Gaëlle Varkas

Brief Report: Dialister as a Microbial Marker of Disease Activity in Spondyloarthritis

Dysbiosis of the intestinal microbiota has been widely established in inflammatory bowel disease (IBD). There is significant clinical and genetic overlap between spondyloarthritis (SpA) and IBD, and up to 50% of all patients with SpA exhibit microscopic signs of bowel inflammation, often bearing particular resemblance to early Crohns disease, a subtype of IBD. This study was undertaken to assess the relationship between intestinal microbial composition, gut histology, and disease activity markers in SpA.

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 α4β7 integrin that modulates gut lymphocyte trafficking. Although an exclusively local effect of vedolizumab could be expected based on the restricted presence of the α4β7–mucosal vascular addressin cell adhesion molecule 1 complex in the gut, past combined success with anti-tumour necrosis factor, and previous demonstration of α4β7 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.

Elevated calprotectin levels reveal bowel inflammation in spondyloarthritis

Introduction Microscopic bowel inflammation is present in up to 50% of patients with spondyloarthritis (SpA) and is associated with more severe disease. Currently no reliable biomarkers exist to identify patients at risk. Calprotectin is a sensitive marker of neutrophilic inflammation, measurable in serum and stool. Objectives To assess whether serum and faecal calprotectin in addition to C-reactive protein (CRP) can be used to identify patients with SpA at risk of microscopic bowel inflammation. Methods Serum calprotectin and CRP were measured in 125 patients with SpA. In 44 of these patients, faecal samples were available for calprotectin measurement. All 125 patients underwent an ileocolonoscopy to assess the presence of microscopic bowel inflammation. Results Microscopic bowel inflammation was present in 53 (42.4%) patients with SpA. Elevated serum calprotectin and CRP were independently associated with microscopic bowel inflammation. Faecal calprotectin was also significantly higher in patients with microscopic bowel inflammation. Patients with CRP and serum calprotectin elevated had a frequency of bowel inflammation of 64% vs 25% in patients with low levels of both. When either CRP or serum calprotectin was elevated, the risk was intermediate (40%) and measuring faecal calprotectin provided further differentiation. Hence we suggest a screening approach where initially serum calprotectin and CRP are assessed and, if necessary, faecal calprotectin. The model using this scenario provided an area under the ROC curve of 74.4% for detection of bowel inflammation. Conclusions Calprotectin measurements in stool and serum, in addition to CRP, may provide a promising strategy to identify patients with SpA at risk of bowel inflammation and could play a role in overall patient stratification.

Relevance of the gut/joint axis for the management of spondyloarthritis in daily clinical practice.

Purpose of reviewThirty years ago, the concept of microscopic gut inflammation in spondyloarthritis (SpA) was established. Over the past decade, there has been tremendous progress in the earlier diagnosis of SpA. In addition, it has been suggested that, because of improved hygiene over the past years, exposure to microorganisms has changed, leading to a shift in diseases, for example, a decreased incidence of reactive arthritis. It is therefore necessary to re-establish the role of gut inflammation in SpA. Recent findingsThe prevalence of microscopic gut inflammation could be confirmed in c. 50% of patients with early axial and/or peripheral SpA. More importantly, a predictive model could be developed linking gut inflammation with clinical factors, that is, higher disease activity, extensive sacroiliac bone marrow edema, and progressive disease. In addition, there is increasing evidence indicating that the presence or absence of gut inflammation in SpA may influence therapeutic decision-making in the future. A clear demonstration of this is the different efficacy of IL-17 blockade in Crohns disease versus SpA. SummaryMicroscopic gut inflammation is present in almost 50% of SpA patients and appears relevant for prognosis and therapeutic decision-making. SpA patients with the chronic type of gut inflammation seem to have a less favorable disease course. It is therefore conceivable that assessment of gut inflammation should be included in future models for risk stratification of SpA.

Spondyloarthritis and inflammatory bowel disease

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.ZusammenfassungSpondylarthritiden (SpA) und chronisch entzündliche Darmerkrankungen (CED) sind chronische, idiopathische inflammatorische Störungen der axialen und peripheren Gelenke bzw. des Intestinaltrakts und betreffen etwa 10% der Bevölkerung. Es gibt klinische und genetische Hinweise auf Überlappungen in der Pathogenese dieser beiden nosologischen Entitäten, doch ihre Behandlungen konfligieren bisweilen. Nichtsteroidale Antiphlogistika sind zwar hilfreich in der Behandlung der SpA, doch sie werden auch als mögliche Risikofaktoren für CED-Schübe angesehen. Ferner ist Etanercept, ein bei SpA gegebener löslicher TNF-Rezeptorblocker, nicht wirksam bei CED. Da SpA-Patienten häufig mikroskopisch sichtbare Darmentzündungen entwickeln, ist es wichtig, den Einfluss auf den Erkrankungsprogress oder sogar auf das Therapieansprechen zu verstehen. In diesem Zusammenhang ist weitere Forschung unbedingt erforderlich.

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).

Anti-TNF-induced remission in very early peripheral spondyloarthritis: the CRESPA study

Objective To evaluate the efficacy and safety of golimumab to induce clinical remission in patients with very early, active peripheral spondyloarthritis (pSpA). Methods Clinical REmission in peripheral SPondyloArthritis is a monocentric study of golimumab treatment in patients with pSpA. All patients fulfilled the Assessment of SpondyloArthritis international Society classification criteria for pSpA, with a symptom duration ≤12 weeks. Patients were randomised 2:1 to receive golimumab 50 mg every 4 weeks or matching placebo for 24 weeks. The primary end point was the percentage of patients achieving clinical remission at week 24, defined as absence of arthritis, enthesitis and dactylitis. Secondary end points included joint and enthesis counts, patient-reported outcomes, erythrocyte sedimentation rate and C reactive protein. From week 12, non-responders were allowed to receive rescue medication with golimumab. Adverse events were recorded. Results 60 patients were randomised with similar baseline characteristics. At week 24, a significantly higher percentage of patients receiving golimumab achieved clinical remission compared with placebo (75% (30/40) vs 20% (4/20); p<0.001). At week 12, similar results were observed (70% (28/40) vs 15% (3/20); p<0.001). All secondary end points were met at week 24. Rescue medication was necessary in 50% in the placebo group opposed to only 10% in the golimumab arm. Rates of adverse events were low and similar in both groups. Conclusions Markedly high remission induction rates were noted with golimumab in very early pSpA. Of interest, in placebo-treated patients, very low spontaneous remission rates were observed. Trial registration number NCT01426815; Results.

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.ZusammenfassungSpondylarthritiden (SpA) und chronisch entzündliche Darmerkrankungen (CED) sind chronische, idiopathische inflammatorische Störungen der axialen und peripheren Gelenke bzw. des Intestinaltrakts und betreffen etwa 10% der Bevölkerung. Es gibt klinische und genetische Hinweise auf Überlappungen in der Pathogenese dieser beiden nosologischen Entitäten, doch ihre Behandlungen konfligieren bisweilen. Nichtsteroidale Antiphlogistika sind zwar hilfreich in der Behandlung der SpA, doch sie werden auch als mögliche Risikofaktoren für CED-Schübe angesehen. Ferner ist Etanercept, ein bei SpA gegebener löslicher TNF-Rezeptorblocker, nicht wirksam bei CED. Da SpA-Patienten häufig mikroskopisch sichtbare Darmentzündungen entwickeln, ist es wichtig, den Einfluss auf den Erkrankungsprogress oder sogar auf das Therapieansprechen zu verstehen. In diesem Zusammenhang ist weitere Forschung unbedingt erforderlich.

Dialister as microbial marker of disease activity in spondyloarthritis.

Dysbiosis of the intestinal microbiota has been widely established in inflammatory bowel disease (IBD). There is significant clinical and genetic overlap between spondyloarthritis (SpA) and IBD, and up to 50% of all patients with SpA exhibit microscopic signs of bowel inflammation, often bearing particular resemblance to early Crohns disease, a subtype of IBD. This study was undertaken to assess the relationship between intestinal microbial composition, gut histology, and disease activity markers in SpA.

ASAS definition for sacroiliitis on MRI in SpA: applicable to children?

BackgroundThe Assessment of Spondyloarthritis International Society (ASAS) definition for a ‘positive’ Magnetic Resonance Imaging (MRI) for sacroiliitis is well studied and validated in adults, but studies about the value of this definition in children are lacking. The aim of this study is to evaluate whether the adult ASAS definition of a positive MRI of the sacroiliac joints can be applied to children with a clinical suspicion of Juvenile Spondyloarthritis (JSpA).MethodsTwo pediatric musculoskeletal radiologists blinded to clinical data independently retrospectively reviewed sacroiliac (SI) joint MRI in 109 children suspected of sacroiliitis. They recorded global impression (sacroiliitis yes/no) and whether the adult ASAS definition for sacroiliitis was met at each joint. This was compared to gold-standard clinical diagnosis of JSpA. Additionally, MRI were scored according to’adapted’ ASAS definitions including other features of sacroiliitis on MRI.ResultsJSpA was diagnosed clinically in 47/109 (43%) patients. On MRI, sacroiliitis was diagnosed by global assessment in 30/109 patients, of whom 14 also fulfilled ASAS criteria. No patients with negative global assessment for sacroiliitis fulfilled ASAS criteria. Sensitivity (SN) for JSpA was higher for global assessment (SN = 49%) than for ASAS definition (SN = 26%), but the ASAS definition was more specific (SP = 97% vs. 89%). Modifying adult ASAS criteria to allow bone marrow edema (BME) lesions seen on only one slice, synovitis or capsulitis, increased SN to 36%, 32% and 32% respectively, only slightly lowering SP. Including structural lesions increased SN to 28%, but lowered specificity to 95%.ConclusionThe adult ASAS definition for sacroiliitis has low sensitivity in children. A pediatric-specific definition of MRI-positive sacroiliitis including BME lesions visible on one slice only, synovitis and/or capsulitis may improve diagnostic utility, and increase relevance of MRI in pediatric rheumatology practice.