Multimodal Imaging of Structural Damage and Inflammation in Psoriatic Arthritis: A comparison of DMARD-Naive and DMARD-Failure Patients.

OBJECTIVES: To compare inflammatory and structural differences in active Psoriatic Arthritis (PsA) between disease-modifying antirheumatic drug (DMARD)-naive and DMARD-failure patients using diverse imaging approaches for future analyses. Additionally, to explore the influence of patient characteristics (clinical and demographic variables) on imaging findings. METHODS: Of the 80 patients included from the first cohort of the ongoing multicentre TOFA-PREDICT trial, 40 were DMARD-naive and 40 were DMARD-failure (csDMARD failure; 1 prior bDMARD excluding etanercept was allowed), all meeting classification criteria for PsA with a minimum disease duration of eight weeks. Baseline conventional radiographs of hands and feet, MRIs of both ankles, and whole-body 18F-FDG PET/CT were evaluated for inflammatory and structural imaging parameters, including Sharp-van der Heijde (SHS), Heel Enthesitis Magnetic Resonance Imaging Scoring System (HEMRIS) and Deauville synovitis scoring. Differences between groups and the influence of patient characteristics were examined with multiple linear regression. RESULTS: At baseline, patient characteristics were similar between groups. Imaging parameters showed limited inflammation and structural damage. Inflammatory imaging parameters were not significantly different (p> 0.200). Among structural parameters, only HEMRIS Achilles tendon structural damage was significantly different (p= 0.024, R2=0.071) and, SHS Joint Space Narrowing was not statistically significant (p= 0.050, R2=0.048) with higher values for both in DMARD-failures. After correction of patient characteristics, these differences in imaging disappeared (both p> 0.600). CONCLUSION: At baseline, PsA patient groups were comparable concerning structural and inflammatory imaging parameters, especially after correcting for patient characteristics. Thus, DMARD-naive and DMARD-failure patient groups may be combined in future PsA progression and treatment decision studies. CLINICAL TRIAL REGISTRATION NUMBER: EudraCT: 2017-003900-28.

Diffuse idiopathic skeletal hyperostosis is associated with incident stroke in patients with increased cardiovascular risk.

OBJECTIVES: Earlier retrospective studies have suggested a relation between DISH and cardiovascular disease, including myocardial infarction. The present study assessed the association between DISH and incidence of cardiovascular events and mortality in patients with high cardiovascular risk. METHODS: In this prospective cohort study, we included 4624 patients (mean age 58.4 years, 69.6% male) from the Second Manifestations of ARTerial disease cohort. The main end point was major cardiovascular events (MACE: stroke, myocardial infarction and vascular death). Secondary endpoints included all-cause mortality and separate vascular events. Cause-specific proportional hazard models were used to evaluate the risk of DISH on all outcomes, and subdistribution hazard models were used to evaluate the effect of DISH on the cumulative incidence. All models were adjusted for age, sex, body mass index, blood pressure, diabetes, non-HDL cholesterol, packyears, renal function and C-reactive protein. RESULTS: DISH was present in 435 (9.4%) patients. After a median follow-up of 8.7 (IQR 5.0-12.0) years, 864 patients had died and 728 patients developed a MACE event. DISH was associated with an increased cumulative incidence of ischaemic stroke. After adjustment in cause-specific modelling, DISH remained significantly associated with ischaemic stroke (HR 1.55; 95% CI: 1.01, 2.38), but not with MACE (HR 0.99; 95% CI: 0.79, 1.24), myocardial infarction (HR 0.88; 95% CI: 0.59, 1.31), vascular death (HR 0.94; 95% CI: 0.68, 1.27) or all-cause mortality (HR 0.94; 95% CI: 0.77, 1.16). CONCLUSION: The presence of DISH is independently associated with an increased incidence and risk for ischaemic stroke, but not with MACE, myocardial infarction, vascular death or all-cause mortality.

Pulmonary Computed Tomography Screening Frequency in Primary Antibody Deficiency.

BACKGROUND: Patients with primary antibody deficiency (PAD) frequently suffer from pulmonary complications, associated with severe morbidity and mortality. Hence, regular pulmonary screening by computed tomography (CT) scanning is advised. However, predictive risk factors for pulmonary morbidity are lacking. OBJECTIVE: To identify patients with PAD at risk for pulmonary complications necessitating regular CT screening. METHODS: A retrospective, longitudinal cohort study of patients with PAD (median follow-up 7.4 [2.3-14.8] years) was performed. CTs were scored using the modified Brody-II scoring system. Clinical and laboratory parameters were retrospectively collected. Potential risk factors were identified by univariate analysis when P < .2 and confirmed by multivariable logistic regression when P < .05. RESULTS: The following independent risk factors for progression of airway disease (AD) were identified: (1) diagnosis of X-linked agammaglobulinemia (XLA), (2) recurrent airway infections (2.5/year), and (3) the presence of AD at baseline. Signs of AD progression were detected in 5 of 11 patients with XLA and in 17 of 80 of the other patients with PAD. Of the 22 patients who progressed, 17 had pre-existent AD scores ≥7.0%. Increased AD scores were related to poorer forced expiratory volume in 1 second values and chronic cough. Common variable immunodeficiency and increased CD4 effector/memory cells were risk factors for an interstitial lung disease (ILD) score ≥13.0%. ILD ≥13.0% occurred in 12 of 80 patients. Signs of ILD progression were detected in 8 of 80 patients, and 4 of 8 patients showing progression had pre-existent ILD scores ≥13.0%. CONCLUSION: We identified risk factors that distinguished patients with PAD at risk for AD and ILD presence and progression, which could guide future screening frequency; however, independent and preferably prospective validation is needed.

Patients with diffuse idiopathic skeletal hyperostosis have an increased burden of thoracic aortic calcifications.

Objectives: DISH has been associated with increased coronary artery calcifications and incident ischaemic stroke. The formation of bone along the spine may share pathways with calcium deposition in the aorta. We hypothesized that patients with DISH have increased vascular calcifications. Therefore we aimed to investigate the presence and extent of DISH in relation to thoracic aortic calcification (TAC) severity. Methods: This cross-sectional study included 4703 patients from the Second Manifestation of ARTerial disease cohort, consisting of patients with cardiovascular events or risk factors for cardiovascular disease. Chest radiographs were scored for DISH using the Resnick criteria. Different severities of TAC were scored arbitrarily from no TAC to mild, moderate or severe TAC. Using multivariate logistic regression, the associations between DISH and TAC were analysed with adjustments for age, sex, BMI, diabetes, smoking status, non-high-density lipoprotein cholesterol, cholesterol lowering drug usage, renal function and blood pressure. Results: A total of 442 patients (9.4%) had evidence of DISH and 1789 (38%) patients had TAC. The prevalence of DISH increased from 6.6% in the no TAC group to 10.8% in the mild, 14.3% in the moderate and 17.1% in the severe TAC group. After adjustments, DISH was significantly associated with the presence of TAC [odds ratio (OR) 1.46 [95% CI 1.17, 1.82)]. In multinomial analyses, DISH was associated with moderate TAC [OR 1.43 (95% CI 1.06, 1.93)] and severe TAC [OR 1.67 (95% CI 1.19, 2.36)]. Conclusions: Subjects with DISH have increased TACs, providing further evidence that patients with DISH have an increased burden of vascular calcifications.

Visceral Adipose Tissue and Different Measures of Adiposity in Different Severities of Diffuse Idiopathic Skeletal Hyperostosis.

BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) is associated with both obesity and type 2 diabetes. Our objective was to investigate the relation between DISH and visceral adipose tissue (VAT) in particular, as this would support a causal role of insulin resistance and low grade inflammation in the development of DISH. METHODS: In 4334 patients with manifest vascular disease, the relation between different adiposity measures and the presence of DISH was compared using z-scores via standard deviation logistic regression analyses. Analyses were stratified by sex and adjusted for age, systolic blood pressure, diabetes, non-HDL cholesterol, smoking status, and renal function. RESULTS: DISH was present in 391 (9%) subjects. The presence of DISH was associated with markers of adiposity and had a strong relation with VAT in males (OR: 1.35; 95%CI: 1.20-1.54) and females (OR: 1.43; 95%CI: 1.06-1.93). In males with the most severe DISH (extensive ossification of seven or more vertebral bodies) the association between DISH and VAT was stronger (OR: 1.61; 95%CI: 1.31-1.98), while increased subcutaneous fat was negatively associated with DISH (OR: 0.65; 95%CI: 0.49-0.95). In females, increased subcutaneous fat was associated with the presence of DISH (OR: 1.43; 95%CI: 1.14-1.80). CONCLUSION: Markers of adiposity, including VAT, are strongly associated with the presence of DISH. Subcutaneous adipose tissue thickness was negatively associated with more severe cases of DISH in males, while in females, increased subcutaneous adipose tissue was associated with the presence of DISH.