Development and initial validation of parent and child versions of the Juvenile Arthritis Disease Activity Score.

OBJECTIVE: To develop parent- and child-centered versions of the Juvenile Arthritis Disease Activity Score (JADAS) and to provide preliminary evidence of their validity. METHODS: Validation analyses were conducted on two large multinational datasets of patients with juvenile idiopathic arthritis (JIA) and included assessment of construct validity, internal consistency and structure, discriminative validity, responsiveness to change, and predictive validity. RESULTS: The parJADAS and patJADAS include four parent/patient-reported outcomes, each measured on a 0-10 scale: assessment of overall disease activity; rating of pain intensity; assessment of activity of joint disease; duration of morning stiffness. Both scores are calculated as the simple linear sum of the scores of their 4 components, which yields for both of them a global score of 0-40. The parJADAS and patJADAS demonstrated good construct validity, yielding high correlations with other JIA composite disease activity measures and moderate correlations with physician global rating and joint counts. Internal consistency was satisfactory, with Cronbach' s alpha > 0.80, and exploratory factor analysis showed that both indices are monodimensional. Both instruments discriminated well between different disease states, with discriminative ability being not affected by the presence of damage, proved able to predict important disease outcomes, and showed fair responsiveness to clinically important change, with standardized response mean of 0.71. CONCLUSION: Both parJADAS and patJADAS were found to possess good measurement properties and to serve as surrogate of physicians' evaluations. Regular home completion of the two instruments through digital technologies offers a suitable and pragmatic approach to deliver remote symptom monitoring and telehealth.

Using HScore for Evaluation of Hemophagocytosis in Multisystem Inflammatory Syndrome Associated with COVID-19 in Children.

Hemophagocytic syndrome is a key point in the pathogenesis of severe forms of multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C). The factors associated with hemophagocytosis in patients with MIS-C were assessed in the present study of 94 boys and 64 girls ranging in age from 4 months to 17 years, each of whose HScore was calculated. In accordance with a previous analysis, patients with HScore ≤ 91 (n = 79) and HScore > 91 (n = 79) were compared. Patients with HScore > 91 had a higher frequency of symptoms such as cervical lymphadenopathy, dry cracked lips, bright mucous, erythema/swelling of hands and feet, peeling of fingers, edematous syndrome, hepatomegaly, splenomegaly, and hypotension/shock. They also had a higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and D-dimer levels, and a tendency to anemia, thrombocytopenia, and hypofibrinogenemia. They more often needed acetylsalicylic acid and biological treatment and were admitted to ICU in 70.9% of cases. Conclusion: The following signs of severe MIS-C were associated with HScore > 91: myocardial involvement, pericarditis, hypotension/shock, and ICU admission.

Determination of Risk Factors for Severe Life-Threatening Course of Multisystem Inflammatory Syndrome Associated with COVID-19 in Children.

Multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C) is a life-threatening condition that often requires intensive care unit (ICU) admission. The aim of this study was to determine risk factors for severe/life-threatening course of MIS-C. The study included 166 patients (99 boys, 67 girls) aged 4 months-17 years (median 8.2 years). The criterion of severity was the fact of ICU admission. To conduct a comparative analysis, MIS-C patients were divided into two groups: patients hospitalized in the ICU (n = 84, 50.6%) and those who did not need ICU admission (n = 82, 49.4%). Patients with a more severe course of MIS-C were significantly older. They had a higher frequency of signs such as rash, swelling, hepatomegaly, splenomegaly, and neurological and respiratory symptoms. Hypotension/shock and myocardial involvement were much more common in patients with severe MIS-C. These patients had a more significant increase in CRP, creatinine, troponin, and D-dimer levels. Additionally, the presence of macrophage activation syndrome was higher in patients admitted to the ICU. Conclusion: Nineteen predictors of severe course of MIS-C were found, out of which hepatomegaly, splenomegaly, D-dimer > 2568 ng/mL, troponin > 10 pg/mL were mainly associated with the probability of being classified as early predictors of severe MIS-C requiring ICU admission.

Validity and Reliability of Four Parent/Patient-Reported Outcome Measures for Juvenile Idiopathic Arthritis Remote Monitoring.

OBJECTIVE: The aim of this work was to provide evidence of validity and reliability for 4 parent/child-reported outcome measures included in the Outcome Measures in Rheumatology juvenile idiopathic arthritis core domain set: the evaluation of the child's pain and level of disease activity, the assessment of morning stiffness duration, and an active joint count for proxy/self-assessment. METHODS: Patients were included in the multinational study Epidemiology Treatment and Outcome of Childhood Arthritis. Criterion validity was assessed by examining the correlation of the 4 tested measures with physician measures and the clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10) in the whole sample and after grouping patients by International League of Associations for Rheumatology (ILAR) category, geographic area, and education level. Reliability was assessed comparing 2 visits 7-14 days apart with intraclass correlation coefficients (ICCs). RESULTS: A total of 8,643 parents and 6,060 patients had all the evaluations available. Correlations of tested measures were moderate (0.4-0.7) with physician-reported measures. The level of correlation with the cJADAS10 remained stable after grouping patients by ILAR category, geographic areas, and level of education of the parent filling the questionnaire. In 442 parents and 344 children, ICCs ranged between 0.79 and 0.87 for parents and 0.81 and 0.88 for children. CONCLUSION: The 4 tested parent/child-reported outcomes showed good criterion validity and excellent reliability. These tools can be considered for remote patient assessment, when in-person evaluation might not be possible.

COVID-19 Associated Vasculitis Confirmed by the Tissues RT-PCR: A Case Series Report.

BACKGROUND: Several cases of skin and central nervous system vasculopathy associated with COVID-19 in children have been published, but the information is rather limited. Our study aimed to describe these cases of vasculitis associated with COVID-19 in children. METHODS: In the retrospective-prospective case series study we included information regarding four children with COVID-19-associated vasculitis. In every case, we had a morphological description and the etiology was confirmed via real-time polymerase chain reaction during a tissue biopsy. RESULTS: The most involved systems were skin (4/4), respiratory (3/4), cardiovascular (2/4), nervous (1/4), eye (1/4), kidney (1/4), and inner year (1/4). All patients had increased inflammatory markers and thrombotic parameters (D-dimer). No patient met the criteria for multisystem inflammatory syndrome in children. Two patients met polyarteritis nodosa criteria, one met Henoch-Schonlein purpura criteria, and one met unclassified vasculitis criteria. All patients were treated with systemic glucocorticosteroids (two-pulse therapy). Non-biologic DMARDs were prescribed in all cases; 1/4 patients (25%) was treated with intravenous immunoglobuline, and 3/4 (75%) were treated with biologics (etanercept, tocilizumab, and adalimumab). CONCLUSIONS: Vasculitis associated with COVID-19 could be a life-threatening condition; SARS-CoV-2 might be a new trigger or etiological agent for vasculitis and other immune-mediated diseases. Further research and collection of similar cases are required.

Heart Involvement in Multisystem Inflammatory Syndrome, Associated With COVID-19 in Children: The Retrospective Multicenter Cohort Data.

Objectives: Heart involvement in multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C) is a new challenging problem, requiring fast and reliable diagnostics and appropriate treatment. The aim of this study is to describe heart involvement in patients with MIS-C. Study Design: In this retrospective, multicenter cohort study, data of 122 patients were included. All patients met WHO and CDC criteria of MIS-C. Results: Various types of heart involvement in MIS-C patients were observed. Patients with solely coronary artery lesions (CAL, n = 10, 8.2%) had typical features of Kawasaki disease: younger age, thrombocytosis and normal ferritin level, without giant CA aneurysms, thrombosis, myocardial infarction, shock, and ICU admission. Patients with solely myocardial involvement (MI, n = 30, 24.6%) had an older onset age, elevated ferritin, LDH, the highest D-dimer, H score, and thrombocytopenia level. The following clinical signs were associated with MI: gastrointestinal and central nervous system disorder, sore throat, swelling face, splenomegaly, shock, and treatment in the intensive care unit required. Patients with a combination of CAL and MI (n = 10, 8.2%) had symptoms similar to patients with solely MI, except for impressive thrombocytopenia. Shock and ICU admission were found in 34.7% of patients without heart involvement (n = 72, 59%). One major criterion [troponin > 32 pg/ml (52 points)] or at least two minor criteria [face swelling (32 points) and D-Dimer > 1,300 ng/ml (29 points)] were associated with MI (>32 points) with a sensitivity of 67.5% and a specificity of 88.9%. Conclusion: The above-suggested criteria can be added to routine diagnostic procedures to confirm MI in MIS-C patients.

Hip Involvement in Juvenile Idiopathic Arthritis: A Roadmap From Arthritis to Total Hip Arthroplasty or How Can We Prevent Hip Damage?

Objectives: To describe the clinical characteristics of hip involvement in juvenile idiopathic arthritis (JIA) from arthritis to hip osteoarthritis (HOA) and total hip arthroplasty (THA). Study Design: Seven hundred fifty-three patients aged 2-17 years with JIA were included in the study. The comparison analysis was performed between the following subgroups: (i) JIA without hip involvement (n = 600; 79.7%) vs. JIA with hip involvement without HOA (n = 105; 13.9%), (ii) JIA with hip involvement with HOA, but without THA (n = 32; 4.3%) and JIA with hip involvement with HOA and with THA (n = 16; 2.1%). Clinical, laboratory characteristics and treatment regimens compared. Results: Hip involvement was present in 20.3% of patients. HOA was present in 6.4% (12*1,000 patient-years) of the entire JIA group and 31.4% of patients with hip involvement. Sixteen patients (2.1%; 4.0*1,000 patient-years) required THA. The following factors were associated with HOA: sJIA (OR = 3.6, p = 0.008; HR = 3.0, p = 0.002), delayed remission (OR = 4.2, p = 0.004; HR = 1.4, p = 0.538), delay in biologic therapy initiation (OR = 7.5, p = 0.00001; HR = 6.7, p = 0.002), alkaline phosphatase <165 U\l (OR = 4.1, p = 0.0003; HR = 5.2, p = 0.000004), treatment with corticosteroids (CS) (OR = 2.6, p = 0.008; HR = 1.2, p = 0.670), cumulative corticosteroids >2,700 mg (OR = 4.3, p = 0.032; HR = 1.4, p = 0.527). The following factors were associated with THA: delay in biologic treatment initiation (OR = 1.04, p = 0.0001; HR = 9.1, p = 0.034), delayed hip involvement (OR = 5.2, p = 0.002; HR = 3.0, p = 0.044), and methylprednisolone pulse therapy (OR = 10.8, p = 0.0000001; HR = 5.6, p = 0.002). Conclusion: Both sJIA and systemic CS, impaired calcium-phosphorus metabolism, and delayed hip arthritis are associated with HOA development in JIA. HOA is considered to be a severe adverse event of CS treatment, especially delayed hip involvement.

Distinguishing Between Multisystem Inflammatory Syndrome, Associated With COVID-19 in Children and the Kawasaki Disease: Development of Preliminary Criteria Based on the Data of the Retrospective Multicenter Cohort Study.

Objectives: Diagnostic between multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C) and Kawasaki disease (KD) can make difficulties due to many similarities. Our study aimed to create a Kawasaki/MIS-C differentiation score (KMDscore) allowing discrimination of MIS-C and KD. Study design: The retrospective multicenter cohort study included clinical, laboratory, and instrumental information about MIS-C (n = 72) and KD (n = 147). The variables allowed to discriminate both conditions used to construct and validate the diagnostic score called the KMDscore. Results: Patients with MIS-C were older, had earlier admission to the hospital, had a shorter time before fever resolution, two times frequently had signs of GI and CNS involvement observed, and had more impressive thrombocytopenia, higher level of CRP, ferritin, ALT, AST, LDH, creatinine, triglycerides, troponin, and D-dimer compared to KD patients. Respiratory signs in MIS-C were presented with pleuritis, acute respiratory distress syndrome, oxygen dependency, lung infiltration, and ground-glass opacities in CT. The heart involvement with fast progression of myocarditis provided the severity of MIS-C and ICU admission due to 12 times higher arterial hypotension or shock and required cardiotonic. No differences in the frequency of CA lesions were seen in the majority of cases. Five criteria, CRP >11 mg/dl (18 points), D-dimer >607 ng/ml (27 points), age >5 years (30 points), thrombocytopenia (25 points), and GI involvement (28 points), were included in the KMDscore. The summa >55 points allowed to discriminate MIS-C from KD with a sensitivity of 87.5% and specificity of 89.1%. Conclusion: The KMDscore can be used to differentiate the diagnostic of MIS-C from KD.