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Background: The evidence shows a reduction in pediatric emergency department (PED) flows during the early stages of the COVID-19 pandemic. Using interrupted time-series analysis, we evaluated the impact of different stages of the pandemic response on overall and cause-specific PED attendance at a tertiary hospital in south Italy. Our methods included evaluations of total visits, hospitalizations, accesses for critical illnesses and four etiological categories (transmissible and non-transmissible infectious diseases, trauma and mental-health) during March–December 2020, which were compared with analogous intervals from 2016 to 2019; the pandemic period was divided into three segments: the “first lockdown” (FL, 9 March–3 May), the “post-lockdown” (PL, 4 May–6 November) and the “second lockdown” (SL, 7 November–31 December). Our results showed that attendance dropped by a mean of 50.09% during the pandemic stages, while hospitalizations increased. Critical illnesses decreased during FL (incidence rate ratio -IRR- 0.37, 95% CI 0.13, 0.88) e SL (IRR 0.09, 95% CI 0.01, 0.74) and transmissible disease related visits reduced more markedly and persistently (FL: IRR 0.18, 95% CI 0.14, 0.24; PL: IRR 0.20, 95% CI 0.13, 0.31, SL: IRR 0.17, 95% CI 0.10, 0.29). Non-infectious diseases returned to pre-COVID-19 pandemic levels by PL. We concluded that that the results highlight the specific effect of the late 2020 containment measures on transmissible infectious diseases and their burden on pediatric emergency resources. This evidence can inform resource allocation and interventions to mitigate the impact of infectious diseases on pediatric populations and the health-care system.

Objective To assess concordance among criteria for inactive disease (ID) and low disease activity (LDA) in juvenile idiopathic arthritis (JIA) and to seek factors driving discordance. Methods The frequency of fulfillment of existing criteria was evaluated in information on 10,186 patients extracted from 3 cross-sectional data sets. Patients were divided up according to the functional phenotypes of oligoarthritis and polyarthritis. Concordance between criteria was examined using weighted Venn diagrams. The role of each individual component in explaining discordance between criteria was assessed by calculating the absolute number and percentage of instances in which the component was responsible for discrepancy between definitions. Results Criteria for ID were met by 28.6–41.1% of patients with oligoarthritis and by 24.0–33.4% of patients with polyarthritis. Criteria for LDA were met by 44.8–62.4% of patients with oligoarthritis and by 44.6–50.4% of patients with polyarthritis. There was a 57.9–62.3% overlap between criteria for ID and a 67.9–85% overlap between criteria for LDA. Parent and physician global assessments and acute-phase reactants were responsible for the majority of instances of discordance among criteria for ID (8.7–15.5%, 10.0–12.3%, and 10.8–17.3%, respectively). Conclusion We found fair concordance between criteria for ID and LDA in JIA, with the main drivers of discordance for ID being physician and parent global assessments and acute-phase reactants. This observation highlights the need for further studies aimed to evaluate the impact of subjective physician and parent perception of disease remission and of laboratory measures of inflammatory activity on the definition of ID.

Objective To develop and validate new Juvenile Arthritis Disease Activity Score 10 (JADAS10) and clinical JADAS10 (cJADAS10) cutoffs to separate the states of inactive disease (ID), minimal disease activity (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with oligoarthritis and with rheumatoid factor-negative polyarthritis, based on subjective disease assessment by the treating pediatric rheumatologist. Methods The cutoffs definition cohort was composed of 1,936 patients included in the multinational Epidemiology, Treatment and Outcome of Childhood Arthritis (EPOCA) study. Using the subjective physician rating as an external criterion, 4 methods were applied to identify the cutoffs: mapping, Youden index, 90% specificity, and maximum agreement. The validation cohort included 4,014 EPOCA patients, patients from 2 randomized trials, and 88 patients from the PharmaChild registry. Cutoff validation was conducted by assessing discriminative and predictive ability. Results The JADAS10 cutoffs were 1.4, 4, and 13, respectively, for oligoarthritis and 2.7, 6, and 17, respectively, for polyarthritis. The cJADAS10 cutoffs were 1.1, 4, and 12, respectively, for oligoarthritis and 2.5, 5, and 16, respectively, for polyarthritis. The cutoffs discriminated strongly among different levels of pain and morning stiffness, between patients who were and those who were not prescribed a new medication, and between different levels of improvement in clinical trials. Achievement of ID and MiDA according to the new JADAS cutoffs at least twice in the first year of disease predicted better outcome at 2 years. Conclusion The 2021 JADAS and cJADAS cutoffs revealed good metrologic properties in both definition and validation samples, and are therefore suitable for use in clinical trials and routine practice.

OBJECTIVE To compare the frequency of joint and tendon disease on ultrasound (US) and clinical examination, and to investigate agreement between US and clinical evaluation in ankles with clinically active juvenile idiopathic arthritis (JIA). METHODS US and clinical evaluation were performed independently in the joint and tendon compartments of 105 ankles. Gray-scale (GS) US and power Doppler (PD) US joint abnormalities were scored on a 4-point semiquantitative scale. A joint with a GS score ≥2 and/or a PD score ≥1 was defined as active on US. Agreement was tested using kappa statistics. RESULTS A total of 163 joints in 89 ankles had active synovitis on US. The tibiotalar (TT) joint was the most commonly affected joint on US and on clinical evaluation. The intertarsal (IT) joint and the subtalar (ST) joint were the second in frequency on US and on clinical evaluation, respectively. Tenosynovitis was found more commonly on US than on clinical evaluation (70.5% and 32.4%, respectively), and was more frequent in the medial and lateral than in the anterior tendon compartment. Isolated tenosynovitis was detected on US in 12 of 105 ankles. Agreement between US and clinical evaluation for detection of active synovitis and tenosynovitis was less than acceptable (κ

ObjectiveTo investigate the frequency in which the physician provides a global assessment of disease activity (PhGA) >0 and an active joint count (AJC)=0 in children with juvenile idiopathic arthritis (JIA) and search for determinants of divergence between the two measures.MethodsData were extracted from a multinational cross-sectional dataset of 9966 patients who had JIA by International League of Associations for Rheumatology criteria, were recruited between 2011 and 2016, and had both PhGA and AJC recorded by the caring paediatric rheumatologist at the study visit. Determinants of discordance between PhGA>0 and AJC=0 were searched for by multivariable logistic regression and dominance analyses.ResultsThe PhGA was scored >0 in 1647 (32.3%) of 5103 patients who had an AJC of 0. Independent associations with discordant assessment were identified for tender or restricted joint count >0, history of enthesitis, presence of active uveitis or systemic features, enthesitis-related or systemic arthritis, increased acute phase reactants, pain visual analogue scale (VAS)>0, and impaired physical or psychosocial well-being. In dominance analysis, tender joint count accounted for 35.43% of PhGA variance, followed by pain VAS>0 (17.72%), restricted joint count >0 (16.14%) and physical health score >0 (11.42%).ConclusionWe found that many paediatric rheumatologists did not mark a score of 0 for patients who they found not to have active joints. The presence of pain in joints not meeting the definition of active joint used in JIA was the main determinant of this phenomenon.

Objective.To investigate the effect of morning stiffness (MS) on parent disease perception in children with juvenile idiopathic arthritis (JIA) with clinically inactive disease (CID).Methods.We examined 652 visits in which patients fulfilled 2004 or 2011 Wallace criteria for CID. Parent-reported outcomes were compared among patients with no MS or with MS < or ≥ 15 min.Results.Among 652 visits with CID by 2004 criteria, no MS was reported in 554 visits (85%), MS < 15 min in 53 (8%), and MS ≥ 15 min in 45 (7%). The frequency of altered physical function, health-related quality of life and well-being, pain, and disease activity visual analog scales was proportionally greater in patients without MS than those with longer MS. The frequency of parent subjective rating of disease state as remission was 87.7%, 58%, and 26.7% among patients with no MS, MS < 15 min, and MS ≥ 15 min, respectively.Conclusion.Our results suggest that a change in 2011 CID criteria to require absence of MS should be considered.

Objective.The current Juvenile Idiopathic Arthritis (JIA) Core Set used in randomized controlled trials (RCT) and longitudinal observational studies (LOS) was developed without the input of patients/parents. At the Outcome Measures in Rheumatology (OMERACT) 2016, a special interest group voted to reconsider the core set, incorporating broader input. We describe subsequent work culminating in an OMERACT 2018 plenary and consensus voting.Methods.Candidate domains were identified through literature review, qualitative surveys, and online discussion boards (ODB) held with patients with JIA and parents in Australia, Italy, and the United States. A Delphi process with parents, patients, healthcare providers, researchers, and regulators served to edit the domain list and prioritize candidate domains. After the presentation of results, OMERACT workshop participants voted, with consensus set at > 70%.Results.Participants in ODB were 53 patients with JIA (ages 15–24 yrs) and 55 parents. Three rounds of Delphi considering 27 domains were completed by 190 (response rate 85%), 201 (84%), and 182 (77%) people, respectively, from 50 countries. There was discordance noted between domains prioritized by patients/parents compared to others. OMERACT conference voting approved domains for JIA RCT and LOS with 83% endorsement. Mandatory domains are pain, joint inflammatory signs, activity limitation/physical function, patient’s perception of disease activity (overall well-being), and adverse events. Mandatory in specific circumstances: inflammation/other features relevant to specific JIA categories.Conclusion.Following the OMERACT methodology, we developed an updated JIA Core Domain Set. Next steps are to identify and systematically evaluate best outcome measures for these domains.

Macrophage activation syndrome (MAS) is a serious, potentially life-threatening, hyperinflammatory condition, which belongs to the spectrum of hemophagocytic lymphohistiocytosis (HLH) and can complicate several immunologic and rheumatic disorders. MAS is characterized by a dysfunctional immune response that is similar to that seen in other forms of HLH. Because MAS may pursue a rapidly fatal course, prompt recognition of its clinical and laboratory features and immediate therapeutic intervention are fundamental. Recently, a set of classification criteria for MAS complicating sJIA has been developed through a multinational collaborative effort. High-dose parenteral corticosteroids remain the mainstay of treatment of MAS.

Background:Juvenile Idiopathic Arthritis (JIA) patients experience impaired health and wellbeing due to multiple causes of physical and psychosocial distress, including treatment burden. Despite emerging evidence of its relevance [1], the contribution of treatment adverse events to patient-reported outcomes (PROs) in JIA has been poorly explored.Objectives:To evaluate and rank the impact of patient-reported adverse events (AEs) on overall wellbeing, health-related quality of life (HRQoL), school problems and self-reported medication adherence using data from Pharmachild, a large international JIA pharmacovigilance registry.Methods:Registry entries on 5340 prospective visits of 2251 patients enrolled till December 2018 were analyzed; all included patients were treated with at least one DMARDS or Biologic agent at the time of visit. In the Juvenile Arthritis Multidimensional Assessment Report (JAMAR), patients and parents compiled a checklist of treatments, side effects, self-reported adherence, administration difficulties and disease-related school problems occurred in the previous 4 weeks. Evaluated outcomes included patient acceptable symptom state (PASS), VAS-measured patient assessment of overall wellbeing (PGA) and HRQoL, assessed through the physical health (PhH) and psychosocial health (PsH) subscales. The relationships between AEs and PROs were tested through generalized linear models, accounting for disease activity and symptoms levels. Bayesian Networks were used to explore the causal effects of specific AEs on outcomes to disentangle the confounding role of disease status.Results:AEs were reported in 22.9% of visits. For similar levels of physician global assessment (MD global), patient-assessed disease activity, pain and function, patients reporting AEs had worse PGA, PsH, and lower probability of reaching PASS (fig. 1, all p-values 20.031) and appears to be mediated by effects on PsH and school problems (p Conclusion:AEs have a measurable effect on the wellbeing and psychosocial health of JIA patients, particularly when disease activity is low, and significantly affect school activity and medication adherence. Mood swings and sleep problems show the strongest influence on HRQoL. Addressing AEs appears important to reduce disease impact, improve patients’ satisfaction and therapeutic compliance.References: :[1]Weitzman, Elissa R., et al. Journal of patient-reported outcomes 2.1 (2018): 1.Acknowledgments:for the Paediatric Rheumatology International Trials Organisation (PRINTO)Disclosure of Interests: :Alessandra Alongi: None declared, Alessandro Consolaro Grant/research support from: Pfizer Inc., AlfaSigma, Speakers bureau: AbbVie, Gordana Vijatov-Djuric: None declared, Giovanni Filocamo: None declared, Olga Vougiouka: None declared, Alma Nunzia Olivieri: None declared, Cristina Herrera Mora: None declared, Wolfgang Emminger: None declared, Angelo Ravelli: None declared, Nicolino Ruperto Grant/research support from: Bristol-Myers Squibb, Eli Lily, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sobi (paid to institution), Consultant of: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda, Speakers bureau: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda

Background The choice of an appropriate definition of inactive disease (ID) is important because ID has been identified as the ideal therapeutic goal in the treat-to-target strategy in juvenile idiopathic arthritis (JIA).1 Several criteria for ID in JIA have been proposed, including Wallace 2004 and 2011 criteria and JADAS10 and clinical JADAS10 (cJADAS10) criteria. However, a recent study2 has shown that these criteria do not always identify the same group of patients. In addition, it is unknown whether and to what extent the formal definitions of ID agree with the subjective perception of disease remission by the physician and the parent.3 Objectives To investigate the concordance between current criteria for ID and subjective judgment of disease remission by physicians and parents in children with JIA. Methods We evaluated the clinical data of the last visits made in 669 children with JIA from March 2007 to December 2010 to identify all visits in which the caring physician and a parent judged subjectively and independently the child’s disease state as remission or non-remission and the parent declared whether he/she was satisfied or non-satisfied with current illness state (i.e. Parent Acceptable Symptom State, PASS).4 All visits judged subjectively by the physician and the parent as remission or judged in PASS by the parent were examined to identify those which met the Wallace 2004 and 2011 criteria and the JADAS10 and cJADAS10 criteria for ID. Visits which met both subjective and objective definitions were defined as concordant. Results Of the 246 visits in which the physician judged subjectively the disease state as remission, 34.6% and 27.6% met the 2004 and 2011 Wallace criteria, respectively, and 38.6% and 54.5% met the JADAS10 and cJADAS10 criteria for ID, respectively.(Figure 1) Of the 338 visits in which the parent judged subjectively the disease state as remission, 19.8% and 18% met the 2004 and 2011 Wallace criteria, respectively, and 34.9% and 48.8% met the JADAS10 and cJADAS10 criteria for ID, respectively.(Figure 2) In 76.4% of visits judged as remission by the physician, the parent provided the same evaluation. In 55.6% of visits judged as remission by the parent, the physician provided the same evaluation.(Figure 1-2) Of 467 visits judged in PASS by the parent, 17.6% and 14.8% met the 2004 and 2011 Wallace criteria, respectively, and 26.6% and 37.5% met the JADAS10 and cJADAS10 criteria for ID, respectively. Conclusion The JADAS10 and cJADAS10 criteria for ID were more concordant with physician’s and parent’s subjective judgment of remission and with parent’s satisfaction with current illness state than Wallace criteria. The cJADAS10, which lacks the acute phase reactant, revealed the best concordance with both physician’s and parent’s subjective assessments. Physician-parent agreement was greater for remission judged by the physician than for remission judged by the parent. References [1] Ravelli A, et al. Ann Rheum Dis. 2018;77:819-828; 2. Shoop-Whorral SJW, et al. Ann Rheum Dis. 2017;76:1381-1388; 3. Giancane G, et al. Nat Rev Rheumatol. 2017;13:460-461. 4. Filocamo G, et al. J Rheumatol. 2012;39:856-63. Disclosure of Interests Gabriella Giancane: None declared, Maria Francesca Gicchino: None declared, Alessandra Alongi: None declared, Chiara Campone: None declared, Alessandro Consolaro Grant/research support from: AbbVie, Pfizer, Angelo Ravelli Grant/research support from: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & johnson, novartis, pfizer, reckitt benkiser, and roche, consultant for: angelini, abbvie, bristol-myers squibb, johnson & johnson, novartis, pfizer, reckitt benkiser, and roche, speakers bureau: angelini, abbvie, bristol-myers squibb, johnson & johnson, novartis, pfizer, reckitt benkiser, and roche

Background Juvenile idiopathic arthritis (JIA) affects patients’ well-being as the result of a complex interplay of multiple factors, including disease activity, symptoms, physical and emotional quality of life, and treatment burden. Little evidence exists about the relative contribution of these elements to disease impact. Objectives 1) To identify direct and indirect determinants of well-being, expressed by VAS-measured patient/parent global assessment of well-being (PGW), in children with oligo- and polyarthritis. 2) To assess whether the impact of the major determinants varies with level of disease activity. Methods We analyzed data of 1873 patients evaluated in 4464 prospective visits from the international JIA pharmacovigilance registry Pharmachild. Patient-reported outcomes were collected through the Juvenile Arthritis Multidimensional Assessment Report (JAMAR). Evaluated predictors of PGW included VAS-measured physician global assessment, inflammatory markers, active joint count, VAS-measured pain, morning stiffness duration, Juvenile Arthritis Functional Score (JAFS), Physical (PhHS) and Psychosocial (PsHS) subscales of the Pediatric Rheumatology Quality of Life (PRQL) scale, disease damage measured through the Juvenile Arthritis Damage Index (JADI) and adverse events (AE). We used path analysis to assess direct and indirect effects of variables on PWG. We repeated the analysis on subsets of visits stratified by disease activity, measured with JADAS10, to test differences across activity states. Results Pain severity proved the strongest direct determinant of PGW (b 0.521, p Conclusion: Pain was the main determinant of PGW in all disease activity states. The level of PGW also reflected other aspects of disease impact, particularly physical and psychosocial distress, and, to a lesser extent, treatment adverse events. The impact of pain and physical functioning on psychosocial health and well-being varies with disease activity, being greater in patients with higher disease activity. Reference [1] Moorthy et al, Pediatric Rheumatology 2010; 8:20 Acknowledgement for the Paediatric Rheumatology International Trials Organisation (PRINTO) Disclosure of Interests Alessandra Alongi: None declared, Alessandro Consolaro Grant/research support from: AbbVie, Pfizer, Gabriella Giancane: None declared, Maria Greca Magnolia: None declared, Giovanni Filocamo: None declared, Esther Hoppenreijs: None declared, Angelo Ravelli Grant/research support from: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Consultant for: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Speakers bureau: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Nicolino Ruperto Grant/research support from: The Gaslini Hospital, where NR works as full-time public employee, has received contributions (> 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Consultant for: Received honoraria for consultancies or speaker bureaus (

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. Morning stiffness is a major symptom of JIA, and is usually associated with active disease. The 2004 preliminary criteria for inactive disease (ID) in JIA did not include the assessment of morning stiffness, whereas the 2011 revision of the criteria has allowed the presence of morning stiffness (MS) lasting ≤ 15 minutes. MS was included in 2011 revision based on the consideration that MS of a short duration (i.e., ≤ 15 minutes) can represent residua of previously active disease without current active disease. However, it is unclear whether the disease status of children with ID who have or do not have morning stiffness is comparable. Objectives: To compare the disease status of children with JIA who met the 2004 and 2011 revised criteria for ID in relation to the presence or absence morning stiffness. Methods: A database of 1208 Italian children included in 2 multicenter studies (1,2) who underwent a total of 3380 visits was examined to identify all visits in which the patients fulfilled the 2004 or 2011 criteria for ID. In case a patient met the ID criteria in more than 1 visit, only the first visit was retained. For each visit with ID, the duration of morning stiffness was categorized as ≤ 15 min or > 15 min. Clinical assessments included demographic features and parent-reported outcomes Results: A total of 668 visits in which patients met the criteria for ID were identified. Absence of morning stiffness was reported in 564 (84.4%) visits, whereas in 104 visits (15.5%) there was morning stiffness. Among the visits with morning stiffness, in 55 (8.2%) duration was ≤15 min, and in 49 (7.3%) duration was > 15 min. The table shows the comparison of disease duration and parent-reported outcomes between patients with absence or presence of morning stiffness. MS: morning stiffness; IQR: interquartile range, *above the mean of healthy children (2) Conclusion: Among patients who met the 2011 criteria for ID, those with morning stiffness ≤15 min had worse parent-reported outcomes than those without morning stiffness. This finding suggests that parents may not perceive their child’s disease state as true remission when lower degrees of morning stiffness are present. Notably, a sizeable proportion (7,3%) of children meeting the 2004 ID criteria had morning stiffness lasting > 15 min. The removal of the criterion “Duration of morning stiffness of ≤ 15 minutes” to “Absence of morning stiffness” in the definition for ID should be considered. References [1] Filocamo, et al. A new approach to clinical care of juvenile idiopathic arthritis: the Juvenile Arthritis Multidimensional Assessment Report. J Reumatol 2011 [2] Verazza, et al. Disease status, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept. PROJ 2016 Disclosure of Interests: Maria Francesca Gicchino: None declared, Gabriella Giancane: None declared, Alessandra Alongi: None declared, Silvia Rosina: None declared, Jessica Tibaldi: None declared, Marta Mazzoni: None declared, Angelo Ravelli Grant/research support from: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Consultant for: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Speakers bureau: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Alessandro Consolaro Grant/research support from: AbbVie, Pfizer

Background: After nearly two decades from the start of the Biologic era, systematic analyses of patient with juvenile idiopathic arthritis (JIA) have shown a high frequency of attainment of inactive disease (ID) and satisfactory levels of physical function and quality of life. However, whether and to what extent the disease prognosis has improved in comparison with the methotrexate (MTX) era is still uncertain. Objectives: To compare the long-term disease state, in terms of activity and damage, of children with JIA who had their disease onset in MTX or Biologic eras. Methods: Patients were included in MTX or Biologic era cohort depending on whether their disease presentation occurred before or after January 2000. Patients in the MTX era cohort and part of the patients in the Biologic era cohort were taken from a previous cross-sectional study published by our group,1 which enrolled 310 patients with disease onset between December 1986 and December 2002. An additional sample of patients with onset in the Biologic era was enrolled in a subsequent prospective cross-sectional study, which included all consecutive patients meeting the ILAR criteria for JIA, who were seen consecutively at the Istituto Gaslini of Genoa, Italy, between January 2015 and June 2017. All patients had disease duration ≥ 5 years and underwent a prospective cross-sectional assessment, which included measurement of disease activity and damage. ID and low disease activity (LDA) states were defined according to Wallace, JADAS10 and cJADAS10 criteria. Articular and extra-articular damage was assessed with the Juvenile Arthritis Damage Index (JADI). Results: MTX and Biologic era cohorts included 239 and 269 patients, respectively. Patients were divided in the “functional phenotypes” of oligoarthritis and polyarthritis. At cross-sectional visit, patients in the Biologic era cohort with either oligoarthritis or polyarthritis had consistently higher frequencies of ID and LDA than patients in the MTX era cohort. The measurement of disease damage at cross-sectional visit revealed that the frequency of impairment of > 1 JADI-Articular items was higher in MTX than in Biologic era cohort (17.6% versus 11% in oligoarthritis and 52.6% versus 21.8% in polyarthritis). Likewise, frequency of involvement of > 1 JADI-Extraarticular item was higher in MTX than in Biologic era cohort (26.5% versus 16.2% in oligoarthritis and 31.4% versus 13.5% in polyarthritis). The sole JADI items that were detected in more than 5% of patients in the Biologic era cohort were temporomandibular damage in oligoarthritis and polyarthritis, ankle damage in polyarthritis and leg-length inequality in oligoarthritis. The analysis of the temporal trend of damage development over the 25 years of our analysis (1986-2011) highlighted the marked decrease in damage over time and the more pronounced decline in the Biologic era (Figure 1). Conclusion: Our study provides evidence of the remarkable prognostic improvement obtained with the recent therapeutic advance in JIA. References: [1] Solari et al. Arthritis Care Res. 2008;59:1571–9. Disclosure of Interests: Gabriella Giancane: None declared, Valentina Muratore: None declared, Valentina Marzetti: None declared, Neus Quilis Marti: None declared, Belen Serrano Benavente: None declared, Francesca Bagnasco: None declared, Alessandra Alongi: None declared, Adele Civino: None declared, Lorenzo Quartulli: None declared, Alessandro Consolaro Grant/research support from: AbbVie, Pfizer, Angelo Ravelli Grant/research support from: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Consultant for: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Speakers bureau: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche

Background: Despite being considered as a distinct diagnostic category in the current ILAR classification criteria, Juvenile Psoriasic Arthritis (JPsA) is known to be a heterogeneous clinical entity, with growing evidence suggesting at least two age-based distinct subgroups(1) Objectives: To identify and characterize subgroups of patients classified as JPsA according to the ILAR criteria and their possible differences in outcomes. Methods: Cross-sectional data from patients enrolled in The EPidemiology, treatment and Outcome of Childhood Arthritis (EPOCA) study and classified as JPsA according to ILAR criteria (n=308) were analyzed. Latent class analysis (LCA) was used to identify subgroups of subjects with similar profiles ILAR criteria for JPsA (presence at onset of psoriasis, dactylitis, nail changes, first-degree relative with psoriasis) and age of arthritis onset. Multinomial logistic regression (three-step method) was performed to explore differences across the obtained classes in clinical-laboratoristic features at onset and outcomes measures collected at visit, namely JADAS scores, VAS-measured Pain, Overall Well-Being (PGA) Pediatric Rheumatology Quality of Life Scale (PRQL). In patients with disease duration more than 2 years (n=233), the relation with Articular and Extraarticular Juvenile Arthritis Damage Index (JADI) was also assessed. Results: LCA revealed 5 classes: 1) late-onset patients with psoriasis, characterized by higher frequency of axial involvement at visit (n = 121); 2) early-onset patients with psoriasis, more likely to be ANA-positive (n = 66); 3) young females with dactylitis at onset and family history of psoriasis, more likely to present with symmetric joint involvement (n = 62); 4) subjects with nail changes and family history of psoriasis(n=34); 5) patients exhibiting dactylitis and nail changes at onset, mostly males, with higher rates of HLA-B27 positivity, small joint involvement and enthesitis at visit (n = 25). Class 1 is associated with higher scores of JADAS10, pain, PGA and JQ; these group also shows higher JADI-A than Class 3. Extraarticular damage is worst for Class 2 subjects. Conclusion: The data driven clustering approach revealed several subgroups, confirming the heterogeneity of JPSA in a multinational cohort. Later-onset subjects with psoriasis have more aggressive disease, being clearly distinct from early-onset ANA-positive patients with psoriasis. The results suggest the need to revise the current classification in order to identify groups that may benefit from different therapeutic choices. References [1] Stoll ML, Nigrovic PA. Clin Dev Immunol. 2006;13(2–4):377–80. Disclosure of Interests: Hala Etayari: None declared, Arūnė Ramanauskiene: None declared, Alessandra Alongi: None declared, Yaryna Boyko: None declared, Yosef Uziel: None declared, Tadej Avcin: None declared, Pierre Quartier Consultant for: AbbVie, Chugai-Roche, lilly, Novartis, Novimmune, Sanofi, and SOBI, Consultant for: AbbVie, Chugai-Roche, Lilly, Novartis, Novimmune, Sanofi, and SOBI, Speakers bureau: AbbVie, BMS, Chugai-Roche, Novartis, Pfizer, and SOBI, Speakers bureau: AbbVie, BMS, Chugai-Roche, Novartis, Pfizer, and SOBI, Nicolino Ruperto Grant/research support from: The Gaslini Hospital, where NR works as full-time public employee, has received contributions (> 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Consultant for: Received honoraria for consultancies or speaker bureaus (

Background: The assessment of disease activity plays a pivotal role in the management of children with juvenile idiopathic arthritis (JIA). Most recent recommendations require that parents’ and children’s perception is incorporated in the evaluation of the disease course and of effectiveness of therapeutic interventions. A new disease activity tool, named parent Juvenile Arthritis Disease Activity Score (parJADAS) and based only on parent-centered outcome measures, is currently under development (1). Objectives: To demonstrate, in a large multinational dataset of JIA patients, the discriminant ability of the parJADAS. Methods: The parJADAS includes 4 measures: 1) parent assessment of disease activity; 2) assessment of pain intensity; 3) proxy assessment of joint disease; 4) assessment of morning stiffness (MS). Disease activity and pain are assessed on a 21-numbered circle VAS (0 = best and 10 = worst). The active joint count is based on the count of any swollen or painful joint, irrespective of its type, up to a maximum of 10 joints. MS duration is assessed on a Likert scale, ranging from no MS (0 points) to > 2 hours of MS (10 points). Validation was conducted on a dataset of 8,656 children with JIA from 49 countries, enrolled in the study of Epidemiology, treatment and Outcome of Childhood Arthritis (2), who had all the variables included in the parJADAS available. Discriminant ability was evaluated by comparing parJADAS levels (median, [IQR]) among patients with inactive disease (ID), low disease activity (LDA), moderate disease activity (MDA), and high disease activity (HDA) according to the cJADAS10; patients in remission, continued activity, or flare according to the attending physician; patients whose parents were satisfied or not with current disease state. To assess the possible influence of the articular and extra-articular damage on the parJADAS, the levels of the score in patients with or without damage (Juvenile Arthritis Damage Index > 0) were compared. For this analysis, only subjects in inactive disease and with at least 2 years of disease course were considered (n = 2,423). Results: The levels of parJADAS in patients in ID, LDA, MDA, and HDA were 0.0 [0.0, 1.0], 3.0 [1.0, 6.0], 6.0 [2.0, 11.5], an 14.5 [8.5, 21.0], respectively (Kruskal-Wallis test, p Conclusion: The parJADAS showed excellent discriminate ability in a large multinational cohort. The score did not show to be relevantly influenced by disease damage in JIA patients in remission. References [1] Consolaro A, et al. “Development and Initial Validation of the Parent and Child Versions of the Juvenile Arthritis Disease Activity Score”. Arthritis Rheumatol. 2016; 68 (suppl 10). [2] Consolaro A, et al. “Phenotypic variability and disparities in treatment and outcomes of childhood arthritis throughout the world: results from an observational cohort study”. The Lancet Child and Adolescent Health, In press. Disclosure of Interests: Francesca Ridella: None declared, Giedre Januskeviciute: None declared, Chiara Trincianti: None declared, Gabriella Giancane: None declared, Alessandra Alongi: None declared, Soamarat Vilaiyuk: None declared, Gaelle Chedeville: None declared, Chris Pruunsild: None declared, Pekka Lahdenne: None declared, Nicolino Ruperto Grant/research support from: The Gaslini Hospital, where NR works as full-time public employee, has received contributions (> 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Consultant for: Received honoraria for consultancies or speaker bureaus (

Objective To compare the long-term disease state, in terms of activity and damage, of children with juvenile idiopathic arthritis (JIA) who had their disease onset in methotrexate (MTX) or biologic eras. Methods Patients were included in MTX or biologic era cohort depending on whether their disease presentation occurred before or after January 2000. All patients had disease duration ≥ 5 years and underwent a prospective cross-sectional assessment, which included measurement of disease activity and damage. Inactive disease (ID) and low disease activity (LDA) states were defined according to Wallace, JADAS10, and cJADAS10 criteria. Articular and extraarticular damage was assessed with the Juvenile Arthritis Damage Index (JADI). Results MTX and biologic era cohorts included 239 and 269 patients, respectively. Patients were divided in the “functional phenotypes” of oligoarthritis and polyarthritis. At cross-sectional visit, patients in the biologic era cohort with either oligoarthritis or polyarthritis had consistently higher frequencies of ID and LDA by all criteria. The measurement of disease damage at cross-sectional visit revealed that the frequency of impairment of > 1 JADI-Articular items was higher in MTX than in biologic era cohort (17.6% versus 11% in oligoarthritis and 52.6% versus 21.8% in polyarthritis). Likewise, frequency of involvement of > 1 JADI-Extraarticular items was higher in the MTX than in the biologic era cohort (26.5% versus 16.2% in oligoarthritis and 31.4% versus 13.5% in polyarthritis). Conclusion Our study provides evidence of the remarkable outcome improvement obtained with the recent therapeutic advance in JIA.

In the past two decades, there has been a great deal of work aimed to devise diagnostic guidelines, classification criteria, and diagnostic scores for cytokine storm syndromes. The most notable effort has been the large-scale multinational study that led to the development of the 2016 classification criteria for macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA). In the context of this project, the laboratory tests whose change over time is most valuable for early diagnosis of MAS in systemic JIA were identified. Other tools are the MH score to distinguish MAS from primary hemophagocytic lymphohistiocytosis, the diagnostic guidelines for MAS in childhood-onset systemic lupus erythematosus, the HScore for reactive hemophagocytic syndromes, and the MS score for early detection of MAS in systemic JIA. Future studies should scrutinize the validity of proposed criteria in different patient populations evaluated prospectively. There is also the specific need to assess the diagnostic performance of criteria in patients with systemic JIA treated with biologics.

Made available in DSpace on 2019-10-05T16:54:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-04-01 IRCCS Istituto Giannina Gaslini Background To our knowledge, the characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate, with a cross-sectional study, the prevalence of disease categories, treatment methods, and disease status in patients from across different geographical areas and from countries with diverse wealth status. Methods In this multinational, cross-sectional, observational cohort study, we asked international paediatric rheumatologists from specialised centres to enrol children with a diagnosis of juvenile idiopathic arthritis, according to International League of Associations for Rheumatology criteria, who were seen consecutively for a period of 6 months. Each patient underwent retrospective and cross-sectional assessments, including measures of disease activity and damage and questionnaires on the wellbeing and quality of life of the children. We qualitatively compared the collected data across eight geographical areas, and we explored an association between disease activity and damage and a country's gross domestic product (GDP) with a multiple logistic regression analysis. Findings Between April 4, 2011, and Nov 21, 2016, 9081 patients were enrolled at 130 centres in 49 countries, grouped into eight geographical areas. Systemic arthritis (125 [33.0%] of 379 patients) and enthesitis-related arthritis (113 [29.8%] of 379) were more common in southeast Asia, whereas oligoarthritis was more prevalent in southern Europe (1360 [56.7%] of 2400) and rheumatoid factor-negative polyarthritis was more frequent in North America (165 [31.5%] of 523) than in the other areas. Prevalence of uveitis was highest in northern Europe (161 [19.1%] of 845 patients) and southern Europe (450 [18.8%] of 2400) and lowest in Latin America (54 [6.4%] of 849), Africa and Middle East (71 [5.9%] of 1209), and southeast Asia (19 [5.0%] of 379). Median age at disease onset was lower in southern Europe (3.5 years, IQR 1.9-7.3) than in other regions. Biological, disease-modifying antirheumatic drugs were prescribed more frequently in northern Europe and North America than in other geographical settings. Patients living in countries with lower GDP had greater disease activity and damage than those living in wealthier countries. Damage was associated with referral delay. Interpretation Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographical areas and wealth status of countries. The greater disease burden in lowerresource settings highlights the need for public health efforts aimed at improving equity in access to effective treatments and care for juvenile idiopathic arthritis. Copyright (C) 2019 Elsevier Ltd. All rights reserved. Univ Genoa, Ist Giannina Gaslini, IRCCS, Clin Paediat & Rheumatol, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Epidemiol & Biostat Serv, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Sci Directory, Genoa, Italy Univ Genoa, PRINTO, IRCCS, Ist Giannina Gaslini, Genoa, Italy Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet & Maternal, Genoa, Italy Wilhelmina Childrens Hosp, Dept Pediat Immunol & Rheumatol, Utrecht, Netherlands Sanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, India Univ Hosp 12 Octubre, Dept Pediat Rheumatol, Madrid, Spain Alfaisal Univ, Dept Pediat Rheumatol, King Faisal Specialist Hosp, Riyadh, Saudi Arabia Alfaisal Univ, Res Ctr, Riyadh, Saudi Arabia Western Univ Childrens Hosp, Hlth Sci Ctr, London, ON, Canada Oslo Univ Hosp, Dept Rheumatol, Oslo, Norway Oslo Univ Hosp, Med Fac, Oslo, Norway Univ Oslo, Oslo, Norway Oslo Univ Hosp, Norwegian Natl Advisory Unit Rheumat Dis Children, Oslo, Norway Univ Hosp Munster, Dept Pediat Rheumatol & Immunol, Munster, Germany Hosp Sor Maria Ludovica, Rheumatol Serv, La Plata, Buenos Aires, Argentina Bucharest Emergency Hosp, Cluj Napoca, Romania Childrens Emergency Hosp, Cluj Napoca, Romania Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA Alberta Childrens Prov Gen Hosp, Div Pediat Rheumatol, Dept Pediat, Calgary, AB, Canada Sofiamed, Pediat Dept, Sofia, Bulgaria Rigshosp, Juliane Marie Ctr, Paediat Rheumatol Unit, Copenhagen, Denmark Natl Inst Rheumatism & Physiotherapy, Clin Immunol Adult & Paediat Rheumatol Dept, Budapest, Hungary Univ Latvia, Pediat Dept, Riga, Latvia Univ Latvia, Univ Childrens Hosp, Riga, Latvia Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil Shariati Hosp, Rheumatol Res Ctr, Dept Pediat & Rheumatol, Tehran, Iran Inst Rheumatol Belgrade, Div Pediat Rheumatol, Belgrade, Serbia Thessaloniki Univ, Dept Pediat 1, Hippokrat Gen Hosp, Sch Med, Thessaloniki, Greece Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil

Background: The characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate prevalence of disease categories, treatment modalities and disease status across different geographic areas. Methods: International paediatric rheumatologists were asked to enrol a consecutive sample of children with juvenile idiopathic arthritis. Each patient underwent retrospective and cross-sectional assessments, including parent-reported outcomes. Level of disease activity and damage were correlated with wealth of the country, expressed as gross domestic product per capita. Findings: Between 2011 and 2016, 9,081 patients were enrolled at 130 centres in 49 countries, grouped in 8 geographic areas. A wide difference in the prevalence of disease categories across areas was seen, with systemic arthritis and oligoarthritis being relatively more common in Southeast Asia (33%) and Southern Europe (56·7%), respectively, and rheumatoid-factor negative polyarthritis and enthesitis related arthritis being relatively more frequent in North America (31·5%) and Southeast Asia (29·8%), respectively. Prevalence of uveitis was highest in Northern Europe and Southern Europe (19·2% and 19%, respectively) and lowest in Latin America (6·5%), Africa & Middle East (6·1%), and Southeast Asia (5·1%). Median age at disease onset was lower in Southern Europe (3·5 years) than in other regions (4·7-7·4 years). Biologic disease-modifying anti-rheumatic drugs (DMARDs) were prescribed more frequently in Western countries (30·5-46%) than in other geographic settings (21·1- 25·1%). Patients living in lower-income countries had greater disease activity and damage than patients cared for in wealthier countries. Damage was associated with referral delay. Interpretation: Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographic areas. The greater disease burden in lower-resource settings highlights the need for public health efforts aimed to improve equity in access to effective treatments and structure and process of care. Funding Statement: IRCCS Istituto Giannina Gaslini, Genoa, Italy. Declaration of Interests: Dr. Bovis reports personal fees from Biogen, Novartis, outside the submitted work. Dr. Foell reports grants from Novartis, Pfizer; personal fees from Novartis, Pfizer, Sobi, Chugai-Roche, during the conduct of the study. Dr. Shafaie reports grants from IRCCS Istituto Giannina Gaslini, during the conduct of the study. Dr. Lazar reports grants from IRCCS Istituto Giannina Gaslini, during the conduct of the study; non- financial support from Abbvie; personal fees from ROCHE, outside the submitted work. Dr. Lovell reports other funding from Astra-Zeneca Pharm, Wyeth Pharm, Amgen, Abbott, Pfizer, Hoffman-La Roche, Novartis, UBC, Takeda, Janssen, GSK, Boehringer Ingelheim, Celgene, Novartis, Roche, Bristol Myers Squibb, Abbvie, Pfizer, Roche, Forest Research, outside the submitted work. Dr. Martini reports grants from Abbvie, Boehringer, Novartis, R-Pharm, BMS, Hoffman-La Roche, Janssen, Novartis, Pfizer, Sobi, outside the submitted work; personal fees from Abbvie, Astrazeneca, Novartis, Pfizer, Roche, R-Pharm, Sanofi, UCB, outside the submitted work. Dr. Ravelli reports personal fees from AbbVie, BMS, Pfizer, Hoffman LaRoche, Novartis, Centocor, "Francesco Angelini" and Reckitt Benckiser, outside the submitted work. Dr. Ruperto reports personal fees from Abbott, AbbVie, Amgen, Biogenidec, Astellas, Alter, AstraZeneca, Baxalta Biosimilars, Boehringer, BMS, CD-Pharma,Celgene, CrescendoBio, EMD Serono, Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Rewind Arms, R-Pharma, Sanofi Aventis, Servier, Sinergie, Takeda, Vertex, UCB Biosciences GmbH, outside the submitted work; grants from Abbott, BMS, "Francesco Angelini", GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma, Wyeth, outside the submitted work. Dr. Trachana reports personal fees from IRCCS Istituto Giannina Gaslini, during the conduct of the study; personal fees from Novartis, Pfizer, IRCCS Istituto Giannina Gaslini, outside the submitted work. Dr. Aggarwal, Dr. Al-Mayouf, Dr. Alongi, Dr. Consolaro, Dr. de Inocencio, Dr. Demirkaya, Dr. Flato, Dr. Garay, Dr. Giancane, Dr. Miettunen, Dr. Mihaylova, Dr. Montobbio, Dr. Nielsen, Dr. Orban, Dr. Pistorio, Dr. Rumba-Rozenfelde, Dr. Saad-Magalhaes, Dr. Susic, Dr. van Dijkhuizen and Dr. Wulffraat have nothing to disclose. Ethics Approval Statement: All participating centres obtained the approval of the study protocol by their local Ethics Committee, according to national laws. The parents or guardians of all patients and healthy children provided written informed consent to participation in the study.

Over the past two decades, the management of juvenile idiopathic arthritis (JIA) has been revolutionized by the increased tendency toward early aggressive interventions and the availability of the novel biologic medications. In 2017, three novel randomized controlled trials have evaluated the effectiveness and tolerability of golimumab and tocilizumab in polyarticular JIA, and shown that methotrexate may increase and prolong the effect of intra-articular corticosteroid injection in children with oligoarthritis. A more rational approach to the management of JIA is being fostered by the recent publication of therapeutic recommendations, consensus treatment plans, and advice for the optimal care. A few months ago, an international consensus effort has led to the development of the recommendations for the treat-to-target in JIA. The application of this strategy in routine care may improve disease outcome. Because the potential of attaining inactive disease in children with JIA has markedly increased, there is an urgent need for randomized controlled trials, analyses of clinical data sets, and expert advice to guide discontinuation of medications once complete disease quiescence has been achieved.

To provide an overview of recently published studies on pathogenesis and management of juvenile idiopathic arthritis (JIA).In the past year, the potential role of network analysis in the understanding of the molecular phenotype of individual JIA subgroups has been highlighted. In addition, potential new targets for pharmacologic interventions have been identified through the elucidation of mechanisms that modulate the function of cells involved in the inflammatory process. There is a growing interest for the role of the gut microbiome in disease pathogenesis, which may open the way to future therapeutic manipulations of fecal microbial population. Recent therapeutic studies have provided important information in large patient samples on the effectiveness and toxicity profile of biologic medications used in JIA. Concomitant administration of methotrexate was found to increase the effectiveness of intra-articular corticosteroid therapy in children with oligoarticular JIA.A great deal of work is being conducted to better define the molecular phenotype of the individual subsets of JIA and to identify potential new targets for therapeutic interventions. The results of the ongoing large-scale international data collections will help establish the long-term safety profiles of biologic medications, in particular the risk of malignancy.

Background: Hypothyroidism has been associated with cognitive and motor impairments, the degree to which mild hypothyroidism, or subclinical hypothyroidism impacts mood and cognitive functions and whether these symptoms respond to treatment, remains controversial. Furthermore, hypothyroidism is associated with an increased susceptibility to depression and reductions in health-related quality of life. Objective and hypotheses: Recent longitudinal studies stressed that the follow-up of children with treated congenital hypothyroidism (CHT) should not be limited to the cognitive domain. This study attempted to evaluate the emotional–behavioural profiles in children with CHT and the parenting stress profiles. Method: Data for children and families characteristics were collected from 33 families with a CHT child (13 males, 20 females; age: 6 months–6 years) diagnosed and treated since the newborn period. We analyzed the children by the Denver intelligence test and the child behaviour checklist (CBCL). Furthermore we proposed the parenting stress index (PSI) to their parents. Results: Denver intelligence test results demonstrated that nine/33 patients were normal, 20/33 were dubious, four/33 were not estimable. However the specific neuropsychiatric evaluation and QI confirmed a reduced performance only in three. The CBCL was normal in 18/33 patients (ten females; eight males), borderline in 8/33 (five females; three males), pathological in 7/33 (five females; two males). The children younger than 2 years showed a pathological or borderline score, with the exception of two. Between these, the more frequently pathological items were somatic complaints (five pathological; four borderline), anxious/depressed (two pathological; four borderline), attention problems (one pathological; four borderline). The PSI revealed a pathological test in six/33 patients. All the items were pathological in two; however in all the six pathological patients the PSI identified a ‘difficult child’. No correlations were found between starting day of treatment and developmental outcome. Initial T4 concentration and initial T4 dose were weak predictors for developmental outcome. Conclusion: The diagnosis of a chronic disease of the son could interfere with the emotional relationship in the family.