An induction or flare of arthritis and/or sacroiliitis by vedolizumab in inflammatory bowel disease: a case series.

BACKGROUND: In inflammatory bowel disease (IBD), a new biological therapy has recently been approved. Vedolizumab is a humanised IgG1 monoclonal antibody to α4ß7 integrin that modulates gut lymphocyte trafficking. Although an exclusively local effect of vedolizumab could be expected based on the restricted presence of the α4ß7-mucosal vascular addressin cell adhesion molecule 1 complex in the gut, past combined success with anti-tumour necrosis factor, and previous demonstration of α4ß7 integrin in the joint, led to the expectation of a therapeutic efficacy in spondyloarthritis. Nonetheless, the effect of vedolizumab on extraintestinal manifestations-and especially the joint-has not been reported so far. CASE REPORT: A series of five patients with IBD who were treated with vedolizumab and promptly developed new onset or exacerbation of sacroiliitis or arthritis are reported. CONCLUSIONS: Vedolizumab therapy does not seem to show any efficacy in and might even induce arthritis and/or sacroiliitis. However, larger cohort studies are needed to provide information on the prevalence, the evolution and underlying mechanism.

Diagnostic value of pelvic enthesitis on MRI of the sacroiliac joints in spondyloarthritis.

OBJECTIVE: To determine the prevalence and diagnostic value of pelvic enthesitis on MRI of the sacroiliac (SI) joints in spondyloarthritis (SpA). MATERIALS AND METHODS: A retrospective study in 444 patients aged 17-45 years old with MRI of the SI joints and with clinically suspected sacroiliitis was performed. Patients were classified as having SpA if they fulfilled the Assessment of Spondyloarthritis International Society (ASAS) criteria. Pelvic enthesitis on MRI was correlated with the final diagnosis. Sensitivity, specificity, positive and negative likelihood ratio (LR) and predictive values (PV) of pelvic enthesitis for the diagnosis of SpA were calculated. RESULTS: MRI showed pelvic enthesitis in 24.4 % of patients with SpA and in 7.1 % of patients without SpA. Presence of any enthesitis had sensitivity, specificity, LR+, LR-, PPV and NPV of 24.4 %, 92.9 %, 3.45, 0.81, 69.4 % and 65.2 % for the diagnosis of SpA, respectively. The most commonly affected entheses were the longitudinal ligament insertion (4.5 %), the retroarticular ligaments (4.1 %) and the pubic symphysis (4.1 %). The sites of enthesitis with the highest PPV for SpA were the iliac crest/wing (85.7 %) and the retroarticular ligaments (81.3 %). CONCLUSION: Nearly one fourth of SpA patients with suspected sacroiliitis showed pelvic enthesitis on MRI. Such pelvic enthesitis has a high specificity for the diagnosis of spondyloarthritis. KEY POINTS: • Enthesitis is the primary clinical feature of spondyloarthritis. • Magnetic resonance imaging of the sacroiliac joints can demonstrate pelvic enthesitis. • Pelvic enthesitis has a high specificity for the diagnosis of spondyloarthritis.

A cross-sectional study on the prevalence of metabolic syndrome in psoriasis compared to psoriatic arthritis.

BACKGROUND: Increasing epidemiological evidence suggests associations between psoriasis, psoriatic arthritis (PsA) and metabolic disease. Elucidating the complex relationship between these comorbidities may have important management implications. OBJECTIVE: The aim of this study was to examine the difference in prevalence of metabolic disease burden between patients with psoriasis who lack arthritic manifestations (PsO) and PsA patients. METHODS: We performed a cross-sectional study in 123 patients with PsO and PsA. Metabolic syndrome was defined using the new criteria developed by the International Diabetes Foundation (IDF) in 2004. Therefore, clinical examination and standard survey were performed and fasting blood samples were collected. RESULTS: One hundred and four patients were analysed, of which 49 were PsO and 55 were PsA patients. We found that prevalence of the metabolic syndrome according to the IDF criteria was significantly higher in the PsO (44.9%) compared with the PsA group (25.5%) (P = 0.037). Looking closer at the individual components of the metabolic syndrome, this difference can mainly be attributed to the significantly higher prevalence of abdominal obesity in PsO (83.7%) vs. PsA (65.5%) (P = 0.034). For other individual components of the metabolic syndrome such as triglycerides, high-density lipoproteins, hypertension and plasma glucose, we could not show statistically significant differences between the groups. CONCLUSION: Metabolic syndrome is more prevalent in patients with PsO than in PsA patients, mainly determined by the higher prevalence of abdominal obesity in PsO compared with PsA group.

Osteoarticular manifestations: specific treatments and/or treating intestinal disease?

Osteoarticular manifestations in inflammatory bowel diseases (IBD) belong to the concept of spondyloarthritis (SpA) including an axial and peripheral SpA according to predominant symptoms (inflammatory back pain vs. peripheral arthritis and enthesopathy). Careful examination of sacroiliac joints on MRI plays a crucial role in the recognition of an early axial SpA in young patients with inflammatory back pain and spinal inflammation on MRI but without structural changes on radiography (non-rx SpA). In this early form of SpA, chronic gut inflammation was already found in about 30% of patients. Moreover, more pronounced bone marrow edema was found in patients with axial SpA and chronic gut inflammation. Identification of a therapeutic window in patients with early gut and spine inflammation is important since anti-TNF suppresses inflammation and seems to prevent evolution to structural changes. Shared genetic factors probably predispose to both diseases. Careful analysis of the effect of medication on gut and spine inflammation in SpA and IBD patients is recommended in order to find new therapeutic agents.

Spondyloarthritis and inflammatory bowel disease. Comorbidity and treatment implications.

Spondyloarthritides (SpA) and inflammatory bowel disease (IBD) are chronic, idiopathic inflammatory disorders of the axial and peripheral joints and the intestinal tract, respectively, affecting up to 1 % of the population. There is clinical and genetic evidence supporting some degree of overlap between the pathogenesis of these two entities. Nevertheless, their treatment is at times conflicting. NSAIDs, although useful in SpA, are considered to be possible risk factors for flares in IBD. Moreover, etanercept, a soluble TNF receptor blocker used in SpA, is ineffective in IBD. As patients with SpA often develop microscopic gut inflammation, it is important to understand the impact on disease progression or even therapeutic response. Further research is mandatory in this regard.

[Early referral of first line patients suspected of axial spondyloarthritis: the Belgian results of the RADAR study]. / Renvoi précoce au spécialiste de patients avec une suspicion de spondyloarthropathie axiale en première ligne: les résultats belges de l'étude RADAR.

Currently, there is a 5 to 7 years gap between the first symptoms and the diagnosis of ankylosing spondylitis. A better patient referral might reduce this gap and accelerate the adequate treatment implementation. The study objective was to compare 2 referral strategies used in first line. In Belgium, 208 referral physicians assigned to 16 rheumatology centres were randomized to refer chronic back pain patients (with onset <45 years) using 1 of the 2 referral strategies: Strategy 1 :1 of 3 criteria (inflammatory back pain, HLA-B27, sacroiliitis on imaging); or Strategy 2: 2 of6 criteria (IBP inflammatory back pain, HLA-B27, sacroiliitis, family history, good response to NSAIDs, extra-articular manifestations). Among the 141 referred patients with strategy 1 and 2, 26.0 and 36.9% respectively were diagnosed with Axial Spondylarthritis (SpA). Inflammatory back pain, sacroiliitis and good respond to NSAIDs were the most frequently used criteria (92.9 %, 36.2 % and 33.3% respectively). This study emphasizes the high prevalence of undiagnosed axial SpA in patients with chronic back pain and stressed the necessity to increase awareness of the disease.

Subclinical gut inflammation in spondyloarthritis is associated with a pro-angiogenic intestinal mucosal phenotype.

BACKGROUND: Vascular endothelial growth factor (VEGF-A) and placental growth factor (PlGF) are major regulators of pathological angiogenesis, which is a prominent feature of both Crohn's disease (CD) and peripheral synovitis in spondyloarthritis. OBJECTIVE: To investigate the presence of VEGF-A and PlGF in the gut of spondyloarthritis patients and to link this finding with subclinical gut inflammation in these patients. METHODS: Intestinal biopsies from healthy controls, CD patients, spondyloarthritis patients with or without subclinical gut inflammation and rheumatoid arthritis (RA) patients were stained for VEGF-A, PlGF, CD31 and vascular cell adhesion molecule 1 (VCAM-1) and digitally analysed. RESULTS: Spondyloarthritis patients with subclinical gut inflammation had markedly increased intestinal VEGF-A expression (p<0.001), mucosal vascularisation (p<0.001) and VCAM-1 expression (p<0.01) compared with healthy controls and RA patients, which, unlike in CD patients, was also seen when the gut inflammation was in a quiescent state. PlGF expression was highly increased in the subclinically inflamed gut of spondyloarthritis (p<0.01 compared with healthy controls), but not at all in CD. CONCLUSION: A pro-angiogenic intestinal phenotype is observed in spondyloarthritis patients with quiescent chronic gut inflammation. This favours an environment for enhanced trafficking of immune cells in this subpopulation.

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.

OBJECTIVE: 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). METHODS: A single-center, 6-week study of a cohort of consecutive patients with clinically suspected axial SpA was conducted. A total of 117 patients were screened. Forty patients who were diagnosed as having axial SpA and had presented with a positive MRI of the SI joints as defined by the Assessment of SpondyloArthritis international Society (ASAS) criteria were considered for a followup MRI after 6 weeks of an optimal dose of NSAIDs. Twenty patients completed the study. Disease activity was monitored by determining the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score every 2 weeks and the Bath Ankylosing Spondylitis Functional Index score at baseline and week 6. NSAID intake was assessed by the ASAS NSAID index. Primary end points were improvement in bone marrow edema of the SI joints on MRI and BASDAI response at week 6. RESULTS: Approximately one-third of eligible patients newly diagnosed as having axial SpA were unable to continue the full-dose NSAID schedule. The median NSAID index was 97% in patients who completed the study. There was a reduction of 1.1 units (10.5%) in mean Spondyloarthritis Research Consortium of Canada (SPARCC) scores at week 6 in comparison to baseline (P = 0.032). Overall, only 30% of the patients (6 of 20) had a minimal clinically important difference of ≥2.5 in SPARCC score. However, 80% of the patients displayed high-intensity lesions on STIR images at baseline, which decreased significantly at week 6 (P = 0.011). There was a significant decrease in the relative intensity of the region of interest (P = 0.007) and a mean decrease of 0.6 in the BASDAI score per 2 weeks of therapy (P = 0.001). Only 29.4% of the patients met the BASDAI criteria for 50% improvement (BASDAI50) at week 6. CONCLUSION: Our findings indicate a high level of dropout among patients receiving full-dose NSAID therapy in daily practice. In those who tolerated NSAID therapy, there was no clinically relevant decrease in SPARCC scores and low BASDAI50 response. However, we found a decrease in signal intensity of bone marrow edema of the SI joints as an early response to 6 weeks of optimal NSAID therapy in patients newly presenting with axial SpA.

Effects of CO2 enrichment, leaf position and clone on stomatal index and epidermal cell density in poplar (Populus).

The effects of CO2 , enrichment and leaf position on stomatal characteristics (stomatal density, stomatal index and stomatal pore length) and epidermal cell density were examined for two different Populus clones, Beaupre and Robusta, grown from cuttings in open-top chambers under ambient and elevated atmospheric CO2 conditions. Both clones had amphistomatous leaves, and stomatal density was significantly larger on the abaxial leaf surface than on the adaxial. Significant interactions between CO2 enrichment, leaf position and clone were observed for most stomatal and epidermal characteristics. A significant reduction of the number of stomata mm-2 under elevated CO2 was observed in expanding leaves near the upper portion of the plant for both leaf surface sides and in both clones. For the abaxial leaf side only, this reduction under elevated CO2 , was accompanied by a similar reduction of the stomatal index in both clones. In mature leaves on the middle and lower portion of the plants, there was no significant effect of the CO2 treatment on stomatal density. In young, expanding leaves near the upper part of the plant there were significant interactions between the CO2 treatment and leaf surface side for epidermal cell density. The latter increased under elevated CO2 at the abaxial leaf surface, but decreased at the adaxial surface on the upper part of the plant. Total epidermal cell numbers of mature, fully expanded leaves increased under elevated CO2 , in both clones. The observation that interactions with leaf age and/or leaf position significantly confound the CO2 , treatment effect on stomatal and epidermal cell densities, might contribute to the elucidation of the problem of the phenomenon of stomatal density reduction under elevated atmospheric CO2 .

How sensitive and specific are MRI features of sacroiliitis for diagnosis of spondyloarthritis in patients with inflammatory back pain?

OBJECTIVE: To determine the sensitivity and specificity of MRI features of sacroiliitis in spondyloarthritis (SpA). MATERIALS AND METHODS: A retrospective study reviewed MRI of the sacroiliac (SI) joints in 517 patients with inflammatory back pain. Sensitivity, specificity, positive and negative likelihood ratios of active and structural lesions of sacroiliitis with final clinical diagnosis as golden standard was calculated. RESULTS: MRI showed active inflammation in 42% of patients (bone marrow oedema (BMO) (41.5%), capsulitis (3.3%), enthesitis (2.5%)) and structural changes in 48.8% of patients (erosion (25%), fat infiltration (31.6%), sclerosis (32%) and ankylosis (7.6%)). BMO was the MRI feature with the highest sensitivity (65.1%) for diagnosis of SpA. Capsulitis (99%), enthesitis (98.4%), ankylosis (97.4%) and erosion (94.8%) had a high specificity for diagnosis of SpA, whereas BMO (74.3%), sclerosis (75.8%) and fat infiltration (84.0%) were less specific. BMO concomitant with enthesitis, capsulitis or erosions increased the specificity. Concomitant presence of BMO and sclerosis or fat infiltration decreased the specificity. CONCLUSION: BMO is moderately sensitive and specific for diagnosis of SpA in patients with inflammatory back pain. BMO concomitant with enthesitis, capsulitis, ankylosis or erosion increases the specificity. Concomitant fat infiltration or sclerosis decreases the specificity for diagnosis of SpA. Of all lesions, erosion had by far the highest positive likelihood ratio for diagnosis of SpA.

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.