Cohort Of Juvenile Idiopathic Arthritis Patients Research Articles

Serum immunoglobulin A (IgA) levels in children affected with Juvenile Idiopathic Arthritis

Background and objectiveImmunoglobulin A (IgA) is the most abundant antibody isotype in the human body, considering its presence on the mucosal surfaces, in addition to the amount circulating in the bloodstream. Serum IgA levels can be variably altered in several pathological settings. However, very few studies specifically investigated serum IgA in Juvenile Idiopathic Arthritis (JIA). In the present study, we specifically assessed serum IgA levels in our cohort of patients affected with JIA. MethodsIn this cross-sectional study, serum IgA levels were measured in patients with JIA (and age-matched controls) and analyzed according to age class. The correlation of serum IgA levels with hematological, inflammatory, and disease activity parameters was assessed. ResultsNo significant difference in the frequency of low IgA levels (according to the definition of complete and partial IgA deficiency) was observed between JIA patients and controls, overall. This pediatric study population showed a progressive increase of total serum IgA concentrations with age, as expected; however, in JIA patients aged 10–17 years, total IgA serum levels resulted to be significantly higher than in age-matched control subjects. No clear correlation between IgA levels and the examined inflammatory, hematological, and disease activity parameters was observed in JIA patients, except for the erythrocyte sedimentation rate (ESR) in oligoarticular JIA patients: here, serum IgA levels showed a positive and moderate covariation with ESR, which was also observed for disease activity (JADAS-10) in selected oJIA patients without biological therapy. ConclusionsIn our cohort of JIA patients, total serum IgA levels were not reduced and were actually increased in adolescents compared to controls. Larger studies are needed to confirm this finding, which cannot be certainly explained based on the available data in this study, even though JIA disease control and/or chronic inflammation may be implicated to some extent.

Musculoskeletal Ultrasound and the Assessment of Disease Activity in Juvenile Idiopathic Arthritis.

To determine the frequency of subclinical synovitis on musculoskeletal ultrasonography (MSUS) in juvenile idiopathic arthritis (JIA) and correlate patient- and provider-reported outcome measures with MSUS synovitis. JIA patients with an active joint count (AJC) of >4 underwent a 42-joint MSUS performed at baseline and 3 months. B-mode and power Doppler images were obtained and scored (range 0-3) for each of the 42 joints. Outcomes evaluated included physician global assessment of disease activity (PhGA), patient global assessment of disease activity (PtGA), patient pain, Childhood Health Assessment Questionnaire (C-HAQ), and AJC. Subclinical synovitis was defined as synovitis detected by MSUS only. Generalized estimation equations were used to test the relationship between clinical arthritis (positive/negative) and subclinical synovitis (positive/negative). Spearman's correlation coefficients (rs ) were calculated to determine the association between MSUS synovitis and patient- and physician-reported outcomes. In 30 patients, subclinical synovitis was detected in 30% of joints. Clinical arthritis of the fingers, wrists, and knee joints was significantly associated with MSUS synovitis in these joints. PtGA and the C-HAQ had a moderate (rs =0.44, P= 0.014) to weak (rs =0.37, P=0.045) correlation with MSUS synovitis. There was a statistically significant strong correlation between MSUS synovitis and PhGA (rs =0.61, P=0.001), but a weak correlation with AJC (rs =0.37, P=0.048) at the follow-up visit. Subclinical synovitis was commonly observed in this cohort of JIA patients. The fair-to-moderate correlation of MSUS synovitis with patient- and provider-reported outcomes suggests that MSUS assesses a different, possibly more objective, domain not determined by traditional JIA outcome measurements.

POS1202 EXPERIENCE WITH COVID-19 IN GERMAN PAEDIATRIC RHEUMATOLOGY CENTRES

Background:COVID-19 is a major challenge worldwide. Although the risk for a severe disease course is low among children with COVID-19, symptoms may be exacerbated by underlying disease and/or immunosuppressive medication. We analysed clinical data from COVID-19 cases in among pediatric patients with juvenile idiopathic arthritis (JIA) in Germany reported to the BIKER registry.Objectives:This is an analysis of clinical data for 56 COVID-19 cases reported to the German BIKER registry from 29 German pediatric rheumatology centers and clinics from February 2020 to January 2021.Methods:The major task of the German BIKER (Biologics in Paediatric Rheumatology) Registry is surveillance of biologics used in pediatric rheumatology patients. Following the start of the COVID-19 pandemic in Germany, a survey was established to proactively interview all participating centers regarding the occurrence, presentation and outcome of SARS-CoV-2-infected children with rheumatic diseases. Initially, the interviews were conducted in weekly intervals, later bi-weekly.A standardized Adverse Event of Special Interest form was developed requesting biographic data, pre-treatment, current medication, data on clinical presentation, course, treatment and outcome of COVID-19 pediatric rheumatology patients.Results:In all, 56 patients with JIA and SARS-CoV-2 infection were reported (Table 1). Of these patients, 71% were 12 or more years old.Table 1.Patient characteristics. COVID-19 positive patients.JIA patients, n=56n (%)Age 0-5 years / 6-11years / 12-18years3 (5.4) / 13 (23.2) / 40 (71.4)JIA category•Systemic JIA5 (8.9)•Oligoarthritis JIA9 (16)•Polyarticular JIA32 (57)•Enthesitis-related JIA2 (3.6)•Psoriatic JIA1 (1.8)•Unknown7 (12.5)Uveitis (concomitant)4 (7.1)Treatment•DMARD / MTX23/ 22 (41/39)•Biologics29 (52)•TNF inhibitors20 (36)•Tocilizumab5 (8.9)•Abatacept1 (1.8)•Anakinra1 (1.8)•Ustekinumab1 (1.8)•JAK inhibitors1 (1.8)•Steroids5 (8.9)Asymptomatic13 (23.2)Hospitalized/ICU/Ventilation/Death1/1/1/1 (1.8)At the time of infection, 41% of the patients received conventional DMARDs and 52% received biologics (Table 1). Forty-four patients (79%) received either a conventional DMARD or a biologic. Most patients had a polyarticular course of their JIA (57%).In 49 of the 56 cases (88%) COVID-19 was detected directly by PCR (n=46), by antigen test only (n=1) or an undisclosed method (n= 2). Six patients had detectable SARS-CoV2 antibodies and reported to have had typical symptoms. One patient tested negative but developed typical symptoms at approximately the same time a positive SARS-CoV-2 test was returned for a family member.Symptoms were reported in 43 of the 56 patients (77%): fever n=15, rhinitis n=14, cough n=12, headache n=10, loss of sense of taste and/or smell n=9, pharyngitis n=8, fatigue n=5, musculoskeletal pain n=5, GI symptoms n=2 (abdominal pain n=1, diarrhoea n=1), dizziness n=3, encephalitis/seizure/respiratory failure/death n=1. Thirteen patients (23%) were asymptomatic.A 3½ -year-old female patient initially diagnosed with systemic JIA developed intracranial oedema and respiratory failure. Her SARS-CoV2 PCR test was positive and pulmonary imaging displayed typical changes in lung texture. Before her SARS-CoV-2 infection, the patient was treated with methotrexate and low-dose steroids. Unfortunately, she died three days following hospital admission. Genetic testing revealed an inborn immunodeficiency. Except for this one patient, all other cases were treated as outpatients and no deaths were reported.Conclusion:Apart from one patient with an inborn immunodeficiency who died from her COVID-19 infection, no case of hospitalization or severe COVID-19 was reported in our cohort of JIA patients. At the time of COVID-19 diagnosis, nearly 80% of patients in our cohort had been treated with conventional DMARD and/or biologics. This seemed not to have a negative effect on severity or outcome of SARS-CoV2 infection.Acknowledgements:Thanks also for contributing Reports for this analysis to: Normi Brück, Frank Dressler, Ivan Foeldvari, Tilman Geikowski, Hermann Girschick, Johannes-Peter Haas, Tilmann Kallinich, Bernd-Ulrich Keck, Eggert Lilienthal, Anna-Hedrich Müller, Ulrich Neudorf, Nils Onken, Peggy Rühmer.Disclosure of Interests:None declared.

PBI91 CHARACTERISTICS AND MANAGEMENT OF JUVENILE IDIOPATHIC ARTHRITIS (JIA) PATIENTS IN A LARGE REPRESENTATIVE REAL WORLD COHORT

Chronic arthritis is estimated to affect approximately 300,000 children in the US, although estimates vary widely. Juvenile idiopathic arthritis (JIA), diagnosed in children under age 16, can manifest as morning stiffness, joint pain & tenderness, fever, rash and uveitis. The course of JIA subtypes is variable, with some patients achieving remission and some converting to a persistent course into adulthood. A cohort of JIA patients was identified in the OM1 Data Cloud (OM1, Boston), an ongoing, continually enrolling, representative sample of over 240 million patients in the US. Clinical (EMR) data and linked administrative claims data from January 2013 - May 2019 were utilized. Cohort included patients <20 years who met criteria of at least two JIA related outpatient diagnosis codes within a 1 year period, one JIA-related inpatient encounter or ≥2 diagnosis codes by a rheumatologist. A total of 30,238 patients with a mean age of 11.6±4.9 years were identified. The majority of patients were female (70.0%) and predominantly white (88.8%). Most patients were characterized as polyarticular (69.2%) and 9.7% of patients were documented as systemic onset of JIA. Uveitis was documented in 3678 patients (12.1%). Approximately 17% of patients were treated with at least one biologic disease-modifying therapy (bDMARD), including tumor necrosis factor alpha inhibitors (TNFa, 12.8%), IL-6 inhibitors (3.1%) and JAK inhibitors (0.3%) and 11% with conventional (c)DMARDs. Treatment with bDMARDs was more common in older patients (age <6 10.8%; age 6-11 15.0%; age ≥12 19.9%). A slightly higher proportion of female patients were treated with bDMARDs (17.5% versus 16.3% male) or cDMARDs (11.8% vs. 10.4% male). Most common cDMARD utilized was methotrexate (6.9%). The increasing use of bDMARDs in JIA may have long term ramifications for JIA patients with sustained disease related to steroid-sparing and cardiovascular risk associated with systemic inflammation.

Orofacial symptoms and oral health-related quality of life in juvenile idiopathic arthritis: a two-year prospective observational study

BackgroundLittle is known about the chronicity of orofacial symptoms and how this influences the oral health-related quality of life in juvenile idiopathic arthritis (JIA). Therefore, our objectives were to study the long-term changes in self-reported orofacial symptoms, and to define the impact of orofacial symptoms on oral health-related quality of life in JIA.MethodsAt baseline (T0), 157 consecutive JIA patients ≤20 years completed a patient pain questionnaire that incorporates domains related to the orofacial area. At the 2 year follow-up (T1), 113 patients completed the same questionnaire (response rate 72%) in addition to the Child Perception’s Questionnaire; a validated 31-item questionnaire addressing oral health-related quality of life.ResultsAt T0, 53% (60/113) of patients reported the presence of orofacial pain, and 36% (41/113) of patients reported compromised orofacial function. At T1, 77% (46/60) of patients with pain at T0 reported persistent pain, and 66% (27/41) of patients with functional disability at T0 reported persistent disability. Patients with orofacial symptoms reported a significantly greater prevalence of negative impact of orofacial conditions on general quality of life and within the domains of emotional and social well-being compared to asymptomatic patients.ConclusionSelf-reported orofacial pain and functional disability were common findings in a cohort of JIA patients followed over 2 years. These symptoms seem to persist over time in most patients, and have a significant negative impact on oral health-related quality of life.

Genetic Screening of Mutations Associated with Fabry Disease in a Nationwide Cohort of Juvenile Idiopathic Arthritis Patients.

Fabry’s disease (FD) is a lysosomal storage disorder associated with an alpha-galactosidase A deficiency. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients with established diagnosis is unknown, but as musculoskeletal pain may be an important complaint at presentation, misdiagnosed cases are anticipated. With this study, we aim to calculate the frequency of FD-associated mutations in a cohort of JIA patients. Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded in the Portuguese rheumatic diseases register (http://Reuma.pt). Molecular genetic testing to detect GLA gene mutations was performed. After the multiplex polymerase chain reactions technique for DNA amplification, direct sequencing of the complete sequence of GLA gene was completed. From a cohort of 292 patients with JIA (188 females, 104 males), mutations were identified in 5 patients (all female). Four patients had the mutation D313Y, a rare GLA variant, which is associated with low enzymatic levels in plasma, but normal lysosomal levels. One patient presented the missense mutation R118C, which was previously described in Mediterranean patients with FD. This is the first screening of FD mutations in a cohort of JIA patients. No “classic” pathogenic FD mutations were reported. The late-onset FD-associated mutation, R118C, was found in a frequency of 0.34% (1/292).

PReS13-SPK-1332: Assessment of disease activity and damage in juvenile idiopathic arthritis

A vast array of instruments are available for measuring disease activity in juvenile idiopathic arthritis (JIA). However, due to the high variability in the clinical presentation and course of JIA, no single measure can reliably capture disease activity in all patients. On the other hand, assessment of all measures individually may cause methodological and statistical problems, especially when these measures are employed as endpoints in clinical trials. Several approaches can be followed to achieve a more rational and standardized evaluation. One of these approaches is based on the so-called composite disease activity scores, which are made of a pool of individual measures and are aimed to quantify the absolute level of disease activity by providing one summary number on a continuous scale. Recently, the first composite disease activity score for JIA, named Juvenile Arthritis Disease Activity Score (JADAS), has been developed. In validation analyses, it was found to have good metrologic properties, including the ability to predict the disease outcome. The cutoff values of the JADAS that corresponded with the states of inactive disease and minimal disease activity, or reflected the physician’s, parent’s or child’s subjective rating of remission or the parent’s or child’s satisfaction with the outcome of the illness were established recently. These cutoffs represent an additional clinical tool that, if applied regularly in daily practice, may allow tighter control of therapy, support the optimization of treatment on an individual patient basis, and help prevent the development of joint damage and physical disability. JIA is characterized by prolonged synovial inflammation that may cause irreversible alterations in joint structures. Permanent changes may also occur in extra-articular organs/systems, such as the eye (as a complication of chronic anterior uveitis), or may result from side effects of medications. The Juvenile Arthritis Damage Index (JADI) was devised to enable a thorough detection of articular and extra-articular damage in children with JIA. The JADI is aimed to capture damage, defined as persistent changes in anatomy, physiology, pathology or function, which may be the consequence of previous active disease, side effects of therapy, or co-morbid conditions, is not due to currently active arthritis, and is present for at least 6 months. Damage is often irreversible and cumulative and, thus, damage scores are most frequently expected to increase or remain stable over time. However, because some forms of damage may improve or even resolve in growing children, in some cases scores may decrease. The index is composed of two parts, one devoted to the assessment of articular damage (JADI-A) and one devoted to the assessment of extraarticular damage (JADI-E). In validation analyses, the JADI was found to be feasible and to possess both face and content validity; furthermore, it exhibited good convergent construct validity, excellent reliability (interrater agreement and internal consistency), and strong discriminative validity in a large cohort of JIA patients with long-standing disease.

FRI0324 Experience with adalimumab in 123 patients with juvenile idiopathic arthritis (JIA)

BackgroundAdalimumab is a fully human anti-TNF monoclonal antibody approved for the treatment of resistant polyarticular juvenile idiopathic arthritis at a dosage of 24 mg/kg/m2. every other week in children below...

AB0696 Predictors of poor response to 6-months methotrexate therapy in a juvenile idiopathic arthritis cohort of patients

BackgroundThe identification of predictive factors of poor response to methotrexate (MTX) in juvenile idiopathic arthritis (JIA) patients could contribute to optimize the treatment strategy, namely by the earlier introduction of...

Early diagnosis of temporomandibular joint involvement in juvenile idiopathic arthritis: a pilot study comparing clinical examination and ultrasound to magnetic resonance imaging

Objectives. To study the validity of both rheumatological and orthodontic examinations and ultrasound (US) as screening methods for early diagnosis of TMJ arthritis against the gold standard MRI.Methods. Thirty consecutive juvenile idiopathic arthritis (JIA) patients were included in this pilot study. Rheumatological and orthodontic examinations as well as US were performed within 1 month of the MRI in a blinded fashion. Joint effusion and/or increased contrast enhancement of synovium or bone were considered signs of active arthritis on MRI.Results. A total of 19/30 (63%) patients and 33/60 (55%) joints had signs of TMJ involvement on MRI. This was associated with condylar deformity in 9/19 (47%) patients and 15/33 (45%) joints. Rheumatological, orthodontic and US examinations correctly diagnosed 11 (58%), 9 (47%) and 6 (33%) patients, respectively, with active TMJ arthritis, but misdiagnosed 8 (42%), 10 (53%) and 12 (67%) patients, respectively, as having no signs of inflammation. The best predictor for active arthritis on MRI was a reduced maximum mouth opening.Conclusion. None of the methods tested was able to reliably predict the presence or absence of MRI-proven inflammation in the TMJ in our cohort of JIA patients. US was the least useful of all methods tested to exclude active TMJ arthritis.

Antibodies against M. Bovis 65 KDa Heat Shock Protein and Its P180-188 Epitope in Sera of Patients with Juvenile Idiopathic Arthritis

We screened the levels of antibodies to M. bovis hsp65 and the 180-188 epitope by using ELISA in a cohort of 72 juvenile idiopathic arthritis (JIA) patients and 38 healthy controls. We analysed an association between antibody levels and rheumatoid factor, antinuclear antibodies, human leukocyte antigen B27 and the severity and the duration of the disease. The majority of anti-hsp65 antibodies in a cohort of JIA patients were of the IgG isotype (54.2 %) with IgM (13.9%) antibodies increased to a lesser degree. IgG antibodies to M. bovis hsp65 (P&lt;0.001) and the 180-188 epitope (P&lt;0.001) were significantly increased in all of three disease onset types when compared with healthy controls. The highest levels of IgG antibodies to M. bovis hsp65 and its P180-188 epitope were observed in oligoarthritis and in patients with no X-ray changes and functional limitation, while the lowest antibody levels were detected in patients with the most severe stage of articular damage. When antibody levels to M. bovis hsp65 and the 180-188 epitope were examined within patient and control populations, significantly higher levels of IgG and IgM antibodies to M. bovis hsp65 were observed in both JIA (P&lt;0.001) and healthy control (P&lt;0.001) cohorts. These findings may suggest that the high levels of IgG antibodies to M. bovis hsp65 and its P180-188 epitope would reflect the least serious cases of JIA. Since IgM antibodies to M. bovis hsp65 and P180-188 M. bovis hsp65 epitope exceeded the control level in a few patients with JIA we believe they are not of concern.