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Erysipelas-like erythema is the pathognomonic skin manifestation of familial Mediterranean fever although not frequently seen in the pediatric population. This study aims to describe the differences between patients presenting with and without erysipelas-like erythema and to examine the relation of erysipelas-like erythema with subclinical inflammation in a large pediatric cohort of familial Mediterranean fever patients.This retrospective study from a single pediatric rheumatology referral center included familial Mediterranean fever patients with a follow-up for at least 6 months in the last 5 years. Patients were grouped according to the presence of erysipelas-like erythema and subclinical inflammation.Among 515 patients with familial Mediterranean fever, 35 patients (6.8%) were found to present with erysipelas-like erythema, and the earliest age for erysipelas-like erythema was 2.9 years. All erysipelas-like erythema lesions were defined on lower extremities with concurrent arthritis in 21 patients (60.0%). Compared to other patients in the cohort, patients presented with erysipelas-like erythema had significantly higher frequencies of acute arthritis, subclinical inflammation, and biallelic exon 10 mutations, and they used significantly higher doses of colchicine at the latest visits (all P ≤ .002). Patients with subclinical inflammation more frequently presented with erysipelas-like erythema compared to others without subclinical inflammation (21.7% vs. 2.9%, Plt; .001).Erysipelas-like erythema is an uncommon but important finding that can be a sign of severe disease course and subclinical inflammation in the pediatric population with familial Mediterranean fever.

In this study, it was aimed to evaluate the demographic, clinical and laboratory characteristics of MIS-C patients in our hospital, to share our treatment approach, and to assess the outcomes of short- and long-term follow-up.MIS-C patients who were admitted and treated in our hospital between July 2020 and July 2021 were evaluated. Demographic, clinical, laboratory, and follow-up data were collected from patient records retrospectively.A total of 123 patients with MIS-C (median age, 9.6 years) were included the study. Nineteen (15.4%) were mild, 56 (45.6%) were moderate, and 48 (39%) were severe MIS-C. High CRP, ferritin, pro-BNP, troponin, IL-6, and D-dimer values were found in proportion to the severity of the disease (p 0.001, p 0.001, p 0.001, p 0.001, p = 0.005, p 0.001), respectively. Two (1.6%) patients died. The mean follow-up period was 7.8 months. Valve failure, left ventricular dysfunction/hypertrophy, coronary involvement, and pericardial effusion were the most common cardiac pathologies in the short- and long-term follow-up of the patients. In the long-term follow-up, the most common reasons for admission to the hospital were recurrent abdominal pain (14.2%), cardiac findings (14.2%), pulmonary symptoms (8%), fever (7.1%), neuropsychiatric findings (6.2%) and hypertension (3.5%). Neuropsychiatric abnormalities were observed significantly more common in severe MIS-C patients at follow-up (p = 0.016). In the follow-up, 6.2% of the patients required recurrent hospitalization.MIS-C is a serious and life-threatening disease, according to short-term outcomes. In addition to the cardiac findings of patients with MIS-C, long-term outcomes such as neuropsychiatric findings, persistent gastrointestinal symptoms, fever and pulmonary symptoms should be monitored. Key Points • In MIS-C patients, attention should be paid not only to cardiac findings, but also to symptoms related to other systems. • Patients should be followed up in terms of neuropsychiatric findings, persistent gastrointestinal symptoms, fever and pulmonary symptoms that may occur during follow-up.

Interleukin-1 inhibitors are effective agents used in colchicine resistance or intoler- ance during the treatment of familial Mediterranean fever. This study aims to review the char- acteristics of patients treated with interleukin-1 inhibitors and their long-term follow-up in a large pediatric cohort of familial Mediterranean fever patients.The study was conducted in a pediatric rheumatology reference cen- ter. The patients treated with interleukin-1 inhibitors for at least 6 months were included and compared to other patients with familial Mediterranean fever. Clinical and laboratory charac- teristics of the cohort were recorded.Among 542 patients with familial Mediterranean fever, 6.1% (n = 33) were treated with interleukin-1 inhibitors. Colchicine resistance was the reason in 82.8% and renal amyloidosis in 17.2% of the patients. Patients with interleukin-1 inhibitors had earlier disease onset and higher frequencies of acute arthritis, chest pain, and erysipelas-like erythema with pathogenic exon 10 mutations of the MEFV gene (all P.04). All patients diagnosed with renal amyloidosis also received interleukin-1 inhibitors. Six patients were switched from anakinra to canakinumab or vice versa to control ongoing disease activity. Attack frequency was reduced in all patients.Interleukin-1 inhibitors are used in a relatively small number of pediatric patients with familial Mediterranean fever. Patients presenting with earlier disease onset, acute arthri- tis, chest pain, and erysipelas-like erythema and carrying pathogenic exon 10 mutations of the MEFV gene may show a higher need for interleukin-1 inhibitors. In pediatric familial Mediterranean fever patients who are resistant to colchicine, interleukin-1 inhibitors seem to be highly effective agents.

Background: Clinical and research use of transcranial magnetic and direct current stimulation are becoming more common in Turkey. However, the opinions of the researchers and ethics committees about the ethical dimension of the issue differ. The aim of this study is to examine the ethical views of the researchers and committees and to review the legal procedures of the clinical and research NIBS applications in Turkey. Methods: The data were collected from researchers working with NIBS, ethics committee representatives and official regulatory agency. The surveys prepared by researchers were sent to them, and an interview was conducted with the TİTCK-KAD representative. Quantitative analysis was performed for multiple-choice and short-answer questions, while thematic analysis was performed for open-ended answers. Results: In the first survey, 99 researchers with a mean age of 38.9±10.5 years and most of them being female (65.65%) participated. 44.4% of the researchers were medical doctors, 21.21% were psychologists, 24.24% were other health professionals (mostly physiotherapists), and 10.10% were from other fields (engineers, educators, etc.). 94% of the researchers stated that the NIBS practitioner should undergo a standardized training. Different rates were obtained in the items related to the effectiveness of NIBS, self-administration, ethical and legal issues. It appeared that 94.37% of the researchers applied to the Clinical Research Ethics Committees in Turkey. Conclusion: Researchers in Turkey agree on the clinical use and efficacy of NIBS. However, when it comes to improving cognitive and physical performance in healthy people, they are largely hesitant both in terms of efficacy and morality. This attitude is very similar to that of other researchers around the world. In terms of ethics committees, it is observed that local ethics committees are not sufficiently aware of the issue and that there are some differences in practice.

To determine the interval between disease onset and admission to pediatric rheumatology clinic of patients with juvenile idiopathic arthritis (JIA) and, to identify the factors that affect the admission time (AT) to rheumatology center.We designed a retrospective observational study in children with JIA. The study variables were age, gender, JIA subtype, acute phase reactants (APR), disease activity scales, presence of a pediatric rheumatologist, and distance to a pediatric rheumatology center. Outcome parameter was the duration between onset of symptoms and first visit of rheumatologist. The parameters were evaluated with variance analysis and regression models.198 patients (female:120 (60.6%)) were included. There were 112 (56.5%) patients in oligo-articular JIA, 27 (13.6%) in rheumatoid factor negative poly-articular JIA, 22 (11.1%) in enthesitis related arthritis (ERA), 29 (14.6%) in systemic-JIA, 4 (2%) in rheumatoid factor positive poly-JIA, two patients each in undifferentiated and psoriatic arthritis. The median AT in the systemic-JIA and other groups was 16 (IQR 10.5-27.5) and 71 (IQR 33.5-211) days, respectively. There was a significantly longer AT in the ERA group than others (p=0.005). We found a correlation between longer AT and older age, low back pain, enthesitis, and low erythrocyte sedimentation rate (ESR). In the multivariate analysis, only low ESR and enthesitis contributed an increase in AT [OR 2.05 (1.07-3.93), 6.22 (1.29-29.99)].The older age, low back pain, enthesitis and low ESR contribute to the late AT. JIA requires high suspicion in children with poorly defined findings and low APR.

Objectives The aims of this study were to describe the clinical features, comorbidities and outcome of systemic childhood polyarteritis nodosa (PAN) and to evaluate PAN-like diseases in differential diagnosis. Methods The study group consisted of patients who were diagnosed as PAN in a referral center in Turkey. The files of all patients were reviewed retrospectively. Disease activity was evaluated with pediatric vasculitis activity score (PVAS). Results A total of 19 (13 boys/six girls) patients were enrolled in the study. The mean age of patients was 10.37 ± 3.6 years. The mean duration of follow-up was 5.73 ± 3.74 years. Eight patients (42.1%) were also diagnosed with familial Mediterranean fever (FMF). The cutaneous involvement was higher in patients with PAN than those with FMF-associated PAN (p = .03). The median (min–max) PVAS at diagnosis was 5 (3–7). There was no correlation between PVAS scores at the time of diagnosis and age, clinical findings and relapse. CECR1 mutation was detected in one patient leading to deficiency of adenosine deaminase 2. Conclusion The clinical presentation is variable in children with PAN. PAN-like diseases characterized by necrotizing vasculitis should be considered. The possibility of FMF should be kept in mind if inflammation cannot be controlled.

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening hyperinflammation syndrome emerging after COVID-19. The serum delta neutrophil index (DNI) reflects the fraction of circulating immature granulocytes and is evaluated in infection and inflammation. The aim of this study is to evaluate the usefulness of DNI as a diagnostic marker in patients with MIS-C and to assess its role in determining the severity of MIS-C. This retrospective, observational study included 83 patients with MIS-C and 113 patients with COVID-19, and 102 healthy controls. C-reactive protein (CRP), the absolute neutrophil count (ANC), absolute lymphocyte count (ALC), DNI, and the platelet count were recorded. The DNI levels were 4.60 ± 5.70% in the MIS C group, 0.30 ± 0.99% in the COVID group, and 0.20 ± 0.56% in the control group (p < 0.001). According to the severity of MIS-C, the DNI level was found to be 1.22% in mild MIS-C, 4.3% in moderate MIS-C, and 5.7% in severe MIS-C. There was a statistically significant correlation between DNI levels and the severity of MIS-C. The cutoff value of DNI for predicting MIS-C was 0.45%. In the analysis of the diagnostic performance of DNI compared with CRP, ANC, ALC and platelet counts, sensitivity, specificity, positive predictive value, and negative predictive value were found to be 79.5%, 97.1%, 95.7%, and 85.3%, respectively.Conclusions: The delta neutrophil index was identified as a diagnostic marker for MIS-C such as ANC, ALC, platelet count, and CRP. DNI levels in hemogram analysis may guide clinicians in determining the diagnosis and severity of MIS-C. What is Known: • Although CRP, sedimentation, ALC, ANC, platelet count, sodium, and albumin are used as first step tests, there is no specific laboratory marker used in the diagnosis of MIS C. • The serum delta neutrophil index (DNI) reflects the fraction of circulating immature granulocytes and is elevated in infection and inflammation. What is New: • DNI is a promising and easily accessible marker that can be used with other markers in the diagnosis and determines the severity of MIS C. • DNI is an easily accessible, inexpensive, and dynamic marker and its levels in simple hemogram analysis will guide pediatricians in determining the diagnosis and severity in MIS C.

Objective: The aim of this study was to assess the factors that cause delay in diagnosis of familial Mediterranean fever (FMF), which is a common disease in our country.Material and Methods: The data of 101 patients diagnosed with FMF in our pediatric rheumatology center between 2010 and 2021 were retrospectively analyzed. The time elapsed from the onset of the patients' symptoms to the time of diagnosis was defined as the delay in diagnosis. Pras disease severity score was used to determine disease severity.Results: Fifty-nine of 101 patients were girls (58.4%). The median age at onset of symptoms was 5 (min-max: 2-8) years. The median age at diagnosis of the patients was 6 (min-max: 4-9) years. Delay in diagnosis was 3 years in 20 patients. There were 39 (38.6%) M694V homozygous, 34 (33.7%) M694V heterozygous, 13 (12.9%) non-M694V mutations, 2 (2%) patients with a single mutation except M694V, and 13 (%13) patients with no mutation. According to the Pras disease severity score, disease severity was classified as mild in 22.8%, moderate in 43.6%, and severe in 33.7% of the patients. There was no relationship between family history of FMF, consanguineous marriage, clinical findings, mutations, and delay in diagnosis. A statistically significant relationship was found between the delay in diagnosis of more than 3 years and the age of onset of symptoms of the patients (p, Amaç: Bu çalışmada ülkemizde sık görülen ailevi Akdeniz ateşinin tanısının konulmasında gecikmeye neden olan faktörlerin ortaya konulması amaçlanmıştır.Gereç ve Yöntemler: Çocuk Romatoloji Polikliniğinde 2010-2021 yılları arasında ailevi Akdeniz ateşi tanısı alan 101 hastanın dosya kayıtları retrospektif olarak incelendi. Hastaların şikâyetlerinin başlama zamanından tanı aldıkları zamana kadar geçen süre tanı gecikmesi olarak tanımlandı. Hastalık ağırlığını belirlemek için Pras hastalık ağırlık skoru kullanıldı.Bulgular: Yüz bir hastanın 59’u kızdı (%58.4). Şikâyetlerin ortanca başlama yaşı 5 yıl (min-maks: 2-8) olarak saptandı. Hastaların ortanca tanı alma yaşı 6 yıl (min-maks:4-9) idi. Tanı gecikmesi 41 hastada 3 yıldı. M694V homozigot olan 39 (%38.6), M694V heterozigot 34 (%33.7), M694V dışı iki mutasyon taşıyan 13 (%12.9), M694V dışında tek mutasyon olan 2 (%2), mutasyon saptanmayan 13 (%13) hasta olduğu görüldü. Pras hastalık ağırlık skoruna göre, hastalık ağırlığı hastaların %22.8’sinde hafif, %43.6’sında orta, %33.7’sinde ağır şiddetli olarak sınıflandırıldı. Tanı gecikmesi ile ailede ailevi Akdeniz ateşi öyküsü, akraba evliliği olması, klinik bulgular ve mutasyonlarla ilişki gösterilemedi. Tanı gecikmesinin >3 yıl olması ile hastaların semptomlarının başlama yaşı arasında istatistiksel olarak anlamlı ilişki saptandı (p3 yıl olması arasında istatistiksel anlamlı ilişki olduğu görüldü (p=0.026).Sonuç: Ailevi Akdeniz ateşi’nin tanısının konulması, şikâyetler süt çocukluğu döneminde başlarsa ve hafif hastalıkla uyumluysa gecikebilir. Erken çocukluk döneminde tekrarlayan ateş ve karın ağrısı gibi bulguları olan çocuklarda ailevi Akdeniz ateşi akılda tutulması gereklidir.

Background: Systemic lupus erythematosus (SLE) is a common multisystemic autoimmune disease characterized by the presence of autoantibodies and multiorgan system involvement. The aim of this study was to describe the presenting clinical manifestations, laboratuary findings, clinical course and prognosis of SLE in children. Methods: We performed a retrospective study patients with SLE, diagnosed before the age of 18 years. Clinical and laboratory data were collected from initial admission to study initiation. Results: Thirty-five children and adolescents SLE (cSLE) were recorded, 85.7% of female. The median age at disease onset was 12(range 4-17) years, and median follow up duration was 5 (1-14) years. The most common clinical feature was arthritis (65.1%), followed by constitutional symptoms (48.6%), malar rash (31.4%), photosensitivity (5.7%), alopecia (5.7%) and oral ulcers (5.7%). Renal involvement accounted 4/5 of the patients (80%). Hematuria and proteinuria were the most frequent presenting findings (48.5% and 45.7% respectively). Renal biopsy was performed in 27 patients. According to WHO classification: 1 patient had classV nephritis, 10 had class IV, 4 had class III and 12 had class II nephritis. 20% of children developed neurologic symptoms. One patient died during the follow-up period. At the last follow up none of the patients had renal failure but, proteinuria persisted in 4 of them (11.4%). All neurological findings of patients are in remission apart from sequelae. Conclusion: Clinical outcome was favorable in our patients. Renal involvement is common but progression to end stage kidney disease, at least in the short term, is rare.

Behcet's disease is an inflammatory vasculitic disease of unknown etiology characterized by recurrent oral and genital ulcers, ocular findings, and multiple organ involvement. Mucocutaneous findings are the most common symptoms. The most used diagnostic criteria are International Criteria for BD (ICBD), International Study Group (ISG) criteria and pediatric Behcet’s disease criteria (PEDBD). Although diagnostic criteria have been defined, the diagnosis is still difficult due to clinical findings developed in pediatric patients. The aim of this study was to evaluate the clinical findings, phenotype characteristics, sensitivity and specificity of diagnostic criteria, and the course of pediatric Behcet's disease (BD). We evaluated retrospectively the files of 67 (29 M/38 F) patients diagnosed with BD according to expert opinion. The patients were reclassified according to ISG, ICBD, and PEDBD criteria. The control group consisted of a total of 69 patients with BD-mimicking diseases or presenting at least one major BD sign followed at the same center. Sensitivity and specificity were evaluated for the criteria. The mean age of diagnosis was 13.38 ± 3.2 years. There were oral aphthous ulcers in 98.5%, genital ulcers in 68.7%, skin lesions in 31.3%, vascular involvement in 17.9%, neurological involvement in 11.9%, positive pathergy test in 33.8%, and positive HLA-B51 in 57.1% of patients. The sensitivity of ICBD, ISG and PEDBD criteria was 88.1, 43.3, and 37.3%, respectively. The specificity of ICBD, ISG, and PEDBD criteria was 100%. Diagnosis of BD in childhood is still difficult. ICBD criteria have the highest sensitivity among the diagnostic criteria. These criteria can also be used in childhood.

Aim The aim of this study is to evaluate the clinical parameters, acute-phase reactants, side effects, genetic mutations among colchicine-resistant Familial Mediterranean fever (FMF) patients who received anti-interleukin-1 (anti-IL-1) treatment. We also evaluate the quality of life and school attendance among colchicine-resistant FMF patients, in relation to treatment with anti-IL-1. Introduction Familial Mediterranean fever is the most common inherited autoinflammatory disorder. Although the main treatment of FMF is colchicine, a small group of patients are resistant to colchicine treatment. Anti-IL-1 treatment is promising in colchicine-resistant patients due to excessive IL-1β production in pathogenesis. The aim of this study is to evaluate the quality of life and school attendance rates among colchicine-resistant FMF patients after anti-IL-1 treatment. Methods This is a single center retrospective study of 25 pediatric colchicine-resistant FMF patients treated with anti-IL-1 treatment. Autoinflammatory Disease Activity Index (AIDAI) was used for disease activity assessment. School attendance rates were evaluated before and after treatment. Results There were 25 patients with FMF (11 M/14 F) who were treated with anakinra or canakinumab for various indications (colchicine-resistant recurrent febrile attacks in 20, colchicine-related side effects in 2, subclinical inflammation in 3 patients). Only 3 patients developed side effects with anakinra (2 headache, 1 urticarial rash). There was a significant decrease in the frequency of attacks, acute-phase reactants (erythrocyte sedimentation rate and C-reactive protein), AIDAI and physician's and patient's global assessment scores and improvement in school attendance rates. At the last follow-up, all patients were in remission, and only 3 had subclinical inflammation. Conclusion Anti-IL-1 treatment is quite effective in children with colchicine-resistant FMF patients, proven with improved AIDAI scores and school attendance rates. In the long term by lowering disease activation even development of amyloidosis may be prevented.

PurposeChronic non-bacterial osteomyelitis is a chronic sterile inflammatory condition of the bone. We aimed to describe the clinical and radiographic findings of patients and to evaluate their response to therapy and quality of life. MethodsThis cross-sectional study included 18 patients whose clinical, radiological features and outcomes were reviewed retrospectively. The quality of patients’ life after treatment was compared to healthy controls by using the Pediatric Quality of Life Inventory 4.0. ResultsThe median age of disease onset was 12 (IQR 10-14) years and 11 (61.1%) patients were male. The median follow-up duration was 15 (IQR 12-22) months. The persistent form of chronic non-bacterial osteomyelitis was the most common pattern in 15 (83.3%) patients and a recurrent pattern was defined in 3 (16.7%) patients. The lesions were multifocal in all patients and 15 (83.3%) patients had symmetric distribution in whole-body magnetic resonance imaging. The most common sites of arthritis were the knee and sacroiliac joints. Methotrexate was used in 16 (88.9%) patients as first-line therapy. However, some patients were unresponsive to first-line therapy and needed tumor necrosis factor-α inhibitors (55.6%) and bisphosphonates (16.7%). We observed remission in only 4 (22.2%) patients and 3 (16.7%) patients were unresponsive. The patients had a significantly poorer quality of life than controls (p=0.005).ConclusionsChronic non-bacterial osteomyelitis is an insidious disease that requires detailed analysis for diagnosis and whole-body magnetic resonance imaging is an effective tool for diagnosis. Despite the advanced treatment, patients with chronic non-bacterial osteomyelitis have a poor quality of life.

Intra-articular corticosteroid injection (IACI) is generally used in the management of juvenile idiopathic arthritis (JIA) to obtain rapid relief of active synovitis and functional recovery and to prevent the need for regular systemic therapy. The aim of this study was to investigate the outcome of IACI treatment and the factors associated with remission of synovitis.The clinical records of JIA patients who received IACI between January 2014 and December 2020 in two pediatric rheumatology centers were reviewed. The procedure was evaluated in terms of efficacy, factors that may affect the duration of remission, procedural and drug-related complications.During the study period, 134 patients received 227 injections and 37 joints were injected more than once. One hundred and six (79%) patients had persistent oligoarticular disease. At the time of injection, all patients were receiving non-steroidal anti-inflammatory drugs, 74 patients were on methotrexate, and 14 patients were on biologics. The median duration of remission without exacerbation of synovitis treated with IACI was 15 (range 1-64) months. The inactivity rate was 81% at the 6th month after the injection. It has been shown that being less than 7 years old at disease onset and low initial CRP levels were correlated with a long remission period (p 0.05). Despite the differences were not statistically significant, the duration of remission was longer in boys, in ANA positives, in HLA-B27 negatives, in patients with concurrent methotrexate treatment and in patients not receiving biologic therapy (p 0.05). Only two patients (1.5%, 95% CI - 0.6 to 3.5) developed cutaneous hypopigmentation and subcutaneous atrophy as side effects of injection.Intra-articular corticosteroid injection was more effective especially in patients with low initial CRP levels and younger than 7 years of age. The duration of remission was longer in these patients. Key Points • Intra-articular corticosteroid injection is an effective method for controlling joint inflammation and achieving long-term remission without significant side effects. • Intra-articular corticosteroid injection can be preferred in all forms of juvenile idiopathic arthritis as primary therapy or to relieve the patient while waiting for the effect of systemic agents or to avoid increasing the dose of systemic drugs. • It can be recommended as a treatment option at any stage of the disease, especially in young patients and patients with low initial CRP values.

Immunoglobulin A vasculitis with nephritis (IgAVN) is the most serious complication affecting long-term prognosis. Understanding the risk factors and markers for the development of IgAVN is essential. The aim of this study is to identify IgAVN-associated factors and to evaluate the usability of Pediatric Vasculitis Activity Score (PVAS) at diagnosis as an early marker for the development of IgAVN.We conducted a retrospective case-control study of 314 patients divided into two groups: those with nephritis (IgAVN) and without nephritis (non-IgAVN). The groups were compared in terms of clinical symptoms, laboratory values, and PVAS values.In total, 18.5% of the patients had IgAVN; they were older than the non-IgAVN patients (median age was 8.8, p 0.05). Arthritis/arthralgia, abdominal pain, and intestinal bleeding were more common, systolic and diastolic BP were higher in IgAVN (p 0.05). CRP, serum creatinine, and urine protein/Cr, PVAS were higher, while serum albumin was lower in IgAVN (p 0.05). The receiver operator characteristic curve (ROC) analysis showed that IgAV patients with a determined cut-off PVAS value greater than 3 had 70.7% sensitivity in predicting whether or not they would develop IgAVN. Logistic regression analysis found that PVAS 3 and low serum albumin at the time of diagnosis were independent risk factors for IgAVN.Our study revealed that PVAS 3 at diagnosis is an independent predictor of IgAVN. Patients with PVAS 3 should be followed more closely to ensure early diagnosis and management of IgAVN. A higher resolution version of the Graphical abstract is available as Supplementary information.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease that can present with various forms of arthritis. This retrospective study aims to evaluate the characteristics of patients with arthritis in a large pediatric cohort of FMF patients.The demographic and clinical data were extracted from electronic medical records. Patients with arthritis were grouped as arthritis of FMF and arthritis of FMF-associated diseases.A total of 541 patients were followed with a diagnosis of FMF in the last 5 years. Acute arthritis of FMF (n: 138) was the most common cause. It showed a recurrent course in the majority with a longer duration than other attack symptoms. Significantly higher frequencies of biallelic exon 10 and M694V mutations, erysipelas-like erythema, and protracted febrile myalgia were detected in these patients, particularly in those older than 2 years of age. Sacroiliitis of FMF was the second most common cause (n: 19). Patients with acute arthritis and sacroiliitis of FMF needed higher doses of colchicine. One patient with neonatal-onset FMF and M694V homozygosity was diagnosed with protracted arthritis. Arthritides of FMF-associated diseases including IgA vasculitis (n: 10), juvenile idiopathic arthritis (n: 9), chronic nonbacterial osteomyelitis (n: 5), and inflammatory bowel disease (n: 2) were detected in 26 patients.Arthritis is an important clinical finding of FMF mostly associated with M694V mutations. The frequency of protracted arthritis is declined, whereas sacroiliitis of FMF and arthritis of associated diseases expand the spectrum of arthritis. This study represents the changing face and current perspectives of arthritis in FMF. Key Points • Arthritis is an important clinical finding of familial Mediterranean fever (FMF) that can present in various forms • Arthritis is most likely associated with M694V mutations • The frequency of protracted arthritis is declined whereas sacroiliitis of FMF and arthritis of associated diseases expand the spectrum of arthritis in FMF.

GirişJuvenil idiopatik artrit (JİA) çocukluk çağının en sık görülenromatolojik hastalığıdır. Kısa ve uzun dönemde ciddi morbiditelere yolaçabilir. JİA’da hastalık aktivasyonu klinik değerlendirme ve inflamasyonunbilinen belirteçleri ile gösterilebilir. Ancak günümüz pratiğinde bu ikiparametre her zaman birbiri ile uyum içerisinde olmamakta, bu durumda daözellikle tedavinin planlanmasında ve izleminde zorluklara yol açmaktadır. Buçalışma ile amacımız interlökin-1β (İL-1β), interlökin-6 (İL-6), tümörnekrozitan faktör alfa (TNF-α)’nın oligoartiküler JİA’da hastalık aktivitesini göstermedekullanılabilirliğini araştırmaktır.Gereç veyöntemlerYeni tanı almış 13 oligoartiküler JİA hastası ve 8 sağlıklıkontrol çalışmaya dâhil edildi. Hastaların başvurularında ve inaktifdönemlerinde İL-1β, TNF-α ve İL-6 düzeyleri bakıldı. Hastaların aktivite veyaşam kalitesi ölçümleri için JADAS-27 (Juvenile Arthritis Disease ActivityScore) ve JAQQ (Juvenile Arthritis Quality of Life Questionnaire) kullanıldı. BulgularHastaların aktif dönemlerinde bakılan İL-6, İL-1β ve TNF-αdüzeyleri ile inaktif dönem ve kontrol grubu arasında anlamlı farklılıksaptanmadı. Hastaların ilk başvurularındaki JADAS-27 skorları ile inaktifdönemdeki JADAS-27 skorları karşılaştırıldığında anlamlı olarak inakif dönemdeskorda azalma olduğu saptandı (p=0,02). Hastaların JAQQ puanlarıkarşılaştırıldığında ise gruplar arasında anlamlı farklılık saptanmadı(p=0,382). JADAS-27 puanları >10 ve ≤10 olanların sitokin düzeyleri karşılaştırıldığında, gruplar arasında düşükpuana sahip hastalarda anlamlı olarak düşük İL-1β düzeyi saptandı. İL-6 veTNF-α düzeyleri için ise fark anlamlı bulunmadı.TartışmaJİA hastalarında aktivasyonun ve remisyonun değerlendirilmesi içinçeşitli laboratuvar değerleri ve aktivite skorları kullanılmaktadır. Sonuçlarımızve literatür ışığında bakıldığında oligoartiküler JİA hastalarında sitokindüzeylerinin hastalık izlem ve aktivitesininin değerlendirilmesindekullanılabilirliği kısıtlıdır., ObjectiveJuvenile idiopathic arthritis (JIA) is the most commonrheumatologic disorder in childhood. It may causeshort and long-term morbidities. Disease activity assessment in JIA patients isbased on clinical examination and conventional parameters of inflammation. However,those parameters are not always in concordance and there could be difficultiesin planning of therapy and management. The aim of this study is to evaluate therole of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factoralfa (TNF-α) in determining disease activity of JIA patients. Materialsand methodsThirteen new diagnosed oligoarticular JIA patients andeight healthy controls were enrolled in the study. We investigated serum levelsof IL-1β, TNF-α and IL-6 during both activeand inactive phases of the disease. To evaluate the disease activity andquality of life we used JADAS-27 (Juvenile ArthritisDisease Activity Score) and JAQQ (JuvenileArthritis Quality of Life Questionnaire).ResultsThere were no statistically significantdifferences regarding IL-6, IL-1β and TNF-α between the active phase, inactivephase and control group. Comparing JADAS-27 scores, there was a statisticallysignificant decrease in inactive period compared with the inactive period (p=0.02).However, no significant difference was obtained about the JAQQ scores betweenactive and inactive stage (p=0.382). Levelsof IL-1β were significantly decreased in patients with low disease activity (JADAS-27score ≤ 10) compared with those of severe and moderate disease activity (JADAS-27score >10). On the other hand, no significant differences were obtained forIL-6 and TNF-α.ConclusionThere are few methods to evaluate theactivation and remission periods of JİA. According to our results and theliterature assessment of cytokine levels has limited value in diagnosis,monitoring and evaluating the severity of the oligoarticular JIA patients.

Amaç: Bu çalışmada, juvenil dermatomiyozit (JDM) tanısı ile takip edilen çocukların klinik özelliklerinin, laboratuvar bulgularının ve prognozunun değerlendirmesi amaçlanmıştır.Gereç ve Yöntemler: Ocak 2005-Nisan 2021 tarihleri arasında merkezimiz Çocuk Romatoloji Kliniği’nde JDM tanısı alan, en az 6 ay izlemine devam edilen, 17 çocuğun tıbbi kayıtları geriye dönük olarak değerlendirildi. Bulgular: JDM tanılı 17 hastanın 10’u (%59) kızdı. Hastaların ortanca yaşı 8 (1.5-14)’dü. Tanıdan önceki semptom süresi ortanca 2.5 (1-36) ay; ortalama takip süresi ortanca 24 (6-156) aydı. İlk başvuruda hastaların 15’inde (%88.2) cilt bulgusu, 14’ünde (%82.4) proksimal kas güçsüzlüğü tespit edildi. Başvuruda hastaların 8’inde (%47) eritrosit sedimantasyon hızı ve C-reaktif proteinde yükseklik saptanırken 12’sinde (%70.6) laktat dehidrogenaz, 12’sinde (%70.6) aspartat aminotransferaz, 13’ünde (%76.5) alanin aminotransferaz, 9’unda (%53) kreatinin kinaz yüksekliği saptandı. Miyozit spesifik antikorlar; 5/17 hastada çalışıldı; 4 hastada pozitif bulundu. Kas biyopsisi 6 hastaya yapıldı ve inflamatuar miyozit ile uyumlu bulundu. On üç hastaya ekstremite manyetik rezonans görüntüleme yapıldı ve 10 hastada aktif miyozit gösterildi. Tüm hastalara başlangıç tedavisi olarak steroid ve eş zamanlı olarak metotreksat başlandı. Üç hastada metotreksat yan etkisi nedeni ile mikofenolat mofetil/ siklosporin A verildi. İki hastada kalsinozis gelişti. Son takipte 13 hastanın steroid tedavisi kesilebildi. Bir hasta immünsüpresif ajan olmaksızın, 16 hasta immünsüpresif ajanlarla remisyondaydı. İki hasta 18 yaşın üzerinde olduğu için erişkin romatoloji kliniğine devredildi.Sonuç: JDM çocukluk çağında nadir görülen bir hastalık olmasına rağmen kalsinozis ve vaskülopatiye ikincil ciddi komplikasyonlara neden olabilir. JDM’li tüm çocuklar yakından takip edilmelidir., Objective: The aim of this study is to evaluate the clinical features, laboratory findings and prognosis of children followed up with a diagnosis of juvenile dermatomyositis (JDM).Material and Methods: The medical records of 17 children who were diagnosed with JDM in the Pediatric Rheumatology Clinic of our center between January 2005 and April 2021 and were followed up for at least 6 months were evaluated retrospectively. Results: Ten of the 17 patients (59%) with a diagnosis of JDM were girls. Median age was 8 (1.5-14). Median duration of symptoms before diagnosis was 2.5 (1-36) months; the median follow-up time was 24 (6-156) months. Skin findings were detected in 15 (88.2%) patients and proximal muscle weakness in 14 (82.4%) patients at the first admission. Erythrocyte sedimentation rate and C-reactive protein elevation were detected in 8 (47%) patients at admission, while 12 (70.6%) had lactate dehydrogenase, 12 (70.6%) aspartate aminotransferase, and 13 (76.5%), alanine aminotransferase and 9 (53%) increased creatine kinase. Myositis-specific antibodies; assessed in 5/17 patients; found positive in 4 patients. Muscle biopsy was performed on 6 patients and was found to be compatible with inflammatory myositis. Magnetic resonance imaging of the limbs was performed in 13 patients and active myositis was demonstrated in 10 patients. Steroid and simultaneous methotrexate were started as initial therapy in all patients. Mycophenolate mofetil/cyclosporine A was given to three patients because of the side effect of methotrexate. Calcinosis developed in two patients. Steroid therapy could be discontinued in 13 patients at the last follow-up. One patient was in remission without an immunosuppressive agent, and 16 patients were in remission with immunosuppressive agents. Two patients were transferred to the adult rheumatology clinic because they were over 18 years old.Conclusion: Although JDM is a rare disease in childhood, it can cause serious complications secondary to calcinosis and vasculopathy. All children with JDM should be closely monitored.

OBJECTIVES: The aims of this study were to evaluate the role of biological agents in the treatment of severe multisystem inflammatory syndrome in children (MIS-C) and to assess the current application, outcomes, and adverse effects in patients who are followed up in a pediatric intensive care unit (PICU). PATIENTS AND METHODS: This observational, descriptive, medical records review study was performed on patients with MIS-C admitted to the PICU between September 1 and November 1, 2020. Through medical records review, we confirmed that patients were positive for current or recent SARS-CoV-2 infection or for COVID-19 exposure history within the 4 weeks before the onset of symptoms. RESULTS: A total of 33 patients with severe MIS-C were included (21 male) with a median age of 9 years. The most common signs and symptoms during disease course were fever (100%) and abdominal pain (75.5%). Clinical features of 63.6% patients were consistent with Kawasaki disease/Kawasaki disease shock syndrome, and 36.4% were consistent with secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Myocardial dysfunction and/or coronary artery abnormalities were detected in 18 patients during the PICU stay. Intravenous immunoglobulin and corticosteroids were given to 33 patients. Anakinra was administered to 23 patients (69.6%). There was a significant increase in lymphocyte and platelet counts and a significant decrease in ferritin, B-type natriuretic peptide, and troponin levels at the end of the first week of treatment in patients who were given biological therapy. Two patients were switched to tocilizumab because of an insufficient response to anakinra. The mortality rate of MIS-C patients admitted in PICU was 6.0%. CONCLUSIONS: Management of systemic inflammation and shock is important to decrease mortality and the development of persistent cardiac dysfunction in MIS-C. The aggressive treatment approach, including biological agents, may be required in patients with severe symptoms and cardiac dysfunction.

AIMS: Recently, multisystem inflammatory syndrome in children (MIS-C) has been recognized in association with coronavirus disease 2019 as a cytokine storm syndrome. MIS-C presents with symptoms similar to Kawasaki disease and macrophage activation syndrome (MAS). We aimed to better understand this cytokine storm syndrome by comparing the initial laboratory findings of MIS-C and MAS. METHODS: Patients who were diagnosed with MAS due to systemic juvenile idiopathic arthritis in our clinic between March 2002 and November 2020 and with MIS-C between 20 September and 20 October 2020 were enrolled into the study. The medical files of all patients were reviewed retrospectively. RESULTS: A total of 13 MAS (9 boys, 4 girls) and 26 MIS-C (16 boys,10 girls) patients were included in the study. Hemoglobin, absolute neutrophil and lymphocyte counts, C-reactive protein (CRP), ferritin, fibrinogen and lactate dehydrogenase (LDH) levels showed significant differences between the two groups (P

TYPE OF THE ARTICLE: LETTERTITLE: BIOLOGICAL THERAPIES IN CHILDREN WITH RHEUMATIC DISEASES DURING THE COVID-19 PANDEMIC: A SINGLE CENTER EXPERIENCERUNNING TITLE: BIOLOGICAL THERAPIES DURING THE COVID-19 PANDEMIC

Behçet's disease is an inflammatory vasculitic disease of unknown etiology characterized by recurrent oral and genital ulcers, ocular findings, and multiple organ involvement. Mucocutaneous findings are the most common symptoms. The most used diagnostic criteria are International Criteria for BD (ICBD), International Study Group (ISG) criteria and pediatric Behçet's disease criteria (PEDBD). Although diagnostic criteria have been defined, the diagnosis is still difficult due to clinical findings developed in pediatric patients. The aim of this study was to evaluate the clinical findings, phenotype characteristics, sensitivity and specificity of diagnostic criteria, and the course of pediatric Behçet's disease (BD). We evaluated retrospectively the files of 67 (29 M/38 F) patients diagnosed with BD according to expert opinion. The patients were reclassified according to ISG, ICBD, and PEDBD criteria. The control group consisted of a total of 69 patients with BD-mimicking diseases or presenting at least one major BD sign followed at the same center. Sensitivity and specificity were evaluated for the criteria. The mean age of diagnosis was 13.38 ± 3.2 years. There were oral aphthous ulcers in 98.5%, genital ulcers in 68.7%, skin lesions in 31.3%, vascular involvement in 17.9%, neurological involvement in 11.9%, positive pathergy test in 33.8%, and positive HLA-B51 in 57.1% of patients. The sensitivity of ICBD, ISG and PEDBD criteria was 88.1, 43.3, and 37.3%, respectively. The specificity of ICBD, ISG, and PEDBD criteria was 100%. Diagnosis of BD in childhood is still difficult. ICBD criteria have the highest sensitivity among the diagnostic criteria. These criteria can also be used in childhood.

The aim of this study is to describe clinical features of patients with oligoarticular juvenile idiopathic arthritis (JIA) who achieved inactive disease at 3rd month and also to determine the predictors of relapse and extended course.In the cohort study, 88 patients with oligoarticular JIA were retrospectively analyzed. The demographic data, clinical features, medications, relapse rates were recorded. Juvenile Arthritis Disease Activity Score (JADAS) and American College of Rheumatology Pediatric criteria were used to measure disease activity and treatment response at 3, 6 and 12 months.Fifty-nine (67%) patients were females and the mean age at diagnosis was 7.9 ± 4.3 years. The odds of achieving inactive disease (JADAS ≤1) at 3rd month were increased by a lower JADAS27 score at admission. Forty-one (48.8%) of 84 patients relapsed. Ankle involvement at onset, high JADAS27 score at admission, increased ESR at admission and presence of synovial hypertrophy in imaging were risk factors for occurrence of relapse.Our results show that a significant proportion of oligoarticular JIA patients relapse after inactive period. JADAS is a useful tool to guide the treatment decisions of patients who may be at risk of high disease activity and relapse.

Amac: Juvenil sistemik lupus eritematozus (jSLE); kronik, sistemik, relaps-remisyon ataklari ile seyreden, bircok sistemi etkileyebilen ve noropsikiyatrik bulgularin da goruldugu otoimmun bir hastaliktir. Bu calisma ile jSLE tanili hastalarin tani esnasinda var olan klinik ve laboratuvar ozelliklerinin arastirilmasi ve norolojik bulgularin degerlendirilmesi amaclanmistir. Gerec ve Yontem: Temmuz 2004-2019 tarihleri arasinda klinigimizde American College of Rheumatology (ACR) 1997 kriterlerine gore jSLE tanisi ile izlenen hastalarin dosyalari retrospektif olarak incelendi. Demografik, klinik, laboratuvar ve goruntuleme bulgulari kaydedilerek noropsikiyatrik tutulumu olan hastalar degerlendirildi. Bulgular: jSLE tanisi ile izlenen 40 hastanin 33’u (%82,5) kizdi (K/E:4,7). Hastalik tani yasi ortalama 10,33 ± 2,56 yildi. Tum hastalarin ortalama izlem suresi 5,9 ± 3,1 yil idi. Renal tutulum 32 (%80), hematolojik tutulum 27 (%67,5), eklem tutulumu 25 (%62,5) ve mukokutanoz bulgular 19 hastada (%47,5) saptandi. Hastalarin 6’sinda (%15) norolojik tutulum tanimlanmisti ve bu hastalarin tumu kizdi. Alti hastanin 5’inde norolojik tutulum ilk basvuruda vardi. Dort hastada bas agrisi, 2 hastada nobet, 2 hastada uyku hali, 1 hastada koreiform hareketler, 1 hastada psikoz ve 1 hastada mononoritis multipleks mevcuttu. 5’inde eslik eden nefrolojik ve hematolojik tutulum vardi ve tedavi eslik eden nefrolojik tutulum goz onune alinarak duzenlendi. Tum hastalar hidroksiklorakin, induksiyon tedavisi olarak pulse metilprednisolon sonrasi oral prednisolon ve intravenoz aylik 6 ay siklofosfamid aldi. Uc hastada mikofenolat mofetil ile idame tedavisi yapildi. Hastalarin izleminde norolojik sekel gozlenmedi. Sonuc: Norolojik bulgular cocukluk cagindaki SLE hastalarinin klinik bulgularina eslik edebilir ve bazen ilk basvuru nedeni olabilir. Ozellikle adelosan donemde aciklanamayan norolojik bulgulari olan kiz cocuklarinda otoantikorlar mutlaka degerlendirilmeli ve jSLE akilda tutulmalidir.

The diagnosis of Familial Mediterranean fever (FMF) based on clinical findings supported by genetic mutation. Recently, the new Eurofever/PRINTO classification criteria including genetic analysis were established. The aim of this study is to evaluate the performance of the new criteria in FMF patients with a single exon 10 mutation in childhood. The study group consisted of FMF patients who had a single exon 10 mutation in a referral center in Turkey. Patients with periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome were included as a control group. The medical charts of all patients were reviewed retrospectively. A total of 106 FMF patients (59 boys) were enrolled in the study group. The median age at first symptom was 5; the median age at diagnosis was 7 years. The mean follow-up was 33 ± 35.4 months. Majority of the patients (n = 58, 54.7%) had heterozygous M694V, 16 (15%) patients had M694V/E148Q and 13 (13.8%) patients had heterozygous M680I mutation. The sensitivity of the Yalcinkaya-Ozen criteria was 98.1% and it was 97.1% for the Eurofever/PRINTO classification criteria. The specificity of the new Eurofever/PRINTO classification criteria was 96.7% and it was 74.1% for the Yalcinkaya-Ozen criteria. The new Eurofever/PRINTO classification criteria have a good sensitivity as the Yalcinkaya-Ozen criteria in patients with a single exon 10 mutation. Additionaly, the new criteria have better specificity. It should be useful to apply the clinical only criteria where the carrier rate is high.

Objectives: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent, self-limited attacks of fever with serositis. Recently, it was shown that FMF patients with early disease onset have more severe disease. The aim of this study was to describe the demographic, clinical and genetic features of FMF patients who had disease onset during the neonatal period. Methods: Medical records of all patients diagnosed as FMF and had been seen in the outpatient clinic of Paediatric Rheumatology department between January 2013 and January 2014 were retrospectively evaluated. Patients with disease onset during the first month of life were included to the study. Results: Among 317 patients; 19 (12 males) were included to the study. Approximately 60% of the patients had family history of FMF. Homozygous p.M694V mutation was detected in 42% of the cases. Thirteen patients present with attacks of fever and remaining had attacks in the form of restlessness, resembling infantile colic starting in the neonatal period. Majority of these patients developed classical abdominal attacks between the ages of 1 and 2.5 years. The diagnosis of FMF was significantly delayed; the median age at onset of therapy was 3.5 years (range 7 months-17 years). Conclusion: Patients with FMF could have complaints even in the neonatal period. Homozygous p.M694V mutation is a prominent mutation in this group of patients. In order to prevent diagnostic delay physicians dealing with these type of patients should be more vigilant.

Henoch-Schonlein purpurasi (HSP), artrit/artralji, gastrointestinal ve genitouriner sistem tutulumunun eslik ettigi non-trombositopenik purpura ile karakterize, cocukluk caginin en sik gorulen vaskulitidir. Solunum sistemi tutulumu nadir olmakla birlikte, morbidite ve mortalitesinin yuksek olmasi nedeniyle onemlidir. Bu yazida atipik cilt tutulumu, gastrointestinal ve solunum sistemi bulgulari olan HSP vakasi sunuldu. Tedavide yuksek doz metilprednisolon uygulandiktan sonra klinik duzelme saglandi. Solunum sistemi tutulumu olan HSP vakalarinda, mortalite ve morbiditesinin yuksek olmasi nedeniyle tedavi hizli ve yogun olmalidir.