Abstract Introduction In chronic inflammatory rheumatic diseases (CIRDs), comorbidities such as cardiovascular disease and infections are sub-optimally managed. EULAR recently developed points to ...consider to collect and report comorbidities. The objective of this present study was to develop a pragmatic guide to collect, report and propose management recommendations for comorbidities, from a rheumatologist perspective. Methods The collection and reporting of comorbidities and risk factors was adapted from the EULAR points to consider. To develop management recommendations, the process comprised (1) systematic literature reviews by 3 fellows and (2) a 2-day consensus process involving 110 experts (rheumatologists and health professionals). Votes of agreement (Likert 1-5 where 5 indicates full agreement) were obtained. Results The six selected comorbidities were ischemic cardiovascular diseases, malignancies, infections, diverticulitis, osteoporosis and depression. The literature review retrieved 97 articles or websites, mostly developed for the general population. The consensus process led to reporting presence of comorbidities, current treatment, risk factors (e.g. hypertension), screening (e.g. mammography) and prevention (e.g. vaccination). Management recommendations include physical examination (e.g. blood pressure or lymph node examination), prescribing screening procedures, and interpreting results to refer in a timely manner to appropriate other health professionals. Agreement was high (mean ± standard deviation, 4.37 ± 0.33). Conclusions Using an evidence-based approach followed by expert consensus, this initiative furthers the dissemination in France of the EULAR points to consider, and clearly defines what part of the management of comorbidities is potentially within the remit of rheumatologists. This initiative should facilitate systematic management of patients with CIRDs.
Despite guidelines, poor access to appropriate care for juvenile idiopathic arthritis (JIA) patients remains a global issue. Prompt referral to a pediatric rheumatology (PR) center and effective care ...is known to be critical for changing the natural history of the disease and improving long-term prognosis. This project assesses socio-economic factors of delayed referral to a pediatric rheumatologist (PRst) for JIA patients in France and Switzerland within the Juvenile Inflammatory Rheumatism (JIR) Cohort.
All patients diagnosed with JIA, presenting at one center of the JIRcohort in France or Switzerland with additional data on referral pathway were included. Patient characteristics at first visit to the PR center, dates of visits to healthcare providers during referral, and parent characteristics were extracted from the JIRcohort database.
Two hundred fifty children were included. The overall median time to first PR assessment was 2.4 months 1.3; 6.9 and ranged widely across the JIA subtypes, from 1.4 months 0.6; 3.8 for children with systemic juvenile idiopathic arthritis (sJIA) to 5.3 months 2.0; 19.1 for children with enthesitis-related arthritis (ERA). A diagnosis of ERA and an appointment with an orthopedist during the referral pathway were significantly associated with a longer time before the first PR visit (hazard ratio HR 0.50 95% CI: 0.29; 0.84) and HR 0.68 95% CI: 0.49; 0.93, respectively) in multivariable analysis. Having a mother with a post-graduate educational attainment level was tendentially associated with a shorter time before the first PR visit, (HR 1.32 95% CI: 0.99; 1.78).
Time to first PRst visit was most often short compared to other studies and close to the British recommendations. However, this time remained too long for many patients. We observed no social inequities in access to a PRst, but we show the need to improve effective pathway and access to a PR center for JIA patients.
Background
The treatment of children with juvenile idiopathic arthritis (JIA) to prevent disability is a major challenge in paediatric rheumatology. The presence of synovitis, which is difficult to ...detect in children, is associated with structural damage. Musculoskeletal ultrasonography (MSUS) can be used in patients with JIA to reveal subclinical synovitis.
Objective
The primary aim was to determine whether the use of MSUS was associated with therapeutic modification in patients with JIA. The secondary aim was to identify other factors associated with therapeutic decisions.
Methods
We conducted an observational study based on the JIRECHO multi-centre cohort, which was developed to provide a systematic MSUS follow-up for patients with JIA. Follow-up occurred every 6 months and included clinical and MSUS examinations. We included children who underwent MSUS of the elbows, wrists, second metacarpophalangeal joints, knees and ankles, which was performed by expert sonographers. Clinical and biological data, disease activity scores and information on therapeutics were collected.
Results
A total of 185 visits concerning 112 patients were recorded. Three groups were defined according to the therapeutic decision: escalation (22%,
n
= 40), de-escalation (14%,
n
= 26) or stable (64%,
n
= 119). In the “therapeutic escalation” group: the presence of ultrasonographic synovitis in B-mode and the presence of grade 2 or 3 synovitis in B-mode were not significantly more frequent than in the “stable therapeutic or de-escalation” group (80% versus 65%,
p
= 0.06; 33% versus 19%,
p
= 0.06), and the patient’s and physician’s visual analogue scale (VAS) scores, the clinical JADAS and the C-reactive protein level were significantly higher, but only physician’s VAS score remained in the model of logistic regression. In the “therapeutic de-escalation” group: there was no difference in the presence of US synovitis compared with the “stable therapeutic or escalation” group (62% versus 69%,
p
= 0.48).
Conclusion
Even though US synovitis tended to be more frequent in patients with therapeutic escalation, the study did not show that the presence of synovitis in MSUS was statistically associated with therapeutic modifications in patients with JIA. Treatment remained stable despite the presence of US synovitis.
Leflunomide can have adverse effects, but cases of subacute cutaneous lupus have more rarely been described. This drug, through its immunomodulatory effect, can favor the appearance of a Th2 ...lymphocyte immune response inducing lupus. A recent study has suggested that Jessner–Kanof disease (JKD) could be a dermal form of lupus. We report a case of subacute cutaneous lupus induced by leflunomide with anti-Ro/SSA Ab and unusual histological presentation, identical to that of JKD. Leflunomide can induce cutaneous lupus characterized by exclusively dermal involvement and histologically comparable to JKD. This observation therefore suggests that JKD could be a dermal variant of lupus. This prompted a revision of the classification of cutaneous lupus, which has until now been divided into acute, subacute and chronic forms but could equally be classed as epidermal, dermal and hypodermal. The last point of interest in our observation is the efficacy of a combination of chloroquine and anakinra, which led to complete remission of the articular and cutaneous symptoms after the failure of corticotherapy.
To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC).
Pragmatic, prospective, cluster-randomised, controlled, ...open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive.
(1)
: visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2)
visits every 12 weeks and treatment at the rheumatologist's discretion.
Percentage of patients with a ≥30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed.
Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC.
160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by ≥30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved €472 compared with UC.
TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective.
NCT03043846.
To evaluate the reliability of the OMERACT paediatric ultrasound (US) synovitis definitions and scoring system in JIA.
Thirteen sonographers analysed 75 images for the presence/absence of elementary ...lesions (binary scoring) and for grading synovitis, synovial hypertrophy, effusion and Doppler signals. Static US images of the second metacarpophalangeal joint (MCP-II), wrist, elbow, knee and ankle in JIA patients at different ages and different disease stages were collected with standardized scanning by two experienced sonographers. Intra- and inter-reader reliability were analysed with kappa coefficients.
Intra-reader reliability was good for binary scoring (Cohen's kappa 0.62, range 0.47-0.75), synovitis and synovial hypertrophy; excellent for Doppler signals (quadratic weighted kappa 0.77, 0.66-0.86; 0.76, 0.61-0.84; and 0.87, 0.77-0.94, respectively); and moderate for effusion (0.55, 0.24-0.76). Inter-reader reliability was good for synovitis and synovial hypertrophy (Light's kappa 0.68, 95% CI: 0.61, 0.75 and 0.63, 0.54-0.71, respectively), excellent for Doppler signals (0.85, 95% CI: 0.77, 0.90), and moderate for binary scoring and effusion (0.48, 95% CI: 0.36, 0.64 and 0.49, 0.40-0.60, respectively). We obtained the best scores for the knee (0.71, 0.54-0.85) except for Doppler signals, with reliability higher for MCP-II. We found a trend toward better results in older children.
This is the first study establishing the reliability of the OMERACT paediatric US synovitis definitions and scoring system in the five most commonly affected joints in JIA. The reliability was good among a large group of sonographers. These results support the applicability of these definitions and scoring system in clinical practice and multicentre studies.
The use of biological therapies for treating autoimmune diseases is increasing. These therapies are sometimes administered to pregnant women as part of a planned therapeutic regimen or to women with ...unexpected or unplanned pregnancies. The safety of biological therapies in this setting is a major issue. Here, we describe three young pregnant patients with autoimmune disorders: two patients with rheumatoid arthritis and one with idiopathic thrombotic thrombocytopenic purpura. These patients were exposed to rituximab (anti-CD20 monoclonal antibody) or abatacept (fusion protein CTLA4Ig) during the first trimester of their pregnancies. No significant adverse effects or complications were observed during the pregnancies, and all three patients delivered healthy newborns. In the rituximab cases, this result might be explained in part by the very low transplacental maternofetal transfer of rituximab during the first trimester of pregnancy. Despite these favorable outcomes, the use of these two biological agents must follow international recommendations. Their use is not currently allowed during pregnancy except in cases where the potential benefit to the mother justifies the potential risk to the fetus. In the case of exposure to the single agent rituximab during the first trimester, current data suggest that the low risk to the fetus may be outweighed by the potential benefit to the mother.
Abstract Objective Few studies have assessed Health-Related Quality of Life (HR-QoL) in adults following juvenile idiopathic arthritis, and none since the advent of biotherapies. The aim of our study ...is to assess the impact of juvenile idiopathic arthritis on quality of life in a large transitional cohort, evaluate which factors influence quality of life in juvenile idiopathic arthritis, and determine which questionnaire should be used in practice. Methods All consecutive juvenile idiopathic arthritis patients followed during adulthood in a transitional care program were included. Demographical, clinical and biological data were collected. The following quality of life questionnaires were administered: SF36 and EuroQoL. Age- and sex-matched controls (without rheumatic disease) were included. Results One hundred and sixty-one juvenile idiopathic arthritis (120 women and 41 men) and 76 (51/25) controls were included. Out of 161, sixty-five (40%) were considered to be in remission. Juvenile idiopathic arthritis had a large impact on the physical scales of quality of life. Pain seemed to be the most important factor affecting quality of life in cases of juvenile idiopathic arthritis. No significant difference was found between sub-types of juvenile idiopathic arthritis. Conclusion In this large transitional cohort of patients at the era of biotherapies, juvenile idiopathic arthritis has a larger effect on physical than mental scale of quality of life measures. Pain was the main factor influencing quality of life. Sub-types of juvenile idiopathic arthritis do not seem to influence quality of life.
Abstract Objectives To evaluate the reliability of the OMERACT paediatric ultrasound (US) synovitis definitions and scoring system in JIA. Methods Thirteen sonographers analysed 75 images for the ...presence/absence of elementary lesions (binary scoring) and for grading synovitis, synovial hypertrophy, effusion and Doppler signals. Static US images of the second metacarpophalangeal joint (MCP-II), wrist, elbow, knee and ankle in JIA patients at different ages and different disease stages were collected with standardized scanning by two experienced sonographers. Intra- and inter-reader reliability were analysed with kappa coefficients. Results Intra-reader reliability was good for binary scoring (Cohen’s kappa 0.62, range 0.47–0.75), synovitis and synovial hypertrophy; excellent for Doppler signals (quadratic weighted kappa 0.77, 0.66–0.86; 0.76, 0.61–0.84; and 0.87, 0.77–0.94, respectively); and moderate for effusion (0.55, 0.24–0.76). Inter-reader reliability was good for synovitis and synovial hypertrophy (Light’s kappa 0.68, 95% CI: 0.61, 0.75 and 0.63, 0.54–0.71, respectively), excellent for Doppler signals (0.85, 95% CI: 0.77, 0.90), and moderate for binary scoring and effusion (0.48, 95% CI: 0.36, 0.64 and 0.49, 0.40–0.60, respectively). We obtained the best scores for the knee (0.71, 0.54–0.85) except for Doppler signals, with reliability higher for MCP-II. We found a trend toward better results in older children. Conclusions This is the first study establishing the reliability of the OMERACT paediatric US synovitis definitions and scoring system in the five most commonly affected joints in JIA. The reliability was good among a large group of sonographers. These results support the applicability of these definitions and scoring system in clinical practice and multicentre studies.
Interleukin-32 (IL-32) is a recently described cytokine that is a strong inducer of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, IL-1β, IL-6, and IL-8. The expression of this ...cytokine is highly increased in the rheumatoid synovium and correlated with the severity of joint inflammation. Little is known regarding the innate immune-related regulation of IL-32 by fibroblast-like synoviocytes (FLSs). We therefore investigated the effect of innate immune stimulation by ligands of Toll-like receptor (TLR)2, TLR3, and TLR4, and cytokines such as TNF-α and interferon (IFN)-γ, on IL-32 expression by FLSs.
FLSs were isolated from patients with rheumatoid arthritis (RA) according to the ACR criteria. Quantitative RT-PCR, confocal analysis, and ELISA were performed to evaluate IL-32 mRNA induction and IL-32 release by FLSs stimulated with TLR2 (BLP), TLR3 (poly I:C), and TLR4 (lipopolysaccharide) ligands, TNF-α and IFN-γ.
TLR2, -3, and -4 ligands as well as IFN-γ and TNF-α induced IL-32 β, γ and δ mRNA expression by RA FLSs. Mature IL-32 was expressed intracellularly and released by cells stimulated with the various activators. The IL-32α isoform was expressed intracellularly in response to TNF-α and poly I:C and not released in culture supernatants. Stimulation of FLS with TNF-α, BLP, lipopolysaccharide, or poly I:C concomitant with IFN-γ increased IL-32 expression compared with stimulation with IFN-γ alone.
IL-32 synthesis by FLSs is tightly regulated by innate immunity in rheumatoid arthritis. Thus TNF-α, IFN-γ, double-strand RNA, hyaluronic acid, or other damage-associated molecular patterns (DAMPs), highly secreted in synovial tissues of RA patients, might trigger IL-32 secretion by FLSs. IL-32 might therefore represent a relevant therapeutic target in RA.
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