Synovitis and tenosynovitis are present in juvenile idiopathic arthritis (JIA), both as joint pain and/or inflammation, making them difficult to detect on physical examination. Although ...ultrasonography (US) allows for discrimination of the 2 entities, only definitions and scoring of synovitis in children have been established. This study was undertaken to produce consensus-based US definitions of tenosynovitis in JIA.
A systematic literature search was performed. Selection criteria included studies focused on US definition and scoring systems for tenosynovitis in children, as well as US metric properties. Through a 2-step Delphi process, a panel of international US experts developed definitions for tenosynovitis components (step 1) and validated them by testing their applicability on US images of tenosynovitis in several age groups (step 2). A 5-point Likert scale was used to rate the level of agreement.
A total of 14 studies were identified. Most used the US definitions developed for adults to define tenosynovitis in children. Construct validity was reported in 86% of articles using physical examination as a comparator. Few studies reported US reliability and responsiveness in JIA. In step 1, experts reached a strong group agreement (>86%) by applying adult definitions in children after one round. After 4 rounds of step 2, the final definitions were validated on all tendons and at all locations, except for biceps tenosynovitis in children <4 years old.
The study shows that the definition of tenosynovitis used in adults is applicable to children with minimal modifications agreed upon through a Delphi process. Further studies are required to confirm our results.
Objective
Musculoskeletal ultrasonography (US) has the potential to be an important tool in the assessment of disease activity in childhood arthritides. To assess pathology, clear definitions for ...synovitis need to be developed first. The aim of this study was to develop and validate these definitions through an international consensus process.
Methods
The decision on which US techniques to use and the components to be included in the definitions, as well as the final wording, were developed by 31 US experts in a consensus process. A Likert scale of 1–5 (where 1 = complete disagreement and 5 = complete agreement) was used. A minimum of 80% of the experts scoring 4 or 5 was required for final approval. The definitions were then validated on 120 standardized US images of the wrist, metacarpophalangeal joints, and tibiotalar joints, displaying various degrees of synovitis at various ages.
Results
B‐mode and Doppler should be used for assessing synovitis in children. A US definition of the various components (i.e., synovial hypertrophy, effusion, and Doppler signal within the synovium) was developed. The definition was validated on still images with a median of 89% of participants (range 80–100) scoring it as 4 or 5 on a Likert scale.
Conclusion
US definitions of synovitis and its elementary components covering the entire pediatric age range were successfully developed through a Delphi process and validated in a web‐based still‐images exercise. These results provide the basis for the standardized US assessment of synovitis in clinical practice and research.
Introduction
Familial Mediterranean fever (FMF), the most frequent autoinflammatory disease, is caused by mutations in the MEFV gene. It is characterized by recurrent febrile attacks of ...polyserositis. Liver abnormalities may develop during its course, but they remain poorly defined.
Objective
To describe liver involvement in FMF patients.
Methods
A systematic search was conducted through PubMed/Medline and Embase from 1946 to January 2020. All articles describing children and adults with FMF and liver involvement were included. Patients with amyloidosis were excluded. The selected full‐text articles were independently reviewed by three investigators.
Results
Forty‐three articles were identified, of which 20 articles with a total of 99 patients were included: 74 adults, 23 children and two patients of unknown age. Ten patients had cryptogenic cirrhosis, 48 had nonalcoholic fatty liver disease (NAFLD), four had Budd‐Chiari syndrome (BCS), 12 had isolated hyperbilirubinaemia and 25 had elevated liver enzymes.
Conclusion
Despite a low prevalence of metabolic risk factors, FMF may be associated with NAFLD and cryptogenic cirrhosis as a consequence of chronic or recurrent inflammation. FMF patients should be regularly screened for liver injury. The latter may be prevented and treated by daily colchicine intake. The evidence was insufficient to establish an association with BCS, hyperbilirubinaemia or autoimmune hepatitis.
Clinical features, complications and treatments of Gaucher's disease (GD), a rare autosomal-recessive disorder due to a confirmed lysosomal enzyme (glucocerebrosidase) deficiency, are described.
All ...patients with known GD, living in France, with ≥ 1 consultations (1980-2010), were included in the French GD registry, yielding the following 4 groups: the entire cohort, with clinical description; and its subgroups: patients with ≥ 1 follow-up visits, to investigate complications; recently followed (2009-2010) patients; and patients treated during 2009-2010, to examine complications before and during treatment. Data are expressed as medians (range) for continuous variables and numbers (%) for categorical variables.
Among the 562 registry patients, 265 (49.6%) were females; 454 (85.0%) had type 1, 22 (4.1%) type 2, 37 (6.9%) perinatal-lethal type and 21 (3.9%) type 3. Median ages at first GD symptoms and diagnosis, respectively, were 15 (0-77) and 22 (0-84) years for all types. The first symptom diagnosing GD was splenomegaly and/or thrombocytopenia (37.6% and 26.3%, respectively). Bone-marrow aspiration and/or biopsy yielded the diagnosis for 54.7% of the patients, with enzyme deficiency confirming GD for all patients. Birth incidence rate was estimated at 1/50,000 and prevalence at 1/136,000. For the 378 followed patients, median follow-up was 16.2 (0.1-67.6) years. Major clinical complications were bone events (BE; avascular necrosis, bone infarct or pathological fracture) for 109 patients, splenectomy for 104, and Parkinson's disease for 14; 38 patients died (neurological complications for 15 type-2 and 3 type-3 patients, GD complications for 11 type-1 and another disease for 9 type-1 patients). Forty-six had monoclonal gammopathy. Among 283 recently followed patients, 36 were untreated and 247 had been treated during 2009-2010; 216 patients received treatment in December 2010 (126 with imiglucerase, 45 velaglucerase, 24 taliglucerase, 21 miglustat). BE occurred before (130 in 67 patients) and under treatment (60 in 41 patients) with respective estimated frequencies (95% CI) of first BE at 10 years of 20.3% (14.1%-26.5%) and 19.8% (13.5%-26.1%).
This registry enabled the epidemiological description of GD in France and showed that BE occur even during treatment.
Conventionally, PFAPA syndrome is considered as a benign disease compared to other recurrent fevers because it completely passes before adulthood. However, in our clinical practice, fever episodes ...have a huge impact on daily activities.
Observational cohort study using the Pediatric Quality of Life Inventory (PedsQL™ 4.0) Generic Core and Fatigue Scales. PedsQL™ uses a modular approach to measure the HRQOL in children with acute and chronic health conditions. We used pediatric FMF patients as the control group.
We included 33 children with PFAPA and compared them to 27 FMF patients matched for age: preschool-age children (2 to 7 years) and school-age children and youths (8 to18 years). PedsQL™ self-reported scores of children with PFAPA were systematically lower than those of FMF peers for general quality of life and physical and psychosocial functioning (significant only in the preschool-age group). PedsQL™ self-reported fatigue scores of children with PFAPA were significantly lower than those of FMF peers for both preschoolers and school-age children and youths. Parent proxy-reports were not significantly different, even though scores were systematically lower for the parents of PFAPA children.
Our study demonstrates, for the first time, that the wellbeing of PFAPA children is poor, with a major impact on psychosocial functioning and increased fatigue. The quality of life of PFAPA children appears to be even lower than that of FMF patients, for whom a lower than normal HRQOL has already been demonstrated.
The interest and application of musculoskeletal ultrasound (MSUS) in juvenile idiopathic arthritis (JIA) are increasing. Numerous studies have shown that MSUS is more sensitive than clinical ...examination for detecting subclinical synovitis. MSUS is a well-accepted tool, easily accessible and non-irradiating. Therefore, it is a useful technique throughout JIA management. In the diagnostic work-up, MSUS allows for better characterizing the inflammatory involvement. It helps to define the disease extension, improving the classification of patients into JIA subtypes. Moreover, it is an essential tool for guiding intra-articular and peritendinous procedures. Finally, during the follow-up, in detecting subclinical disease activity, MSUS can be helpful in therapeutic decision-making. Because of several peculiarities related to the growing skeleton, the MSUS standards defined for adults do not apply to children. During the last decade, many teams have made large efforts to define normal and pathological US features in children in different age groups, which should be considered during the US examination. This review describes the specificities of MSUS in children, its applications in clinical practice, and its integration into the new JIA treat-to-target therapeutic approach.
Current management of patients with pediatric rheumatic diseases (PRD) should aim at achieving the best possible well-being. To identify sociodemographic/clinical characteristics, needed paramedical ...services and school accommodations associated with well-being in patients at inclusion in a French health network Réseau pour les Rhumatismes Inflammatoires Pédiatriques (RESRIP) that supports coordination of the patient's health pathway. To evaluate the evolution of well-being over time in this patients benefiting from such support.
Patients > 3 years old enrolled in RESRIP (2013-2020) were included. At enrollment, data were collected on sociodemographic/clinical characteristics, ongoing medications, and paramedical and educational actions to be implemented by RESRIP. Well-being during the last 6 months was reported with a standardized questionnaire at enrollment and every 6 months. A well-being score was calculated with scores ranging from 0 to 18, 18 corresponding to absolute well-being. Patients were followed up from inclusion until June 2020.
In total, 406 patients were included and followed up for 36 months on average: 205 juvenile idiopathic arthritis, 68 connective tissue diseases, 81 auto-inflammatory diseases and 52 other diseases. The well-being score did not differ between the groups and improved significantly, by 0.04 score units, every 6 months (95% confidence interval 0.03; 0.06). At inclusion, use of homeopathy, need for implementation of hypnosis or psychological support, occupational therapy or for adjustment of school tests were associated with worse well-being score.
Well-being seems associated more with the impact of chronic illness than the type of PRD underlining the importance of a comprehensive patient care.
Systemic juvenile idiopathic arthritis (sJIA), formerly called Still's disease, is officially classified as a subset of juvenile idiopathic arthritis (JIA). Beside arthritis, it is characterized by ...prominent systemic features and a marked inflammatory response. Even if it is still included in the group of juvenile arthritides, sJIA is set apart from all the other forms of JIA. This disorder has markedly distinct clinical and laboratory features suggesting a different pathogenesis. sJIA does not show any association with HLA genes or with autoantibodies and is characterised by an uncontrolled activation of phagocytes with hypersecretion of IL-1 and IL-6. Based on clinical and laboratory features, as well as on new acquisitions on the pathogenesis, it seems evident that sJIA is an autoinflammatory disease related to abnormality in innate immune system. The new insights on the pathogenesis of sJIA have therefore dramatically changed the approach to treatment, with the development of targeted treatments (anti-IL-1 and anti-IL-6 agents) more effective and safer than earlier medications.
Despite their limited licensed indications, anti-interleukin-1 (anti-IL-1) agents are often used in clinical practice for an increasing number of auto-inflammatory diseases. We conducted a national ...cross-sectional observational study from January 2011 to January 2013 to record the off-label use of such agents in France. We aimed to estimate the off-label use of anti-IL-1 treatments in France, assess their efficacy in rare diseases, and increase the reporting of their possible side effects.
Physicians answered a questionnaire that covered patient and disease data, anti-IL-1 agent use, efficacy and adverse events. The study involved adult or paediatric patient who had received an anti-IL-1 agent after January 2005 in France.
In total, 189 patients from 38 centres were included. The main diseases were adult-onset Still's disease (AOSD) (35), gout (28), systemic juvenile idiopathic arthritis (27), cryopyrin-associated periodic syndrome (CAPS) (21), familial Mediterranean fever (14) and mevalonate kinase deficiency (12). The main off-label used agent was anakinra, used at least once for 185 patients, with canakinumab used for 25. Anakinra was effective in most patients (90%), with higher complete clinical response rates for Schnitzler's syndrome, gout, CAPS and AOSD. Overall, 58% of patients showed at least one adverse event, mainly minor injection-site reactions. The main reported serious adverse event was severe infection. Injection-site reactions and liver toxicity were significantly more frequent in children than adults. The main non-cutaneous adverse event was liver toxicity, significantly associated with treatment duration. Weight gain was reported in about 10% of patients and was associated with treatment duration and CAPS. Canakinumab was rarely used and showed better cutaneous tolerance than anakinra but similar rates of non-cutaneous and severe adverse events.
Anakinra was well tolerated and effective in most patients with various inflammatory diseases. The main adverse events were mild injection-site reactions, especially in children. The survey allowed for collecting limited information on the off-label use of canakinumab.
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.
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