OBJECTIVES:JIA is the most common rheumatic disease of childhood; the pathogenesis is associated with T-cell activation. T-cell activation can be counterbalanced by signals generated by inhibitory receptors (IRs) such as CTLA-4, PD-1, LAG-3 and TIM-3. Here, we identify the role of IRs in the pathogenesis of different JIA subtypes. METHODS:In total, we included 67 oligoarticular JIA, 12 IgM-RF negative polyarticular JIA, 17 enthesitis-related arthritis, 11 systemic JIA patients and 10 healthy controls. We collected plasma (and SF) samples from the patients either at the onset or during a flare of their disease. We measured the soluble levels of co-IRs (IL-2Rα, 4-1BB, CD86, TGF-β1, CTLA-4, PD-L1, PD-1, TIM-3, LAG- 3, Galectin-9) by cytometric bead array kits and their cellular expression (PD-1, CTLA-4, TIM-3, LAG-3) by flow cytometry. We compared the plasma levels and cellular expressions of different co-IRs within different JIA subgroups. RESULTS:The polyarticular JIA group was different from the three other examined JIA subgroups, having higher levels of plasma sCTLA-4 (P < 0.001), sPD-1 (P < 0.05) and s4-1BB (P < 0.05) when compared with the other JIA subgroups and healthy controls. We analysed the cellular surface expression of different co-IRs on the peripheral blood mononuclear cells of different JIA subtypes. Similar to plasma levels, both the percentage (P < 0.05) and the mean fluorescence intensity (P < 0.01) of CTLA4 expression were higher in the polyarticular JIA subgroup. CONCLUSION:This is the first report studying the expression profile of different co-IRs in different subtypes of JIA. Polyarticular JIA patients had a different co-IR profile, having more CTLA-4, PD-1 and 4-1BB in their plasma than the other subtypes of JIA.

OBJECTIVES:FMF is characterized by febrile polyserositis attacks. Menstruation could be a trigger for attacks. We aimed to analyse the features of adolescent FMF patients with menstruation-associated attacks and propose a management algorithm. METHODS:All female FMF patients who had menarche and visited the Pediatric Rheumatology Unit between January and December 2022, were included into this study. Demographics, general characteristics and the features of menstrual cycle and FMF attacks were noted. RESULTS:A total of 151 female FMF patients were included. Thirty-five (23.2%) had menstruation-associated attacks. Fever and arthritis were less frequent during the menstruation-associated attacks than the attacks not associated with menstruation in these patients (65.7% vs 88.6%, P = 0.01 and 2.9% vs 20%, P = 0.04, respectively). Patients with menstruation-associated FMF attacks were younger at symptom onset and diagnosis (2.5 vs 5 years, P = 0.004 and 4 vs 7 years, P = 0.01; respectively), had a higher rate of dysmenorrhea (74.3% vs 38.8%, P < 0.001, respectively) and higher pre- and post-menarche attack frequency (4 vs 2 and 10 vs 0, respectively; P < 0.001 for both) than patients whose attacks were not associated with menstruation. The interventions for menstruation-associated attacks included initiating colchicine, increasing the dose of colchicine, switching from coated to compressed colchicine tablets or adding anti-interleukin 1 drugs and initiating on-demand non-steroidal anti-inflammatory drugs, on-demand glucocorticoids and on-demand anakinra. On-demand therapies were beneficial in controlling menstruation-associated attacks. CONCLUSIONS:This is the largest cohort of adolescent FMF patients with menstruation-associated attacks. Severe FMF may cause a tendency to this association. On-demand therapies could be preferred in the management.

[This corrects the article on p. 963 in vol. 54, PMID: 39473760.].

OBJECTIVES:The transition of adolescents and young adults (AYAs) from pediatric to adult-oriented healthcare may be affected by many factors, including the personal and cultural settings. We aimed to analyse the transition readiness and the factors affecting the transition success in rheumatology. METHODS:Patients older than 12 years were included in this prospective study. All filled out the Transition Readiness Assessment Questionnaire (TRAQ) 5.0. AYAs were phone-interviewed after their transfer to adult-oriented healthcare. Drug adherence was evaluated with 4-item Morisky Medication Adherence Scale (MMAS-4). AYAs rated their transitional care experience with visual analogue scale (VAS 0-10; 0, the worst; 10, the best). RESULTS:A total of 504 TRAQs were filled out by 406 patients (F/M = 1.5). The total TRAQ score was positively correlated with age and higher in the forms filled out by girls than boys (4.2 vs 4.0, respectively; P = 0.005). The transition was successful for 78 (83.9%) out of 93 patients transferred to adult-oriented healthcare. The VAS for the transition process was lower and the post-transfer MMAS-4 score was worse (8 vs 9, P = 0.030 and 3 vs 4, P = 0.020, respectively) in patients whose transition was not successful when compared with those that successfully transitioned. The best-performing TRAQ cut-off value was >4.0 for predicting transfer readiness in rheumatology. CONCLUSION:A TRAQ score of >4 could be used while deciding about the transfer readiness of AYAs in rheumatology. Improving the AYAs' experience of the transition process and closely monitoring medication adherence during transition are essential for a successful transition.

Background/aim:The transition from pediatric to adult-oriented care for individuals with juvenile-onset systemic lupus erythematosus (SLE) poses significant challenges. This study aimed to assess the outcomes of transitioning patients with juvenile-onset SLE from pediatric to adult-oriented care. Materials and methods:Patients with juvenile-onset SLE were included in the study. They were transferred in face-to-face meetings where at least one pediatric rheumatologist and one adult rheumatologist were present (transition time: October-December 2020). Results:The median (25th-75th percentile) age at diagnosis and the time of the first examination in an adult-oriented rheumatology department of the included 65 SLE patients were 14.3 (10.9-15.1) years and 19.2 (18.5-20.4) years, respectively (female/male ratio: 7.1). There was no difference in clinical findings related to SLE between the last pediatric care visit and the last adult-oriented care visit other than constitutional symptoms being more prevalent in adult-oriented care (p = 0.039). There was a higher rate of low medication adherence in the post- than pretransition period (p = 0.003). The number of patients admitted to the emergency department during follow-up in adult-oriented care was higher (p = 0.009). Additionally, patients were more likely to miss at least one scheduled appointment in the post- than pretransition period (p = 0.002). Conclusion:We observed that patients with juvenile-onset SLE had more constitutional symptoms, lower medication compliance, higher rates of emergency department visits, and more missed appointments in the posttransition period despite a face-to-face structured transition process. We hope that future studies will offer solutions to the problems in transitional care.

Objectives In our study, we investigated the presence of subclinical enthesitis by ultrasonography (US) in asymptomatic patients with enthesitis-related arthritis (ERA) and sacroiliitis associated with familial Mediterranean fever (FMF). Methods A total of 50 patients, including 35 patients with ERA and 15 with sacroiliitis associated with FMF, were included in the study. All patients were evaluated with US by a paediatric radiologist. Enthesis of seven tendons (common extensor and flexor tendons, quadriceps tendon, proximal and distal patellar tendon, Achilles tendon, and plantar fascia) was examined on both sides. Results Subclinical enthesitis was detected in 10 ERA (28.5%) and three FMF (20%) patients. Enthesitis was radiologically diagnosed in 16 (2.3%) out of 700 evaluated entheseal sites. The most frequent sites of enthesitis were Achilles (37.5%) and quadriceps (31.3%) tendons. All patients were in clinical remission and had no active complaints, and acute phase reactants were within normal limits. Therefore, the patients were followed up without treatment change. However, disease flare-up was observed in three of these patients (23.1%) during the follow-up, and their treatments were intensified. Conclusions Our results showed that the US can be particularly helpful in detecting subclinical enthesitis and predicting disease flare-ups.

Background: Chronic uveitis in pediatric rheumatology practice have due to diagnostic difficulties, latent course and treatment-resistant conditions. The most common non-infectious cause of chronic uveitis in children is Juvenile Idiopathic Arthritis, but idiopathic uveitis is also not rare. The importance of environmental factors in the development of rheumatological diseases is increasing day by day. Objectives: The aim of this study was to investigate the effects of air pollution and some other environmental factors on the development of non-infectious uveitis. Methods: The study was planned as a case-control study. The data of 102 patients (<18 years of age) who were followed up in Hacettepe University between January 2015 and January 2023 were reviewed using electronic medical records. Patients were divided into 3 groups as juvenile idiopathic arthritis, idiopathic uveitis and uveitis associated with juvenile idiopathic arthritis, 34 patients from each group. Demographic and clinical characteristics of the patients, recurrence frequency, treatments, various familial and environmental factors (exposure to secondhand smoke during pregnancy, breast milk use), and Mediterranean diet compliance were assessed with questionnaires during outpatient clinic visits. [1,2] Air quality indexes and air pollutant data were recorded for the place of residence 1 year before the last uveitis attack, and for the place of residence of those without remission of the attack and those with a diagnosis of JIA. Results: The patients with juvenile idiopathic arthritis (JIA) and JIA-associated uveitis, 73.9% were female. In idiopathic uveitis, male gender was dominant in 52.9%. The median age at diagnosis was 4.6 (1-16.8) years in JIA, 7.4 (1.5-20) years in JIA-U, and 9.5 (3.6-17.6) years in idiopathic uveitis. Secondhand smoke during pregnancy was most common in JIA-associated uveitis and least common in JIA (p=<0.001). Elective caesarean section was more common in idiopathic uveitis, which was statistically significant (p=0.036). There was no significant difference between the parameters such as breast milk use, duration of breast milk use, formula consuming, duration of formula use, type of pregnancy, birth weight, and age at first exposure to the screen. The total score of the Mediterranean type nutrition survey (KIDMED) evaluation was not statistically significant on the basis of groups. (p=061) When the sub-parameters of KIDMED were evaluated, it was determined that consuming one/two fruits and/or vegetables every day and consuming legumes more than once a week was significantly lower in the JIA group (p<0.001). When the air quality indexes of the city in which the patients lived at the time of uveitis and JIA were evaluated, the highest median air quality index ratio (53) was found in JIA-related uveitis, followed by idiopathic uveitis (42) and the lowest in JIA (39) (p=0.303). In terms of air pollutants, PM10 (P<0.001), SO2 (p=0.023), NOX (p=0.037) exposure was significantly higher in JIA-U and idiopathic uveitis and lower in JIA. There was no significant difference between PM2.5 (p=0.326), CO (p=0.872), NO (p=0.326), NO2 (p=0.156), 03 (p=0.537) exposure. Conclusion: When the causes of uveitis other than chronic infection and environmental factors were evaluated, air pollutants such as PM10, SO2, NOX and smoking exposure during pregnancy were found to be very important in the development of uveitis and in the evaluation of the causes of uveitis. REFERENCES: [1] Şahingoz, S. A. Ozgen, L., & Yalcin, E. (2019). Akdeniz Diyet Kalitesi Olceginin (Mediterranean Diet Quality-KIDMED) Ge.erlik ve Güvenirlik Calismasi. Proceedings Book of 5th International Eurasian Congress on Natural Nutrition, Healthy Life & Sport, 1078-1088. 02-06 October 2019, Ankara/Turkey. [2] Serra-Majem, L., Ribas, L., Ngo, J., Ortega, R. M., Garc.a, A., P.rez-Rodrigo, C., & Aranceta, J. (2004). Food, youth and the Mediterranean diet in Spain. Development of KIDMED, Mediterranean Diet Quality Index in children and adolescents. Public Health Nutrition, 7(7), 931–935. https://doi.org/10.1079/phn2004556. Acknowledgements: NIL. Disclosure of Interests: None declared.

OBJECTIVE:We aimed to delineate the distinctive characteristics that aid in distinguishing between Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) with KD-like manifestations during the pandemic.MATERIALS AND METHODS:We evaluated KD patients and MIS-C patients with KD-like symptoms admitted during the pandemic (between January 2021 and December 2022).RESULTS:Thirty-three MIS-C patients and 15 KD patients were included. Kawasaki disease patients were younger than MIS-C patients (3.4 vs. 7.6 years). Rash (P = .044, 100% vs. 75.7%), oral mucosal changes (P = .044, 100% vs. 75.7%), and cervical lymphadenopathy (P = .001, 93.3% vs. 42.4%) were more common in KD. Multisystem inflammatory syndrome in children: patients had more hypotension (P = .002, 45.4% vs. 0), gastrointestinal (P .001, 72.7% vs. 13.3%), and respiratory symptoms (P = .044, 24.2% vs. 0). Multisystem inflammatory syndrome in children patients also had low lymphocyte and thrombocyte counts and elevated levels of d-dimer, ferritin, and cardiac parameters, unlike KD patients. Multisystem inflammatory syndrome in children patients exhibited a notable reduction in left ventricular systolic function in echocardiography. Another significant difference with regard to management was the anakinra treatment, which was prescribed for MIS-C patients.CONCLUSION:Although MIS-C patients might display a clinical resemblance to KD, several features could help differentiate between MIS-C and classical KD. Specific clinical (hypotension, gastrointestinal, and respiratory symptoms) and laboratory (low lymphocyte and thrombocyte counts with higher C-reactive protein, ferritin, d-dimer, and cardiac parameters) features are characteristic of MIS-C. In addition, divergence in management strategies is evident between the 2 diseases, as biologic drugs were more prevalently employed in MIS-C patients than in classical KD patients.

Background/aim:Video pediatric gait, arms, leg, and spine (v-pGALS) is a virtual application of the pediatric gait, arms, leg, and spine (pGALS) examination performed by video. We aimed to verify the applicability, validity, and accuracy of the Turkish translation of v-pGALS in a large pediatric patient cohort. Materials and methods:Children aged 4-18 years seen between May and June 2022 were included. A hands-on physical examination and v-pGALS were performed. Demographics, active symptoms, physical examination findings, diagnosis, and v-pGALS findings were recorded. The acceptability of v-pGALS, in terms of additional distress and duration, was measured by the parent/patient using a visual analog scale (VAS). Results:102 patients (median age 12.41 years) were included. Juvenile idiopathic arthritis (JIA) was the most common diagnosis. The median duration of v-pGALS was 7 min. An abnormal v-pGALS was identified in 25 patients while the hands-on physical examination was abnormal in 27 patients. Scoliosis and pes planus were missed in v-pGALS. Both children and parents gave a median VAS score of 0 for additional discomfort and duration. That is, the duration of v-pGALS was acceptable for ≥98% of the patients/parents, and ≥98% mentioned that it caused little/no discomfort. The sensitivity and specificity of v-pGALS were 92.6% and 100%, respectively, for the detection of musculoskeletal (MSK) abnormalities. Conclusion:The v-pGALS is an applicable, accurate, and practical tool for evaluating MSK problems in children. The Turkish translation was also conveniently acceptable.

Background Chronic nonbacterial osteomyelitis (CNO) is an inflammatory bone disorder that generally affects children.[1] In the absence of accepted diagnostic criteria or clinical/radiological biomarkers, CNO remains a diagnosis of exclusion.[2] Chronic pain and/or bone fractures (vertebral compression fractures) are observed in patients with CNO, just as in severe vitamin D deficiency and osteoporosis. Objectives We aim to show the relationship between CNO and bone mineral density and investigate whether osteoporosis with/without vitamin D deficiency can cause challenges in the treatment of CNO. Methods We reviewed the charts of all CNO patients followed up between January 2015 and April 2022 in the Department of Pediatric Rheumatology in Hacettepe University, Ankara, Turkey. The diagnosis was confirmed by expert consultant pediatric rheumatologists and radiologists. Demographic and clinical characteristics of patients, 25 OH vitamin D (25[OH]D) level status (N:>20 ng/ml [50 nmol/L]), radiological findings as well as medical treatments were evaluated. A score between -1.1 and -2.4 is classified as osteopenia. A score of -2.5 and below is defined as osteoporosis. In the pediatric population, osteoporosis is a clinical diagnosis and is reserved for those patients with a BMD Z- score less than or equal to -2.0 in combination with a significant fracture. In addition, patients were divided into two groups: receiving nonsteroidal anti-inflammatory drugs (NSAIDs) and/or cDMARDs (Group 1) and receiving TNF inhibitors (TNFi) and/or bisphosphonate (Group 2). Results A total of 80 patients (females 53%) were included in this study. The median age at diagnosis of CNO was 7 (1-17) years. Overall, vitamin D level was available before diagnosis in 52/80 (65%) patients, 17 of which were normal, while 35 patients had deficiency (25[OH]D <20 ng/ml [50 nmol/L]). Bone mineral density was studied in 39 patients, normal in 18, osteoporotic in 13, and osteopenic in 8 patients. 23 patients were treated with IV bisphosphonate (pamidronate [PAM]). Among the patients receiving PAM, 10 had a severe deficiency of 25[OH]D (<10 ng/ml), and 1 had osteopenia, 10 had osteoporosis in DEXA. Forty-one patients were treated with TNFi (34 used ETA, 5 ADA, 2 INF). There was no patient with osteoporosis in Group 1 (n=26), it was statistically significant. (p=0.031). In Group 2 (n=54), 12 patients (38.7%) were normal, 13 patients (41.9%) had osteoporosis, and six patients (19.3%) had osteopenia. The overall history of bone fractures (long bone, vertebral body) was present on admission in eleven patients (7 osteoporosis, 2 normal BMD, 2 NA). All patients with fractures were treated with PAM as the first-line treatment, and they benefited from this drug (p=0.013). In Group 2, 25[OH]D vitamin level was lower than Group 1, although it was not statistically significant. (p=0.183) (Table 1) Conclusion Patients with normal bone mineral density responded well to DMARD/NSAID, better than the remaining patients, and they did not need alternative treatment. Vitamin D deficiency and/or osteopenia may lead to a more refractory course; thus, it should be monitored effectively in patients with CNO. References [1]Zhao Y, Ferguson PJ. Chronic Nonbacterial Osteomyelitis and Chronic Recurrent Multifocal Osteomyelitis in Children. Pediatr Clin North Am. 2018;65(4):783-800. doi:10.1016/j.pcl.2018.04.003 [2]Oliver M, Jayatilleke A, Wu E, et al. Establishing core domain sets for Chronic Nonbacterial Osteomyelitis (CNO) and Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis (SAPHO): A report from the OMERACT 2020 special interest group. Semin Arthritis Rheum. 2021;51(4):957-961. doi:10.1016/j.semarthrit.2021.05.015 Acknowledgements: NIL. Disclosure of Interests None Declared.

Objectives Macrophage activation syndrome (MAS) is a severe complication of systemic juvenile idiopathic arthritis (SJIA). We aimed to compare the characteristics of SJIA patients who developed MAS in the disease course to those who never experienced MAS. Methods Patients with SJIA were included. The features of the patients at the time of SJIA diagnosis were compared. Multivariate logistic regression and ROC analyses were used while evaluating factors associated with MAS. Results Overall, 126 SJIA patients (M/F:1.17) were included. Eighty-six (68.2%) never had MAS. At the time of SJIA diagnosis, age was younger; the duration of fever was longer; rash, hepatomegaly, and splenomegaly were more frequent and arthralgia/arthritis was less common among patients who had MAS in the follow-up than those who never had MAS. Also, white blood cell, neutrophil, and platelet counts and fibrinogen were lower, while transaminases, lactate dehydrogenase, triglyceride (TG), and ferritin levels were higher among patients with MAS than those without MAS. The multivariate regression analysis disclosed age at symptom onset, duration of fever, platelet count, TG and ferritin levels as independent MAS predictors. For ferritin level/platelet count (F/P) ratio at the time of SJIA diagnosis, a threshold of ≥1.1 performed best to predict a MAS-prone disease course with a sensitivity of 90% and a specificity of 82.6%. Conclusion The F/P ratio at the time of SJIA diagnosis may be a promising biomarker to predict MAS-prone disease course in SJIA. Determining MAS-prone patients at the time of SJIA diagnosis could assist physicians while tailoring SJIA treatment individually. Key points • Systemic juvenile idiopathic arthritis (SJIA) patients with macrophage activation syndrome (MAS) differ from SJIA patients who never have MAS, at the time of SJIA diagnosis. • It could be possible to predict a MAS-prone disease course at the time of SJIA diagnosis. • The ferritin/platelet ratio is a promising biomarker for predicting MAS-prone SJIA disease course.

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 Pediatric patients classified with BD according to the 2015 international pediatric BD criteria in our center 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 (VSM), vena saphena parva (VSP), 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 63-86%, while specificity rates were between 71-100%. 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.

OBJECTIVE:Children with suspicious complaints of rheumatic diseases are generally referred toa 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 theimpact of the coronavirus disease-2019 pandemic on referral complaints.MATERIALS AND METHODS:All new outpatients who applied to the pediatric rheumatology department between March 2019 and February 2021 and were not diagnosed with rheumatic diseasewere included. We also compared the frequency of admission symptoms during the pre-pandemic (March 2019-February 2020) and pandemic periods (March 2020-February 2021).RESULTS: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 mutationsin the Mediterranean fever gene (6.9%). During the pandemic year, the number of patientsreferred for back pain increased significantly (P = .028). A total of 682 of 1089 patients wereconsulted 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.CONCLUSION:Prolonged or recurrent fever and anti-nuclear antibody positivity were the mostfrequent complaints of referrals to a pediatric rheumatology unit in patients who did not havea rheumatic disease. The rate of back pain was more common in children during the pandemicperiod.

Objectives Colchicine forms the mainstay of treatment in FMF. Approximately 5-10% of FMF patients are colchicine resistant and require anti-IL-1 drugs. We aimed to compare the characteristics of colchicine-resistant and colchicine-responsive patients and to develop a score for predicting colchicine resistance at the time of FMF diagnosis. Methods FMF patients (0-18 years) enrolled in the Turkish Paediatric Autoinflammatory Diseases (TURPAID) registry were included. The predictive score for colchicine resistance was developed by using univariate/multivariate regression and receiver operating characteristics analyses. Results A total of 3445 FMF patients [256 (7.4%) colchicine-resistant and 3189 colchicine-responsive) were included (female:male ratio 1.02; median age at diagnosis 67.4 months). Colchicine-resistant patients had longer, more frequent attacks and were younger at symptom onset and diagnosis (P < 0.05). Fever, erysipelas-like erythema, arthralgia, arthritis, myalgia, abdominal pain, diarrhoea, chest pain, comorbidities, parental consanguinity and homozygosity/compound heterozygosity for exon 10 MEFV mutations were significantly more prevalent among colchicine-resistant than colchicine-responsive patients (P < 0.05). Multivariate logistic regression analysis in the training cohort (n = 2684) showed that age at symptom onset, attack frequency, arthritis, chest pain and having two exon 10 mutations were the strongest predictors of colchicine resistance. The score including these items had a sensitivity of 81.3% and a specificity of 49.1%. In the validation cohort (n = 671), its sensitivity was 93.5% and specificity was 53.8%. Conclusion We developed a clinician-friendly and practical predictive score that could help us identify FMF patients with a greater risk of colchicine resistance and tailor disease management individually at the time of diagnosis.

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.

BACKGROUND/OBJECTIVE:Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) myopathy is rare in children. Here, we present a boy with relapsing refractory anti-HMGCR myopathy along with a systematic literature review.CASE REPORT:17-year-old boy with five years of muscle weakness, rash, high creatinine kinase (CK) levels, and muscle biopsy compatible with inflammatory myopathy was diagnosed with juvenile dermatomyositis. He was treated with corticosteroids, intravenous immunoglobulin (IVIG), and methotrexate. His muscle weakness improved with this treatment although never completely resolved. CK levels decreased from ∼15000 U/L to ∼3000 U/L. At the age of 15, muscle weakness relapsed after an upper respiratory tract infection; pulse corticosteroid treatment was administered. The re-evaluated muscle biopsy showed a necrotizing pattern and the HMGCR antibody was positive confirming anti-HMGCR myopathy when he was 16. The diagnostic delay was 50 months. Disease activity was monitored by Medical Research Council score, MRI and functional tests. Despite corticosteroids, methotrexate, IVIG, cyclosporine A, and rituximab therapies, muscle weakness improved only slightly during the first three months and remained stable afterwards.Results of the Literature Search:We identified 16 articles describing 50 children (76% female) with anti-HMGCR myopathy by reviewing the English literature up to March 1st, 2022. Proximal muscle weakness was the most common clinical symptom (70.8%). Corticosteroids (84.8%), IVIG (58.7%), and methotrexate (56.5%) were preferred in most cases. Complete remission was achieved in nine patients (28.1%).CONCLUSION:Diagnosis and management of children with anti-HMGCR myopathy are challenging. Complete remission is achieved in only one third of these patients. Imaging biomarkers may aid treatment.

Pediatric mixed connective tissue disease (MCTD) is a subgroup of overlap syndromes. We aimed to compare the characteristics and outcomes in children with MCTD and other overlap syndromes. All MCTD patients met either Kasukawa or Alarcon-Segovia and Villareal criteria. The patients with other overlap syndromes had the features of ≥ 2 autoimmune rheumatic diseases but did not meet MCTD diagnostic criteria. Thirty MCTD (F/M = 28/2) and thirty (F/M = 29/1) overlap patients were included (disease onset < 18 years). The most prominent phenotype at disease onset and the last visit was systemic lupus erythematosus (SLE) in the MCTD group; juvenile idiopathic arthritis and dermatomyositis/polymyositis, respectively, in the overlap group. At the last visit, systemic sclerosis (SSc) phenotype was more frequent among MCTD than overlap patients (60% vs. 33.3%; p = 0.038). The frequency of the predominant SLE phenotype had decreased (60% to 36.7%), while predominant SSc phenotype had increased (13.3% to 33.3%) during follow-up in MCTD patients. Weight loss (36.7% vs. 13.3%), digital ulcers (20% vs. 0), swollen hands (60% vs. 20%), Raynaud phenomenon (86.7% vs. 46.7%), hematologic involvement (70% vs. 26.7%), and anti-Sm positivity (29% vs. 3.3%) were more common, while Gottron papules (16.7% vs. 40%) were less frequent among MCTD than overlap patients (p < 0.05). A higher percentage of overlap patients achieved complete remission than MCTD patients (51.7% vs. 24.1%; p = 0.047). The disease phenotype and outcome differ between pediatric MCTD and other overlap syndromes where MCTD may be regarded as a more severe disease. Analyzing these patients could pave the way for early and effective treatment.

BACKGROUND:In this study, we aimed to evaluate choices and changes of biologic drugs in juvenile idiopathic arthritis (JIA) patients according to disease subtypes.METHODS:We retrospectively analyzed JIA patients who received biologic treatment between January 2004 and July 2022.RESULTS:Of 294 JIA patients, 80 (27.2%) had systemic JIA, 68 (23.1%) had oligoarticular JIA, 61 (20.7%) had polyarticular JIA, 79 (26.9%) had enthesitis-associated arthritis (ERA), and six (2.1%) had psoriatic arthritis (PsA). Anakinra (n=66, 82.5%) was the most commonly preferred first line biologic in systemic JIA. Etanercept was the most frequently used biologic drug in patients with ERA (n=69, 87.3%), oligoarticular (n=37, 54.4%) and polyarticular JIA (n=43, 70.5%). Adalimumab was used as a first-line biologic drug in all PsA patients (n=6, 100%). One hundred-fourteen patients (38.8%) were switched to second-line and 29 (9.9%) to third-line biologic drugs. While the most common reason for switching to a second-line biologic was difficulty in usage of daily injections (n=37, 60.6%) in systemic JIA patients, it was an inadequate response to first biologics in non-systemic JIA patients (n=42, 79.2%). Side effects were detected in only seven patients (2.4%) during the follow-up.CONCLUSION:In this study, we revealed the biologic drug usage and switch strategies in our JIA patients. Good responses were obtained in most of our patients with a reliable profile. However, studies on larger patient groups are needed to clarify these results.

Objectives There is no consensus on canakinumab treatment tapering and discontinuation strategies in colchicine-resistant FMF patients. In this study, we aimed to establish a treatment management and discontinuation protocol in paediatric FMF patients treated with canakinumab. Methods Fifty-eight FMF patients treated with canakinumab were included. Since 2020, we have applied a protocol based on our experience whereby canakinumab is administered monthly in the first 6 months, followed by bimonthly for 6 months, and a final period of every 3 months (for 6 months). The patients were divided into two groups: 2012-2019 (group A) and 2020-2022 (group B). Results In group A (n = 33), the median duration of canakinumab treatment was 2.5 years [interquartile range (IQR) 1.9-3.7]. A total of 25 of 33 patients discontinued canakinumab after a median of 2.1 years (IQR 1.8-3.4). In two patients, canakinumab was restarted because of relapse. In group B (n = 25), canakinumab was discontinued in 18 patients at the end of 18 months. After a median follow-up of 0.8 years (IQR 0.6-1.1), two patients had a relapse and canakinumab treatment was reinitiated. The remaining 16 patients still have clinically inactive disease and are receiving only colchicine. When we compared the characteristics between groups A and B, there were no significant differences regarding demographics, clinical features, and outcomes. Conclusion This is the largest study in the literature suggesting a protocol for discontinuing canakinumab in paediatric FMF patients. It was possible to discontinue canakinumab successfully in more than half of the patients in 18 months. Thus we suggest that this protocol can be used in paediatric FMF patients.