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Multisystem inflammatory syndrome in children (MIS-C) is a serious condition characterized by excessive inflammation that can arise as a complication of SARS-CoV-2 infection in children. While our understanding of COVID-19 and MIS-C has been advancing, there is still uncertainty regarding the optimal treatment for MIS-C. In this study, we aimed to compare the clinical and laboratory outcomes of MIS-C patients treated with IVIG plus corticosteroids (CS) to those treated with IVIG plus CS and an additional biologic drug. We used the propensity score (PS)-matching method to assess the relationships between initial treatment and outcomes. The primary outcome was a left ventricular ejection fraction of less than 55% on day 2 or beyond and/or the requirement of inotrope support on day 2 or beyond. We included 79 MIS-C patients (median age 8.51 years, 33 boys) followed in our center. Among them, 50 children (25 in each group) were allocated to the PS-matched cohort sample. The primary outcome was observed in none of the patients in the IVIG and CS group, while it occurred in eight patients in the IVIG plus CS and biologic group (p = 0.04). MIS-C is a disorder that may progress rapidly and calls for extensive care. For definitive recommendations, further studies, including randomized control trials, are required.

Pediatric primary antiphospholipid syndrome (APS) is a very rare disease with significant distinctions from the APS in adults. Herein, we present our experience in the diagnosis and treatment of six pediatric primary APS patients, who met the updated Sapporo criteria for the APS diagnosis. One of them was also diagnosed as having probable catastrophic APS (CAPS) due to the involvement of three different organ systems simultaneously. Besides vascular involvement, four patients had thrombocytopenia, one had psychiatric disorder, and one had chorea and valvular heart disease. All patients received immunosuppressive treatment along with long-term anticoagulation therapy. Specific neurologic and hematologic manifestations that are not part of the classification criteria can be seen in children with primary APS. Therefore, using the adult criteria for diagnosing pediatric APS may result in missed or delayed diagnoses in children.

Objectives The lower extremity venous wall thickness (VWT) of Behçet’s disease (BD) patients was reported to be significantly increased in adults, suggesting its use for the support of BD diagnosis. This prospective study aimed to investigate the lower extremity VWT in childhood-onset definite and incomplete BD patients and compare it to healthy age-matched controls. Methods Paediatric patients classified with BD according to the 2015 international paediatric BD criteria in our centre were included in the study. Intima-media thickness of the lower extremity veins to evaluate VWT was measured by ultrasonography, including common femoral vein (CFV), femoral vein (FV), vena saphena magna, vena saphena parva and popliteal vein (PV). Results In this cross-sectional study, VWT was measured in 35 patients (63% male) and 27 healthy controls (55% male). Thirteen (37%) of 35 patients met the criteria for the diagnosis of BD. The remaining 22 (63%) had incomplete BD and met two criteria. The median VWT values of both definite and incomplete BD patients were significantly higher than the control group in all veins on both sides. Regarding the best cut-off values of VWT for all lower extremity veins, the sensitivity rates were between 63% and 86%, while specificity rates were between 71% and 100%. Conclusion Increased VWT was present not only in BD patients with vascular involvement but also in those without. We suggest that VWT may be a new criterion in supporting the diagnosis of childhood BD both in definite and incomplete BD patients.

Objectives Biologics are new treatment alternatives in Takayasu arteritis (TA), although data in childhood are limited. The aim of this study was to share our experience in seven childhood-onset TA patients who received a TNF-α inhibitor (adalimumab) or an IL-6 receptor inhibitor (tocilizumab) and the effect of switching therapy. Methods We retrospectively evaluated the medical treatment records of seven patients with TA, followed between August 2005 and January 2021 at the Pediatric Rheumatology Department of Hacettepe University Faculty of Medicine. Results The median age of patients was 14 (IQR 4) years, and six were female. All of the patients had severe disease and high acute-phase reactants. The patients initially received only steroids or steroids+CYC. Prednisone was decreased, and biologic agents were started once the acute phase reactants decreased, and the Indian Takayasu Activity Score (ITAS) returned to normal. Initially, four patients received tocilizumab (TCZ) [median 25.5 (IQR 41) months] and three patients received adalimumab (ADA) [median 13 (IQR 31) months]. However, due to the progression of MR angiography findings or persistent elevation in acute-phase reactants, the biologic agents were switched from TCZ to ADA in four patients and from ADA to TCZ in three patients. The patients' median follow-up time after changing was 50 (IQR 77) months, and median ITAS was evaluated as ‘0’ after 2 (IQR 4) months. Conclusions In conclusion, both TNF-α and IL-6 inhibitors are effective alternatives in treating patients with childhood-onset TA. However, prospective randomized controlled trials are needed for the comparison of their effectiveness.

Enthesitis-related arthritis (ERA) could be considered the pediatric equivalent of ankylosing spondylitis in adults albeit with certain significant differences. We aim to evaluate the sensitivity and specificity of the International League of Associations for Rheumatology (ILAR), the Assessment of Spondyloarthritis International Society (ASAS), and the preliminary Pediatric Rheumatology International Trials Organization (PRINTO) classification criteria in ERA patients.The medical records of ERA patients who were followed up between January 2005 and September 2020 have been analyzed. The control group consisted of patients with oligoarticular JIA (n = 146), polyarticular JIA (n = 55), and psoriatic arthritis (n = 20).This retrospective study included 108 ERA (73.1% male) and 221 control patients (25.8% male). The median age at diagnosis for ERA and control patients were 12.5 and 4.0 years, respectively (p 0.001). Arthritis was observed more frequently in the control group at diagnosis and in the follow-up (p 0.001 for both), while enthesitis, sacroiliac joint tenderness, and inflammatory back pain were more common in the ERA group both at diagnosis and in the follow-up (p 0.001 for all). In sacroiliac imaging, 70.1% of ERA patients had positive findings suggestive of sacroiliitis at diagnosis and 78% in the follow-up. The sensitivities of ILAR, PRINTO, ASAS criteria for axial SpA, and peripheral SpA at diagnosis were 74.0%, 57.4%, 21.3%, and 85.1%, respectively which increased to 82.4%, 78.7%, 35.1%, and 92.5%, respectively at follow-up. The specificities were 100%, 100%, 99.1%, and 90.9%, respectively at both diagnosis and follow-up.The ASAS criteria for peripheral SpA were the most sensitive while ILAR and the preliminary PRINTO criteria were the most specific criteria for classifying ERA patients.The ASAS criteria for peripheral SpA were the most sensitive criteria for classifying ERA patients. The use of ASAS axial SpA criteria may provide early detection of axial involvement.

Children with suspicious complaints of rheumatic diseases are generally referred to a pediatric rheumatologist. We aimed to evaluate the profile of patients referred to the pediatric rheumatology unit and were not diagnosed with a rheumatic disease and to assess the impact of the coronavirus disease-2019 pandemic on referral complaints.All new outpatients who applied to the pediatric rheumatology department between March 2019 and February 2021 and were not diagnosed with rheumatic disease were included. We also compared the frequency of admission symptoms during the pre-pandemic (March 2019-February 2020) and pandemic periods (March 2020-February 2021).A total of 1089 patients without a rheumatic disease diagnosis (568 female, 52.2%; median age 10.0 years) were included in this study. The most common complaint for referral was prolonged or recurrent fevers (13.4%) followed by anti-nuclear antibody positivity (13.1%), arthralgia (13.0%), skin findings (7.5%), and the presence of heterozygous mutations in the Mediterranean fever gene (6.9%). During the pandemic year, the number of patients referred for back pain increased significantly (P = .028). A total of 682 of 1089 patients were consulted from other departments in our center (62.6%). Of these, the most frequent consultation request was from general pediatrics (43.6%). The rheumatic disease was excluded in 11.3% of the patients.Prolonged or recurrent fever and anti-nuclear antibody positivity were the most frequent complaints of referrals to a pediatric rheumatology unit in patients who did not have a rheumatic disease. The rate of back pain was more common in children during the pandemic period.

The impact of the COVID-19 pandemic, and implemented restrictions on the frequency of pediatric rheumatic diseases remain unknown, while they have probably prevented common infections in children. We present the effects of the COVID-19 on our pediatric rheumatology practice in a main referral center. We retrospectively reviewed the medical records of patients presenting to pediatric rheumatology department in 4 years before March 2020 and compared it to the pandemic year (March 2020–March 2021). Since there was an overall decrease in patient numbers, we calculated the percentage according to the total number of that year. A total of 32,333 patients were evaluated. The mean annual number of patients decreased by 42% during the COVID-19 pandemic. When follow-up visits (25,156) were excluded, there were 2818 new diagnoses of rheumatic diseases. In the pre-pandemic period, familial Mediterranean fever (FMF) (n = 695, 28.1%) was the most frequent, whereas in the pandemic period multisystem inflammatory syndrome in children (MIS-C) (n = 68, 19.2%) was the most common diagnosis. There were no significant differences in the percentages of juvenile idiopathic arthritis, autoimmune diseases, rare autoinflammatory diseases, and other vasculitides. However, there was a significant decrease in patients diagnosed with FMF, IgA vasculitis (IgAV), acute rheumatic fever (ARF), classic Kawasaki disease (KD), and macrophage activation syndrome (MAS) (all p

Objective To evaluate the course of coronavirus-19 (COVID-19) infection in paediatric familial Mediterranean fever (FMF) patients and to investigate the risk factors for COVID-19 infection. Methods Medical records of 100 consecutive paediatric FMF patients and their COVID-19 infection status were evaluated. Age- and gender-matched control group consisted of 51 patients with positive results for severe acute respiratory syndrome coronavirus 2. Results Twenty-five of 100 paediatric FMF patients were detected to have COVID-19 infection. A history of contact with a COVID-19 case was present in ∼95% of patients in both the FMF and control groups with COVID-19 infection. Asymptomatic infection was detected in two patients in the paediatric FMF group (8.0%) and 17 patients in the control group (33.3%) (P = .017). Mild disease was observed in 23 paediatric FMF patients (92.0%) and 28 control patients (54.9%) (P = .001), whereas moderate disease was present in only 6 control patients (11.7%) (0 vs 11.7%, P = .074). Severe or critical disease was not observed in any patients. Conclusion Paediatric FMF patients receiving colchicine had no moderate COVID-19 disease compared to the control group. We suggest that colchicine use may tune down the severity of the disease even if it does not prevent COVID-19 infection.

Methotrexate (MTX) is one of the most commonly used disease-modifying anti-rheumatic drugs which can cause gastrointestinal side effects. MTX intolerance is defined as gastrointestinal and behavioral symptoms occurring before and after MTX administration. This study aims to evaluate and compare the frequency of methotrexate intolerance in adult and pediatric patients. Patients with a rheumatic disease who used oral or parenteral methotrexate for at least 3 months were included in the study. Methotrexate intolerance was assessed using the Methotrexate Intolerance Severity Score (MISS) questionnaire and visual analog scale (VAS). In the pediatric patient group, the MISS questionnaire and VAS assessment were applied to both patients and families. A total of 200 patients, 100 of whom were children, were enrolled in the study. The mean age for children and adults were 11.9 (± 3.7) and 52.0 (± 10.9). The prevalence of MTX intolerance was higher in the pediatric group, 64.0 and 10.0% (p

SLE is a disease of the adaptive immune system where T lymphocyte dysfunction has an important role as well. We assessed the plasma levels of checkpoint receptors expressed on T cells, along with Galectin-9 to reflect type-1 IFN activity and IL-2Rα in childhood SLE patients. Forty-nine children with SLE and15 healthy controls were included. SLEDAI scores were evaluated at the time of sampling. CD25 (IL-2Rα), 4-1BB, B7.2 (CD86), TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG- 3, Galectin-9 levels were studied by cytometric bead-based multiplex assay panel. Galectin-9 and PD-L1 were significantly higher in SLE patients. Other checkpoint proteins and IL-2Rα were also higher but did not reach statistical significance. There were significant correlations between SLEDAI and IL-2Rα, Galectin-9 and PDL1. There were three clinical clusters: Cluster 1 included patients with no major organ involvement, cluster 2 had predominantly haematological involvement(n=16) and cluster 3 (n=11) had predominantly renal involvement. Checkpoint proteins were not different among these three clusters. Our data supports that Galectin 9 and IL-2Rα are good markers for disease activity in childhood SLE. We need larger series to evaluate differences between disease clusters in SLE. We failed to show a significant correlation with checkpoint proteins and SLEDAI except for PDL1.

Takayasu arteritis (TAK) has been rarely reported in patients with immunodeficiency. In this review, we present two cases with childhood-onset TAK (c-TAK) and primary immunodeficiency while reviewing similar cases in the literature. We reviewed the data for our two pediatric patients with c-TAK and primary immunodeficiency. We also reviewed the literature for patients with c-TAK and immunodeficiency from the inceptions of the databases up to November 2021. A 14-year-old patient had lipopolysaccharide-sensitive beige-like anchor (LRBA) deficiency, and a 16-year-old had X-linked severe combined immunodeficiency (X-linked SCID). During the follow-up, they developed findings suggestive of vasculitides such as hypertension, elevation in acute phase reactants, weakness, and weight loss. Thoracoabdominal computed tomography angiography revealed findings consistent with vasculitis involving the aorta and its major branches. Patients were diagnosed with c-TAK, and corticosteroids were given to both patients in the treatment. We identified 11 articles describing 17 TAK patients with immunodeficiency in our literature search. Two of the patients with c-TAK were infected with human immunodeficiency virus (HIV), another patient had Wiskott-Aldrich syndrome, and the other had idiopathic CD4 + T lymphocytopenia. Nine adult patients with TAK were infected with HIV, three patients had common variable immunodeficiency disorder (CVID), and the other had STAT1 gain-of-function mutation. Clinicians should consider that immunodeficiencies may be accompanied by vasculitic conditions such as TAK. Hypertension, increased inflammatory markers, and constitutional symptoms may be red flags for the development of TAK.

Objective Recently a new set of criteria proposed for the classification of auto inflammatory recurrent fevers including familial Mediterranean Fever (FMF). We aimed to compare the sensitivity and specificity of the new Eurofever/PRINTO classification criteria with those of the Tel Hashomer and Yalcinkaya–Ozen criteria. Methods 151 consecutive FMF patients between February and May 2019 who were followed at Hacettepe University Department of Pediatric Rheumatology were included in this study. A group of 82 patients with periodic fever 66 periodic fever, aphthosis, pharyngitis and adenitis syndrome (PFAPA), nine cryopyrin-associated periodic syndrome (CAPS) and seven mevalonate kinase deficiency/hyperimmunoglobulin D syndrome (MKD/HIDS) patients) served as controls. GraphPad 6.0 was used for statistical analysis. Results Three different classification criteria were analyzed in 151 FMF patients with a median age at diagnosis of 5 years and in 82 controls with a median age at diagnosis of 3 years. The sensitivity of the new Eurofever/PRINTO criteria (96%) was highest (Tel Hashomer criteria-88.4% and Yalcinkaya–Ozen criteria-93.4%). However, the specificity of these criteria (73.1%) was lowest (Tel Hashomer criteria-92.6% and Yalcinkaya–Ozen criteria-84.1%). The new Eurofever/PRINTO criteria achieved the highest sensitivity (100%) in biallelic exon 10 mutation patients (Tel Hashomer criteria-87.4% and Yalcinkaya–Ozen criteria-94.2%). However, the new set had the lowest sensitivity (88.2%) in heterozygote exon 10 mutation patients (Tel Hashomer criteria 94.1% and Yalcinkaya–Ozen criteria 94.1%). Conclusion In this Turkish cohort, the new Eurofever/PRINTO criteria have a better sensitivity but lower specificity with higher misclassifications than other two well-known criteria. The combination of clinical manifestations with genotype increased the sensitivity. The lower specificity may be due to the high carrier rate in our population. Although the ethnicity information lowers the specificity, ‘clinical-only’ criteria set may still guide the clinician to perform appropriate genetic testing in patients with recurrent fever.

Objectives Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe condition associated with coronavirus disease 2019. Here we aimed to raise awareness for the symptoms of MIS-C in patients with rheumatic diseases, emphasizing the challenges of the differential features. Methods We retrospectively evaluated the demographic and clinical characteristics, laboratory and imaging findings, treatments, and outcomes of six MIS-C patients with previous rheumatic disease. Results Three of the patients had familial Mediterranean fever (FMF), one had juvenile dermatomyositis, one had systemic juvenile idiopathic arthritis (JIA), and another patient had oligoarticular JIA. All FMF patients presented with fever and abdominal pain, two also had chest pain. The patient with systemic JIA presented with fever, rash, and myalgia. All patients had elevated inflammatory markers and high d-dimer levels. Chest imaging of two FMF patients showed infiltrations compatible with pneumonia. One FMF patient had mildly decreased systolic functions with a shortening fraction of 48% in his echocardiography. Intravenous immunoglobulin and methylprednisolone were administered to all patients. Anakinra was given to four patients. Conclusions Clinical and laboratory signs of MIS-C may overlap with the findings of various rheumatic diseases, and this may cause a delay in diagnosis.

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. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Introduction: Systemic lupus erythematosus (SLE) may present with features of several systems, including hematological manifestations. In this study, we aimed to evaluate the characteristics of hematological involvement and assess possible associations and correlations in pediatric SLE patients. Method: This is a retrospective multi-center study. The medical records of pediatric SLE patients followed between January 2000 and June 2020 were analyzed. All children fulfilled the criteria of the Systemic Lupus International Collaborating Clinics. Results: The study included 215 children with SLE, 118 of whom had hematological manifestations. Concomitant renal involvement and low C3 levels were significantly more frequent in patients with hematological involvement ( p = 0.04, p = 0.008, respectively). Also, anti-cardiolipin, anti-beta-2-glycoprotein I (anti-β2 GP1), and anti-Sm antibody positivity, and the presence of lupus anticoagulant were more common in the group with hematological findings ( p = 0.001 for anti-cardiolipin antibody positivity and p < 0.001 for the positivity of anti-β2 GP1 antibody, anti-Sm antibody, and lupus anticoagulant). The most common hematologic abnormality was anemia (n = 88, 74.5%), with autoimmune hemolytic anemia constituting the majority (n = 40). Corticosteroids followed by IVIG were the mainstay of treatment. In patients resistant to corticosteroid and IVIG treatments, the most preferred drug was rituximab. Low levels of C3, high SLEDAI score, high incidence of renal involvement, and positive antiphospholipid antibodies were associated with hematological involvement in the univariate analysis. The presence of antiphospholipid antibodies and high SLEDAI score were independently associated with hematological involvement in multivariate analysis (OR: 4.021; 95% CI: 2.041–7.921; p < 0.001 and OR: 1.136; 95% CI: 1.065–1.212; p < 0.001). Conclusion: Hematological abnormalities are frequently encountered in pediatric SLE. Positive antiphospholipid antibodies and high SLEDAI scores were associated with hematological involvement.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic, immune-mediated, and fibroinflammatory disease that can affect almost any organ system. We aimed to present our single-center experience of pediatric patients with IgG4-RD, a rare disease in children. Pediatric patients diagnosed with IgG4-RD at the Hacettepe University between June 2014 and September 2020 were evaluated retrospectively. Patients with definite, probable, or possible diagnosis of IgG4-RD were included. A total of eight patients with a median age of 13.4 (IQR 9.5–15.0) years were included in the study. Clinical presentations were IgG4-related ophthalmic disease in six patients, IgG4-related lymphadenopathy in one patient, and IgG4-related sialadenitis and lymphadenopathy of several lymph nodes accompanied by pancreatitis, ulcerative colitis, and pulmonary manifestations in one patient. Elevated serum IgG4 was detected in three of eight patients (37.5%). The main histopathological feature was fibrosis and lymphoplasmacytic infiltrates. Corticosteroids were used as first-line treatment in almost all patients with or without steroid-sparing agents. Azathioprine, methotrexate and rituximab were used as steroid-sparing agents. Relapse occurred in two of seven patients. Radiotherapy was used as the last resort in one patient with severe orbital disease. IgG4 RD mainly presents with orbital manifestations in pediatric population but has wide phenotypic clinical variability. Although rare, early recognition and treatment are essential for a better outcome in these patients.

Background Diagnosis of childhood polyarteritis nodosa (PAN) has become challenging after the definition of deficiency of adenosine deaminase 2 (DADA2). We aimed to define the differential features of pediatric PAN and DADA2 patients in our center and in the literature. Methods The charts of pediatric PAN and DADA2 patients followed at the Pediatric Rheumatology Unit of Hacettepe University between 2010–2020 were analyzed. A systematic literature review was conducted for articles regarding pediatric PAN or DADA2. Results Thirty-four pediatric PAN and 18 pediatric DADA2 patients were included. The age at onset was younger, parental consanguinity, livedo reticularis, neurologic involvement (especially strokes), lymphopenia, and hypogammaglobulinemia were more frequent, while thrombocytosis and panniculitis were less frequent in DADA2 patients. The primary treatment was anti-tumor necrosis factor (anti-TNF) in DADA2. For induction treatment, all systemic PAN patients received corticosteroids, and cyclophosphamide (n=11) or mycophenolate mofetil (MMF) (n = 3). Cyclophosphamide was replaced with MMF in nine once remission was confirmed with PVAS. In the literature, 28 articles describing 613 pediatric PAN patients and 26 articles describing 207 pediatric DADA2 patients were identified. Neurologic, gastrointestinal, and cardiac involvements were more frequent in DADA2, while constitutional symptoms and testis involvement were more common in PAN. Conclusion In a child with PAN-like phenotype, DADA2 should be considered in the presence of young age at disease onset, parental consanguinity, strokes, lymphopenia, and lack of thrombocytosis during active disease. Anti-TNF treatment is indicated for vasculitic DADA2. Cyclophosphamide could be switched to MMF when remission is confirmed with PVAS in severe PAN.

Macrophage activation syndrome (MAS) is a devastating complication of systemic JIA (sJIA), seen in approximately 10–25% of the sJIA patients. A number of criteria have been proposed to differentiate between activation of sJIA and MAS, including HScore and the recently proposed MS-score. This is the first study comparing the performances of MS-score and HScore for the diagnosis of MAS in sJIA patients. Systemic JIA patients followed at Hacettepe University Pediatric Rheumatology Unit were included in the study. Clinical features and laboratory findings at the time when the disease was most active or patients were diagnosed with MAS were recorded retrospectively. HScore and MS-score were calculated and the diagnostic performance for MAS was compared by receiver operating characteristic (ROC) curve analysis. Seventy-one sJIA patients were included (23 MAS, 48 activation). There was no difference in age of onset (median 4.7 vs. 5.0 years) and gender (73.9% vs. 54.2%) between patients who had MAS and sJIA activation. Median MS-score and HScore were higher in the MAS group. ROC curve analysis revealed that the HScore performed slightly better in diagnosing MAS, compared with the MS-score (AUC = 0.965 and 0.901 for HScore and MS-score respectively, P

Children with Coronavirus disease 2019 (COVID-19) are being reported to have manifestations of hyperinflammatory states and/or Kawasaki-like disease. In this study, we investigated children with typical and atypical Kawasaki disease (KD) likely to be associated with COVID-19. We have reported four children with Kawasaki-like disease probably associated with COVID-19. The clinical features were consistent with incomplete KD in three patients. SARS-CoV-2 RT-PCR was positive in one and the serology was positive in one patient with negative RT-PCR. Corticosteroids, anakinra, intravenous immunoglobulin (IVIG), and acetylsalicylic acid were used in the treatment. Three patients recovered after the treatment while one patient died. The literature review revealed 36 articles describing 320 children with Kawasaki-like disease associated with COVID-19. SARS-CoV-2 RT-PCR was negative in 120 (65.5%) of 183 patients while the serology was positive in 130 (83.8%) of 155 patients. The therapeutic options have included IVIG, acetylsalicylic acid, tocilizumab, anakinra, enoxaparin, and methylprednisolone. Pediatric COVID-19 cases may present with atypical/incomplete Kawasaki-like disease. Thus, pediatricians need to be aware of such atypical presentations resembling KD for early diagnosis of COVID-19.

Background We aimed to compare the ten different scores (by Kobayashi, Egami, Harada, Formosa, Sano, Piram et al., Wu et al., Yang et al., Tan et al., and Kanai et al.) to assess their performance in predicting IVIG resistance in Turkish children. Methods Complete and incomplete KD patients diagnosed with KD at Hacettepe University between June 2007 and September 2019 were evaluated retrospectively. Results A total of 129 patients, 79 boys (61.2%), with a median age 36 (IQR 19.5-57.0) months were evaluated. Sixteen patients (12.4%) had IVIG resistance. Sensitivity was low for all the ten scores. Tan, Sano, and Egami predictive models had the highest specificity (97.3, 89.4, 86.7%, respectively). Almost all scoring systems distinguished the group of patients with low risk for IVIG resistance but could not differentiate IVIG-resistant patients. Multivariate analysis for the laboratory features showed that platelet count Conclusions The current scoring systems had a low sensitivity for predicting the risk for IVIG resistance in Turkish children. On the other hand, increased serum GGT levels and low platelet count were risk factors for predicting IVIG resistance. Impact Intravenous immunoglobulin (IVIG) resistance may be observed in 10-20% of patients diagnosed with Kawasaki disease. Coronary artery involvement is more frequent in IVIG-resistant patients. It is important to predict the patients who might develop IVIG resistance to improve prognosis. The performance of the IVIG resistance predictive models in Kawasaki disease in our population is limited due to the low sensitivity.

BackgroundMusculoskeletal symptoms may be due to non-inflammatory causes including genetic disorders. We aimed to examine the final genetic diagnosis in patients who had presented with musculoskeletal complaints to rheumatology department.MethodsPatients presenting to the department of pediatric rheumatology and consulted to the genetic department between January 2015 and May 2019 were evaluated retrospectively. ResultsA total of 60 patients, 19 boys (31.66%), with a mean age 12.46 ± 1.41 years were included in the study. Total consanguinity rate was 25%. The most common (29.5%) cause of referral to the genetic department was the presence of skeletal anomalies (such as camptodactyly, clinodactyly, and short stature) with accompanying joint findings. Approximately one third of the patients (n: 19) were diagnosed and followed up by the genetic department. The diagnoses of patients were as follows; CACP syndrome (n:3), trichorhinophalangeal syndrome (n:1), progressive pseudoromatoid dysplasia (n:2), LIG4 syndrome (n:1), H syndrome (n:1), SPENCD syndrome (n:3), and nonspecific connective tissue disease (n:8).ConclusionsIn the differential diagnosis of patients who are referred to the department of pediatric rheumatology with complaints of the musculoskeletal system, genetic disorders should also be taken into consideration.Clinical Trial Registration: Hacettepe University Ethics Commission (Approval number: GO 19/781)

Objectives FMF is a prototype of autoinflammatory diseases associated with excess IL1 production. Anti-IL1 treatments are the first-line alternatives in colchicine-resistant/intolerant FMF patients. We aimed to investigate the efficacy and safety of anti-IL1 treatment in paediatric FMF patients in our local [Hacettepe univErsity eLectronIc research fOrmS (HELIOS)] registry. Methods HELIOS is a web-based biologic drug registry for paediatric rheumatology patients. We have analysed the clinical features, disease activity parameters, treatment responses and safety outcomes in FMF patients treated with anti-IL1 agents. Results Forty paediatric FMF patients (34 continuous and six on-demand use) were included. Among the continuously treated group (61.7% female), the mean age at the start of colchicine was 5.55 (3.87) years. Age at onset of the anti-IL1 treatment was 11.47 (5.41) years with a mean follow-up duration of 3.87 (1.96) years. Apart from two, all patients had biallelic exon-10 mutations. We also gave anti-IL1 treatment on an on-demand basis in six patients. Anakinra was used as the first-line anti-IL1 treatment. During the last visit, six patients were treated with anakinra and 28 patients with canakinumab. Anti-IL1 treatment decreased the CRP levels and number and severity of the attacks. There were three hospitalizations reported due to mild infections. Eleven patients had local skin reactions, two patients had leucopenia with anakinra and one patient had thrombocytopenia with canakinumab. There was no malignancy or other severe adverse reactions. Conclusion Anakinra and canakinumab are efficient and safe alternatives in colchicine-resistant or -intolerant paediatric FMF patients. We also, for the first time, report on-demand use of anti-IL1 in paediatric FMF patients.

Background:Systemic Lupus Erythematosus (SLE) is the prototype for a systemic autoimmune disease. SLE is a disease of the adaptive immune system where T lymphocyte dysfunction has an important role as well. Checkpoint proteins have become an important topic in the study of Tcell. The balance of T cell co-stimulatory and co-inhibitory receptors is important for the regulation of the adaptive immune system response.Objectives:In this study we aimed to assess the checkpoint proteins in childhood SLE patientsMethods:Fourty-nine jSLE patients together with 15 age- and gender- matched controls were included. Clinical features, disease activity scores and laboratory parameters were recorded both retrospectively and at the time of samplimg. Patient samples were collected at their last visit, Plasma CD25 (IL-2Rα), 4-1BB, B7.2 (CD86), TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG- 3, Galectin-9 levels were studied by the cytometric bead-based multiplex assay panel according to manufacturer’s instruction (LEGENDplex HU Immune Checkpoint Panel 1 (10-plex); catalogue number 740962, Biolegend) and analysed by Novocyte 3005 flow cytometer. Two-step cluster analysis procedure was conducted over the chosen 7 symptom status and 3 clusters were chosen for the final analysisResults:A total of 49 patients (71.4% female) diagnosed with SLE according to the SLICC criteria and 15 healthy controls (73.3% female) were included in the study. The mean age of the patients was 17.7 ± 2.6 years and the controls was 13.3±1.4 years. The median disease duration was 5.7 years. At the time of sampling fifteen of the patients had a SLEDAI score of zero (no activity), 21 of them had between 1-5 (mild activity), 7 of them had between 6-10 (moderate activity), 5 of them had between 11-19 (high activity), 1 of them had >20 (very high activity).Galectin-9 and PD-L1 were significantly higher in SLE patients. Other checkpoint proteins and IL-2Rα were also higher but did not reach statistical significance. There were significant correlations between SLEDAI and IL-2Rα, Galectin-9 and PDL1. (Figure 1) There were three clinical clusters: Cluster 1 included patients with no major organ involvement, cluster 2 had predominantly haematological involvement (n=16) and cluster 3 (n=11) had predominantly renal involvement. Checkpoint proteins were not different among these three clusters.Figure 1.Table 1.Demographic, Clinical and Laboratory Features of Patients (n=49)Female gender, n (%)35 (%71.4)Mean age at diagnosis, years (mean±SD)12.5±3.3Mean age at the time of inclusion, years (mean±SD)17.7±2.6Duration of illness, years (median/IQR)5.7 (3.0-7.0) yearsActive system involvement at study,n (%) Renal14 (28.5) Skin11 (22.4) Musculoskeletal9 (18.3) Hematologic9 (18.3) Neurologic1 (2.0) Serositis1 (2.0)Laboratory findings (median/minimum-maximum) Hemoglobin, gr/dl12.7 (7.3-18.3) WBC, /mm36.900 (2.600-26.200) Platelet, /mm3252.000 (39.000-529.000) Erythrocyte sedimentation rate, mm/hour10 (1-71) C-reactive protein, mg/dl0.1 (0-21.1) Complement 3, mg/dl87.6 (25.4-186.0) Complement 4, mg/dl15.3 (0-45.8) Anti-ds DNA, IU/ml12.8 (0-741.7) SLEDAI score (mean±SD)4.69±6.69Conclusion:Our data supports that Galectin 9 and IL-2Rα are good markers for disease activity in childhood SLE. We need larger series to evaluate differences between disease clusters in SLE. We failed to show a significant correlation with checkpoint proteins and SLEDAI except for PDL1.References:[1]Sharabi A and Tsokos GC. T cell metabolism: new insights in systemic lupus erythematosus pathogenesis and therapy. Nature reviews Rheumatology 2020; 16: 100-112[2]Nishimura H, Nose M, Hiai H, et al. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 1999; 11: 141-151.[3]McKinney EF, Lee JC, Jayne DR, et al. T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection. Nature 2015[4]Wherry EJ and Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 2015; 15: 486-499Disclosure of Interests:None declared

BackgroundMusculoskeletal symptoms may be due to noninflammatory causes, including genetic disorders. We aimed to examine the final genetic diagnosis in patients who presented with musculoskeletal complaints to the rheumatology department.MethodsPatients who presented to the Department of Pediatric Rheumatology and were referred to the pediatric genetic department between January 2015 and May 2019 were evaluated retrospectively. ResultsA total of 60 patients, 19 boys (31.66%), with a mean age of 12.46 ± 1.41 years were included in the study. The total consanguinity rate was 25%. The most common (29.5%) cause of referral to the pediatric genetic department was the presence of skeletal anomalies (such as camptodactyly, clinodactyly, and short stature) with accompanying joint findings. Approximately one-third of the patients (n: 19) were diagnosed and followed up by the pediatric genetics department. The diagnoses of patients were as follows: camptodactyly, arthropathy, coxa vara, and pericarditis (CACP) syndrome (n: 3); trichorhinophalangeal syndrome (n: 1); progressive pseudorheumatoid dysplasia (n: 2); LIG4 syndrome (n: 1); H syndrome (n: 1); spondyloenchondrodysplasia (SPENCD) (n: 3); and nonspecific connective tissue disorders (n: 8).ConclusionsIn the differential diagnosis of patients who are referred to the Department of Pediatric Rheumatology with complaints of the musculoskeletal system, genetic disorders should also be considered.

Background:FMF is a prototype of autoinflammatory diseases associated with excess IL1 production. Anti-IL1 treatments are the first-line alternatives in colchicine resistant/intolerant FMF patients.Objectives:We aimed to investigate the efficacy and safety of anti-IL1 treatment in pediatric FMF patients in our local (HELIOS) registry.Methods:HELIOS (Hacettepe univErsity eLectronIc research fOrmS) is a web-based biological drug registry for pediatric rheumatology patients (helios.hacettepe.edu.tr). Data were recorded at biological treatment onset (month 0), at month 6 and yearly thereafter in patients. We have analysed the clinical features, disease activity parameters, treatment responses and safety outcomes in FMF patients treated with anti-IL1 agent.Results:Forty pediatric FMF patients were included to the study group (67% female).Thirty-four patients received continous anti-IL1 treatment. The mean age at the start of the colchicine was 5.55±3.87 years. Age at onset of the anti-IL1 treatment was 11.47±5.41 with a mean follow-up duration of 3.87±1.96 years. Apart from two patients, all of them had biallelic exon-10 mutations.We have also given anti-IL1 treatment on an on-demand basis in six adolescent patients. Five of them were having very severe attacks during menstrual periods and one was having attacks during extreme stress periods along with very high CRP levels. The quality of life has markedly improved and these patients no longer reveal any CRP elevation.Anakinra was used as the first-line anti-IL1 treatment. During the last visit, six patients were treated with anakinra and 28 patients were treated with canakinumab. Anti-IL1 treatment decreased the CRP levels, number and severity of the attacks. (Figure 1.) There were three hospitalizations reported due to mild infections. Eleven patients had local skin reactions, two patients had leukopenia with anakinra and one patient had thrombocytopenia with canakinumab. We have discontinued anti-IL1 treatment until the cytopenia subsided. We have switched to on-demand therapy in one patient, started the same treatment and gradually increased the dose in the other two patients. There were no malignancy or other severe adverse reactions.Figure 1.Conclusion:Anakinra and canakinumab are efficient and safe alternatives in colchicine resistant and intolerant pediatric FMF patients. We also for the first time, report on-demand use of anti-IL1 in pediatric FMF patients. We suggest that on-demand treatment should be considered under certain circumstances where the trigger is known and short-lasting (such as menstruation and periods of extreme stress)Acknowledgments:Authors would like to thank Elif Arslanoglu Aydin, Armagan Keskin, Kubra Yuksel and Emil Aliyev for their contribution to the HELIOS registryDisclosure of Interests:Erdal Sag Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Fuat Akal Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Erdal Atalay Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Ummusen Kaya Akca Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Selcan Demir Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Dilara Demirel Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Ezgi Deniz Batu Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Yelda Bilginer Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Seza Özen Consultant of: Novartis, Pfizer, Speakers bureau: SOBI, Novartis