The HyperPed-COVID international registry: Impact of age of onset, disease presentation and geographical distribution on the final outcome of MIS-C.

OBJECTIVES: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome. STUDY DESIGN: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected. Five age groups (<1, 1-4, 5-11, 12-16, >16 years) and four geographic macro-areas, Western Europe, Central-Eastern Europe, Latin America, Asian-African resource-limited countries (LRC), were identified. RESULTS: Time to referral was significantly higher in LRC. Intensive anti-inflammatory treatment, including biologics, respiratory support and mechanic ventilation were more frequently used in older children and in European countries. The mortality rate was higher in very young children (<1 year), in older patients (>16 years of age) and in LRC. Multivariate analysis identified the residence in LRC, presence of severe cardiac involvement, renal hypertension, lymphopenia and non-use of heparin prophylaxis, as the factors most strongly associated with unfavorable outcomes. CONCLUSIONS: The stratification of patients by age and geographic macro-area provided insights into the clinical presentation, treatment and outcome of MIS-C. The mortality and sequelae rates exhibited a correlation with the age and geographical areas. Patients admitted and treated in LRC displayed more severe outcomes, possibly due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities.

Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis on anti-interleukin-1 or -6 therapy.

OBJECTIVES: The aim of this study is to investigate the effect of anti-interleukin (IL)-1/-6 biologics on systemic juvenile idiopathic arthritis (sJIA)-associated macrophage activation syndrome (MAS). METHODS: Demographic, clinical, and laboratory data of patients followed up with a diagnosis of sJIA-associated MAS assessed from sixteen pediatric rheumatology centers across the country. The clinical and laboratory features of MAS developing while on biological drugs were compared with those without this treatment. RESULTS: One hundred and sixty-two patients were included in the study. 45 of the MAS events were detected under the effect of anti-IL-1/-6 biologics, while the patients experiencing the remaining 155 events have not received biological treatment in the last three months. Platelet count [128 (72-232) vs 199 (130-371) 109/l], ferritin level on admission [1107 (676-2050) vs 2863 (1193-9562) ng/ml], C-reactive protein level [15.4 (2.9-56) vs 90 (32-160) mg/l], erythrocyte sedimentation rate [13 (3-36) vs 43.5 (13-77) mm/h] and fever duration [5 (4-7.5) vs 10 (7-14.3) days] were found lower in the group under the impact of anti-IL-1/-6 biologics. Among patients treated with biologics, 26.6% did not meet the published 2016 MAS classification criteria at presentation. The rates of hepatomegaly and splenomegaly were relatively lower in the canakinumab-treated group when compared with those receiving other biologicals or to patients, not on biologicals. CONCLUSION: Anti-IL-1/-6 therapies can mask the clinical and laboratory features of MAS, and proposed guidelines for MAS classification criteria may not be met.

Cardiac evaluation of patients with juvenile dermatomyositis.

BACKGROUND: The present study aims to evaluate possible cardiac involvement in juvenile dermatomyositis (JDM) patients by conventional methods and cardiac magnetic resonance imaging (MRI) along with a systematic review of the literature on cardiac features in JDM. METHODS: The study group consisted of JDM patients who underwent cardiac MRI. We conducted a systematic review of the published literature involving JDM patients with cardiac involvement. RESULTS: In the present study, although baseline cardiologic evaluations including electrocardiography and echocardiography were within normal limits, we showed late gadolinium enhancement on cardiac MRI in 3 of 11 JDM patients. In the literature review, we identified 25 articles related to cardiac involvement in JDM. However, none of them, except one case report, included cardiac MRI of JDM patients. CONCLUSION: Cardiac abnormalities have been reported among the less frequent findings in patients with JDM. Cardiovascular complications during the long-term disease course are a leading cause of morbidity and mortality in these patients. Early detection of cardiac involvement by cardiac MRI in patients with JDM and aggressive treatment of them may improve the clinical course of these patients. IMPACT: The myocardium in patients with JDM may be involved by inflammation. Myocardial involvement may be evaluated by using contrast-enhanced cardiac MRI. This is the first study evaluating cardiac involvement by cardiac MRI in JDM patients. MRI may show early cardiac involvement in patients whose baseline cardiologic evaluations are within normal limits. Early detection of cardiac involvement by cardiac MRI may improve the long-term prognosis of patients with JDM.

Not easy-peasy to diagnose: familial Mediterranean fever unaccompanied by fever.

Classical attacks of familial Mediterranean fever (FMF) are often accompanied by fever, but some of the patients have attacks without fever. This study aimed to compare the characteristics of FMF patients with and without fever during their attacks and draw attention to the different clinical presentations of FMF in children. Medical files of patients aged 0-18 years who were followed up with the diagnosis of FMF in two reference pediatric rheumatology centers were reviewed retrospectively. The patients were divided into two groups: children who had had no fever in any of their attacks were assigned as group 1, and those who had fever during their attacks were classified as group 2. Out of 2003 patients evaluated, 191 (9.53%) patients had attacks not accompanied by fever and their median age at onset of symptoms (7.0 vs. 4.0 years, p < 0.001) and the median age at diagnosis (8.6 vs. 6.0 years, p < 0.001) were significantly higher; however, group 2 had a delay in diagnosis. The annual number of attacks and abdominal attacks were more common in group 2; arthritis, arthralgia, erysipelas-like rash, exercise-induced leg pain, and myalgia were more common in group 1.    Conclusion: The data from the assessment of children with FMF attacks not accompanied with fever were presented for the first time. Children with late age onset of FMF and dominance of musculoskeletal features may display attacks not accompanied with fever. What is Known: • Familial Mediterranean fever (FMF) is the most common inherited auto-inflammatory disease, characterized by recurrent attacks of fever, serositis, and musculoskeletal symptoms. • Although fever is the most common symptom, few studies have reported attacks without fever. What is New: • The aim of this study was to identify patients with FMF but without fever during attacks and to demonstrate their distinctive presentations. • We found that 7% of our patients had afebrile attacks with predominant musculoskeletal symptoms and were diagnosed earlier than patients with febrile attacks, probably due to early referral to pediatric rheumatology clinics.

Chronic recurrent multifocal osteomyelitis: A multidisciplinary experience of 22 pediatric cases with a mean follow-up of 27 months.

BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO) is not a well known disorder among nonpediatricians. The aim of this study is to retrospectively evaluate the clinical outcomes of twenty-two CRMO patients presenting to two referral centres. METHODS: This retrospective study included twenty-two children (12 males, 10 females; mean age 13 years; range 7-17 years). The diagnosis was based on clinical, radiological, and pathological findings. Data were retrieved from hospital charts. RESULTS: The mean delay in diagnosis was 26 months (range, 0-96 months). The mean follow-up after diagnosis was 27.4 months (range, 6-47 months). Symptoms included pain, limping, local swelling, morning stiffness, and fever. 18 patients had multifocal and 4 patients had unifocal disease. Bone lesions were detected with whole-body or local MRI (Magnetic Resonance Imaging). The mean number of bone lesions was 2.5 (range, 1-8). Ten cases underwent biopsy to exclude malignancy and infection. Prior to diagnosis, cast immobilization or curettage was erroneously performed in four patients. One patient suffered from vertebral compression fracture. There is no growth disturbance or deformity in any patient. CONCLUSION: This study demonstrated that early recognition of the disease can be improved by using Bristol criteria which should be evaluated by a multidisciplinary team rather than one single specialist. In this way, the reliability of these criteria is improved and the treatment could be given earlier with decreased delay in diagnosis. This multidisciplinary approach is also important for decision for biopsy, timely aggressive medical treatment, and follow-up of the disease to minimise possible complications.

PREDICT-crFMF score: A novel model for predicting colchicine resistance in children with familial Mediterranean fever.

OBJECTIVES: To develop a novel scoring system to predict colchicine resistance in Familial Mediterranean fever (FMF) based on the initial features of the patients. METHODS: The medical records of patients were analyzed prior to the initiation of colchicine. After generating a predictive score in the initial cohort, it was applied to an independent cohort for external validation of effectiveness and reliability. RESULTS: Among 1418 patients with FMF, 56 (3.9%) were colchicine resistant (cr) and 1312 (96.1%) were colchicine responsive. Recurrent arthritis (4 points), protracted febrile myalgia (8 points), erysipelas-like erythema (2 points), exertional leg pain (2 points), and carrying M694V homozygous mutation (4 points) were determined as the parameters for predicting cr-FMF in the logistic regression model. The cut-off value of 9 was 87% sensitive and 82% specific to foresee the risk of cr-FMF in the receiver operating characteristic. Validation of the scoring system with an independent group (cr-FMF = 107, colchicine responsive = 1935) revealed that the cut-off value was 82% sensitive and 79% specific to identify the risk of cr-FMF. CONCLUSIONS: By constructing this reliable and predictor tool, we enunciate that predicting cr-FMF at the initiation of the disease and interfering timely before the emergence of complications will be possible.

Clinical characteristics and predictors for recurrence in chronic nonbacterial osteomyelitis: a retrospective multicenter analysis.

Background/aim: Chronic nonbacterial osteomyelitis (CNO) is a rare disease of unknown etiology and most commonly occurs during childhood or adolescence. The purpose of this study is to collect data on the clinical features, outcomes, and management of the disease and to identify the factors affecting recurrence. Materials and methods: This is a retrospective multicenter cross-sectional study of pediatric patients diagnosed with CNO. A total of 87 patients with a diagnosis of CNO followed for at least 6 months in 8 pediatric rheumatology centers across the country between January 2010 and December 2021 were included in this study. Results: The study included 87 patients (38 girls, 49 boys; median age: 12.5 years). The median follow-up time was 20 months (IQR: 8.5-40). The median time of diagnostic delay was 9.9 months (IQR: 3-24). Arthralgia and bone pain were the most common presenting symptoms. Multifocal involvement was detected in 86.2% of the cases and a recurrent course was reported in one-third of those included in the study. The most commonly involved bones were the femur and tibia. Vertebrae and clavicles were affected in 19.5% and 20.6% of cases, respectively. The erythrocyte sedimentation rate (ESR) values of 60.9% of the patients were above 20 mm/h and the C-reactive protein values of 44.8% were above 5 mg/L. The remission rate was 13.3% in patients using nonsteroidal antiinflammatory drugs and 75.0% in those using biological drugs. Vertebral and mandibular involvement and high ESR values at the time of diagnosis were associated with recurrence. Conclusion: In this multicenter study, CNO with vertebral and mandibular involvement and high ESR at diagnosis were associated with recurrence.

The clinical course of SARS-CoV-2 infection among children with rheumatic disease under biologic therapy: a retrospective and multicenter study.

The effects of biological disease-modifying antirheumatic drugs (bDMARDs) in the clinical course of COVID-19 on children with underlying rheumatologic diseases have not been fully demonstrated. To evaluate the course of COVID-19 infection in patients with rheumatic disease receiving bDMARD treatment. This was a retrospective, multicenter study conducted in pediatric patients infected by SARS-CoV-2 and under bDMARDs therapy. The study population consisted of 113 patients (72 female/41 male). The mean age of the patients was 12.87 ± 4.69 years. The primary diagnosis of the cohort was as follows: 63 juvenile idiopathic arthritis, 35 systemic autoinflammatory diseases, 10 vasculitides, and five cases of connective tissue diseases. The mean duration of the primary disease was 4.62 ± 3.65 years. A total of 19 patients had additional comorbid diseases. Thirty-five patients were treated with canakinumab, 25 with adalimumab, 18 with etanercept, 10 with infliximab, nine with tocilizumab, six with rituximab, four with anakinra, three with tofacitinib, and one with abatacept. The median exposure time of the biological drug was 13.5 months. Seventy-one patients had symptomatic COVID-19, while 42 were asymptomatic. Twenty-four patients required hospitalization. Five patients presented with MIS-C. The hospitalized patients were younger and had a shorter duration of rheumatic disease compared to ambulatory patients, although the difference was not statistically significant. Steroid usage, presence of fever, and dyspnea were more common among the hospitalized patients. A worsening in the course of both COVID-19 and current disease was not noticed under bDMARDs, however, to end with a strong conclusion multicentric international studies are required.

Differences and similarities of multisystem inflammatory syndrome in children, Kawasaki disease and macrophage activating syndrome due to systemic juvenile idiopathic arthritis: a comparative study.

To compare the clinical and laboratory findings of multisystem inflammatory syndrome in children (MIS-C), patients with Kawasaki disease (KD) and with macrophage activating syndrome due to systemic juvenile idiopathic arthritis (sJIA-MAS) on real-life data. Patients diagnosed with MIS-C, KD, and sJIA-MAS from 12 different centers in Turkey who were followed for at least 6 months were included in the study. Demographic, clinical, and laboratory findings of all patients were analyzed. A total of 154 MIS-C, 59 KD, and 31 sJIA-MAS patients were included. The median age of patients with MIS-C were higher than those with KD while lower than those with sJIA-MAS (8.2, 3, 12 years, respectively). Myalgia (39.6%), cardiac (50.6%), gastrointestinal (72.7%), and neurological (22.1%) involvements were more common in patients with MIS-C compared to others. MIS-C patients had lower levels of lymphocyte (950 vs 1700 cells/µl) and thrombocyte (173,000 vs 355,000 cells/µl) counts and higher pro-BNP (1108 vs 55 pg/ml) levels than KD. Ferritin levels were higher in patients with MIS-C compared to patients with KD while they were lower than patients with sJIA-MAS (440, 170, 10,442 ng/ml, respectively). Patients with MIS-C had a shorter duration of hospitalization than sJIA-MAS (p = 0.02) while they required intensive care unit admission more frequently (55 vs 8 patients, p < 0.001). The median MAS/sJIA score of MIS-C patients was - 1.64 (- 5.23 to 9.68) and the median MAS/sJIA score of sJIA-MAS patients was -2.81 ([- 3.79] to [- 1.27]). MIS-C patients displayed certain differences in clinical and laboratory features when compared to KD and sJIA-MAS. Definition of the differences and similarities between MIS-C and the other intense inflammatory syndromes of childhood such as KD and MAS will help the clinicians while making timely diagnosis.

Towards a standardized program of transitional care for adolescents with juvenile idiopathic arthritis for Turkey: a national survey study.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a prevalent childhood chronic arthritis, often persisting into adulthood. Effective transitional care becomes crucial as these patients transition from pediatric to adult healthcare systems. Despite the concept of transitional care being recognized, its real-world implementation remains inadequately explored. This study aims to evaluate the thoughts and practices of healthcare providers regarding transitional care for JIA patients. METHODS: A cross-sectional survey was conducted among pediatric and adult rheumatologists in Turkey. Based on the American Academy of Pediatrics' six core elements of transitional care, the survey included 86 questions. The respondents' demographic data, attitudes towards transitional care, and practical implementation were assessed. RESULTS: The survey included 48 rheumatologists, with 43.7% having a transition clinic. The main barriers to establishing transition programs were the absence of adult rheumatologists, lack of time, and financial constraints. Only 23.8% had a multidisciplinary team for transition care. Participants agreed on the importance of coordination and cooperation between pediatric and adult healthcare services. The timing of the transition process varied, with no consensus on when to initiate or complete it. Participants advocated for validated questionnaires adapted to local conditions to assess transition readiness. CONCLUSIONS: The study sheds light on the challenges and perspectives surrounding transitional care for JIA patients in Turkey. Despite recognized needs and intentions, practical implementation remains limited due to various barriers. Cultural factors and resource constraints affect the transition process. While acknowledging the existing shortcomings, the research serves as a ground for further efforts to improve transitional care and ensure better outcomes for JIA patients transitioning into adulthood.

A pediatric case of Takayasu's arteritis with anti-neutrophil cytoplasmic antibody-associated vasculitis triggered by COVID-19 infection.

Takayasu's arteritis (TA) is a rare chronic granulomatous vasculitis characterized by large-vessel involvement. The aorta and its main branches are most commonly involved. Although pulmonary artery involvement is common, hemoptysis or respiratory findings are rarely seen. Herein, we present a case of TA who developed anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with diffuse alveolar hemorrhage after coronavirus disease 2019 (COVID-19) infection. A 17-year-old female patient with the diagnosis of TA presented with cough, bloody vomiting, and diarrhea. In follow-up, she developed tachypnea and dyspnea and was transferred to the pediatric intensive care unit. The findings on the chest computed tomography were compatible with acute COVID-19 infection, but the SARS-CoV2 reverse transcription-polymerase chain reaction test was negative, but SARS-CoV2 immunoglobulin (Ig) G and IgM antibody tests were positive. The patient was not vaccinated against COVID-19. The bronchoscopy showed bronchial mucosal fragility, bleeding foci, and mucosal bleeding. The broncoalveolar lavage hemosiderin-laden macrophages were seen in the histopathologic examination. The indirect immunofluorescence assay-ANCA test became 3 (+) with myeloperoxidase (MPO)-ANCA of 125 RU/ml (normal: <20). Cyclophosphamide and pulse steroid treatment were started. After immunosuppressive therapy, the patient condition improved and did not have hemoptysis again. The successful response was obtained by applying balloon angioplasty to the patient with bilateral renal artery stenosis. Types of post-COVID vasculitis include thromboembolic events, cutaneous vasculitis, Kawasaki-like vasculitis, myopericarditis, and ANCA-associated vasculitis. It is thought that COVID-19 may impair immune tolerance and trigger autoimmunity with cross-reaction. To the best of our knowledge, the third pediatric case was reported with MPO-ANCA-positive COVID-associated ANCA vasculitis.

Real-life data on efficacy and safety of original Adalimumab and biosimilar Adalimumab (ABP 501) in pediatric rheumatic diseases.

BACKGROUND: We aimed to compare the efficacy and safety of the original product (OP) and biosimilar product (BP) of adalimumab in pediatric rheumatic diseases. RESEARCH DESIGN AND METHODS: The study group consisted of patients who had received original or biosimilar adalimumab (ABP 501) therapy for at least 3 months. The patients were divided into uveitis and arthritis groups based on the indication of adalimumab treatment. Assessment of disease activity was performed by Juvenile Arthritis Disease Activity Score in patients with juvenile idiopathic arthritis, and by standardization of uveitis nomenclature criteria in patients with uveitis. RESULTS: The study included 140 patients, of which 87 were treated with OP and 53 with BP. In the arthritis group, 26 (63.4%) and 20 (57.1%) patients reached inactive disease according to JADAS-27 in the original and biosimilar adalimumab groups, respectively. In the uveitis group the mean number of exacerbations throughout the treatment period was 0.84 ± 1.07 in the OP group, and 0.58 ± 0.79 in the BP group. There were 71 treatment-emergent adverse events in the OP group and 38 in the BP group. CONCLUSION: There was no significant difference between the biosimilar and the original product in efficacy and safety.

The assessment of autoinflammatory disease classification criteria (Eurofever/PRINTO) in a real-life cohort.

OBJECTIVE: The aim of the study was to determine the sensitivity and specificity rates of Eurofever/PRINTO autoinflammatory recurrent fever classification criteria with real-life data in patients with an autoinflammatory disease. METHODS: A total of 119 patients were included in the study. Based on clinical symptoms, they were divided into four subgroups: cryopyrin-associated periodic syndromes (CAPS), TNF receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), and syndrome of undifferentiated recurrent fever (SURF) using the Eurofever/PRINTO clinical classification criteria. In the last step, the patients were re-evaluated in the light of genetic results and their final diagnosis was reached. RESULTS: A total of 119 patients, including 37 CAPS, 13 TRAPS, 8 MKD, 39 SURF, 14 NLRP12-related autoinflammatory disease (NLRP12-AID), and 8 familial Mediterranean fever (FMF) patients were evaluated in the study. While the sensitivity of the new clinical Eurofever/PRINTO criteria was 48% for CAPS, 77% for TRAPS, 87.5%for MKD, and the specificity of the clinical criteria was 86% for CAPS, 85% for TRAPS, and 60% for MKD. The sensitivity of the new mixed (genetic plus clinical variables) Eurofever/PRINTO criteria was 27% for CAPS, 61% forTRAPS, 85% for MKD, and the specificity of the mixed criteria for each group was 100%. CONCLUSION: We found the sensitivity of the Eurofever/PRINTO classification criteria to be low as genotypic changes between populations cause phenotypic differences. For this reason, we think that patient-based evaluation is correct rather than standard classification criteria in real life. Key-points • In systemic autoinflammatory diseases, common variants in the populations may alter the phenotype, and making it difficult to classify some patients with the current classification criteria. • In populations with common genetic variants, the classification criteria should be modified according to the clinical phenotype.

Initial manifestations and risk factors for calcinosis in juvenile dermatomyositis: A retrospective multicenter study.

OBJECTIVE: This study aimed to look for the initial manifestations of juvenile dermatomyositis (JDM), give follow-up results, and search for risk factors for the development of calcinosis. METHODS: The files of children with JDM diagnosed between 2005 and 2020 were reviewed retrospectively. RESULTS: The study included 48 children, 33 girls and 15 boys. The mean age at the onset of the disease was 7.6±3.6 years. The median duration of follow-up was 35 (6-144) months. Twenty-nine patients (60.4%) had monocyclic, 7 (14.6%) patients had polycyclic, and 12 (25%) patients had chronic persistent disease course. At the time of enrollment, 35 (72.9%) patients were in remission, while 13 (27.1%) patients had active disease. Calcinosis developed in 11 patients (22.9%). Children having myalgia, livedo racemosa, skin hypopigmentation, lower alanine aminotransferase (ALT) levels, and higher physician visual analog scores at the time of diagnosis had a higher risk for calcinosis. Calcinosis was also more common in children with diagnostic delay and chronic persistent disease course. None of these parameters remained independent risk factors for calcinosis in multivariate logistic regression analysis. CONCLUSION: The rate of mortality has decreased dramatically over decades in JDM, but the rate of calcinosis has not changed proportionately. Long duration of active, untreated disease is accepted as the main risk factor for calcinosis. We have seen that calcinosis was more common in children having myalgia, livedo racemosa, skin hypopigmentation, lower ALT levels, and higher physician visual analog scores at the time of diagnosis.

Clinical features, treatment and outcome of pediatric patients with severe cutaneous manifestations in IgA vasculitis: Multicenter international study.

OBJECTIVE: IgA vasculitis (IgAV) (formerly Henoch-Schönlein Purpura, HSP) rarely causes severe skin lesions in children. The purpose of the research was to determine whether severe skin manifestations were associated with a more severe disease course. METHODS: Severe cutaneous manifestations were defined as presence of hemorrhagic vesicles, bullae, ulcerations and/or necroses. Data were collected retrospectively from 12 international tertiary university medical centers. RESULTS: A total of 64 patients with the most severe skin changes in IgAV/HSP and median (Q1, Q3) age of 8.08 (5.08, 11.92) years at the disease onset were compared with 596 IgAV/HSP patients without these manfiestations and median (Q1, Q3) age of 6.33 (4.50, 8.92) years. The patients with severe cutaneous manifestations were older in comparison to other patients with IgAV/HSP (p<0.001), they developed nephritis more frequently (40.6% vs. 20.6%, p = 0.001) with worse outcome of renal disease (p = 0.001). This group of patients also had higher frequencies of severe gastrointestinal complications like hematochezia, massive bleeding and/or intussusception (29.3% vs. 14.8%, p<0.001). d-dimer concentrations were significantly higher in these patients (4.60 mg/L vs. 2.72 mg/L, p = 0.003) and they had more frequent need for treatment with systemic glucocorticoids (84.4% vs. 37.2%, p<0.001) in comparison with the control group. Further multivariate analysis showed that severe cutaneous changes were associated with higher risk of developing nephritis [OR=3.1 (95%CI 1.04-9.21), p = 0.042] and severe gastrointestinal complications [OR=3.65 (95%CI 1.08-12.37), p = 0.038]. CONCLUSION: Patients with IgAV/HSP and severe skin manifestations had a more severe clinical course and more frequently required glucocorticoids compared to classic IgAV/HSP patients.

The Multifaceted Presentation of the Multisystem Inflammatory Syndrome in Children: Data from a Cluster Analysis.

BACKGROUND: The aim of this study was to evaluate the outcomes of patients with the multisystem inflammatory syndrome in children (MIS-C) according to phenotypes of disease and define the prognostic factors for the severe course. METHODS: This cross-sectional study included 293 patients with MIS-C from seven pediatric rheumatology centers. A two-step cluster analysis was performed to define the spectrum of disease and their outcomes were compared between each group. RESULTS: Four subgroups were identified as follows: cluster I, predominantly Kawasaki-like features (n = 100); cluster II, predominantly MAS-like features (n = 34); cluster III, predominantly LV dysfunction (n = 47); cluster IV, other presentations (n = 112). The duration of fever was longer in cluster II and the length of hospitalization was longer in both clusters II and III. Laboratory findings revealed lower lymphocyte and platelet counts and higher acute phase reactants (APRs) in cluster II, while patients in cluster IV showed less inflammation with lower APRs. The resolution of abnormal laboratory findings was longer in clusters II and III, while it was shortest in cluster IV. Seven patients died. Among them, four belonged to cluster II, while three were labeled as cluster III. Patients with severe course had higher levels of neutrophil-lymphocyte ratio, mean platelet volume, procalcitonin, ferritin, interleukin-6, fibrinogen, D-Dimer, BNP, and troponin-I, and lower levels of lymphocyte and platelet counts. CONCLUSION: As shown, MIS-C is not a single disease presenting with various clinical features and outcomes. Understanding the disease spectrum will provide individualized management.

Toward the integration of biosimilars into pediatric rheumatology: adalimumab ABP 501 experience of PeRA research group.

OBJECTIVES: To review the real-life data, to provide an input to the literature concerning treatment of juvenile idiopathic arthritis (JIA) with adalimumab (ADL) biosimilar. METHOD: This multi-centric retrospective study was conducted among children with JIA, followed up for at least 24-weeks from the initiation of ADL biosimilar (ABP 501) treatment. Adverse events and alterations in disease activity scores were figured out. RESULTS: The median age of the group was 15.5 (5-18) years. JIA categories were oligoarticular (n =12), enthesitis-related (ERA) (n=24), psoriatic (PsA) (n=6), and polyarticular (n=4). Uveitis was detected at the initiation of the disease (n=3), during the disease course (n=5), or before the diagnosis (n=1). The first-line treatment preferences were ADL biosimilar (n=37) and etanercept (n=9). On the 6th month of ABP 501, 40 (86.9%) patients had achieved complete remission. Six patients (1 PsA, 1 polyarticular JIA, and 4 ERA) had ongoing active arthritis. Furthermore, all except one of the patients had remission of ophthalmologic findings. No life-threatening adverse events were observed. CONCLUSIONS: ABP 501 has a gradual increase in prescription in pediatric rheumatology. Real-life data of the cohort announce that ADL biosimilar is a suitable and effective treatment option for patients with JIA in case of indication.