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Dysregulated IL-23/IL-17 responses have been linked to psoriatic arthritis and other forms of spondyloarthritides (SpA). RORγt, the key Thelper17 (Th17) cell transcriptional regulator, is also expressed by subsets of innate-like T cells, including invariant natural killer T (iNKT) and γδ-T cells, but their contribution to SpA is still unclear. Here we describe the presence of particular RORγt + T-bet lo PLZF − iNKT and γδ-hi T cell subsets in healthy peripheral blood. RORγt + iNKT and γδ-hi T cells show IL-23 mediated Th17-like immune responses and were clearly enriched within inflamed joints of SpA patients where they act as major IL-17 secretors. SpA derived iNKT and γδ-T cells showed unique and Th17-skewed phenotype and gene expression profiles. Strikingly, RORγt inhibition blocked γδ17 and iNKT17 cell function while selectively sparing IL-22 + subsets. Overall, our findings highlight a unique diversity of human RORγt + T cells and underscore the potential of RORγt antagonism to modulate aberrant type 17 responses. The role of innate T cell subsets in the pathogenesis of spondyloarthritis (SpA) is not well understood. Here, the authors examine the role of invariant natural killer T (iNKT) and γδ-T cells in SpA and show that disease-derived iNKT and γδ-T cells have unique and Th17-skewed phenotype and gene expression profiles within inflamed joints.

ObjectivesBone marrow oedema (BMO) on MRI of sacroiliac joints (SIJs) represents a hallmark of axial spondyloarthritis (SpA), yet such lesions may also occur under augmented mechanical stress in healthy subjects. We therefore sought to delineate the relationship between pregnancy/delivery and pelvic stress through a prospective study with repeated MRI. Results were matched with maternal, child and birth characteristics.MethodsThirty-five women underwent a baseline MRI-SIJ within the first 10 days after giving birth. MRI was repeated after 6 months and, if positive for sacroiliitis according to the Assessment of SpondyloArthritis International Society (ASAS) definition, after 12 months. BMO and structural lesions were scored by three trained readers using the Spondyloarthritis Research Consortium of Canada (SPARCC) method.ResultsSeventy-seven per cent of the subjects (27/35) displayed sacroiliac BMO immediately postpartum, 60% fulfilled the ASAS definition of a positive MRI. After 6 months, 46% of the subjects (15/33) still showed BMO, representing 15% (5/33) with a positive MRI. After 12 months, MRI was still positive in 12% of the subjects (4/33). Few structural lesions were detected. Intriguingly, in this study, the presence of BMO was related to a shorter duration of labour and lack of epidural anaesthesia.ConclusionA surprisingly high prevalence of sacroiliac BMO occurs in women immediately postpartum. Our data reveal a need for a waiting period of at least 6 months to perform an MRI-SIJ in postpartum women with back pain. This study also underscores the importance of interpreting MRI-SIJ findings in the appropriate clinical context.

ObjectiveTo determine the prevalence of sacroiliac joint variants in patients with axial spondyloarthritis (axSpA) using MRI-based synthetic CT images and to evaluate their relationships with the presence of bone marrow edema, as this may potentially complicate diagnosing active sacroiliitis on MRI in patients with suspected axSpA.Methods172 patients were retrospectively included. All patients underwent MRI because of clinical suspicion of sacroiliitis. The diagnosis of axSpA was made by a tertiary hospital rheumatologist. Two readers independently determined the presence of bone marrow edema and the presence of one or more of the nine known sacroiliac joint (SIJ) variants.ResultsSIJ variants were common in axSpA patients (82.9%) and the non-SpA group (85.4%); there were no significant differences in prevalence. Bone marrow edema was frequently found in axSpA (86.8%) and non-SpA patients (34%). AxSpA patients with SIJ variants (except for accessory joint) demonstrated 4 to 10 times higher odds for bone marrow edema, however not statistically significant. The more variants were present in this group, the higher the chance of bone marrow edema. However, some multicollinearity cannot be excluded, since bone marrow edema is very frequent in the axSpA group by definition.ConclusionSIJ variants are common in axSpA and non-SpA patients. SIJ variants were associated with higher prevalence of bone marrow edema in axSpA patients, potentially due to altered biomechanics, except for accessory joint which may act as a stabilizer.

IntroductionBone marrow oedema (BME) on MRI of the sacroiliac joints (SIJ) commonly occurs after pregnancy. Our goal was to assess the evolution of BME over a period of 5 years and the potential development of structural lesions.MethodsMRI-SIJ was performed after an uncomplicated vaginal delivery, with a follow-up 5 years later, evaluating both inflammatory and structural lesions.Results19 women were assessed. Mean age was 35.3 years, with median body mass index of 20.8. Six subjects reported back pain, of which only one reported inflammatory back pain (IBP). No association was found between IBP and Spondyloarthritis Research Consortium of Canada (SPARCC) score (p=0.24), nor with a positive MRI according to the Assessment of SpondyloArthritis international Society (ASAS) definition at baseline (p=0.64). Thirty-two percent (6/19) presented with BME after 5 years, 3 of whom met the ASAS definition of a positive MRI-SIJ, irrespective of subsequent pregnancies. A new delivery during follow-up was linked to the total number of structural lesions at year 5, whereas mean weight gain across all pregnancies correlated with sclerosis. Sclerosis and erosions were more frequently detected by synthetic CT compared with T1-weighted MRI.ConclusionsIn postpartum women, no significant development of structural MRI lesions was observed 5 years after a single delivery, despite the presence of BME in a significant number of individuals postpartum and at follow-up. These results support the hypothesis that, unlike BME in SpA, childbirth-related mechanical stress-induced BME does not lead to structural lesions. However, subsequent pregnancies may contribute to their development.

Background The 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). Methods Two 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. Results JSpA 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%. Conclusion The 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.

To evaluate the efficacy and safety of golimumab to induce clinical remission in patients with very early, active peripheral spondyloarthritis (pSpA). 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. 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. 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. NCT01426815; Results.

In these cases, anti-TNF therapy has failed to confine gut inflammation. [...]the use of monoclonal antibodies for treatment of extra-articular manifestations may be redundant, unless other EAMs such as psoriasis or uveitis occurred in the disease course. [...]in case of predictable flare of SpA in patients displaying both diseases, the withdrawal of anti-TNF should be avoided. [...]for now, rheumatologists and gastroenterologists might have to rely on medical need programmes to treat their patients accordingly. [...]the use of vedolizumab monotherapy after loss of efficacy of anti-TNF at the level of the gut in patients displaying both SpA and IBD should be taken with caution as flares may be expected short term.

Background Autoimmune Syndrome Induced by Adjuvants (ASIA) is a concept introduced by Shoenfeld to group various disease entities believed to be triggered by an infection, silicone exposure or other external stimuli. A causal link between the use of silicone and the development of autoimmune diseases and lymphoma has been suggested in the past. Sjögren’s Syndrome (SS) is one of the autoimmune diseases that has been postulated as an example of ASIA syndrome. Although typically characterized by sicca, SS can manifest as a ganglionopathy as the primary presenting symptom. To our knowledge, this is the first case report in which a ganglionopathy unveiled an underlying SS in the context of a possible ASIA syndrome. Case presentation We describe a case of a 44-year-old woman who developed rapidly progressive sensory loss in the 4 limbs with a walking impairment due to the severe sensory ataxia. After extensive work-up, she was diagnosed with a ganglionopathy as the first symptom of SS, and the concurrent diagnosis of a bilateral breast implant leakage with severe inflammation due to silicone bleeding. After surgical removal of the prostheses and initiation of immunosuppressive therapy, stabilization of symptoms was achieved. Conclusion This case report brings to attention the possibility of a sensory ganglionopathy as first and isolated symptom of SS. The occurrence of SS in the setting of ASIA stir up the discussion about the safety of silicone breast implants.

BackgroundBiologicals 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’.ObjectivesOur 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.MethodsCZP 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.ResultsIn 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).ConclusionsImmunoscintigraphy with radiolabelled CZP demonstrated both axial and peripheral inflammation, and displayed good correlation with clinical features, conventional imaging and therapy response.Trial registration numberNCT01590966; Results.