Search

Background Intra-articular venous malformations (IAVM) are rare benign vascular anomalies that usually affect young patients and most common locate in the knee. The terminology of these lesions is still ill-defined, as they are often termed in the literature as synovial hemangiomas. Early diagnosis can be difficult, because they usually present with nonspecific clinical manifestations that are similar those of other rheumatic diseases, especially juvenile idiopathic arthritis (JIA). Case series We conducted a retrospective analysis of five pediatric patients admitted to our units for recurrent swelling of the knee, and compared their characteristics with those of literature reports. The average age at first symptom and time from onset to diagnosis was 3.9 years (range 18 months-7 years) and 3.5 years (range 1-7 years), respectively. In our patients, an initial misdiagnosis of JIA, bleeding disorder or traumatic arthropathy was made. On MRI imaging, the features of the lesion were similar in all patients, and were marked by isointense-to-hypointense signal in T1-weighted images, and hyperintense signal in T2-weighted images. When performed, arthrocentesis led to aspiration of bloody fluid. The diagnosis was confirmed with a biopsy and histopathologic assessment in all patients. Open surgery enabled complete excision of the mass and was followed by stable remission over time in all cases. Conclusions Our report highlights the challenges that may be posed by the detection of knee IAVM and the frequent long delay between onset of symptoms and diagnosis. The key elements for early recognition include careful assessment of patient history, demonstration of bloody fluid on arthrocentesis, and proper interpretation of MRI scanning.

Objective Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design Retrospective analysis of the Italian data set of patients with TNDM. Methods Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. Results Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; −2.27 SD) than those with KATP mutations (4.0 weeks; −1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.

Objectives Henoch–Schönlein purpura (HScP) may present in children with severe, occasionally refractory, gastrointestinal (GI) involvement. The use of corticosteroids (CSs) is commonplace in the management of the disease, but to date no standardized protocol is available and, although rare, resistance to CS therapy may be challenging to clinicians. IVIG has been proposed as an effective alternative to CSs, but to date no controlled trial has been conducted to ascertain their real efficacy. We share our personal experience of successful IVIG treatment in two cases of GI HScP, comparing it with similar experiences reported in literature. Methods Retrospective clinical data collection, comparison with available literature. Results We describe two children with severe HScP GI vasculitis refractory to high-dose intravenous CSs that responded rapidly to IVIG administration, with complete recovery within a few days. Patient characteristics and response to IVIG administration were comparable to those of other previously reported cases. Conclusion Our observation confirms that IVIG may be useful in the treatment of CS-resistant HScP-related GI vasculitis in children, and highlights the need for more structured research, including a randomized trial against CSs, in order to ascertain their real effectiveness.

Background To investigate the frequency of achievement of inactive disease (ID) in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX) as the sole disease-modifyng antirheumatic (DMARD) therapy and to develop a prediction model for lack of attainment of ID. Methods The clinical charts of consecutive patients started with MTX as the sole DMARD between 2000 and 2013 were reviewed. Patient follow-up was censored at first episode of ID or, in case ID was not reached, at last follow-up visit or when a biologic DMARD was prescribed. The characteristic at MTX start of patients who achieved or did not achieve ID were compared with univariate and multivariable analyses. Regression coefficients (β) of variables that entered the best-fitting logistic regression model were converted and summed to obtain a “prediction score” for lack of achievement of ID. Results A total of 375 patients were included in the study. During MTX administration, 8.8% were given systemic corticosteroids and 44.1% intra-articular corticosteroids. After MTX start, 229 (61%) patients achieved ID after a median of 1.7 years, whereas 146 patients (39%) did not reach ID after a median of 1.2 years. On multivariable analysis, independent correlations with lack of achievement of ID were identified for the disease categories of systemic arthritis, enthesitis-related arthritis (ERA) and polyarthritis and C-reactive protein (CRP) > 1.4 mg/dl. The prediction score ranged from 0 to 3 and its cutoff that discriminated best between patients who achieved or did not achieve ID was > 0.5. The categories of systemic arthritis or ERA, both of which had a score greater than 0.5, were sufficient alone to predict a lower likelihood to reach ID. Polyarthritis and increased CRP, whose score was 0.5, assumed a predictive value only when present in association. Conclusion A conventional treatment regimen based on MTX as the sole DMARD led to achievement of ID in a sizeable proportion of children with JIA. Our findings help to outline the characteristics of patients who may deserve a synthetic DMARD other than MTX or the introduction of a biologic DMARD from disease outset.

Objective To determine cutoff values for defining the states of inactive disease (ID), low disease activity (LDA; or minimal disease activity), moderate disease activity (MDA), and high disease activity (HDA) using the clinical (3-variable) Juvenile Arthritis Disease Activity Score (cJADAS). Methods For selection of cutoffs, data from a clinical database including 609 children with juvenile idiopathic arthritis (JIA) were used. Optimal cutoffs were determined against external criteria by calculating the 75th and 90th percentile (for ID and LDA) and 10th and 25th percentile (for HDA) of cumulative score distribution and through receiver operating characteristic curve analysis. External criteria included definitions for ID and LDA cutoffs and therapeutic decisions for HDA cutoffs. MDA cutoffs were set at the score interval in-between LDA and HDA cutoffs. Crossvalidation was performed using 2 JIA patient samples (n = 485) and was based on assessment of construct and discriminant validity. Results The selected cutoffs were as follows: ≤1 for ID in both oligoarthritis and polyarthritis; ≤1.5 and ≤2.5 for LDA in oligoarthritis and polyarthritis, respectively; 1.51–4 and 2.51–8.5 for MDA in oligoarthritis and polyarthritis, respectively; and >4 and >8.5 for HDA in oligoarthritis and polyarthritis, respectively. In crossvalidation analyses, the cutoffs showed a strong ability to discriminate between disease activity states defined subjectively by physicians and parents, levels of pain, and presence/absence of functional impairment and disease damage. Conclusion Cutoff values for classifying various disease states in nonsystemic JIA using the cJADAS were developed. The cutoffs revealed good measurement characteristics in crossvalidation analyses and are suited for application in clinical practice and research.

Summary Background Little evidence-based information is available to guide the treatment of oligoarticular juvenile idiopathic arthritis. We aimed to investigate whether oral methotrexate increases the efficacy of intra-articular corticosteroid therapy. Methods We did this prospective, open-label, randomised trial at ten hospitals in Italy. Using a concealed computer-generated list, children younger than 18 years with oligoarticular-onset disease were randomly assigned (1:1) to intra-articular corticosteroids alone or in combination with oral methotrexate (15 mg/m 2 ; maximum 20 mg). Corticosteroids used were triamcinolone hexacetonide (shoulder, elbow, wrist, knee, and tibiotalar joints) or methylprednisolone acetate (ie, subtalar and tarsal joints). We did not mask patients or investigators to treatment assignments. Our primary outcome was the proportion of patients in the intention-to-treat population who had remission of arthritis in all injected joints at 12 months. This trial is registered with European Union Clinical Trials Register, EudraCT number 2008-006741-70. Findings Between July 7, 2009, and March 31, 2013, we screened 226 participants and randomly assigned 102 to intra-articular corticosteroids alone and 105 to intra-articular corticosteroids plus methotrexate. 33 (32%) patients assigned to intra-articular corticosteroids alone and 39 (37%) assigned to intra-articular corticosteroids and methotrexate therapy had remission of arthritis in all injected joints (p=0·48). Adverse events were recorded for 20 (17%) patients who received methotrexate, which led to permanent treatment discontinuation in two patients (one due to increased liver transaminases and one due to gastrointestinal discomfort). No patient had a serious adverse event. Interpretation Concomitant administration of methotrexate did not augment the effectiveness of intra-articular corticosteroid therapy. Future studies are needed to define the optimal therapeutic strategies for oligoarticular juvenile idiopathic arthritis. Funding Italian Agency of Drug Evaluation.

Systemic juvenile idiopathic arthritis (sJIA) is the form of childhood arthritis whose treatment is most challenging. The demonstration of the prominent involvement of interleukin (IL)-1 in disease pathogenesis has provided the rationale for the treatment with biologic medications that antagonize this cytokine. The three IL-1 blockers that have been tested so far (anakinra, canakinumab, and rilonacept) have all been proven effective and safe, although only canakinumab is currently approved for use in sJIA. The studies on IL-1 inhibition in sJIA published in the past few years suggest that children with fewer affected joints, higher neutrophil count, younger age at disease onset, shorter disease duration, or, possibly, higher ferritin level may respond better to anti-IL-1 treatment. In addition, it has been postulated that use of IL-1 blockade as first-line therapy may take advantage of a “window of opportunity,” in which disease pathophysiology can be altered to prevent the occurrence of chronic arthritis. In this review, we analyze the published literature on IL-1 inhibitors in sJIA and discuss the rationale underlying the use of these medications, the results of therapeutic studies, and the controversial issues.

Macrophage activation syndrome (MAS) is a serious, potentially life-threatening complication of rheumatic disorders, which is seen most commonly in systemic juvenile idiopathic arthritis (sJIA). It is characterised clinically by unremitting high fever, pancytopaenia, hepatosplenomegaly, hepatic dysfunction, encephalopathy, coagulation abnormalities and sharply increased levels of ferritin. The pathognomonic feature of the syndrome is seen on bone marrow examination, which frequently, though not always, reveals numerous morphologically benign macrophages exhibiting haemophagocytic activity. Macrophage activation syndrome is overt in 10% of children with sJIA but occurs subclinically in another 30–40%. Because MAS can follow a rapidly fatal course, prompt recognition of its clinical and laboratory features and immediate therapeutic intervention are essential. However, it is difficult to distinguish sJIA disease flare, infectious complications or medication side effects from MAS. A multinational collaborative effort aimed to develop diagnostic criteria for MAS in sJIA is under way. Although, the pathogenesis of MAS is unclear, the hallmark of the syndrome is an uncontrolled activation and proliferation of T lymphocytes and macrophages, leading to massive hypersecretion of pro-inflammatory cytokines. Mutations in cytolytic pathway genes are increasingly being recognised in children who develop MAS as part of sJIA. Recently, a mouse model of MAS dependent on repeated stimulation through toll-like receptors was developed. The first-line therapy of MAS complicating sJIA is based on the parenteral administration of high doses of corticosteroids, with or without cyclosporine A. There is increasing evidence that biological therapies, particularly interleukin-1 inhibitors, represent a valuable adjunct to corticosteroids and cyclosporine A in treating MAS complicating sJIA.

In contrast with the numerous controlled trials conducted in polyarticular or systemic juvenile idiopathic arthritis (JIA), little evidence-based information is available for oligoarticular JIA. As a result, the management of children with this subtype, which is the most prevalent in Western countries, is largely empiric. Intra-articular corticosteroid (IAC) injection is the therapy of first choice for oligoarthritis in many pediatric rheumatology centers. However, although IAC injections are usually highly efficacious, relapses of synovitis are common and sometimes occur only a few months after the procedure. It is still unclear whether concomitant administration of methotrexate (MTX) may increase and prolong the effectiveness of IAC injections.

Objective To determine cutoff values for defining the state of high disease activity (HDA) in juvenile idiopathic arthritis (JIA) using the Juvenile Arthritis Disease Activity Score (JADAS). Methods For the selection of cutoff values, data from a clinical database including 609 patients were used. Optimal cutoff values were determined against external criteria by calculating the 25th and 10th centile of cumulative score distribution and through receiver operating characteristic curve analysis. External criteria were based on the therapeutic decision made by the attending doctor. Cross-validation was performed using five patient samples that included 1421 patients. Results The optimal cutoff values were those obtained through the 90% fixed sensitivity method. The selected JADAS cutoff values were the following: 4.2 and 8.5 for JADAS27 in oligoarthritis and polyarthritis, respectively; 4.2 and 10.5 for both JADAS10 and JADAS71 in oligoarthritis and polyarthritis, respectively. In cross-validation analyses, the cutoff values showed strong ability to discriminate between different levels of American College of Rheumatology paediatric response in two clinical trials and could predict worse functional and radiographic outcome. Conclusions Cutoff values for classifying HDA in JIA using the JADAS were developed. In cross-validation analyses, they proved to have good construct and discriminant validity and ability to predict disease outcome.

Assessment of disease activity is a fundamental component of the clinical evaluation of children with juvenile idiopathic arthritis (JIA) because persistently active disease plays a major role in causing joint damage and physical functional disability. Furthermore, measurement of the level of disease activity over time is important in monitoring the disease course and in assessing the effectiveness of therapeutic interventions.

The epidemiology of juvenile idiopathic arthritis (JIA) is variable worldwide. In particular, a wide disparity exists in the prevalence of the diverse disease subtypes across different geographic areas. The therapeutic approach to JIA is not standardized and no established and widely accepted guidelines are available. In the past decade, there have been important progresses in the management of the disease, but the availability of the novel and costly biologic medications is not uniform throughout the world. This issue may have significant impact on disease prognosis, with children living in poorer countries being at greater risk of accumulating disease- and treatment-related damage than children followed in Western pediatric rheumatology centers. The multinational study of the EPidemiology, treatment and Outcome of Childhood Arthritis (EPOCA study) is aimed to obtain information on the frequency of JIA subtypes in different geographic areas, the therapeutic approaches adopted by pediatric rheumatologists practicing in diverse countries or continents, and the disease and health status of children with JIA currently followed worldwide. Parent- and child-reported outcomes are meant to be recorded through the administration of a new multidimensional questionnaire, the Juvenile Arthritis Multidimensional Assessment Report (JAMAR). The first step of the study is based on the translation and cross-cultural adaptation of the questionnaire in the national language of each participating country. Each center is, then, asked to enroll a sample of consecutive JIA patients, who should undergo a retrospective assessment and a cross-sectional evaluation, including completion of the JAMAR, a standardized joint examination, and the assessment of articular and extra-articular damage. At the end of May 2012, 124 centers in 55 countries have agreed to participate in the study. The JAMAR has been or is currently being translated in 38 national languages. The target patient sample is more than 10,000 JIA children worldwide.

Objective To determine cutoff values for defining remission, minimal disease activity, and parent and child acceptable symptom state in juvenile idiopathic arthritis (JIA) using the Juvenile Arthritis Disease Activity Score (JADAS). Methods For the selection of cutoff values, data from a clinical database including 609 children with JIA were used. Optimal cutoff values were determined against external criteria by calculating the 75th percentile of cumulative score distribution and through receiver operating characteristic curve analysis. External criteria included formal definitions of inactive disease and minimal disease activity, subjective rating of remission by physicians, parents, and children, and rating of acceptable symptom state by parents and children. The choice of cutoffs was made based on clinical and statistical grounds. Cross-validation was performed using 4 JIA patient samples that included a total of 1,323 patients, and was based on assessment of construct, discriminant, and predictive validity. Results With all versions of the JADAS, the cutoff score for classifying a patient as having inactive disease was 1, whereas the cutoff for classification of minimal disease activity was 2 for oligoarticular JIA and 3.8 for polyarticular JIA. Cutoffs for physicians', parents', and children's subjective rating of remission ranged from 2 to 2.3. Cutoffs for acceptable symptom state ranged from 3.2 to 5.4 for parents and from 3 to 4.5 for children. Results of cross-validation analyses strongly supported the selected cutoff values. Conclusion Cutoff values for classifying various disease states in JIA using the JADAS were developed. In cross-validation analyses, they proved to have good construct and discriminant validity and ability to predict disease outcome.

Background In juvenile idiopathic arthritis (JIA), substantial disagreement between physicians, parents and children over disease remission can lead to difficulty in assessing the efficacy of treatments. It is, therefore, important to ascertain whether clinicians’, parents’ and children’s opinions converge and diverge and whether the recently developed criteria for inactive disease (ID) or minimal disease activity (MDA) may help enhance concordance. Objective

Background Recent advances in treatment of juvenile idiopathic arthritis (JIA) have markedly increased the potential for achieving a remission or minimal disease activity (MDA) state. So far, these states have been defined using a categorical model, which requires simultaneous fulfillment of multiple criteria. However, a dimensional model, based on pooling individual measures into a composite score, has the advantage of providing one summary number on a continuous scale.

Background The results obtained with the novel biologic agents have increased the expectations of benefit of treatment of juvenile idiopathic arthritis (JIA), with disease remission being now the therapeutic goal in all patients. However, the assessment of remission has seldom been incorporated in clinical trials of biologics in JIA. Moreover, little information exists on the prediction of the efficacy of biologic medications. Objectives To evaluate the proportion of children with JIA treated with etanercept (ETN) who achieved the state of inactive disease (ID) and to search for predictors of ID. Methods The clinical chart of all consecutive JIA patients who were given ETN between 2002 and 2011, and had a follow-up of at least 6 months after ETN start were reviewed. The achievement of ID, defined by the Wallace criteria (J Rheum 2004;31:2290-4), was assessed at each visit from the start of ETN. The primary study outcomes were: 1) proportion of patients who had ID at last follow-up visit while still on ETN; 2) time to achievement of ID after ETN start. Predictors of treatment outcomes included demographic data, JIA subset, type of affected joints, medications received before and during ETN administration, and JIA activity measures at ETN start. The search for predictors was conducted by means of univariate and multivariate analyses. Results A total of 187 patients were given ETN at the standard dose of 0.8 mg/kg/week in the study period. The disease duration at ETN start ranged from 3 months to 21.2 years (median 5.0 years). Fourteen patients had received ETN for less than 6 months or were lost to follow-up. In the remaining 173 patients, treatment duration from baseline to last follow-up visit ranged from 6 months to 10.5 years (median 2.4 years). At last follow-up visit, 87 (50.3%) patients had ID. The time to ID ranged from 2 months to 6.3 years (median 0.7 years). An age at disease onset

Background Methotrexate (MTX) is the disease-modifying medication of first-choice for the treatment of juvenile idiopathic arthritis (JIA). Although serious adverse effects are rare, MTX intolerance, particularly gastrointestinal discomfort, is frequently observed. However, it is unclear whether the prevalence of adverse events varies across different routes of administration. Objectives To compare the rate of parent proxy-reported or child self-reported side effects of MTX administered orally, subcutaneously or intramuscularly. Methods The parents of children with JIA who were seen at our center from March 2007 and September 2011 and were receiving MTX therapy were asked to complete the proxy-report version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR), which includes a checklist of medication side effects. The self-report version of the same questionnaire was also completed by children, if aged more than 7-8 years. The JAMAR lists 18 side effects and offers the possibility to record up to 2 side effects not included in the list. MTX therapy was started in all patients, irrespective of the route of administration, at 15 mg/m2/week. All patents were given folate supplementation with folinic acid. Results The JAMAR was completed by 337 parents in 1007 visits and by 183 children in 419 visits. The frequency of parent proxy-reported side effects by route of administration is shown in the Table. Conclusions The frequency of nausea and vomiting was greater in children receiving MTX parenterally than in those on oral MTX. Children taking MTX orally had more frequently stomach pain/burning or sleep disturbances than those on parenteral MTX. Disclosure of Interest None Declared

Background In the last decade, there have been major advances in the management of juvenile idiopathic arthritis (JIA). A reliable documentation of these progresses creates the need for validated criteria that describe precisely patient states. We recently, developed the cut-off values for remission, minimal disease activity and acceptable symptom states in JIA based on the JADAS (1). Objectives To determine the JADAS cut-offs for high disease activity (HDA) in JIA. Methods For the selection of cut-offs, data from a clinical database including 618 children with JIA were used. Patients were defined as having HDA when the physician made one of the following therapeutic interventions: 1) start of methotrexate (MTX); 2) intra-articular corticosteroid injection; 3) start of a biologic medication; 4) start of systemic corticosteroids. Patients were defined as having low disease activity (LDA) when they were receiving no therapy or had therapy discontinued, tapered or left unchanged for >1 year. For each patient, 1 visit in HDA and 1 visit in LDA was retained for the analyses. “Optimal” JADAS cut-offs were determined by calculating the 25th percentile of cumulative score distribution in patients with HDA and by assessing their ability to discriminate between HDA and LDA through ROC curve analysis (including calculation of Youden index and fixed 90% specificity). Cross-validation of cut-offs was performed in 490 JIA patients enrolled in the PRINTO MTX trial (2) and was based on assessment of discriminant validity. Results The cut-offs were calculated separately for patients with oligoarticular and polyarticular course of joint disease (irrespective of ILAR category) owing to the different severity of these 2 JIA phenotypes. The table shows the cut-offs for HDA for JADAS-71 version, defined according to the different statistical methods. The cut-offs that showed the best trade-off between sensitivity and specificity were selected for cross-validation analyses. These analyses showed that at baseline visit of MTX trial 94.7% of patients had a JADAS-71 higher than the HDA cut-off for polyarthritis. At 6-month visit, the percentage of patients with a JADAS-71 higher than the cut-off was 85.6% among nonresponders and 23.8% among responders. Conclusions We developed the JADAS cut-offs for HDA in JIA. The cut-offs revealed strong discriminant ability in a clinical trial and are, therefore, potentially applicable in clinical practice, observational investigations, and therapeutic studies. References Consolaro A et al. AR50:2191-201 Disclosure of Interest None Declared

Background In the last decade, there have been major advances in the management of juvenile idiopathic arthritis (JIA), which include the shift towards early aggressive interventions and the development of new therapeutic agents and combination treatment strategies. A reliable documentation of the advances in therapeutic effectiveness creates the need for validated and clinically useful criteria that describe precisely the clinical states of the patient. Objectives To determine cut-off values for high disease activity (HDA) based on the original Juvenile Arthritis Disease Activity Score (JADAS) (1) and a simplified 3-item version of the JADAS (clinical JADAS- cJADAS), which does not include the acute phase reactant (2). Methods For the selection of cut-offs, data from a clinical database including 618 children with JIA followed at study center were used. ‘Optimal’ cut-offs were determined against external criteria by calculating the 25 th percentile of cumulative score distribution and through receiver operating characteristic curve analysis. Patients were identified as being in HDA when the physician decided a major therapeutic intervention, defined as follows: 1) start of methotrexate therapy; 2) intraarticular corticosteroid injection (IAC); 3) start of biologic treatment; 4) start of systemic corticosteroid therapy. For each patient, 1 visit with HDA and 1 visit with no-HDA (i.e. visit in which none of the major therapeutic interventions listed above was made) were retained. The choice of cut-offs was made on clinical and statistical grounds. Results A total of 364 visits for oligoarticular-course patients (134 with HDA) and 412 visits for polyarticular-course patients (147 with HDA) were retained. The table shows the cutoffs (sensitivity/specificity) defined according to the different statistical methods and the AUC of the ROC curve. Proposed HDA cutoffs in oligoarticular-course JIA are 7.9 for JADAS10 and JADAS71, 7.2 for JADAS27, 7 for cJADAS10 and cJADAS71, and 6.5 for cJADAS 27. Proposed HDA cutoffs in polyarticular-course JIA are 12 for JADAS10 and JADAS71, 11 for JADAS27, cJADAS10 and cJADAS71, and 10 for cJADAS27. Conclusions We developed the HDA cutoffs for the JADAS and the cJADAS. The cutoffs need a thorough validation before being introduced in daily practice and clinical trials. References Consolaro A et al. Arthritis Rheum. 2009 May 15;61(5):658-66 McErlane F et al. Ann Rheum Dis. 2012 Epub ahead of print Disclosure of Interest None Declared

Macrophage activation syndrome (MAS) is a severe, potentially fatal complication of systemic juvenile idiopathic arthritis (sJIA) with features of hemophagocytosis, leading to coagulopathy, pancytopenia, and liver and central nervous system dysfunction. MAS is overt in about 10% of children with sJIA but may occur subclinically in another 30-40% of patients. The diagnosis of MAS in sJIA can be challenging because it may mimic a flare of the underlying disease or be confounded with an infectious complication or a medication side effect. So far, universally agreed upon diagnostic criteria for MAS are not available. A multinational collaborative effort is under way that is aimed to generate new criteria for diagnosing MAS as a complication of sJIA. The first step of the project has led to the identification of, by means of a Delphi survey, the clinical, laboratory and histopatho logic features of MAS that were felt to be most important by a large sample of international pediatric rheumatologists with experience with MAS in children with sJIA. The diagnostic performance of potential criteria will be scrutinized further in the second phase of the study, through the analysis (ongoing) of real patient data. The final set of criteria is meant to be established in a consensus conference of experts using a combination of statistical and consensus formation techniques. The ultimate goal of the project is to develop a core set of criteria that is both highly sensitive and specific. These criteria will assist physicians in MAS diagnosis in children with sJIA and enable quick institution of appropriate therapy.

The recent advances in the management of juvenile idiopathic arthritis (JIA) have increased considerably the potential to achieve disease remission or, at least, low levels of disease activity, and have consequently moved the therapeutic aims towards the attainment of inactive disease (ID). Complete disease quiescence is regarded as the ideal therapeutic target because its achievement helps preventing further joint damage and disability and may enhance physical function and quality of life.