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Copyright of Journal of Turkish Society for Rheumatology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Turkish Society for Rheumatology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Amaç: Uvea gözün damar ve pigmentten zengin orta tabakasıdır. Üvea tabakasının inflamasyonuna üveit denilir ve tutulan bölümün yerine göre ön, orta, arka ve panüveit olarak isimlendirilir. Üveit nedenleri arasında enfeksiyonlar, non-enfeksiyöz nedenler ve maligniteler yer almaktadır. Non-enfeksiyöz nedenler arasında en sık romatolojik hastalıklar (JIA, Behçet hastalığı, sarkoidoz, vaskülitler), TINU ve idiyopatik üveit yer almaktadır. Çalışmamızın amacı çocuk romatoloji klüıiğimizde non-enfeksiyöz üveit tanısıyla takip ve tedavi edilen hastalarımızın demografik özelliklerini saptamaktır. Yöntem: Çalışmamıza Mayıs 2010 ile Eylül 2017 tarihleri arasında üveit tanısı alan, düzenli kontrollere gelen ve en az 6 ay süre ile kliniğimizden takip edilen hastalar alınmıştır. Bulgular: Çalışmaya 54 jüvenil üveit hastası dahil edilmiştir. Üveit nedeni olarak 27 hasta da (%50) JIA, 6 hastada (%11) Behçet hastalığı, 4 hastada (%7) TINU saptandı. On yedi (%31) hastada idiyopatik üveit tanısıyla takipli idi. Üveit nedeniyle hastalarımızın ortalama takip süresi 18.6 ay (6-60 ay) idi. Cinsiyet dağılımma bakıldığında 28 laz, 26 erkek hasta vardı. JIA olgularında hu oran yine birbirine yalan (15 kız, 12 erkek) idi. idiyopatik üveitte belirgin kız hakimiyeti (11 laz, 6 erkek) var iken, Behçet üveiti (5 erkek, 1 laz) ve TINU da (3 erkek, 1 laz) erkek hakimiyeti mevcuttu. Tüm JIA'larda üveit görülme sıklığı %6.6 (27/405) iken bu oran Behçet hastalarında %22.2 (6/27) olarak bulundu. JIA hastalarının 18'i (%67) persistan oli-goJIA idi. Beş hastada JIA taıusı konulduğu anda (4 persistan oligoJIA, 1 RF negatif poliJIA) üveit saptandı. JIA hastalarında JIA tanısı ile ilk üveit saptanması arasındaki ortalama süre 21.2 (0-77) ay idi. Üveit tanısı konulduğunda ortalama yaş 9.1 yıl (1-17.5) iken, persistan oligoJIA 1ar da ortalama 5, idiyopatik üveitte 11.8, Behçet hastalarında 13.7 ve ERA'larda 16.6 yaş olarak bulundu. Çalışmaya alınma anında 45 hasta remisyonda iken 9 hastanın göz bulguları aktif idi. İdiyopatik üveitte 5 hasta, JLA grubunda 2 hasta, Behçet ve TINU'da birer hastanın göz bulguları remisyonda değildi. JIA'larda metotreksat dirençli üveit nedeniyle biyolojik ajan 14 hastada (%52; adalimumab 11 hasta, tosilizumab 3 hasta) kullanıldı. Sonuç: Erken taıu ve tedavi ile komplikasyon gelişimi engellenebileceği içüı JIA ve Behçet hastalarında düzenli aralıklarla üveit açısından detaylı göz muayenesi yapılması önemlidir. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Turkish Society for Rheumatology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Turkish Society for Rheumatology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To describe the demographic characteristics and clinical features of patients referred to a pediatric rheumatology outpatient clinic in Turkey and to compare the final diagnoses with the previous literature data. All new patients referred to pediatric rheumatology outpatient clinic of Kanuni Sultan Süleyman Research and Training Hospital between March 2018 and March 2019 were enrolled to the study. Demographic data, referral patterns, disease related features, physical examination findings and final diagnoses of new referrals were collected prospectively. A total of 2982 new referrals were evaluated in 1-year period. Among them 1561 (52%) had a diagnosis of a rheumatic disease. The frequencies of most common rheumatic diseases were; periodic fever syndromes (47.3%), juvenile idiopathic arthritis (18%) and vasculitis (14.4%), respectively. Non-rheumatic conditions were diagnosed in 1243 patients, among them orthopedic/mechanic problems (27.4%) were the most frequent ones followed by vitamin D deficiency (17.5%) and dermatological problems (9.8%). Patients with non-rheumatic conditions comprised a large part of the pediatric rheumatology outpatient clinic. National registries are required to establish the frequencies of pediatric rheumatic diseases in Turkey. [ABSTRACT FROM AUTHOR]

Until now, the diagnosis of familial Mediterranean fever (FMF) was based on validated subsets of clinical criteria, but recently new Eurofever/PRINTO classification criteria concerning genetic analyses were proposed. The study aimed to compare the performances of three validated diagnostic criteria (Tel-Hashomer, Livneh, pediatric criteria) and new Eurofever/PRINTO classification criteria. The medical charts of study and control groups were reviewed retrospectively. Patients were evaluated for three diagnostic criteria and new Eurofever/PRINTO classification criteria. Control group consists of patients with other autoinflammatory diseases. A total of 1291 patients were classified into three groups according to their mutations: group 1: 447 patients with homozygous mutations; group 2: 429 patients with compound heterozygous mutations; and group 3: 415 patients with one heterozygous mutation. Similar diagnostic utility was found according to Livneh criteria between groups. But, proportion of patients fulfilling Tel-Hashomer and pediatric criteria was higher in groups 1 and 2. According to Eurofever/PRINTO criteria, 98.2% of patients with homozygous mutations, 94.2% of patients with compound heterozygous mutations and 80.2% of patients with heterozygous mutations were classified as FMF. In control group, 99.2% of them fulfilled the Livneh criteria, 66.9% met the pediatric criteria and 0.8% satisfied the Tel-Hashomer criteria, while none of control patients met the Eurofever/PRINTO classification criteria. Performances of three validated diagnostic criteria and new Eurofever/PRINTO classification criteria for FMF were similar and provide high utility in diagnosing/classifying patients with homozygous and compound heterozygous mutations. However, both Eurofever/PRINTO classification criteria and Tel-Hashomer criteria had significantly lower performance in heterozygous patients. [ABSTRACT FROM AUTHOR]

Systemic autoinflammatory diseases (sAIDs) are a heterogeneous group of disorders, having monogenic inherited forms with overlapping clinical manifestations. More than half of patients do not carry any pathogenic variant in formerly associated disease genes. Here, we report a cross-sectional study on targeted Next-Generation Sequencing (NGS) screening in patients with suspected sAIDs to determine the diagnostic utility of genetic screening. Fifteen autoinflammation/immune-related genes (ADA2-CARD14-IL10RA-LPIN2-MEFV-MVK-NLRC4-NLRP12-NLRP3-NOD2-PLCG2-PSTPIP1-SLC29A3-TMEM173-TNFRSF1A) were used to screen 196 subjects from adult/pediatric clinics, each with an initial clinical suspicion of one or more sAID diagnosis with the exclusion of typical familial Mediterranean fever (FMF) patients. Following the genetic screening, 140 patients (71.4%) were clinically followed-up and re-evaluated. Fifty rare variants in 41 patients (20.9%) were classified as pathogenic or likely pathogenic and 32 of those variants were located on the MEFV gene. We detected pathogenic or likely pathogenic variants compatible with the final diagnoses and inheritance patterns in 14/140 (10%) of patients for the following sAIDs: familial Mediterranean fever (n = 7), deficiency of adenosine deaminase 2 (n = 2), mevalonate kinase deficiency (n = 2), Muckle–Wells syndrome (n = 1), Majeed syndrome (n = 1), and STING-associated vasculopathy with onset in infancy (n = 1). Targeted NGS panels have impact on diagnosing rare monogenic sAIDs for a group of patients. We suggest that MEFV gene screening should be first-tier genetic testing especially in regions with high carrier rates. Clinical utility of multi-gene testing in sAIDs was as low as expected, but extensive genome-wide familial analyses in combination with exome screening would enlighten additional genetic factors causing disease. [ABSTRACT FROM AUTHOR]

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Turkish language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach’s alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 466 JIA patients (13.7% systemic, 40.6% oligoarticular, 22.5% RF negative poly-arthritis, and 23.2% other categories) and 93 healthy children were enrolled in four centres. The JAMAR components discriminated well-healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Turkish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research. [ABSTRACT FROM AUTHOR]

The hyperinflammatory state and the viral invasion may result in endothelial dysfunction in SARS-CoV-2 infection. Although a method foreseeing microvascular dysfunction has not been defined yet, studies conducted in patients diagnosed with COVID-19 have demonstrated the presence of endotheliitis. With this study, we aimed to investigate the microvascular circulation in patients diagnosed with COVID-19 and multisystem inflammatory syndrome in children (MIS-C) by nailfold videocapillaroscopy (NVC). Thirty-one patients with SARS-CoV-2 infection, 25 of whom were diagnosed with COVID-19 and 6 with MIS-C and 58 healthy peers were included in the study. NVC was performed in eight fingers with 2 images per finger and 16 images were examined for the morphology of capillaries, presence of pericapillary edema, microhemorrhage, avascular area, and neoangiogenesis. Capillary length, capillary width, apical loop, arterial and venous width, and intercapillary distance were measured from three consecutive capillaries from the ring finger of the non-dominant hand. COVID-19 patients showed significantly more capillary ramification (p < 0.001), capillary meandering (p = 0.04), microhemorrhage (p < 0.001), neoangiogenesis (p < 0.001), capillary tortuosity (p = 0.003). Capillary density (p = 0.002) and capillary length (p = 0.002) were significantly lower in the patient group while intercapillary distance (p = 0.01) was significantly longer compared with healthy volunteers. Morphologically, patients with MIS-C had a higher frequency of capillary ramification and neoangiogenesis compared with COVID-19 patients (p = 0.04). Abnormal capillary alterations seen in COVID-19 and MIS-C patients indicate both similar and different aspects of these two spectra of SARS-CoV-2 infection and NVC appears to be a simple and non-invasive method for evaluation of microvascular involvement. • Children diagnosed with SARS-CoV-2 infection present with abnormal capillary alterations on Nailfold Videocapillaroscopy. • COVID-19 and MIS-C patients were characterized by different clinical and microvascular abnormalities. • Patients with capillary abnormalities had significantly higher levels of C-reactive protein (CRP) and D-dimer. [ABSTRACT FROM AUTHOR]

The second affiliation of the corresponding author Eda Tahir Turanlı was incorrectly published as İstanbul Medeniyet University instead of Istanbul Technical University. [ABSTRACT FROM AUTHOR]

Background: Nailfold videocapillaroscopy (NVC) is the primary diagnostic tool for the assessment of microcirculation in the pediatric population., Objective: To define and standardize age-specific normal NVC patterns in healthy children and adolescents., Methods: A cross-sectional observational multicentric study was conducted in 564 participants aged 5-17 years. Dino-Lite CapillaryScope 200 Pro Model MEDL4N Pro was performed at 200× magnification. Quantitative and qualitative NVC parameters were analysed separately for each age group and divided into four groups based on age categories., Results: Of the 564 healthy participants, 54.9% were female. A total of 1184 images and 3384 capillaries were analysed. Positive correlations were observed between age and capillary density (P < 0.001, R = 0.450, CI95% 0.398-0.503). There was also a positive correlation between age and arterial/venous, loop diameter and capillary length, whereas there was a weak negative correlation between intercapillary distance. However, no correlation was found between age and capillary width. In addition, capillary density was significantly lower in the 5-7 age group compared with the other patient groups. Arterial limb diameter was lower in the 5-7 age group, while venous limb diameter was significantly wider in the 15-17 age group compared with the other patient groups. Dilated capillaries (8.7%), capillary tortuosity (14.4%), crossed capillaries (43.1%), micro-haemorrhages (2.7%) and avascular area (4.8%) were present in all age groups. Excellent intra- and interobserver ICC values were obtained for all parameters., Conclusion: These findings hold potential significance for future studies, aiding in the analysis and differentiation of children suspected of rheumatological diseases with potential microangiopathy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

To evaluate the sleep quality and fatigue levels in children with familial Mediterranean fever (FMF) in comparison to healthy children. The Pediatric Quality of Life Multidimensional Fatigue Scale (PedsQL-MFS) and the Pittsburgh Sleep Quality Index (PSQI) were the instruments utilized to assess fatigue and sleep quality in children with FMF and controls, respectively. Spearman's rank coefficient was decisive in determining the association between patient-reported outcome measures and disease-related features. Two hundred twenty-five (59.3% female) patients and 182 (51.6% female) healthy counterparts were enrolled in the study. In PSQI, where high scores indicate sleep disturbance, the median score was significantly higher in the patient group (5; 3-6) than the control group (3; 2-4) (p < 0.001). PEDsQL-MFS demonstrated significantly lower fatigue levels in the control group than patients (p = 0.01). The level of fatigue in the patient group was found to increase in correlation with sleep problems (r: - 0.750, p < 0.001). Additionally, a high correlation was present between the PSQI/PedsQL-MFS scores and the number of attacks in the last year (r: - 0.645, p < 0.001/r: 0.721, p < 0.001, respectively). There was no difference in terms of fatigue and sleep disorders between mutations (homozygous, heterozygous, or compound heterozygous) in the MEFV gene (p > 0.05).    Conclusion: High disease activity has a significant negative impact on the sleep quality and fatigue levels of patients with FMF. This study emphasizes the importance of assessing fatigue and sleep quality with objective outcome tools periodically in FMF patients throughout the disease course. What is Known: • Fatigue is a common matter that often accompanies rheumatic diseases and causes disability. • Chronic rheumatic diseases often experience poor sleep quality. What is New: • In high correlation with the disease severity of familial Mediterranean fever, sleep quality decreases and fatigue level increases significantly. • In familial Mediterranean fever patients, a negative correlation is present between age and the general fatigue and sleep/rest related fatigue scores (low scores indicating greater fatigue) and sleep quality is poorer in the adolescent age group., (© 2024. The Author(s).)

Aim: The aim of this study was to investigate the frequency and type of FMF-associated inflammatory diseases in a large FMF pediatric patients and to compare them to those FMF patients without concomitant inflammatory diseases., Materials and Methods: Familial Mediterranean fever patients enrolled in the Pediatric Rheumatology Academy (PeRA)-Research Group (RG) were included. The patients were divided into two groups according to concomitant inflammatory disease as FMF patients who had a concomitant inflammatory disease (group 1) and FMF patients who did not have a concomitant inflammatory disease (group 1). The clinical findings and treatments were compared between the two groups., Results: The study group comprised 3475 patients with FMF. There were 294 patients (8.5%) in group 1 and 3181 patients (91.5%) in group 2. Juvenile idiopathic arthritis (n = 136) was the most common accompanying inflammatory disease. Arthritis, M694V homozygosity, and the need for biological therapy were more frequently observed in Group 1 (p < 0.05). Fever and abdominal pain were more frequently detected in Group 2 (p < 0.05). FMF patients with concomitant inflammatory diseas more frequently demonstrated colchicine resistance. There were no significant differences in the median attack frequency, chest pain, amyloidosis, erysipelas-like erythema, or family history of FMF between the two patient groups., Conclusion: To the best of our knowledge, this is the largest pediatric cohort reviewed to date. FMF patients may have different clinical profiles and colchicine responses if they have with concomitant inflammatory diseases. Key points • FMF is associated with some inflammatory comorbidities diseases. • To the best of our knowledge, this is the largest cohort evlauated pediatric FMF associated inflammatory comorbidities diseases reviewed to date., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: The aim of the study was to evaluate the approaches of pediatric rheumatologists and pediatric hematologists to patients with similar musculoskeletal (MSK) complaints and to highlight the differences that general pediatricians should consider when referring patients to these specialties., Methods: This is a cross-sectional study involving the patients who applied to pediatric rheumatology centers with MSK complaints and were diagnosed with malignancy, as well as patients who were followed up in pediatric hematology centers with a malignancy diagnosis, and had MSK complaints at the time of admission., Results: A total of 142 patients were enrolled in the study. Of these patients, 83 (58.4%) applied to pediatric rheumatology centers, and 59 (41.6%) applied to pediatric hematology centers. Acute lymphoblastic leukemia (ALL) was the most common diagnosis among the patients who applied to both centers, with 80 cases (56.3%). The median age of diagnosis was 87 (interquartile range, IQR: 48-140) months. The most common preliminary diagnosis in pediatric rheumatology centers was juvenile idiopathic arthritis (JIA), with 37 cases (44.5%). MSK involvement was mainly seen as arthralgia, and bone pain. While arthralgia (92.7%) was the most common complaint in rheumatology centers, bone pain (88.1%) was more common in hematology centers. The most frequently involved joints were the knee (62.9%), ankle (25.9%), hip (25%), and wrist (14%). The most common laboratory abnormalities were high lactate dehydrogenase (LDH), high C-reactive protein (CRP), anemia, and high erythrocyte sedimentation rate (ESR). Thrombocytopenia, neutropenia, and high LDH were statistically significantly more frequent in patients admitted to hematology centers than in patients admitted to rheumatology centers (p < 0.001, p=0.014, p=0.028, respectively). Patients who applied to rheumatology clinics were found to have statistically significantly higher CRP levels (p=0.032)., Conclusions: Malignancies may present with only MSK system complaints in childhood. Therefore, malignancies should be included in the differential diagnosis of patients presenting with MSK complaints.

Objectives: The rapid expansion in the use of telemedicine after the COVID-19 pandemic has led many patients with chronic diseases to seek alternative ways for follow-ups. This study aimed to investigate the demands and opinions of parents of children with rheumatic diseases toward telemedicine and to examine the factors affecting telemedicine preference. Methods: A single-center, cross-sectional, Web-based survey study was conducted. Sociodemographic data, characteristics of the disease, access to the clinic, internet use, and views on telemedicine were assessed. Factors effecting telemedicine preference were evaluated by multivariate analysis. Results: A total of 245 parents have completed the survey. The diagnoses of patients were recurrent fever syndromes (55.1%), juvenile idiopathic arthritis (31.0%), systemic connective tissue diseases (8.2%), and vasculitis (5.7%). The majority of patients came to the clinic by public transport ( n  = 190, 77.6%). Sixty-eight (27.8%) patients missed at least one outpatient appointment in the last year. Majority ( n  = 172, 70.2%) of parents stated that they would prefer telemedicine visits if it becomes available. Multivariate analysis revealed that the most related factors to telemedicine preference were higher education level (odds ratio [OR]: 6.69, confidence interval [95% CI]: 2.21-20.25, p  = 0.001), missing an appointment (OR: 3.04, 95% CI: 1.41-6.56, p  = 0.004), and travel time longer than 1 h (OR: 2.13, 95% CI: 1.13-3.86, p  = 0.012). Conclusion: Telemedicine visits are in demand in pediatric rheumatology and should be considered an alternative method to ensure continuity of patient follow-up. A personal approach should be followed when selecting patients for telemedicine.

Aim: Morphea, also known as localized scleroderma, is an immune-mediated disease and the most common form of scleroderma in children. It is a localized sclerosing disease of the skin, but can also involve such adjacent tissues as the fascia, muscle, bone, and underlying tissues. This multicenter study aimed to evaluate Turkish pediatric morphea patients, regarding demographics, treatments, and response to treatment., Materials and Methods: The study was performed by the Pediatric Rheumatology Academy and included pediatric morphea patients from 6 Turkish pediatric rheumatology centers who were followed up for ≥6 months. Demographic, clinical, and laboratory findings and treatment modalities were analyzed. The patients were divided into 3 groups according to treatment response, as follows: group 1: topical treatment response, group 2: methotrexate response, and group 3: methotrexate resistance. Clinical findings were compared between the 3 groups., Results: The study included 76 patients, of which 53 (69.7%) were female. Mean age at diagnosis of morphea was 9.7 ± 4.3 years and mean duration of follow-up was 3.2 ± 2.9 years. Linear morphea was the most common form, accounting for 43.4% (n = 33) of the patients. Extracutaneous features were noted in 17 patients (22.4%) and anti-nuclear antibody positivity was noted in 32 (42.1%). In all, 14.4% of the patients received topical treatment only, whereas 86.6% received both topical and systemic treatment. The methotrexate response rate was 76.9% in the patients that received systemic immunosuppressive therapy. The overall relapse rate while under treatment was 19.7%., Conclusion: In this study, most of the pediatric morphea patients responded well to methotrexate. Bilateral lesions were more common in the methotrexate-resistant group. Multiple involvement, and bilateral lesions, were more common in relapsed patients than in non-relapsed patients. Key points • Most of the pediatric morphea patients respond well to MTX. • Multiple involvement, and bilateral involvement, were more common in relapsed patients than in non-relapsed patients. • Presence of extracutaneous findings in patients increased relapse rate 5.7 times., (© 2023. International League of Associations for Rheumatology (ILAR).)

Classical attacks of familial Mediterranean fever (FMF) are often accompanied by fever, but some of the patients have attacks without fever. This study aimed to compare the characteristics of FMF patients with and without fever during their attacks and draw attention to the different clinical presentations of FMF in children. Medical files of patients aged 0-18 years who were followed up with the diagnosis of FMF in two reference pediatric rheumatology centers were reviewed retrospectively. The patients were divided into two groups: children who had had no fever in any of their attacks were assigned as group 1, and those who had fever during their attacks were classified as group 2. Out of 2003 patients evaluated, 191 (9.53%) patients had attacks not accompanied by fever and their median age at onset of symptoms (7.0 vs. 4.0 years, p < 0.001) and the median age at diagnosis (8.6 vs. 6.0 years, p < 0.001) were significantly higher; however, group 2 had a delay in diagnosis. The annual number of attacks and abdominal attacks were more common in group 2; arthritis, arthralgia, erysipelas-like rash, exercise-induced leg pain, and myalgia were more common in group 1.    Conclusion: The data from the assessment of children with FMF attacks not accompanied with fever were presented for the first time. Children with late age onset of FMF and dominance of musculoskeletal features may display attacks not accompanied with fever. What is Known: • Familial Mediterranean fever (FMF) is the most common inherited auto-inflammatory disease, characterized by recurrent attacks of fever, serositis, and musculoskeletal symptoms. • Although fever is the most common symptom, few studies have reported attacks without fever. What is New: • The aim of this study was to identify patients with FMF but without fever during attacks and to demonstrate their distinctive presentations. • We found that 7% of our patients had afebrile attacks with predominant musculoskeletal symptoms and were diagnosed earlier than patients with febrile attacks, probably due to early referral to pediatric rheumatology clinics., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Rheumatoid factor (RF)-positive polyarthritis is the least common type of juvenile idiopathic arthritis (JIA). Functional disability in RF-positive polyarthritis patients is much more severe than in patients with other subtypes; but data on this subtype alone is limited. This study aimed to analyze clinical features, long-term follow-up, treatment response, and remission status in a large multicenter cohort of RF-positive polyarthritis patients., Methods: This retrospective study included RF-positive polyarthritis patients that were followed up for ≥ 6 months between 2017 and 2022 by the Pediatric Rheumatology Academy (PeRA)-Research Group (RG). Data on patient demographics, clinical and laboratory characteristics were obtained from medical charts. JIA treatments and duration of treatment were also recorded. The patients were divided into 2 groups based on methotrexate (MTX) response, as follows: group 1: MTX responsive, group 2: MTX unresponsive. Clinical and laboratory findings were compared between the 2 groups., Results: The study included 56 (45 female and 11 male) patients. The median age at onset of RF-positive polyarthritis was 13.2 years [(interquartile range) (IQR): 9.0-15.0 years] and the median duration of follow-up was 41.5 months (IQR: 19.5-75.7 months). Symmetrical arthritis affecting the metacarpophalangeal and proximal interphalangeal joints of the hands was commonly observed. Subcutaneous MTX was the preferred initial treatment; however, it was ineffective in 39 (69.6%) of the patients. Of 25 patients followed for 24 months, 56% still had active disease at 24 months., Conclusion: During 2 years of treatment, 44% of RF-positive polyarthritis patients have inactive disease, and they should be considered as a distinct and important clinical entity requiring aggressive and early treatment., (© 2023. The Author(s).)

Introduction: Neuropsychiatric (NP) involvement is a restricted area in juvenile-onset systemic lupus erythematosus (jSLE)., Aim: To investigate the prevalence, demographic and clinical features, and outcomes of the neurological involvement in the Turkish jSLE population., Methods: This study was based upon 24 referral centers' SLE cohorts, multicenter and multidisciplinary network in Turkey. Patient data were collected by a case report form which was standardized for NP definitions according to American Collage of Rheumatology (ACR). Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) neuropsychiatric part was used to determine NP damage. Variables were evaluated Ward's hierarchical clustering analyses, univariate, and multivariate logistic regression analyses., Results: A hundred forty-nine of 1107 jSLE patients had NP involvement (13.5%). The most common NPSLE findings were headache (50.3%), seizure (38.3%), and acute confusional state (33.6%). Five clusters were identified with all clinical and laboratory findings. The first two clusters involved neuropathies, demyelinating diseases, aseptic meningitis, and movement disorder. Cluster 3 involved headache, activity markers and other SLE involvements. Idiopathic intracranial hypertension, cerebrovascular disease, cognitive dysfunction, psychiatric disorders and SLE antibodies were in the fourth, and acute confusional state was in the fifth cluster. In multivariate analysis, APA positivity; OR: 2.820, (%95CI: 1.002-7.939), P: 0,050, plasmapheresis; OR: 13.804 (%95CI: 2.785-68.432), P: 0,001, SLEDAI scores; OR: 1.115 (%95CI: (1.049-1.186), P: 0,001 were associated with increased risk for neurologic sequelae., Conclusion: We detected the prevalence of juvenile NPSLE manifestations in Turkey. We have identified five clusters that may shed light pathogenesis, treatment and prognosis of NP involvements. We also determined risk factors of neurological sequelae. Our study showed that new definitions NP involvements and sequelae for childhood period are needed., (Copyright © 2023 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Objective: This study aimed to look for the initial manifestations of juvenile dermatomyositis (JDM), give follow-up results, and search for risk factors for the development of calcinosis., Methods: The files of children with JDM diagnosed between 2005 and 2020 were reviewed retrospectively., Results: The study included 48 children, 33 girls and 15 boys. The mean age at the onset of the disease was 7.6±3.6 years. The median duration of follow-up was 35 (6-144) months. Twenty-nine patients (60.4%) had monocyclic, 7 (14.6%) patients had polycyclic, and 12 (25%) patients had chronic persistent disease course. At the time of enrollment, 35 (72.9%) patients were in remission, while 13 (27.1%) patients had active disease. Calcinosis developed in 11 patients (22.9%). Children having myalgia, livedo racemosa, skin hypopigmentation, lower alanine aminotransferase (ALT) levels, and higher physician visual analog scores at the time of diagnosis had a higher risk for calcinosis. Calcinosis was also more common in children with diagnostic delay and chronic persistent disease course. None of these parameters remained independent risk factors for calcinosis in multivariate logistic regression analysis., Conclusion: The rate of mortality has decreased dramatically over decades in JDM, but the rate of calcinosis has not changed proportionately. Long duration of active, untreated disease is accepted as the main risk factor for calcinosis. We have seen that calcinosis was more common in children having myalgia, livedo racemosa, skin hypopigmentation, lower ALT levels, and higher physician visual analog scores at the time of diagnosis., Competing Interests: No conflict of interest was declared by the authors., (© Copyright 2023 by Istanbul Provincial Directorate of Health.)

Objectives: Behçet's disease (BD) is a systemic vasculitis affecting many organ systems, with the involvement of all-sized arteries and veins. The study aims to determine the main characteristics of paediatric BD patients and also analyse the clustering phenotypes., Methods: Demographic data, clinical manifestations, laboratory features, treatment schedules, and disease outcomes were achieved from patients' charts retrospectively. A cluster analysis was performed according to the phenotype., Results: A total of 225 (109 male/116 female) patients with BD were enrolled in the study. The median ages of disease onset and diagnosis were 131 (36-151) and 156 (36-192) months, respectively. According to cluster analysis, 132 (58.6%) patients belonged to the mucocutaneous-only cluster (C1), while 35 (15.6%) patients fitted to articular type (C2), 25 (11.1%) were in the ocular cluster (C3), 26 (11.6%) were in the vascular cluster (C4), and 7(3.1%) belonged to the gastrointestinal cluster (C5). Ocular and vascular clusters were more common in boys (p < .001), while girls usually presented with the mucocutaneous-only cluster. The disease activity at the diagnosis and the last control was higher in ocular, vascular, and gastrointestinal clusters., Conclusions: These identified juvenile BD clusters express different phenotypes with different outcomes Our analysis may help clinicians to identify the disease subtypes accurately and to arrange personalized treatment., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The objectives of this study were to determine the musculoskeletal (MSK) conditions associated with pediatric psoriasis (Pso) and to evaluate the thickness of Achilles tendon of children with Pso and healthy controls (HCs)., Methods: Pso patients who were followed-up in dermatology outpatient clinic were referred to a pediatric rheumatology center. All patients and healthy peers were evaluated with standardized forms. Both patients and controls underwent ultrasonographic evaluation for Achilles tendon thickness., Results: A total of 55 pediatric Pso and 46 healthy children were included in the study. Of patients with Pso 56.4% had arthralgia, 25.5% had lower back pain, 18.2% had heel pain, 12.7% had hip pain, and 10.9% described morning stiffness. Arthritis was detected in 7.3%, sacroiliac tenderness in 12.7%, and enthesitis in 9.1% of the patients. Arthralgia, lower back pain, and heel pain were significantly frequent in Pso group than healthy children median left and right Achilles tendon thicknesses of Pso patients who were significantly greater than that of HCs prevalence of psoriatic arthritis (PsA) among Pso patients was 7.3%., Conclusion: Evaluation of a child with Pso regularly for the MSK complaints is critical for the early recognition of PsA. Ultrasonography is a useful technique for screening Pso patients for early detection of enthesopaty., Competing Interests: No conflict of interest was declared by the authors., (© Copyright 2023 by Istanbul Provincial Directorate of Health.)

Background: Coronary arterial lesions (CALs) are the major component of Kawasaki disease (KD), associated with significant morbidity, which affect a substantial proportion of patients despite proper treatment. The aim of this study was to define the risk factors for CALs in Turkish children with KD., Methods: Medical records of 399 KD patients from five pediatric rheumatology centers in Turkey were reviewed retrospectively. Demographic, clinical (including duration of fever before intravenous immunoglobulin [IVIG] and resistance to IVIG), laboratory and echocardiographic data were noted., Results: The patients with CALs were younger, had a higher male ratio and a longer duration of fever before IVIG. They also had higher lymphocyte and lower hemoglobin values before the initial treatment. Multiple logistic regression analyses defined the following three criteria as independent risk factors for predicting CALs in Turkish children with KD: age ≤12 months, male gender and duration of fever before IVIG ≥9.5 days. High sensitivity rates of elevated risk of CALs up to 94.5% were calculated despite specificity values falling to 16.5%, depending on which of these three parameters are taken into account., Conclusions: Based on the demographic and clinical features, we established an easily applicable risk-scoring system for predicting CALs in Turkish children with KD. This may be useful for choosing appropriate treatment and follow-up for KD to prevent coronary artery involvement. Further studies will show whether these risk factors can be used in other Caucasian populations as well.

To evaluate the safety profile of measles, mumps and rubella (MMR) booster in children diagnosed with rheumatic diseases receiving biological agents. The study included retrospective safety data of children administered MMR booster dose receiving biologics or biologics with methotrexate. The files of 182 patients were accessed from the pediatric rheumatology biological therapy archive, and the vaccination status of these children was obtained by accessing electronic records. Of 182 patients, 14 patients were vaccinated with MMR booster dose. Thirteen of the patients were followed up with a diagnosis of juvenile idiopathic arthritis and one with colchicine-resistant familial Mediterranean fever. None of the patients had disease exacerbation after vaccination, and three patients had mild side effects consisting of rash, angioedema, joint pain, and fatigue.    Conclusion: This study supports the data regarding evidence of the safety of MMR booster dose administration in children with rheumatic diseases receiving bDMARDs. What is Known: • MMR booster is avoided in immunocompromised pediatric patients receiving bDMARDs except in specific conditions. What is New: • The MMR booster dose may be safe in children with PedRD receiving bDMARDs or bDMARDs with MTX. These bullets can be added to the manuscript., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Growing pains (GP) are the most common cause of recurrent musculoskeletal pain in children. There are no diagnostic criteria for GP. We aimed at analyzing GP-related characteristics and assisting GP diagnosis by using machine learning (ML). Children with GP and diseased controls were enrolled between February and August 2019. ML models were developed by using tenfold cross-validation to classify GP patients. A total of 398 patients with GP (F/M:1.3; median age 102 months) and 254 patients with other diseases causing limb pain were enrolled. The pain was bilateral (86.2%), localized in the lower extremities (89.7%), nocturnal (74%), and led to awakening at night (60.8%) in most GP patients. History of arthritis, trauma, morning stiffness, limping, limitation of activities, and school abstinence were more prevalent among controls than in GP patients (p = 0.016 for trauma; p < 0.001 for others). The experiments with different ML models revealed that the Random Forest algorithm had the best performance with 0.98 accuracy, 0.99 sensitivity, and 0.97 specificity for GP diagnosis. This is the largest cohort study of children with GP and the first study that attempts to diagnose GP by using ML techniques. Our ML model may be used to facilitate diagnosing GP., (© 2022. International Federation for Medical and Biological Engineering.)

To evaluate the vaccine response of treatment-naive juvenile idiopathic arthritis (JIA) patients who were fully vaccinated against Hepatitis B Virus (HBV) and then compare their antibody status with healthy controls. In this multicenter study, initial visit hepatitis B surface antigen (HbsAg) and anti-hepatitis B surface antibody (anti-Hbs) titers of 262 treatment-naive JIA patients who were followed up regularly between May 2015 and October 2019 were evaluated retrospectively from patients' medical records and compared with 276 healthy peers. Both HbsAg and anti-Hbs antibody titers were tested by the ELISA technique. Anti-HBs titers ≥ 10 IU/L were considered as reactive indicating seroprotection against HBV. In the JIA group, seropositivity rate was 59.1% while 72.9% of the control group were immune against HBV (p = 0.002). The median titer for anti-Hbs was 14 (range: 0-1000) IU/L in the patient group and 43.3 (range: 0-1000) IU/L in the control group (p = 0.01). Neither JIA patients nor healthy controls were positive for HbsAg. Patients with JIA vaccinated according to the national vaccination schedule were evaluated at their first visit in pediatric rheumatology outpatient clinics for anti-Hbs presence and it was found that they have lesser seroprotectivity than their age and sex-matched routinely vaccinated, healthy peers. So, to complete missing vaccines and booster vaccine doses, assessing the immune status of the patients at the time of diagnosis against HBV should be in the check-list of physicians dealing with pediatric rheumatic diseases., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Biosimilars have been adopted by clinicians more slowly than anticipated in the post-marketing phase., Objectives: We aimed to reveal the perceptions and attitudes of pediatric rheumatologists towards biosimilars and the obstacles to biosimilar therapy., Methods: A web-based survey designed to determine the knowledge, experience, and perceptions of pediatric rheumatologists about biosimilars was electronically mailed to the participants between April and August 2021. Responses were collected anonymously and subsequently analyzed., Results: A total of 114 pediatric rheumatologists including fellows (32.4%), specialists (29.8%), and seniors (37.7%) responded to the questionnaire. According to the data, 75 (65.8%) physicians had already prescribed at least one biosimilar. The vast majority of participants were aware of the potential cost savings of biosimilars (84, 73.3%). Participants who felt insufficiently informed were 41.8%, 67.6%, and 83.7% among seniors, specialists, and fellows, respectively. In pediatric rheumatology, the scarcity of clinical trials and real-life data (64%) and inadequate information about tolerance to the biosimilars and related side effects in children (49.1%) were the most common barriers expressed by prescribers. Nearly half (45%) of the pediatric rheumatologists preferred to prescribe biosimilars in the treatment of biologic-naive cases. However, most (93%) were reluctant to switch a reference molecule to a biosimilar while the patient was doing well under the originator medicine., Conclusions: This survey provided insights into the concerns about prescribing biosimilars among pediatric rheumatologists. In the field of pediatric rheumatology, further education about biosimilars and real-life experiences is required to better inform about treatment options in children., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Vaccination programs are effective strategies in preventing infectious diseases and controlling epidemics. Vaccination against SARS-CoV-2 in children has not yet been approved globally, and it is unclear what attitude families will take when it is approved in children. We aimed to investigate the underlying causes of vaccine acceptance, hesitation, and refusal, as well as concerns about the acceptability of the COVID-19 vaccine by parents of children with rheumatic diseases., Methods: Parents of children followed up with a diagnosis of rheumatic disease in the pediatric rheumatology outpatient clinic of a university hospital were included in the study. We applied a closed web-based online survey conducted cross-sectionally and sent to the participants via mobile smartphones., Results: For fathers, mothers, and their children, acceptance rates for a COVID-19 vaccine were 64.2%, 57.7%, and 41.8%, respectively. In the multivariate analysis, factors affecting parents' acceptance of vaccines for their children were as follows: "Receiving antirheumatic medications regularly (AOR 5.40, 95% CI 1.10-26.33, p = 0.03), the previous history of getting special recommended vaccines (AOR 4.12, 95% CI 1.12-27.85, p = 0.03), relying on vaccines for ending pandemic (AOR 8.84, 95% CI 2.80-27.85, p = 0.001), complying with the pandemic measures entirely (AOR 5.24, 95% CI 1.46-18.74, p = 0.01)". The two most common reasons for vaccine rejection were fear of the side effects of the vaccine and its possible interaction with rheumatic drugs used by children., Conclusion: According to our survey, parents were more likely to accept a COVID-19 vaccine for themselves than their children. The success of COVID-19 vaccination programs sources highly on people's willingness to accept the vaccine. It is crucial to vaccinate children for achieving herd immunity and in terms of avoiding vaccine hesitancy. Larger data examining the causes of concerns in parents of both healthy children and children with chronic diseases should be delineated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The aims of this study were to compare demographic data, clinical features, and severity scores of familial Mediterranean fever patients carrying E148Q variant with the patients having homozygous pathogenic MEFV mutations and to evaluate both of these groups for the performance of Tel-Hashomer, Livneh, and pediatric diagnostic criteria., Methods: The demographic and clinical data of patients with familial Mediterranean fever either heterozygous or homozygous for E148Q variant (group 1) and patients with homozygous mutations (M694V, M694I, M680I, V726A) (group 2) were collected retrospectively. All patients were evaluated for 3 diagnostic criteria., Results: E148Q variant was present in 128 patients (22.9%), 112 of whom had heterozygous and 16 of whom had homozygous E148Q mutation. Group 2 had 430 patients (77.1%), 372 of whom had homozygous M694V mutation, 50 of whom had homozygous M680I mutation, 5 of whom had homozygous V726A mutation, and 3 of whom had homozygous M694I mutation. Pleuritis, arthritis, recurrent fever, erysipelas-like erythema, and anemia were significantly more common in group 2 than group 1 (p < 0.05). Moderate and severe Pras scores were significantly higher in group 2 (p < 0.001). During attack-free periods, C-reactive protein, erythrocyte sedimentation rate, and serum amyloid A were found significantly higher in group 2 than in group 1 (p < 0.05). The percentage of children diagnosed according to Tel-Hashomer and pediatric criteria was significantly higher in group 2 than in group 1 (p < 0.05). Both groups show similar diagnostic utility by Livneh criteria., Conclusions: Children with the E148Q variant met the 3 diagnostic criteria; they had a milder disease course both clinically and in laboratory means., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent episodes of fever and serositis. Sacroiliitis can be observed in some FMF patients. This study aimed to compare the demographic, clinical, and laboratory findings, and treatment in children with FMF and sacroiliitis, and children with juvenile spondyloarthropathy (JSpA)., Methods: In total, 1687 pediatric FMF patients that were followed-up between May 2010 and June 2020 were evaluated retrospectively. Among them, those with sacroiliitis (n = 63) were included in the study and compared to patients with JSpA (n = 102)., Results: The study included 63 FMF patients with sacroiliitis (38 males [60.3%] and 25 females [39.7%]) with a mean age of 15.2 ± 4.1 years. Mean age at symptom onset was 7.2 ± 5.05 years and mean age at diagnosis was 9.74 ± 4.67 years. The most common mutation in the FMF patients was M694V/M694V (n = 22). Patients were diagnosed with sacroiliitis with a mean of 12 months (range: 6-36 months) after the diagnosis of FMF. Among the FMF patients, 28 (44.4%) had enthesitis, 23 (36.5%) had heel pain, and 11 (17.4%) had low back pain. The study also included 102 JSpA patients (90 males [88.2%] and 12 females [11.8%]). Mean age of patients with JSpA was 16.1 ± 2.8 years. As compared to 102 JSpA patients, patients with FMF and sacroiliitis had higher acute phase reactants, whereas HLA-B27 positivity rate was lower. In addition, axial involvement rate was higher in the JSpA patients., Conclusion: Sacroiliitis is a common co-morbidity in FMF patients. The phenotypic features of these patients are different from patients with JSpA.

Introduction/objectives: The clinicians initially prefer to define patients with the systemic autoinflammatory disease (SAID)'s based on recommended clinical classification criteria; then, they confirm the diagnosis with genetic testing. We aimed to compare the initial phenotypic diagnoses of the patients who were followed up with the preliminary diagnosis of a monogenic SAID, and the genotypic results obtained from the next-generation sequence (NGS) panel., Method: Seventy-one patients with the preliminary diagnosis of cryopyrin-associated periodic fever syndrome (CAPS), mevalonate kinase deficiency (MKD), or tumor necrosis factor-alpha receptor-associated periodic fever syndrome (TRAPS) were included in the study. The demographic data, clinical findings, laboratory results, and treatments were recorded. All patients were examined by NGS panel analysis including 16 genes. The genetic results were compared with the initial Federici score to determine whether they were compatible with each other., Results: Thirty patients were initially classified as MKD, 22 as CAPS, and 19 as TRAPS. The frequency of clinical manifestations was urticarial rash 57.7%, diarrhea 49.2%, abdominal pain 47.8%, arthralgia 45%, oral aphthae 43.6%, myalgia 32.3%, tonsillitis 28.1%, and conjunctivitis 25.3%, respectively. After NGS gene panel screening, 13 patients were diagnosed with CAPS, 8 with MKD, 7 with familial Mediterranean fever, 5 with TRAPS, and 2 with NLRP12-associated periodic syndrome. The remaining 36 patients were genetically identified as undefined SAID since they were not classified as one of the defined SAIDs after the result of the NGS panel., Conclusions: We have demonstrated that clinical diagnostic criteria may not always be sufficient to establish the correct diagnosis. There is still low accordance between clinical diagnoses and molecular analyses. In the case of a patient with a preliminary diagnosis of a monogenic SAID with the negative result of target gene analysis, other autoinflammatory diseases should also be kept in mind in the differential diagnosis. Key Points • Monogenic autoinflammatory diseases can present with different clinical manifestations. • The clinical diagnostic criteria may not always be sufficient to reach the correct diagnosis in autoinflammatory diseases. • In the case of a patient with a preliminary diagnosis of a monogenic SAID with the negative result of target gene analysis, other autoinflammatory diseases should be kept in mind in the differential diagnosis.

There is no single diagnostic test for any rheumatic disease. The diagnosis of a rheumatic disease is made by the sum of the findings in history, physical examination, laboratory, and imaging tests. A differential diagnosis list in pediatric rheumatology is quite long and mainly includes malignant, infectious, and inherited metabolic disorders. We aim to present cases that were referred to a pediatric rheumatology outpatient clinic with provisional diagnosis of a rheumatic disease but finally diagnosed with a non-rheumatic disease in order to emphasize the importance of differential diagnoses. Eight cases were presented in this manuscript. Five cases were referred with the provisional diagnosis of juvenile idiopathic arthritis. Sarcoidosis, chronic non-bacterial osteomyelitis, and autoinflammatory disease were the provisional referral diagnoses in three patients. Definitive diagnoses of the patients were as follows: acute lymphoblastic leukemia (two cases), bilineage acute leukemia, Hodgkin lymphoma, brucellosis, mucolipidosis type III, anhidrotic ectodermal dysplasia, and Freiberg disease. In children presenting with rheumatic complaints malignant, infectious and inherited metabolic disorders should always be in the differential diagnosis list of a pediatric rheumatologist. Alternative diagnoses should always be considered even in patients with a rheumatic disease when the patient does not respond to treatment or follows an unusual clinical course. Key Points • Diagnosis of a rheumatic disease is made by exclusion of all other pathologies. • Malignant and infectious diseases may mimic the signs and symptoms of a rheumatic disease.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease manifesting with phenotypic heterogeneity. The phenotype-genotype correlation is not established clearly yet. Furthermore, some comorbidities such as vasculitis and inflammatory arthritis may accompany FMF. Herein, we aimed to define phenotype-genotype correlation and comorbid diseases of children with FMF. The medical records of 1687 children diagnosed and followed up as FMF were reviewed retrospectively. Disease severity was assessed by PRAS score. A total of 1687 children (841 girls, 846 boys) were involved in the study. The mean ± standard deviation of current age, age at symptom onset, and age at diagnosis were 13.1 ± 5.4, 5.4 ± 4, and 8 ± 4.2 years, respectively. Median (min-max) follow-up period was 3 (0.5-18) years. Among them, 118 (7%) patients had at least one concomitant disease and 72% of them were carrying at least one M694V mutation. Patients with a concomitant disease expressed a more severe course of disease when compared to ones without a concomitant disease (23.7% vs 8.8%, p < 0.001). Children carrying homozygous M694V mutation had significantly earlier age of disease onset and severe disease course (p < 0.001). Forty-four patients (2.6%) were colchicine resistant and most of them were carrying homozygous M694V mutation. Sixteen colchicine-resistant patients were treated with anakinra while 28 received canakinumab. Juvenile idiopathic arthritis (JIA) and immunoglobulin A vasculitis were the most commonly seen associated diseases and the patients with a concomitant disease demonstrated more severe course. This is the largest pediatric cohort studied and presented since now. We confirmed that carrying M694V mutation is associated both with a severe disease course and a predisposition to comorbidities.

Juvenile-onset systemic lupus erythematosus (jSLE) patients typically have a more severe disease course than adults with SLE. We aimed to assess the prevalence and disease course of jSLE patients carrying MEFV variants. MEFV variant analyses were performed in 44 jSLE patients and effect of these variants on disease severity and course was analyzed by SLEDAI score and SLICC/ACR index. Ten of the patients (22.7%) had a MEFV variant. The median (min-max) SLEDAI score and SLICC/ACR index were 2(0-13) and 0(0-3), respectively. Median age at disease onset, disease duration, SLICC/ACR indexes, SLEDAI scores, clinical and laboratory findings of the patients were comparable in carriers of variants and non-carriers. Nineteen patients (43.2%) had biopsy-proven lupus nephritis and four of these patients had MEFV variants. There was no significant difference between patients with and without MEFV carriers in terms of lupus nephritis. Even though not significant statistically, renal involvement was milder in MEFV carriers than non-carriers. The presence of MEFV variants does not increase the overall susceptibility to jSLE in our cohort, while larger number of patients is required to display the protective role of MEFV variants in jSLE.

Objective: The aim of this observational study was to evaluate whether there was any correlation between the acute phase reactants in children with familial Mediterranean fever (FMF) during attack and attack-free periods., Methods: The study was conducted between June 2016 and January 2018. Clinical features and laboratory parameters of children with FMF during attack and attack-free periods were recorded longitudinally., Results: The cohort consisted of 168 children with FMF (84 boys, 84 girls). Median values of acute phase reactants during FMF attacks were 433.5 mg/L (34.0-1780.0 mg/L) for serum amyloid A (SAA), 56.7 mg/L (7.6-379.0 mg/L) for C-reactive protein (CRP), and 37.5 mm/h (5-100 mm/h) for erythrocyte sedimentation rate (ESR). Median values for the same tests in attack-free periods were 3.2 mg/L (0.1-25.0 mg/L), 1.7 mg/L (0.1-12.7 mg/L), and 8 mm/h (1-30 mm/h), respectively. Correlation analyses showed that SAA and CRP were highly correlated in FMF attack (r = 0.67, p < 0.01), but no correlation was found between SAA and ESR levels. C-reactive protein was elevated in 13.6%, ESR in 20.8%, and SAA in 28.5% of the patients during attack-free period. Age at onset, sex of the patients, and characteristics of attacks were found to be not associated with elevated SAA in attack-free period. On the other hand, having homozygous exon 10 mutation and having elevated CRP were found to be associated with high SAA in attack-free period., Conclusions: C-reactive protein and SAA correlate well with FMF attacks. Therefore, checking for SAA during a FMF attack is not required. However, SAA seems to be the most sensitive method for demonstrating subclinical inflammation in attack-free period. Thus, checking SAA levels might be a valuable tool in selected FMF patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Systemic autoinflammatory diseases (SAIDs) may not always present with typical clinical findings of a monogenic disease. We aimed to genetically screen and diagnose these clinically unclassified patients by next-generation sequencing (NGS) analysis., Method: A total of 64 patients who had clinical findings of a periodic fever syndrome but did not meet the clinical diagnostic criteria for any SAID or had clinical findings for more than one monogenic SAID were identified as "clinically unclassified SAIDs." NGS panel analysis, including 16 genes, was performed in these patients. Patients, who could not be classified as one of the defined SAID after the result of the NGS gene analysis, were identified as "undefined SAID.", Results: The most common autoinflammatory symptoms in unclassified SAID patients were abdominal pain (60.9%), arthralgia (48.4%), urticarial rash (43.8%), myalgia (40.6%), oral aphthae (28.1%), and conjunctivitis (20.3%), respectively. In the result of the NGS gene panel screening, pathogenic, likely pathogenic variants, or VUS (variants of uncertain significance) were detected in 36 of 64 patients in at least one gene in the NGS panel. A total of 15 patients were diagnosed with a monogenic SAID according to both phenotypic and genotypic data; 12 patients as FMF, two patients as FCAS, and one patient as TRAPS, respectively. A total of 49 patients who did not meet the classification criteria including genetic results for a monogenic SAID were followed as undefined SAID., Conclusions: The classification criteria described for SAIDs so far unfortunately do not cover all patients with signs of periodic fevers. The NGS gene panel appears to be a useful diagnostic tool for some of the patients with clinically unclassified SAID findings. Key Points • The classification criteria described for SAIDs do not cover all patients with signs of periodic fevers • The use of the undefined SAID nomenclature will benefit clinicians for diagnosis and initiating early treatment • The NGS panel appears to be a useful diagnostic tool in patients with clinically unclassified SAIDs.

Objective: Dermatological findings may be the sole complaints of diseases in pediatric rheumatology practice. Evaluating patients with a multi-disciplinary approach may facilitate access to an accurate diagnosis. Herein, we reported our one-year experience in collaborative pediatric rheumatology-dermatology., Methods: Patients were initially evaluated separately in pediatric rheumatology-dermatology outpatient clinics. Subsequently, once a week, the final diagnoses of patients with suspected skin rash were collaboratively discussed by two pediatric rheumatologists and a dermatologist., Results: A hundred and one patients were included in this study. Of these 101 patients, 65 attended to dermatology outpatient clinic initially, while the remaining 36 applied to the pediatric rheumatology outpatient clinic. The most common mucocutaneous finding was squamous lesions in 30 patients, followed by erythematous lesions in 28 and mucosal ulcers in 14. Finally, 69 patients were diagnosed with a rheumatic disease while 32 had differential diagnoses apart from rheumatic diseases., Conclusion: Patients with rheumatologic diseases frequently present with only mucocutaneous findings. Thus, a detailed examination of the mucosa, skin and its attachments is of paramount importance in rheumatology practice. We suggest that a close interaction between pediatric rheumatology-dermatology and the formation of consensus clinics are going to assist clinicians in making easier and accurate diagnoses., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (Copyright: © 2021 by Istanbul Northern Anatolian Association of Public Hospitals.)

Introduction: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of idiopathic inflammatory arthritis affecting children younger than 16 years of age. Tocilizumab (TCZ) is a humanized anti-interleukin 6 (IL-6) receptor antibody that was approved for systemic and polyarticular JIA patients. However, the studies regarding patients' satisfaction while receiving TCZ therapy is scarce. Herein, we aimed to evaluate the effect of subcutaneous (SC) TCZ administration on patient satisfaction and disease control of JIA patients., Methods: All JIA patients receiving TCZ were included in the study. Clinical features, laboratory findings and JADAS71 scores were recorded at baseline and every 3 months during follow-up. Nine of the patients on intravenous (IV) TCZ treatment were switched to SC form. All patients receiving TCZ-SC were questioned by a clinical nurse specialist (CNS) to assess patient satisfaction., Results: A total of 39 patients receiving TCZ were included in the study. Among them, treatment of nine patients (five female, four male) was switched to SC form with a median of 11.5 (8-69) months after initiation of TCZ. Patients were stable both clinically and in laboratory means at the 3rd month of TCZ-SC treatment. There was no deterioration in terms of active joint counts, physician's VAS, patient's VAS and JADAS71. According to patient satisfaction questionnaire, eight of the patients felt satisfied with SC administrations in terms of life quality, school success and reduced school absenteeism. However, one patient did not agree that the SC form is as effective as IV form and wanted to continue with IV form., Conclusion: TCZ is an effective treatment option in JIA and switching from IV to SC route when necessary is found to be an effective and acceptable alternative by the patients as well.

Purpose of Review: Antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are autoimmune diseases that can affect multiple organ systems. Increased awareness and new treatment strategies ultimately improved the survival of patients, and disease-related comorbidities became more important. The purpose of this review is to focus on comorbidities in these diseases that had a negative influence on the course of the disease., Recent Findings: There are limited numbers of studies regarding to comorbidities associated with these diseases during childhood. Infections were found to be the most common comorbidity as a result of immunosuppressive agents and dysregulations of the immune system. Other common comorbidities after infections are cardiovascular and cerebrovascular diseases as important causes of mortality and morbidity. In addition, the risk of malignancies, ophthalmologic manifestations, neurologic and renal diseases, musculoskeletal diseases such as vitamin D deficiency, low bone mineral density, and the risk of avascular necrosis were increased in both patient groups. For clinicians, it is important to be aware of the comorbidities that may develop during follow-up of APS and SLE patients. Further studies will shed more light on the comorbidities of these diseases.

Objective: Juvenile idiopathic arthritis (JIA) is the most common cause of chronic arthritis in children. Biologics have changed the faith of children with rheumatic diseases. The main objective of this study was to demonstrate the rate of usage, efficacy and safety of biologics in JIA subtypes., Methods: This retrospective observational cohort study was conducted between May 2010 and September 2017. All children with the diagnosis of JIA and children under a biological agent treatment were recorded into the local registry system. Age, gender, JIA subtype, medications used, the clinical status of the patient, tuberculosis screening results, and side effects observed under biologics were retrieved from the registry., Results: There were 405 patients with the diagnosis of JIA in the cohort. Biologics were used in 123 (30.3%) JIA patients. Subtype frequencies of JIA patients were as follows: persistent oligoarticular JIA (33.6%), enthesitis-related arthritis (29.2%), systemic JIA (13%), rheumatoid factor (RF)-negative polyarticular JIA (13%), extended oligoarticular JIA (4.2%), RF-positive polyarticular JIA (3.4%), psoriatic arthritis (1.8%) and unclassified arthritis (1.8%). The rate of biologic use was high in extended oligoarticular JIA (64.7% of the cases), RF-positive polyarticular JIA (57.1%), psoriatic arthritis (57.1%), RF-negative polyarticular JIA (41.5%), and in systemic JIA (39.6%). Enthesitis-related arthritis (27.1%), persistent oligoarticular JIA (17.6%) and unclassified arthritis (16.6%) patients were the cases that needed a biologic agent in the last order. At the last control, 78.9% of the cases were in remission, while 21.1% of them were active despite biologic treatment. Isoniazid prophylaxis was used in 30.8% of the patients. None of the patients developed active tuberculosis infection under prophylaxis. Adverse events were observed in 18.6% of patients under biologics as recurrent uncomplicated upper respiratory tract infections being the most common., Conclusion: Biologics are safe and effective treatment options in children with JIA. Most of the JIA patients with polyarticular involvement require biologics earlier in the disease course. The risk of tuberculosis infection seems not to be increased after appropriate screening and prophylaxis., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (Copyright: © 2020 by Istanbul Northern Anatolian Association of Public Hospitals.)

Background: LPS-responsive beige-like anchor (LRBA) deficiency presents with susceptibility to infections, autoimmunity, and lymphoproliferation. The long-term efficacy of cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin (abatacept) as targeted therapy for its immune dysregulatory features remains to be established., Objective: To determine the clinical and immunologic features of LRBA deficiency and long-term efficacy of abatacept treatment in controlling the different disease manifestations., Methods: Twenty-two LRBA-deficient patients were recruited from different immunology centers and followed prospectively. Eighteen patients on abatacept were evaluated every 3 months for long-term clinical and immunologic responses. LRBA expression, lymphocyte subpopulations, and circulating T follicular helper cells were determined by flow cytometry., Results: The mean age of the patients was 13.4 ± 7.9 years, and the follow-up period was 3.4 ± 2.3 years. Recurrent infections (n = 19 [86.4%]), immune dysregulation (n = 18 [81.8%]), and lymphoproliferation (n = 16 [72.7%]) were common clinical features. The long-term benefits of abatacept in 16 patients were demonstrated by complete control of lymphoproliferation and chronic diarrhea followed by immune dysregulation, most notably autoimmune cytopenias. Weekly or every other week administration of abatacept gave better disease control compared with every 4 weeks. There were no serious side effects related to the abatacept therapy. Circulating T follicular helper cell frequencies were found to be a reliable biomarker of disease activity, which decreased on abatacept therapy in most subjects. However, high circulating T follicular helper cell frequencies persisted in 2 patients who had a more severe disease phenotype that was relatively resistant to abatacept therapy., Conclusions: Long-term abatacept therapy is effective in most patients with LRBA deficiency., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Juvenile idiopathic arthritis is the most common chronic rheumatic disease of childhood resulting in disability in untreated cases. Disease modifying anti-rheumatic drugs form the first-line treatment in JIA. However, the data about leflunomide (LFN) in treatment of JIA is limited. We reviewed the medical files of JIA patients who were followed-up regularly and had received LFN. A total of 38 patients were included to the study. Among them, 24 had oligoarticular JIA, eleven had polyarticular JIA, two had ERA and one had psoriatic arthritis. 36 were initially treated with methotrexate and two patients diagnosed with ERA were treated with sulfasalazine. Sulfasalazine treatment was switched to LFN due to inadequate response at the 3rd month of therapy. Methotrexate was ceased due to gastrointestinal intolerance in 36 patients. Of these 36 patients, 19 patients had either low disease activity (n = 13) or remission (n = 6). LFN was administered to 13 patients with low disease activity. During the follow-up of the six patients in remission, relapse ensued and LFN treatment was started. The remaining 17 patients had moderate (n = 10) or high (n = 7) disease activity requiring biologic agents. But due to inadequate response to biologic agents, LFN was added to the therapy. All of the patients were clinically inactive at the last visit. Only two adverse events resolving within 2 weeks were noted (Lymphopenia = 1, elevated liver enzymes = 1). LFN may be an alternative therapy in case of MTX intolerance or toxicity.

Objectives: To develop and assess the validity and reliability of an adherence scale concerning medical treatment in paediatric FMF patients., Methods: The Medication Adherence Scale in FMF Patients (MASIF) is a 18-item questionnaire that evaluates adherence to medication in four domains. Validation of the instrument was accomplished in paediatric FMF patients (aged 2-18 years) under medication at least for 6 months. The first step was to build up the scale through qualitative approach (with interviews using semi-structured questions). Validation analyses included assessment of feasibility, face and content validity; construct validity, internal consistency and test-retest reliability., Results: One hundred and fifty patients with FMF were enrolled in the study. The mean age of the patients was 11.11±4.02 years and 48.7% of them were male. The MASIF was found to be feasible and valid for both face and content. It correlated with the Morisky Medication Adherence Scale as a gold standard thereby demonstrating good construct validity (r=0.515, p<0.001). Assessment of content validity identified four subscales. The internal consistency, Cronbach's alpha was 0.728. There was a positive and significant correlation between test and retest scores (r=0.843; p<0.001). Also, a significant correlation between parents' and children's reports (r=0.781, p<0.001)., Conclusions: Based on these results, the use of this scale to assess and follow up the adherence to treatment in paediatric FMF patients under medical treatment is recommended.

Objectives: The aim of the study was to compare the cochlear functions of children diagnosed with familial Mediterranean fever (FMF) with healthy controls and to determine their cochlear functions according to their disease severity., Methods: Seventy-three children with FMF and 30 healthy controls were included in the study. All the patients and controls were evaluated by audiologic evaluation, including high-frequency pure-tone audiometry and distortion product otoacoustic emission tests (DPOAE). The disease severity was evaluated by scoring systems adapted from those used by Pras et al. and with severity scoring systems from the Sheba Medical Center., Results: High-frequency pure-tone audiometry and DPOAE levels were normal in both patients and controls. Significant differences in the hearing levels of FMF patients were not found, according to both adapted severity scoring systems., Conclusions: Cochlear functions in children with FMF had been evaluated by previous studies, but in our study we evaluated hearing functions according to both controls and disease severity. As a unique study comparing cochlear functions according to severity scores, no significant differences were shown between the groups and controls., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Childhood systemic vasculitides are a group of rare diseases with multi-organ involvement and potentially devastating consequences. After establishment of new classification criteria (Ankara consensus conference in 2008), it is now time to establish measures for proper definition of activity and damage in childhood primary vasculitis. By comparison to adult vasculitis, there is no consensus for indices of activity and damage assessment in childhood vasculitis. Assessment of disease activity is likely to become a major area of interest in pediatric rheumatology in the near future. After defining the classification criteria for primary systemic childhood vasculitis, the next step was to perform a validation study using the original Birmingham vasculitis activity score as well as the disease extent index to measure disease activity in childhood vasculitis. Presently, there are efforts in place to develop a pediatric vasculitis activity score. This paper reviews the current understanding about the assessment tools (i.e., clinical features, laboratory tests, radiologic assessments, etc.) widely used for evaluation of the disease activity and damage status of the children with vasculitis.

Objectives: To analyse the demographics, main clinical and laboratory features and subtype distribution of juvenile idiopathic arthritis (JIA) in an eastern Mediterranean country, based on a multicentre registry., Methods: Between March 2008 and February 2009 with this cross-sectional study, consecutive patients seen with JIA in selected centres were registered through a web-based registry. All patients were classified according to the International League of Associations for Rheumatology (ILAR) criteria., Results: There were 634 patients with a mean age of 11.84 ± 4.66 years and the female/male ratio was 1.2. The distributions of JIA patients according to onset of disease were as follows: systemic 92 (14.5%), oligoarticular extended 26 (4.1%), oligoarticular persistent 234 (36.9%), rheumatoid factor (RF) positive polyarthritis 20 (3.2%), RF negative polyarthritis 129 (20.3%), enthesitis-related 120 (18.9%), psoriatic 13(2.1%). The frequency of uveitis was 15.7% among all of the oligoarthritis patients. Anti-nuclear antibody (ANA) was positive mainly among the oligoarticular onset patients. Twenty-one patients also had Familial Mediterranean fever (FMF). Among systemic JIA patients, the frequency of macrophage activation syndrome (MAS) was 15.2% (n=14). At the end of the mean follow-up of 7.6 ± 4.4 years, 305 (48.1%) patients were defined to have inactive disease on medication, and 106 (16.7%) were completely free of any disease symptoms without medication., Conclusions: Enthesitis related arthritis had a high frequency whereas psoriatic arthritis was very rare compared to other series. We suggest that there are certain differences in the characteristics of JIA in our eastern Mediterranean population. Thus, genetic studies need to be assessed in these populations separately and findings of genome wide association studies need to be confirmed in different populations.