Philippe Carron

Microscopic gut inflammation in axial spondyloarthritis: a multiparametric predictive model

Objective To assess the rates and explore predictors of microscopic gut inflammation in a cohort of patients with axial and peripheral spondyloarthritis (SpA). Methods Ileocolonoscopy was performed in 65 patients with axial and peripheral SpA from the Gent Inflammatory Arthritis and spoNdylitis cohorT. Histopathological analysis and scoring were performed by an experienced pathologist. Results Overall, 46.2% of the patients with SpA showed microscopic gut inflammation. In axial SpA, the following parameters were independently associated with gut involvement: male sex (OR=8.9, p=0.035); high disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (OR=2.05, p=0.032); restricted spinal mobility measured by the Bath Ankylosing Spondylitis Metrology Index (OR=1.94, p=0.009); and younger age (OR=0.85, p=0.013). No clear association was found for human leucocyte antigen-B27 status, presence of peripheral arthritis, enthesitis, uveitis, psoriasis, intake of non-steroidal anti-inflammatory drugs and family history of SpA. The prevalence of gut inflammation in non-radiographic axial SpA and ankylosing spondylitis was comparable. Conclusions The prevalence of microscopic gut inflammation in SpA remains unaltered over time. Younger age (shorter symptom duration), progressive disease, male sex and higher disease activity are independently associated with microscopic gut inflammation in axial SpA.

Degree of bone marrow oedema in sacroiliac joints of patients with axial spondyloarthritis is linked to gut inflammation and male sex: results from the GIANT cohort

Introduction Bone marrow oedema (BMO) of the sacroiliac joints (SIJs) is a hallmark of axial spondyloarthritis (SpA). However, the relationship between the extent of BMO and disease phenotype is poorly understood. Objective To assess the link between BMO of the SIJs and gut inflammation. We have also evaluated the correlation between BMO and established disease activity parameters. Methods Sixty-eight patients with axial SpA from the Gent Inflammatory Arthritis and spoNdylitis cohorT underwent ileocolonoscopy and MRI of the SIJs. Histopathological analysis and SPondyloArthritis Research Consortium of Canada (SPARCC) scores were performed. Results A significant higher SPARCC score (median (range)) was observed in axial SpA patients showing chronic gut inflammation (16.9 (3.8–68.3)) compared with axial SpA patients showing normal gut histology (9.8 (0.0–45.0); p<0.05). In a multiple linear regression model, we identified, besides chronic gut inflammation (effect size of 11.3, 95% CI (2.1 to 20.4)), male sex (effect size of 10.5, 95% CI (3.3 to 17.8)) to be independently associated to the extent of BMO. There was a low to moderate correlation between the degree of BMO and C-reactive protein(r=0.39, p=0.002) and Ankylosing Spondylitis Disease Activity Score (r=0.35, p=0.007). Conclusions Higher degrees of BMO were observed in patients showing chronic gut inflammation. These data solidify a link between mucosal inflammation and progressive disease in axial SpA.

Reliability and construct validity of ultrasonography of soft tissue and destructive changes in erosive osteoarthritis of the interphalangeal finger joints: a comparison with MRI

Objectives To study the reliability and construct validity of ultrasound in interphalangeal finger joints affected by erosive osteoarthritis (EOA) and non-EOA with MRI as the reference method. Methods 252 joints were examined by ultrasound, conventional radiography and clinical examination. Ultrasound was performed using a high-frequency linear transducer (12×18 MHz). On the same day, magnetic resonance images of 112 joints were obtained on a 3.0 T magnetic resonance unit. The ultrasound and MRI images were re-read independently by other readers unaware of the diagnosis, clinical and other imaging findings. Interobserver reliability was calculated by the percentage of exact agreement obtained and κ statistics. With MRI as the reference method, the sensitivity and specificity of ultrasound in detecting structural (bone erosions and osteophytes) and soft tissue (effusion and grey-scale synovitis) changes in EOA were calculated. Results Ultrasound and MRI were found to be more sensitive in detecting erosions than conventional radiography in EOA. A high agreement between ultrasound and MRI in the assessment of bone erosions (77.7%), osteophytes (75.9%) and synovitis (86.5%) was present. A high percentage of inflammatory changes was found in EOA, and in smaller amount in non-EOA, both confirmed by MRI. Good interobserver reliability of ultrasound was obtained for all variables (all median κ >0.8). Conclusion Grey-scale ultrasound proved to be a reliable and valid imaging technique to assess erosions and soft tissue changes, compared with MRI as a reference method in EOA.

Structural and inflammatory sonographic findings in erosive and non-erosive osteoarthritis of the interphalangeal finger joints

Objective The objectives were: (1) to determine if ultrasound (US) can detect more erosions in erosive osteoarthritis (EOA) of the interphalangeal (IP) joints than conventional radiography (CR); and (2) to explore the frequency of structural and inflammatory findings in EOA and non-EOA. Methods Structural changes and the anatomical phase were scored on CR in IP joints of 31 patients with EOA and 7 patients with non-EOA. Structural and inflammatory changes were scored by US. The frequency of sonographic findings was compared between the anatomical phases and between EOA and non-EOA by generalised estimation equation (GEE) modelling. Results US detected 68 of 72 (94.4%) erosions seen on CR. US detected 45 additional erosive joints in EOA. The frequency of joint effusion and power Doppler signal was similar in EOA compared to non-EOA (p=0.91 and p=0.68, respectively). Statistically significantly more synovitis was present in full erosive phase compared to non-erosive phases in EOA (p=0.04). No differences in inflammatory findings were found between non-erosive phases in EOA and non-EOA. Conclusion US is capable of detecting erosions in radiographic non-erosive phases. The highest frequency of synovitis is present in erosive joints but inflammatory findings are common in all anatomical phases of EOA and non-EOA.

MRI of the SI joints commonly shows non-inflammatory disease in patients clinically suspected of sacroiliitis.

PURPOSE To determine the prevalence of clinically relevant non-inflammatory disease on MRI of the sacroiliac (SI) joints in patients suspected of sacroiliitis. To assess the added value of axial imaging of the pelvis in these patients. METHODS In a retrospective study of 691 patients undergoing MRI of the SI joints from January 2006 to December 2012 for inflammatory back pain the prevalence of sacroiliitis and non-inflammatory disease was recorded. RESULTS In 285 (41%) patients MRI did not show any abnormal findings. In 36% of patients MRI features of sacroiliitis were present. Spinal degenerative changes were the most common non-inflammatory finding in 305 patients (44.1%) and consisted of disc degeneration in 222 (32%) patients, facet joint arthrosis in 58 (8.4%) patients and disc herniation in 25 (3.6%) patients. Hip joint disease in 44 (6.4%) patients, lumbosacral transitional anomaly in 41 (5.9%) patients, SI joint degenerative changes in 25 (3.6%) patients and diffuse idiopathic skeletal hyperostosis in 24 (3.5%) patients were also common. Osteitis condensans ilii in 17 (2.5%) patients, tumour in 11 (1.6%) patients, fracture in 8 (1.2%) patients, infection in 4 (0.6%) patients and acute spondylolysis in 2 patients (0.3%) were less frequently seen. CONCLUSION Our study shows that non-inflammatory disease is more common than true sacroiliitis on MRI of the SI joints in patients with inflammatory type back pain. Axial pulse sequences may demonstrate unexpected findings that remain undetected if only coronal images are obtained. Clinical relevance statement:, MRI of the SI joints may demonstrate conditions that clinically mimic sacroiliitis. Axial imaging of the pelvis may help detect these unexpected findings.

Pathophysiology and Role of the Gastrointestinal System in Spondyloarthritides

Inflammatory bowel disease (IBD) is a well-known extra-articular manifestation in spondyloarthritis (SpA); about 6.5% of patients with ankylosing spondylitis develop IBD during the course of the disease. The pathogenesis of both SpA and IBD is considered to be the result of a complex interplay between the host (genetic predisposition), the immune system and environmental factors, notably microorganisms, leading to a disturbed immune system and chronic inflammation. Over the past decade, the role of tumor necrosis factor inhibition (infliximab, etanercept, adalimumab, golimumab) in improving signs and symptoms and overall quality of life has been well documented in various forms of SpA. Future research will clarify the role of other potential targets.

Brief Report: Six-Week Treatment of Axial Spondyloarthritis Patients With an Optimal Dose of Nonsteroidal Antiinflammatory Drugs: Early Response to Treatment in Signal Intensity on Magnetic Resonance Imaging of the Sacroiliac Joints.

To evaluate the early effect of full‐dose nonsteroidal antiinflammatory drugs (NSAIDs) on the extent and intensity of bone marrow edema of the sacroiliac (SI) joints on magnetic resonance imaging (MRI) in axial spondyloarthritis (SpA).

Scintigraphic detection of TNF-driven inflammation by radiolabelled certolizumab pegol in patients with rheumatoid arthritis and spondyloarthritis

Background Biologicals are the cornerstone for many treatment algorithms in inflammatory arthritis. While tumour necrosis factor (TNF) inhibitors may achieve important responses in ∼50% of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA), a significant fraction of patients are partial or non-responders. We hypothesised that in vivo assessment of TNF by scintigraphy with 99mTc-radiolabelled certolizumab pegol (CZP) might lead to a more ‘evidence-based biological therapy’. Objectives Our goal was to perform a proof-of-concept study of in vivo detection of TNF by immunoscintigraphy of a radiolabelled TNF inhibitor in RA and SpA, and correlate this with clinical, imaging findings and therapeutic outcome. Methods CZP was conjugated with succinimidyl-6-hydrazino-nicotinamide and subsequently radiolabelled with Tc99m. Whole body and static images of hands, feet and sacroiliac joints of 20 patients (5 RA; 15 SpA) were acquired at 3 time points. Immunoscintigraphic findings were scored semiquantitatively. Subsequently, all patients were treated with CZP. Results In peripheral joints, clinically affected joints or abnormal ultrasound findings were observed more frequently (p<0.001) in the scintigraphic-positive group. In patients with axial SpA, bone marrow edema on MRI was detected more frequently (p<0.001) in quadrants with tracer uptake. At the patient level, the odds of a joint remaining tender despite 24 weeks of CZP treatment was significantly smaller in joints with clear tracer uptake as compared with those with no uptake (OR=0.42, p=0.04). Conclusions Immunoscintigraphy with radiolabelled CZP demonstrated both axial and peripheral inflammation, and displayed good correlation with clinical features, conventional imaging and therapy response. Trial registration number NCT01590966; Results.

Peripheral manifestations in spondyloarthritis: relevance for diagnosis, classification and follow-up

Purpose of reviewThe field of spondyloarthritis (SpA) has evolved enormously over the last few years, starting with the advent of biological therapies at the end of the previous millenium. A lot of work has been done to construct valid outcome measures and treatment guidelines based upon the results of pivotal studies with Tumor necrosis factor (TNF)-blocking agents. Most of these trials were performed in well described populations, such as patients suffering from ankylosing spondylitis (AS) or psoriatic arthritis. Recent findingsOver recent years a reappraisal has been done with regard to considering again the full spectrum of diseases belonging to the SpA concept, especially in early disease stages. This effort culminated in the construction of new classification criteria for axial and peripheral SpA. Around the same time, a number of patient registries were set up, allowing the follow-up of patients in order to study the natural evolution of patients classified early. The first data from these cohorts provide interesting information on peripheral joint manifestations such as arthritis, enthesitis or dactylitis. Recognition and monitoring of these manifestations are essential for clinicians in order to provide comprehensive patient care. SummaryThere is a growing interest in the field of SpA to move from rather restricted and longstanding diseases such as AS to a more comprehensive view, encompassing not only inflammatory back pain, but also peripheral arthritis and enthesitis, as well as extra-articular manifestations. The new classification criteria and guidelines for follow-up are applied now in a number of prospective patient registries, and provide us with valuable information on the early disease stages of SpA.

Six‐week treatment of axial spondyloarthritis patients with an optimal dose of NSAIDs: early response to treatment in signal intensity on magnetic resonance imaging of the sacroiliac joints

To evaluate the early effect of full‐dose nonsteroidal antiinflammatory drugs (NSAIDs) on the extent and intensity of bone marrow edema of the sacroiliac (SI) joints on magnetic resonance imaging (MRI) in axial spondyloarthritis (SpA).