Rheumatoid arthritis (RA) is classified as an inflammatory, chronic autoimmune and disabling disease based on the intricate interplay between environmental and genetic factors. With a prevalence ranging from 0.3 to 1%, RA is the most prevalent inflammatory joint disease observed in adults. Disruption of immune tolerance becomes evident when abnormal stimulation of the innate and adaptive immune system occurs. This cascade of events causes persistent joint inflammation, proliferative synovitis and, ultimately, damage of the underlying cartilage as well as the subchondral bone, leading to permanent joint destruction, deformity and subsequent loss of function. With cytokines being the key to a multitude of biological processes, including inflammation, hematopoiesis and overall immune response, one must inevitably look at the main pathways through which a significant number of those molecules exert their function. Janus kinase/signal transducers and activators of transcription (JAK/STATs) represent one such pathway and, recently, JAK inhibitors (JAKinibs) have shown promise in the treatment of several inflammatory diseases, including RA. This narrative review focuses on the intricate signaling pathways involved as well as on the clinical aspects and safety profiles of JAKinibs approved for the treatment of RA.

Ankylosing spondylitis (AS) is a progressive common autoimmune inflammatory disease, part of the spondylarthritis group, characterized, besides clinical spinal and peripheral joint inflammation, by enthesitis and new bone formation, that can lead to severe functional impairment. Beyond intensive and continuous research on the pathogenic process extensively performed in recent years, their impact on therapeutic management remains open to future development. Better knowledge of AS pathogenesis have shown results progressively and studies are being performed to advance our current understanding of the disease. It is well known that tumor necrosis factor (TNF) exerts a central role, along with interleukin-17 (IL-17) and interleukin-23 (IL-23), demonstrated by several clinical studies. Similar to other rheumatic inflammatory conditions, SA is associated with an early process of systemic bone loss, both trabecular and cortical, consecutive osteopenia, osteoporosis, and high fracture risk. Current personalized therapeutic options benefit from new published data, to prevent future complications and to improve quality of life. Contents 1. Introduction 2. Immunopathogenesis of ankylosing spondylitis 3. Effects of IL-23 and IL-17 on the bone 4. Conclusions

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ObjectivesThis study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range.MethodsAdult HS (age 18–80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1–5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort.Results939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups.ConclusionsUltrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA.

Background:Tenosynovitis (TS) is a common, often clinically undetectable finding in Rheumatoid Arthritis (RA). Recent data showed TS on ultrasound (US) has a role in predicting outcome in early disease and flare in clinical remission. However data is limited on US measured TS in healthy subjects (HS), none specifically encompassing the older age range when RA commonly presents.Objectives:This OMERACT study aimed to determine prevalence of US measured tendon abnormalities in HS throughout the age range.Methods:Adult HS without: joint pain (VAS <10/100), hand osteoarthritis (ACR criteria), or inflammatory arthritis were recruited in 23 international centres from Aug 2017-Dec 2018. MCP, PIP and wrist joints were clinically examined. Bilateral digit flexor (DF) 1-5 and extensor carpi ulnaris (ECU) tendons were scanned for tenosynovial hypertrophy (TSH) and power Doppler (PD) signal and graded (OMERACT US scoring system1).A comparison cohort of DMARD-naive patients with RA (ACR-EULAR 2010 and/or 1987 criteria) at presentation was taken from the Birmingham Early Arthritis (BEACON) inception cohort, who underwent identical tendon US assessment. They were grouped into ≤12 and > 12 weeks from symptom onset.Results:Data from 899 HS and 144 RA patients were included. HS 18-39 y HS 40-59 y HS ≥60 y RA ≤12 RA > 12 5 groups p value RA ≤12 vs >12 p value n 40831118030114 Age, y (IQR) 29 (25-33)49 (44-55)68 (62-72)58 (52-69)53 (42-65)<0.0010.03 Female (%) 270 (66)270 (83)114 (62)20 (67)86 (75)<0.0010.2 DAS 28 CRP (IQR) ---5.4 (4.2-6.1)4.8 (4.1-5.7)-0.1 Tender joint* (IQR) 0 0 0 18 (10-23)17 (11-29)<0.0010.9 Swollen joint* (IQR) 0 0 0 8 (3-18)6 (3-9)<0.0010.1 DF 1-5 TSH gd ≥1 (%) 8 (0.2)9 (0.3)2 (0.1)54 (18)125 (11)<0.0010.06 DF 1-5 PD gd ≥1 (%) 3 (0.05)2 (0.06)0 49 (16)85 (8)<0.0010.02 ECU TSH gd ≥1 (%) 1 (0.1)11 (1.8)5 (1.4)13 (22)52 (23)<0.0010.8 ECU PD gd ≥1 (%) 0 0 0 12 (20)50 (22)<0.0010.7*RA had 66/68 joint countPrevalence of TSH and particularly PD abnormalities in HS was very low at all ages, and was all grade 1 except in one individual ECU tendon. ECU TSH grade≥1 was more common than DF grade≥1 in the older HS groups, and less common in the 18-39 age group (p=0.011). TSH and PD of grade ≥1 were common in RA patients, with DF PD abnormalities more common in early disease (p=0.02).Conclusion:Low prevalence of TSH or PD abnormalities in tendons of HS even in old age suggests US determined TS will be a robust tool in clinically managing RA.References:[1] Naredo E, D’Agostino MA, et al. Reliability consensus-based US score TS RA. ARD.2013;72(8):1328-34Disclosure of Interests:Jeanette Trickey: None declared, Ilfita Sahbudin: None declared, Alessandra Bortoluzzi: None declared, Annamaria Iagnocco: None declared, Carlos Pineda: None declared, Cesar Sifuentes-Cantú: None declared, Coziana Ciurtin: None declared, Cristina Reategui Sokolova: None declared, Daniela Fodor: None declared, Ellen-Margrethe Hauge: None declared, Esperanza Naredo Consultant for: Abbvie, Speakers bureau: AbbVie, Roche, Bristol-Myers Squibb, Pfizer...

Objectives To investigate the reliability of the OMERACT ultrasound (US) Task Force definition of US enthesitis in spondyloarthritis (SpA). Methods In this web exercise, based on the evaluation of 101 images and 39 clips of the main entheses of the lower limbs, the elementary components included in the OMERACT definition of US enthesitis in SpA [hypoechoic areas, entheseal thickening, power Doppler signal (PD) at the enthesis, enthesophytes/calcifications, bone erosions] were assessed by 47 rheumatologists from 37 rheumatology centres in 15 countries. Inter and intra-observer reliability of the US components of enthesitis was calculated using Light’s kappa, Cohen’s kappa, Prevalence and Bias Adjusted Kappa (PABAK) and their 95% confidence intervals. Results Bone erosions and PD showed the highest overall inter-reliability [Light’s kappa: 0.77 (0.76–0.78), 0.72 (0.71–0.73), respectively; PABAK: 0.86 (0.86–0.87), 0.73 (0.73–0.74), respectively], followed by enthesophytes/calcifications [Light’s kappa: 0.65 (0.64–0.65), PABAK: 0.67 (0.67–0.68)]. This was moderate for entheseal thickening [Light’s kappa: 0.41 (0.41–0.42), PABAK: 0.41 (0.40–0.42)], and fair for hypoechoic areas [Light’s kappa: 0.37 (0.36–0.38); PABAK: 0.37 (0.37–0.38)]. A similar trend was observed in the intra-reliability exercise, although this was characterized by an overall higher degree of reliability for all US elementary components compared with the inter-observer evaluation. Conclusions The results of this multicentre, international, web-based study show a good reliability of the OMERACT US definition of bone erosions, PD, and enthesophytes/calcifications. The low reliability of entheseal thickening and hypoechoic areas raises questions about the opportunity to revise the definition of these two major components for the US diagnosis of enthesitis.

Livedoid vasculopathy is a rare vascular disease which typically manifests as recurrent ulcerative lesions on the lower extremities. It is classified as a vasculopathy, not a true vasculitis, and defined as a vasooclusive syndrome, caused by non-inflammatory thrombosis of the upper and mid-dermal venulae. Main disorders associated with LV include thrombophilias, autoimmune diseases and neoplasia. A triad of clinical features is present in most patients and consist of livedo racemosa (less frequently livedo reticularis), ulcerations and atrophie blanche. Management generally relies on antiplatelet drugs, anticoagulants, vasodilators and fibrinolytic therapy. Some benefit has been observed with intravenous immunoglobulin, colchicine, hyperbaric oxygen, while glucocorticoids are efficient to a lesser extent. This case report highlights a refractory clinical form with no identifiable predisposing condition, which proved responsive only to intravenous immunoglobulin.

ObjectivesTo investigate the inter/intra-reliability of ultrasound (US) muscle echogenicity in patients with rheumatic diseases.MethodsForty-two rheumatologists and 2 radiologists from 13 countries were asked to assess US muscle echogenicity of quadriceps muscle in 80 static images and 20 clips from 64 patients with different rheumatic diseases and 8 healthy subjects. Two visual scales were evaluated, a visual semi-quantitative scale (0–3) and a continuous quantitative measurement (“VAS echogenicity,” 0–100). The same assessment was repeated to calculate intra-observer reliability. US muscle echogenicity was also calculated by an independent research assistant using a software for the analysis of scientific images (ImageJ). Inter and intra reliabilities were assessed by means of prevalence-adjusted bias-adjusted Kappa (PABAK), intraclass correlation coefficient (ICC) and correlations through Kendall’s Tau and Pearson’s Rho coefficients.ResultsThe semi-quantitative scale showed a moderate inter-reliability [PABAK = 0.58 (0.57–0.59)] and a substantial intra-reliability [PABAK = 0.71 (0.68–0.73)]. The lowest inter and intra-reliability results were obtained for the intermediate grades (i.e., grade 1 and 2) of the semi-quantitative scale. “VAS echogenicity” showed a high reliability both in the inter-observer [ICC = 0.80 (0.75–0.85)] and intra-observer [ICC = 0.88 (0.88–0.89)] evaluations. A substantial association was found between the participants assessment of the semi-quantitative scale and “VAS echogenicity” [ICC = 0.52 (0.50–0.54)]. The correlation between these two visual scales and ImageJ analysis was high (tau = 0.76 and rho = 0.89, respectively).ConclusionThe results of this large, multicenter study highlighted the overall good inter and intra-reliability of the US assessment of muscle echogenicity in patients with different rheumatic diseases.