Maka Ioseliani

Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis: a comparative study

Objectives Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint disease affecting children. Even if remission is successfully induced, about half of the patients experience a relapse after stopping anti-inflammatory therapy. The present study investigated whether patients with JIA at risk of relapse can be identified by biomarkers even if clinical signs of disease activity are absent. Methods Patients fulfilling the criteria of inactive disease on medication were included at the time when all medication was withdrawn. The phagocyte activation markers S100A12 and myeloid-related proteins 8/14 (MRP8/14) were compared as well as the acute phase reactant high-sensitivity C reactive protein (hsCRP) as predictive biomarkers for the risk of a flare within a time frame of 6 months. Results 35 of 188 enrolled patients experienced a flare within 6 months. Clinical or standard laboratory parameters could not differentiate between patients at risk of relapse and those not at risk. S100A12 and MRP8/14 levels were significantly higher in patients who subsequently developed flares than in patients with stable remission. The best single biomarker for the prediction of flare was S100A12 (HR 2.81). The predictive performance may be improved if a combination with hsCRP is used. Conclusions Subclinical disease activity may result in unstable remission (ie, a status of clinical but not immunological remission). Biomarkers such as S100A12 and MRP8/14 inform about the activation status of innate immunity at the molecular level and thereby identify patients with unstable remission and an increased risk of relapse.

Development and preliminary validation of a paediatric-targeted MRI scoring system for the assessment of disease activity and damage in juvenile idiopathic arthritis

Objectives To develop and validate a paediatric-targeted MRI scoring system for the assessment of disease activity and damage in juvenile idiopathic arthritis (JIA). To compare the paediatric MRI score with the adult-designed. Outcome Measures in Rheumatology Clinical Trials—Rheumatoid Arthritis MRI Score (RAMRIS), whose suitability for assessing growing joints was tested. Methods In 66 patients with JIA the clinically more affected wrist was studied. Thirty-nine patients had a 1-year MRI follow-up. Two readers independently assigned the paediatric score and the RAMRIS to all studies. Validation procedures included analysis of reliability, construct validity and responsiveness to change. A reduced version of the bone erosion score was also developed and tested. Results The paediatric score showed an excellent reproducibility (interclass correlation coefficient >0.9). The interobserver agreement of RAMRIS was moderate for bone erosions and excellent for bone marrow oedema (BMO). The paediatric score and RAMRIS provided similar results for construct validity. The responsiveness to change of the paediatric score was moderate for synovitis and bone erosion, and poor for BMO and did not improve when RAMRIS was applied. The reduced version of the bone erosion was valuable for the assessment of joint damage, and provided time-saving advantages. Conclusion The results demonstrate that the paediatric MRI score is a reliable and valid method for assessing disease activity and damage in JIA. Unexpectedly, the RAMRIS provides acceptable suitability for use in the paediatric age group. Further work, especially in a longitudinal setting, is required before defining the most suitable MRI scale for assessing growing joints.

Dissecting the heterogeneity of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis.

Objective. To seek insights into the heterogeneity of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA) through the analysis of a large patient sample collected in a multinational survey. Methods. International pediatric rheumatologists and hemato-oncologists entered their patient data, collected retrospectively, in a Web-based database. The demographic, clinical, laboratory, histopathologic, therapeutic, and outcome data were analyzed in relation to (1) geographic location of caring hospital, (2) subspecialty of attending physician, (3) demonstration of hemophagocytosis, and (4) severity of clinical course. Results. A total of 362 patients were included by 95 investigators from 33 countries. Demographic, clinical, laboratory, and histopathologic features were comparable among patients seen in diverse geographic areas or by different pediatric specialists. Patients seen in North America were given biologics more frequently. Patients entered by pediatric hemato-oncologists were treated more commonly with biologics and etoposide, whereas patients seen by pediatric rheumatologists more frequently received cyclosporine. Patients with demonstration of hemophagocytosis had shorter duration of sJIA at MAS onset, higher prevalence of hepatosplenomegaly, lower levels of platelets and fibrinogen, and were more frequently administered cyclosporine, intravenous immunoglobulin (IVIG), and etoposide. Patients with severe course were older, had longer duration of sJIA at MAS onset, had more full-blown clinical picture, and were more commonly given cyclosporine, IVIG, and etoposide. Conclusion. The clinical spectrum of MAS is comparable across patients seen in different geographic settings or by diverse pediatric subspecialists. There was a disparity in the therapeutic choices among physicians that underscores the need to establish uniform therapeutic protocols.

Frequency of Radiographic Damage and Progression in Individual Joints in Children With Juvenile Idiopathic Arthritis

To evaluate the presence and progression of radiographic joint damage, as assessed with the adapted Sharp/van der Heijde score (SHS), in individual joints in the hand and wrist in patients with juvenile idiopathic arthritis (JIA) and to compare progression of damage among different JIA categories.

Agreement Among Musculoskeletal Pediatric Specialists in the Assessment of Radiographic Joint Damage in Juvenile Idiopathic Arthritis

To evaluate agreement among musculoskeletal pediatric specialists in assessing radiographic joint damage in juvenile idiopathic arthritis (JIA).

The Georgian version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR)

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Georgian language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach’s alpha, interscale correlations, test–retest reliability, and construct validity (convergent and discriminant validity). A total of 100 JIA patients (26% systemic, 57% oligoarticular, 16% RF negative polyarthritis, and 1% RF positive polyarthritis) and 100 healthy children, were enrolled at two paediatric rheumatology centre. Notably, none of the enrolled JIA patients is affected with psoriatic arthritis or with enthesitis-related arthritis or with undifferentiated arthritis. The JAMAR components discriminated healthy subjects from JIA patients, except for the school-related problems variable. All JAMAR components revealed good psychometric performances. In conclusion, the Georgian version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Dissecting the heterogeneity of macrophage activation syndrome

Methods Patient data were collected retrospectively by pediatric rheumatologists (PR) or pediatric hemato-oncologists (PHO). Clinical features, treatments and outcome were compared between groups by Mann-Whitney or chisquare tests. “Severe course” was defined as ICU admission or death. Results 362 patients with MAS in sJIA were collected by 95 investigators from 33 countries. 179 patients (49.4%) were enrolled in Europe (EU), 72 (19.9%) in North America (NA) and 111 (30.7%) in other continents (OC). 79 (21.8%) patients were included by PHO. HP was detected in 44% of patients and was not detected or looked for in 56%. Severe course was reported in 92 (25%) patients. Comparison by geographic origin showed a lower frequency of CNS disease in EU patients. NA physicians used more frequently ivIg and biologics. Patients entered by PHO had greater frequency of multiorgan failure and were given more commonly biologics and etoposide, whereas PR used more frequently cyclosporine (CsA). Patients with HP had shorter duration of sJIA at MAS onset, higher prevalence of hepatosplenomegaly, lower levels of platelets and fibrinogen and received more frequently CsA, ivIg and etoposide. Patients with severe course were older, had longer duration of sJIA at MAS onset, greater frequency of haemorrhages and CNS dysfunction, lower levels of ESR, albumin and fibrinogen, higher levels of LDH and D-dimer and were treated more commonly with CsA, ivIg and etoposide. Conclusion

Familian Mediterranean Fever: genetic characterization in Georgian population

FMF is the most common mendelian autoinflamatory syndrome, resulting from autosomal recessive mutations in the MEFV locus. This disorder occurs most frequently among Sephardic Jewish, Arab, Armenian andTurkish populations. FMF occurs at lower frequeccies in other Mediterranean populations and ethnicities.

PReS-FINAL-2164: Agreement among musculoskeletal pediatric specialists in the assessment of radiographic joint damage in juvenile idiopathic arthritis

The management of children juvenile idiopathic arthritis (JIA) is ideally conducted through the establishment of a multidisciplinary team of musculoskeletal pediatric specialists. Some therapeutic decisions, either medical or surgical, are made through discussion and consensus between specialists by viewing patient radiographs. However, it is unknown whether and to what extent different specialists agree in the assessment of the amount of radiographic joint damage.

PReS-FINAL-2345: Frequency of radiographic damage and progression in individual joints in children with juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) may lead to permanent damage of the articular cartilage and bone. Because the prevention of irreversible joint changes is a key objective in the long-term management of chronic arthritis, evaluation of radiographic joint damage represents an important clinical tool for assessing disease severity and progression and for monitoring the effectiveness of therapeutic interventions. Although newer imaging techniques, such as MRI and ultrasound, allow earlier detection of bone and cartilage changes, conventional radiography remains the gold standard for the demonstration of structural joint lesions in patients with JIA. Importantly, mapping the prevalence and location of structural abnormalities in different sites on conventional radiology may provide useful information to guide future investigations with MRI and ultrasound.