases the risk for misdiagnosis of PG and misdirected treatment with immunosuppressants for presumptive PG in cases of PG mimickers. Moreover, comorbidities associated with PG may occur, or be identified in, a lower proportion of patients as compared with what is reported in the existing literature. Study limitations include a population restricted to < 65 years with commercial insurance and the reliance upon ICD diagnostic coding to capture the population.

Management of chronic rheumatic diseases in women 18-45 years of age in Asia Pacific: insights from patient and clinician surveys.

OBJECTIVE: Perspectives of women aged 18-45 years with chronic rheumatic diseases (CRD), and clinicians, in the Asia-Pacific (APAC) region are reported. METHODS: Online surveys were completed by women, pregnant in the past 2-5 years, with moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), and rheumatologists, obstetricians, orthopaedic surgeons who medically manage CRDs. RESULTS: Among 210 (RA 122, PsA 48, axSpA 40) patients, 52% (n = 109/210) delayed their decision to have children, most commonly due to concerns of passing on disease to offspring. 33% (n = 70/210) discussed family planning with a healthcare professional at diagnosis. Patients most often initiated discussions. 94% (n = 193/205) stopped treatment around pregnancy due to fear of fetal harm. 66% (n = 139/210) of patients felt they did not receive all relevant information on the impact of CRDs and treatment on pregnancy. Among 335 clinicians who participated, 82% (n = 143/174) of rheumatologists, 86% (n = 72/84) of obstetricians and 43% (n = 33/77) of orthopaedic surgeons agreed good disease control during pregnancy was their primary goal. 69% (n = 120/174) of rheumatologists were 'very comfortable' with prescribing tumour necrosis factor inhibitors (TNFi) for women aged 18-45 years. Comfort levels generally decreased with the onset of family planning. More obstetricians and orthopaedic surgeons supported avoiding TNFi during pregnancy than rheumatologists (40% [n = 34/84]/38% [n = 29/77] versus 16% [n = 28/174]). Access to more TNFi safety data during pregnancy was considered paramount for increasing clinician comfort. CONCLUSIONS: Patients and physicians need current information and multidisciplinary discussions for improved management of CRD in women in APAC.

Serum Calprotectin Level Is Independently Associated With Carotid Plaque Presence in Patients With Psoriatic Arthritis.

Background: Whether calprotectin could play a role in augmenting cardiovascular (CV) risk in patients with psoriatic arthritis (PsA) remains uncertain. The aim of this study is to elucidate the association between serum calprotectin level and subclinical atherosclerosis in patient with PsA. Method: Seventy-eight PsA patients (age: 52 ± 10 years, 41 [52.6%] male) without CV disease were recruited into this cross-sectional study. Carotid intima-media thickness (cIMT) and the presence of plaque were determined by high-resolution ultrasound. Calprotectin levels in serum were quantified by enzyme-linked immunosorbent assay. The variables associated with the presence of carotid plaque (CP) were selected from the least absolute shrinkage and selection operator (LASSO) regression analysis. Results: 29/78 (37.2%) of patient had carotid plaque (CP+ group). Serum calprotectin level was significantly higher in the CP+ group (CP- group: 564.6 [329.3-910.5] ng/ml; CP+ group: 721.3 [329.3-910.5] ng/ml, P = 0.005). Serum calprotectin level correlated with PsA disease duration (rho = 0.280, P = 0.013) and mean cIMT (rho = 0.249, P = 0.038). Using LASSO regression analysis, the levels of Ln-calprotectin (OR: 3.38, 95% CI [1.37, 9.47]; P = 0.026) and PsA disease duration (OR: 1.09, 95% CI [1.01, 1.18]; P = 0.013) were screened out from a total of 19 variables. The model in predicting the presence of CP was constructed by Ln-calprotectin and PsA disease duration with an area under the receiver-operating characteristic (ROC) curve of 0.744, (95 CI% [0.59, 0.80], P = 0.037). Conclusion: Serum calprotectin level is associated with the presence of CP in PsA. Further studies are required to confirm whether this pathway is associated with CV events in PsA.

Jagged Ends on Multinucleosomal Cell-Free DNA Serve as a Biomarker for Nuclease Activity and Systemic Lupus Erythematosus.

BACKGROUND: Jagged ends of plasma DNA are a recently recognized class of fragmentomic markers for cell-free DNA, reflecting the activity of nucleases. A number of recent studies have also highlighted the importance of jagged ends in the context of pregnancy and oncology. However, knowledge regarding the generation of jagged ends is incomplete. METHODS: Jaggedness of plasma DNA was analyzed based on Jag-seq, which utilized the differential methylation signals introduced by the DNA end-repair process. We investigated the jagged ends in plasma DNA using mouse models by deleting the deoxyribonuclease 1 (Dnase1), DNA fragmentation factor subunit beta (Dffb), or deoxyribonuclease 1 like 3 (Dnase1l3) gene. RESULTS: Aberrations in the profile of plasma DNA jagged ends correlated with the type of nuclease that had been genetically deleted, depending on nucleosomal structures. The deletion of Dnase1l3 led to a significant reduction of jaggedness for those plasma DNA molecules involving more than 1 nucleosome (e.g., size ranges 240-290 bp, 330-380 bp, and 420-470 bp). However, less significant effects of Dnase1 and Dffb deletions were observed regarding different sizes of DNA fragments. Interestingly, the aberration in plasma DNA jagged ends related to multinucleosomes was observed in human subjects with familial systemic lupus erythematosus with Dnase1l3 deficiency and human subjects with sporadic systemic lupus erythematosus. CONCLUSIONS: Detailed understanding of the relationship between nuclease and plasma DNA jaggedness has opened up avenues for biomarker development.

Predictors of rapidly progressive interstitial lung disease and mortality in patients with autoantibodies against melanoma differentiation-associated protein 5 dermatomyositis.

OBJECTIVE: Anti-melanoma differentiation-associated protein 5 (MDA5)-positive DM is associated with rapidly progressive interstitial lung disease (RP-ILD) and high mortality. This multicentre retrospective study aimed to identify predictors of mortality and RP-ILD. METHODS: Anti-MDA5-positive DM patients were identified from the Hong Kong Myositis Registry and the Clinical Data Analysis and Reporting System. Clinical characteristics were reviewed. Risk factors for mortality and RP-ILD were identified. RESULTS: Among the 116 recruited patients, 100 (86.2%) had ILD, 47 (40.5%) had RP-ILD and 44 (37.9%) patients died. Cox regression analysis revealed RP-ILD [hazard ratio (HR) 9.735 (95% CI 3.905, 24.272)], age >52 years [HR 4.750 (95% CI 1.692, 13.333)], ferritin level >2800 pmol/l [HR 3.042 (95% CI 1.323, 6.997)] and lactate dehydrogenase (LDH) >400 IU/l [HR 2.290 (95% CI 1.009, 5.198)] were independent predictors of mortality. With regard to RP-ILD, analyses showed that potential predictors at baseline included age >50 years [HR 2.640 (95% CI 1.277, 5.455)], LDH >300 IU/l [HR 3.189 (95% CI 1.469, 6.918)], fever [HR 1.903 (95% CI 0.956, 3.790)] and neutrophil:lymphocyte ratio >7.0 [HR 1.967 (95% CI 0.942, 4.107)]. We proposed a prediction model based on fever, LDH, age and white cell count (FLAW) to stratify the risk of development of RP-ILD. The probability of RP-ILD in a patient with a score of 4 was 100%. A small internal validation cohort showed the odds of RP-ILD with FLAW scores of 0, 1, 2 and 3 were 0%, 0%, 42.9% and 75%, respectively. CONCLUSIONS: Anti-MDA5-associated RP-ILD is significantly associated with poor survival rates. The FLAW model maybe useful to predict the development of RP-ILD.

Association of C-reactive protein and non-steroidal anti-inflammatory drugs with cardiovascular events in patients with psoriatic arthritis: a time-dependent Cox regression analysis.

AIMS: Psoriatic arthritis (PsA) is associated with accelerated atherosclerosis due to underlying inflammation. Whether inflammatory burden and drugs used to suppress inflammation over time are associated with cardiovascular (CV) events remained unclear. This study aims to examine the time-varying effect of C-reactive protein (CRP) levels and the use of drugs, including non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying anti-rheumatic drugs, on the risk of CV events independent of traditional CV risk factors in PsA patients. METHODS: A retrospective cohort analysis was performed in patients with PsA who were recruited from 2008 to 2015 and followed until the end of 2019. The outcome was occurrence of a first CV event. Framingham risk score (FRS) was used to quantify the traditional CV risk. Cox proportional hazard models with time-varying CRP levels and drugs used were analysed to identify the risk factors for CV events in PsA patients. RESULTS: Two hundred patients with PsA [median age: 47.5 (40.0-56.0); male: 119 (59.5%)] were recruited. After a mean follow-up of 8.8 ± 3.8 years, 30 (15%) patients developed a first CV event. The multivariable Cox regression model showed that time-varying CRP level [hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.00-1.04] and NSAIDs exposure (HR 0.38, 95% CI 0.15-0.96) were significantly associated with CV events after adjusting for baseline FRS (HR 5.06, 95% CI 1.84-13.92). CONCLUSION: Increased inflammatory burden as reflected by elevated CRP level was associated with increased risk of CV events, while the risk was significantly reduced with NSAIDs use in PsA patients.

Pattern and trend of five major musculoskeletal disorders in China from 1990 to 2017: findings from the Global Burden of Disease Study 2017.

BACKGROUND: With increasing life expectancy in China, no large population-based studies have been done on the trend for musculoskeletal disorders in China. We have investigated the pattern and trend of five major musculoskeletal disorders in China from the Global Burden of Disease Study 2017 and its association with sociodemographic index (SDI). METHODS: The main outcome measures were incidence, prevalence, and disability-adjusted life years (DALYs) for rheumatoid arthritis, osteoarthritis, low back pain, neck pain, and gout. Average annual percent change (AAPC) and annual percent change (APC) between 1990 and 2017 were analyzed with Joinpoint regression. RESULTS: The age-standardized rate of incidence, prevalence, and DALYs for the five major musculoskeletal disorders increased with age. For SDI, the age-standardized rate of DALYs was zigzagged increasing for rheumatoid arthritis and curvilinear increasing for gout, curvilinear decreasing for low back pain, and reaching to the highest point for osteoarthritis and neck pain with an SDI value of 0.61. The AAPC in age-standardized rate of DALYs indicated an increasing trend for rheumatoid arthritis (0.20, 95% CI 0.07, 0.34), osteoarthritis (0.26, 95% CI 0.20, 0.31), neck pain (0.09, 95% CI 0.07, 0.12), and gout (0.25, 95% CI 0.23, 0.27), but a decreasing trend for low back pain (- 0.96, 95% CI - 0.98, - 0.93). The AAPC of risk factors indicated a decreasing trend in smoking (- 0.14, 95% CI - 0.24, - 0.04) for rheumatoid arthritis, smoking (- 0.22, 95% CI - 0.24, - 0.19) and occupational ergonomic factors (- 1.25, 95% CI - 1.29, - 1.21) for low back pain, and impaired kidney function (- 0.95, 95% CI - 1.00, - 0.90) for gout, but an increasing trend in high body-mass index for osteoarthritis (3.10, 95% CI 3.03, 3.17), low back pain (3.07, 95% CI 2.99, 3.14), and gout (3.12, 95% CI 3.04, 3.20). Comparing the burden of five musculoskeletal diseases in China with the 19 countries of G20, China ranked first to second in the number of DALYs, and 12th to 16th in age-standardized rate of DALYs. CONCLUSION: There are remarkably complex temporal patterns in disease burden and risk factors for five major musculoskeletal disorders across past three decades. Population-wide initiatives targeting high body-mass index may mitigate the burden of musculoskeletal disorders.

The causal effect of interleukin-17 on the risk of psoriatic arthritis: a Mendelian randomization study.

OBJECTIVE: To determine causal associations between genetically predicted TNF-α, IL-12p70 and IL-17 levels and risk of PsA. METHODS: The publicly available summary-level findings from genome-wide association studies (GWAS) was used to identify loci influencing normal physiological concentrations of TNF-α, IL-12p70 and IL-17 (n = 8293) among healthy individuals as exposure and a GWAS for PsA from the UK Biobank (PsA = 900, control = 462 033) as the outcome. A two-sample Mendelian randomization (MR) analysis was performed using the inverse-variance weighted (IVW), weighted median and MR-Egger regression methods. Sensitivity analysis and MR-Egger regression analysis were performed to evaluate the heterogeneity and pleiotropic effects of each variant. RESULTS: Single-nucleotide polymorphisms (SNPs) at genome-wide significance from GWASs on TNF-α, IL-12p70 and IL-17 were identified as the instrumental variables. The IVW method indicated a causal association between increased IL-17 level and risk of PsA (ß = -0.00186 per allele, s.e. = 0.00043, P = 0.002). Results were consistent in the weighted median method (ß = -0.00145 per allele, s.e. = 0.00059, P = 0.014) although the MR-Egger method suggested a non-significant association (ß = -0.00133 per allele, s.e. = 0.00087; P = 0.087). Single SNP MR results revealed that the C allele of rs117556572 was robustly associated with risk of PsA (ß = 0.00210, s.e. = 0.00069, P = 0.002). However, no evidence for a causal effect was observed between TNF-α, IL-12p70, decreased IL-17 levels and risk of PsA. CONCLUSION: Our findings provide preliminary evidence that genetic variants predisposing to higher physiological IL-17 level are associated with decreased risk of PsA.

Plasma DNA Profile Associated with DNASE1L3 Gene Mutations: Clinical Observations, Relationships to Nuclease Substrate Preference, and In Vivo Correction.

Plasma DNA fragmentomics is an emerging area in cell-free DNA diagnostics and research. In murine models, it has been shown that the extracellular DNase, DNASE1L3, plays a role in the fragmentation of plasma DNA. In humans, DNASE1L3 deficiency causes familial monogenic systemic lupus erythematosus with childhood onset and anti-dsDNA reactivity. In this study, we found that human patients with DNASE1L3 disease-associated gene variations showed aberrations in size and a reduction of a "CC" end motif of plasma DNA. Furthermore, we demonstrated that DNA from DNASE1L3-digested cell nuclei showed a median length of 153 bp with CC motif frequencies resembling plasma DNA from healthy individuals. Adeno-associated virus-based transduction of Dnase1l3 into Dnase1l3-deficient mice restored the end motif profiles to those seen in the plasma DNA of wild-type mice. Our findings demonstrate that DNASE1L3 is an important player in the fragmentation of plasma DNA, which appears to act in a cell-extrinsic manner to regulate plasma DNA size and motif frequency.

Comparison of carotid artery ultrasound and Framingham risk score for discriminating coronary artery disease in patients with psoriatic arthritis.

OBJECTIVES: This study aimed to assess the performance of carotid ultrasound (US) parameters alone or in combination with Framingham Risk Score (FRS) in discriminating patients with psoriatic arthritis (PsA) with and without coronary artery disease (CAD). METHODS: Ninety-one patients with PsA (56 males; age: 50±11 years, disease duration: 9.4±9.2 years) without overt cardiovascular (CV) diseases were recruited. Carotid intima-media thickness (cIMT), the presence of plaque and total plaque area (TPA) was determined by high-resolution US. CAD was defined as the presence of any coronary plaque on coronary CT angiography (CCTA). Obstructive-CAD (O-CAD) was defined as >50% stenosis of the lumen. RESULTS: Thirty-five (38%) patients had carotid plaque. Fifty-four (59%) patients had CAD (CAD+) and 9 (10%) patients had O-CAD (O-CAD+). No significant associations between the presence of carotid plaque and CAD were found. However, cIMT and TPA were higher in both the CAD+ and O-CAD+ group compared with the CAD- or O-CAD- groups, respectively. Multivariate logistic regression analysis revealed that mean cIMT was an independent explanatory variable associated with CAD and O-CAD, while maximum cIMT and TPA were independent explanatory variables associated with O-CAD after adjusting for covariates. The optimal cut-offs for detecting the presence of CAD were FRS >5% and mean cIMT at 0.62 mm (AUC: 0.71; sensitivity: 67%; specificity: 76%), while the optimal cut-offs for detecting the presence of O-CAD were FRS >10% in combination with mean cIMT at 0.73 mm (AUC: 0.71; sensitivity: 56%; specificity: 85%). CONCLUSION: US parameters including cIMT and TPA may be considered in addition to FRS for CV risk stratification in patients with PsA.

Effect of biologics on radiographic progression of peripheral joint in patients with psoriatic arthritis: meta-analysis.

OBJECTIVES: To determine the efficacy of biologics in preventing radiographic progression in peripheral joints of PsA patients. METHODS: Studies were searched in MEDLINE, Web of Science, and abstracts from the last three EULAR and ACR meetings up to 31 December 2019. Primary and secondary endpoints were the proportion of patients without radiographic progression and the mean change in total radiographic score at week 24. RESULTS: Eleven studies, involving 5382 patients, 9 drugs and 18 treatments, were included. Patients receiving biologics were more likely to achieve radiographic non-progression compared with placebo [odds ratio: pooled: 2.40, 95% CI: 2.00, 2.87; TNF inhibitors (TNFi): 2.94, 95% CI: 2.38, 3.63; IL inhibitors (ILi): 2.15, 95% CI: 1.69, 2.74; abatacept: 1.54, 95% CI: 1.03, 2.28] and have significantly lower radiographic progression [standardized mean difference (SMD): pooled: -2.16, 95% CI: -2.91, -1.41; TNFi: -2.82, 95% CI: -4.31, -1.33; ILi: -1.60, 95% CI: -2.49, -0.72; abatacept: -0.40, 95% CI: -0.59, -0.21]. Concomitant MTX therapy was not superior to monotherapy (SMD: pooled: 0.01, 95% CI: -0.07, 0.08; biologics: 0.01, 95% CI: -0.09, 0.11; placebo: -0.01, 95% CI: -0.13, 0.12). The effect of ustekinumab and secukinumab on radiographic progression was not influenced by prior anti-TNF therapy (SMD: -0.08, 95% CI: -0.25, 0.10). CONCLUSION: Biologic agents may retard radiographic progression in PsA patients in terms of bone erosion and joint space narrowing compared with placebo. MTX seems to have no added effect. Prior anti-TNF therapy seems to not influence the radiographic efficacy of IL blockers.

DAPSA, carotid plaque and cardiovascular events in psoriatic arthritis: a longitudinal study.

OBJECTIVE: To examine whether Disease Activity in Psoriatic Arthritis (DAPSA) reflecting the inflammatory component of psoriatic arthritis (PsA) can predict cardiovascular (CV) events independent of traditional CV risk factors and subclinical carotid atherosclerosis. METHODS: A cohort analysis was performed in patients with PsA who had been followed since 2006. The outcome of interest was first CV event. Four different CV disease (CVD) risk scores and DAPSA were computed at baseline. The presence of carotid plaque (CP) and carotid intima-media thickness (CIMT) was also determined in a subgroup of patients using high-resolution ultrasound. The association between DAPSA, CVD risk scores, CP, CIMT and the occurrence of CV events was assessed using Cox proportional hazard models. RESULTS: 189 patients with PsA (mean age: 48.9 years; male: 104 (55.0%)) were recruited. After a median follow-up of 9.9 years, 27 (14.3%) patients developed a CV event. Higher DAPSA was significantly associated with an increased risk of developing CV events (HR: 1.04, 95% CI (1.01 to 1.08), p=0.009). The association remained significant after adjusting for all CV risk scores in the multivariable models. In the subgroup analysis, 154 patients underwent carotid ultrasound assessment and 23 (14.9%) of them experienced a CV event. CP was associated with increased risk of developing CV events after adjusting for three CV risk scores and DAPSA, with HR ranging from 2.35 to 3.42. CONCLUSION: Higher DAPSA and the presence of CP could independently predict CVD events in addition to traditional CV risk scores in patients with PsA.

Race and socioeconomic status in pediatric allogeneic hematopoietic cell transplantation for nonmalignant conditions.

BACKGROUND: Survival disparities by race/ethnicity and socioeconomic status (SES) are observed in a wide range of pediatric treatment settings including oncology and solid organ transplantation. To date, few studies have examined the effects of race and SES on outcomes in pediatric allogeneic hematopoietic cell transplantation (HCT). We explored whether survival differed by race/ethnicity or SES in children receiving HCT for nonmalignant conditions at a single institution serving a diverse patient population. PROCEDURES: The Kaplan-Meier method was used to estimate overall survival (OS) with the log-rank test for between-group comparisons. Cox proportional hazards models were used to identify risk factors for OS, adjusting for treatment- and disease-related factors. RESULTS: Of 133 subjects, 0 to 21 years, 19% were non-Hispanic (NH) white, 34% were NH black, 40% were Hispanic, and 7% were Asian. Sixty-seven percent of the subjects had public insurance; 49% lived in neighborhoods with poverty rate ≥20%. Primary diagnoses included hemoglobinopathies (56%), bone marrow failure (22%), and other conditions (22%). Median follow-up was 5.8 years (range 0.1-14.5). Analysis revealed no difference in OS by race, insurance type, or neighborhood SES. CONCLUSIONS: Findings from this single-institution study suggest that in pediatric patients undergoing HCT for nonmalignant conditions, treatment at a tertiary care center with a multidisciplinary approach may mitigate drivers of disparities observed in other settings. Additional studies are now needed to further elucidate the complex interrelationships among race, SES, and clinical outcomes for children undergoing HCT.

Treat to target and prevention of subclinical atherosclerosis in psoriatic arthritis-which target should we choose?

OBJECTIVE: PsA patients who achieved sustained minimal disease activity (sMDA) had less subclinical atherosclerosis progression. The vascular effects of achieving other potential treatment targets, including the PsA Disease Activity Score (PASDAS) and the Disease Activity in PsA (DAPSA) score, remained uncertain. This study aimed to compare the vascular effects of achieving different treatment targets in PsA patients. METHOD: This is a post hoc analysis of a 2 year treat-to-target study aimed at MDA. A total of 101 consecutive PsA patients without overt cardiovascular disease were recruited. High-resolution carotid ultrasound and arterial stiffness markers were assessed annually. Low disease activity (LDA) was defined as MDA, DAPSA ≤14 or PASDAS ≤3.2. Sustained disease control was defined as achieving these targets at each visit from month 12 until month 24. RESULTS: Ninety patients [52 male (57.8%), age 50 years (s.d. 11)] who completed 24 months of follow-up were included in this analysis. A total of 44%, 48% and 45% of patients achieved sustained DAPSA LDA (sDAPDA-LDA), sustained PASDAS LDA (sPASDAS-LDA) and sMDA, respectively. Patients who achieved sMDA had significantly less progression of carotid intima-media thickness than those who did not (P = 0.031). Using multivariate analysis, achieving sMDA and sPASDAS-LDA had a protective effect on plaque progression, less increase in total plaque area, reduced mean intima-media thickness and reduced augmentation index after adjusting for covariates. In contrast, no significant differences in the progression of vascular parameters were demonstrated between patients who did or did not achieve sDAPSA-LDA. CONCLUSION: Achieving sMDA/sDASPAS-LDA, but not sDAPSA-LDA, was associated with a protective effect in subclinical atherosclerosis and arterial stiffness progression. A multidimensional domain of disease control might be better in minimizing cardiovascular risk in PsA.

Progressive structural bone changes and their relationship with treatment in patients with psoriatic arthritis: a longitudinal HR-pQCT study.

BACKGROUND: Although the short-term effects of tumor necrosis factor alpha (TNF-α) and interleukin-17A (IL-17A) inhibition on the structural changes in psoriatic arthritis (PsA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) have been reported, no studies have investigated the long-term structural changes in PsA patients receiving routine care. We reported longitudinal changes of erosions and enthesiophytes using HR-pQCT and their relationship with treatments in PsA patients over a 5-year period. METHODS: HR-pQCT examination at the second and third metacarpal heads (MCH2 and MCH3) was performed in 60 PsA patients at baseline and after 5 years. The size of each individual lesion was quantified. Erosion and enthesiophyte progression were defined as change exceeding the smallest detectable change (SDC). RESULTS: A total of 108 bone erosions and 99 enthesiophytes were detected at baseline. Three new bone erosions but no new enthesiophytes were evident at 5 years. A significant increase in mean (±SD) erosion (0.58 ± 1.50 mm3, P < 0.001) and enthesiophyte (0.47 ± 0.76 mm3, P < 0.001) volume was observed. Erosion and enthesiophyte progression were found in 37/111 (33.3%) and 50/99 (50.5%) lesions, respectively. During this 5-year period, 26 (43%) out of the 60 patients achieved sustained Disease Activity index for PSoriatic Arthritis (DAPSA) low disease activity (LDA) (SDL group, defined as achieving DAPSA-LDA at both baseline and 5 years). Fourteen (23%) out of 60 patients received a TNF inhibitor throughout the 5-year period (TNFi group). Fewer erosions progressed (12/51 [23.5%] vs 25/60 [41.7%], P = 0.047) and the increased in enthesiophyte volume was significantly less (0.28 ± 0.67 vs 0.61 ± 0.80 mm3, P = 0.048) in the SDL group than in the non-SDL group. However, no significant difference between the TNFi and non-TNFi groups was detected in terms of the change in volume or progression of bone erosion and enthesiophyte. CONCLUSION: Damage accrual in terms of bone erosion and enthesiophyte was observed in PsA patients over a period of 5 years despite receiving routine clinical care. Nonetheless, sustained control of disease activity may be able to prevent these bony damages.

Imaging of sacroiliitis: Current status, limitations and pitfalls.

The clinical need to diagnose sacroiliitis at an earlier stage has led to the sacroiliac joints being more frequently imaged, particularly with magnetic resonance imaging (MRI). This review outlines the imaging approach to sacroiliitis, emphasizing the imaging protocols, diagnostic criteria, limitations and potential mimics of MRI examination. The value of imaging-guided intervention in sacroiliac joint disease is also briefly outlined.

Effect of Achieving Minimal Disease Activity on the Progression of Subclinical Atherosclerosis and Arterial Stiffness: A Prospective Cohort Study in Psoriatic Arthritis.

OBJECTIVE: To investigate the effects of achieving minimal disease activity (MDA) on the progression of subclinical atherosclerosis and arterial stiffness in patients with psoriatic arthritis (PsA). METHODS: A total of 101 consecutive patients with PsA were recruited for this prospective cohort study. All patients received protocolized treatment targeting MDA for a period of 2 years. High-resolution carotid ultrasound and arterial stiffness markers were assessed annually. The primary outcome measure was the effect of achieving MDA at 12 months (MDA group) on the progression of subclinical atherosclerosis over a period of 24 months. Secondary objectives were to compare the changes in arterial stiffness markers over 24 months between the MDA and non-MDA groups, as well as the changes in subclinical atherosclerosis and arterial stiffness markers in patients who achieved MDA at each visit from month 12 through month 24 (sustained MDA [sMDA]). RESULTS: Ninety PsA patients (mean ± SD age 50 ± 11 years, 58% male [n = 52]) who completed 24 months of follow-up were included in this analysis. Fifty-seven patients (63%) had achieved MDA at 12 months. Subclinical atherosclerosis and arterial stiffness outcomes were similar between the MDA and non-MDA groups. Forty-one patients (46%) achieved sMDA. As shown by multivariate analysis, achieving sMDA had a protective effect on plaque progression (odds ratio 0.273 [95% confidence interval 0.088-0.846], P = 0.024), and less of an increase in total plaque area, mean intima-media thickness, and augmentation index values after adjustment for covariates. CONCLUSION: Our results support the recommendation that once MDA is achieved, it should ideally be maintained for a prolonged period in order to prevent progression of carotid atherosclerosis and arterial stiffness in patients with PsA.