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Purpose 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.Methods 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.Results 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 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.

In the evaluation of children with Kawasaki disease (KD), the age of onset is important and complications may occur if the distinctive features are not assessed accordingly. The objective of the study is to define the clinical and laboratory presentations and treatment outcomes of KD in infants ≤6 months of age compared to those >6 months multicentrically. This retrospective study reviewed the medical records of the patients diagnosed with KD and followed up between January 2009 and January 2019. A total of 204 KD patients were enrolled and grouped according to age as Group I (≤6 months, n = 31) and Group II (>6 months, n = 173). Except for cervical adenopathy (19.3% vs. 47.4%, p = 0.03), the major clinical manifestations of KD were similar between groups I and II. However, the frequency of incomplete and atypical KD was higher in Group I (38.7% vs. 24.8%, p = 0.04, 38.7% vs. 8.1% p < 0.001, respectively). Clinical features such as vomiting/diarrhea (19.3% vs. 1.1% p < 0.001), aseptic meningitis (19.3% vs. 2.3%, p = 0.001) were more common in Group I. Percentage of neutrophils (45.5 vs. 36, p = 0.004) and hemoglobin levels (8 vs. 10.5 gr/dL, p = 0.02) were statistically lower and platelet count (737,000 vs 400,000/mm3, p = 0.004) was statistically higher in group I. Coronary artery lesions (CALs) were more common in Group I (48% vs. 20%, p < 0.001). Harada and Kobayashi scores appear to be effective in predicting coronary artery lesions (CALs) and IVIG resistance in the entire cohort. There was no diagnostic delay in group I (5.5 vs 6.5 days, p = 0.88). Since clinical presentations and laboratory features of KD may vary with age, and the frequency of atypical and incomplete presentations is high, awareness of KD in young children should be raised among pediatricians.

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

Introduction Transition is a planned process of pediatric patients from child-centered to adult-oriented treatment. Transitional care for patients with chronic diseases is essential. The present study aimed to evaluate the readiness of patients with rheumatic diseases and their parents for transition process. Method This is a cross-sectional, single-center study. All patients and their parents were questioned about their awareness of and willingness to undergo transitional care. Transition Readiness Assessment Questionnaire (TRAQ) was applied to all the participants. TRAQ is a tool for measuring readiness for transitional care in adolescents with chronic diseases. TRAQ includes 20 items that are divided into 2 domains: self-management and self-advocacy. Results A total of 157 (87 girls/70 boys) patients and their parents were enrolled. Of them 64 were diagnosed with familial Mediterranean fever, 52 with juvenile idiopathic arthritis, 21 with systemic lupus erythematosus, and 20 with Behcet's disease. The median age of the patients was 16 years (15-18). However, all patients and parents accepted that transition to adult-oriented care is necessary; only one-third of them were aware about transitional care. Eighty (50.9%) patients and 147 (93.6%) of the parents stated that they were wishing to continue pediatric rheumatology treatment. The mean TRAQ self-management domain and self-advocacy domain total scores in the patients were 1.76 ± 0.51 and 1.72 ± 0.49, respectively (P = .48). The mean TRAQ total score was not different between patients and parents. When we assessed the factors affecting transition process, the TRAQ score was lower among patients with active disease, and requiring hospitalization during the previous year. Conclusion Assessment od the readiness of patients with chronic rheumatic diseases for transition care will increase the awareness of patients and their parents as well, and provide determination of the optimal time for transition.

Behçet's disease (BD) is a variable vessel vasculitis which is rare in children.We aimed to compare the main characteristics of pediatric BD patients from Turkey versus Israel.Three centers from Turkey and two centers from Israel participated in this study. The BD diagnosis was before 16 years of age and based on expert opinion. Disease activity was assessed with BD current activity form (BDCAF).A total of 205 patients were included (165 from Turkey; 40 from Israel). HLA-B51 positivity (68.3% vs. 46.2%, p = 0.028), male gender (52% vs. 30%, p = 0.012), and skin involvement (55.2% vs. 22.5%, p0.001) were more frequent among patients from Turkey compared to patients from Israel. Tests of pathergy and HLA-B51 were more frequently performed in patients from Turkey than patients from Israel (93.3% vs. 32.5%, p0.001 and 97.6% vs. 65%, p0.001; respectively). For BD classification in the whole group, International Criteria for BD (ICBD) had the highest sensitivity (73.2%), followed by pediatric BD (PED-BD) (47.8%), and The International Study Group (ISG) (42%) criteria sets. The most commonly prescribed drug was colchicine in the whole group (96.6%). Significantly more patients were treated with corticosteroids (50% vs. 28.5%, p = 0.006), methotrexate (17.5% vs. 3%, p = 0.002), and nonsteroidal anti-inflammatory drugs (12.5% vs. 1.8%, p = 0.007) in Israel than in Turkey. The median BDCAF values were higher at the first visit for patients from Turkey compared to those in Israel (4 vs. 2, p0.001).This is the largest cohort of pediatric BD reported to date. The disease characteristics significantly differ among pediatric BD patients from Turkey and Israel, which may be due to different ethnicity and environmental factors.

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.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."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.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.

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. 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. 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. 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.

Since the Syrian civil war in 2011, an estimated number of 3.6 million Syrian refugees crossed into Turkey, and almost half of them were children. The distribution of rheumatic diseases in Syrian refugee children is not known. The aim of this study was to describe the profile of rheumatic diseases in Syrian refugee children living in Turkey. The demographic data, clinical and laboratory findings, medications, complications and outcome results of Syrian refugee children who had visited Pediatric Rheumatology Departments of University of Health Science Kanuni Sultan Süleyman Research and Training Hospital, Ümraniye Research and Training Hospital, Şanlıurfa Research and Training Hospital, and Cengiz Gökçek Maternity and Gynecology Hospital between April 1, 2011, and September 1, 2019, were evaluated retrospectively. A total of 151 patients were included in the study. Among them, 51 patients had juvenile idiopathic arthritis (JIA), 49 had familial Mediterranean fever (FMF), 43 had vasculitis, and 8 had connective tissue diseases. Homozygous M694V mutation was the most common mutation among FMF patients. Oligoarticular JIA (41.2%) was the most frequent type of JIA, and enthesitis-related arthritis (ERA) (27.5%) was the second one. The frequency of systemic JIA was 11.8%. One patient with SLE died due to complicated meningitis. This is the first study evaluating the distribution of rheumatic diseases in Syrian refugee children. Clinical follow-up of rheumatologic diseases is difficult in Syrian refugees due to language barriers, social and cultural differences. Health care systems should be well organized to provide appropriate care to asylum seekers.

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

Background Although not validated fully, recommendations are present for diagnosis, screening and treatment modalities of patients with familial Mediterranean fever (FMF). Objective To review the current practices of clinicians regarding FMF and reveal their adherence to consensus guidelines. Methods Fifteen key points selected regarding the diagnosis and management of FMF were assessed by 14 paediatric rheumatologists with a three-round modified Delphi panel. Results Consensus was reached on the following aspects: genetic analysis should be ordered to all patients when clinical findings support FMF, but its result is not decisive alone. In the absence of clinical features, colchicine should be commenced when two pathogenic alleles and family history of amyloidosis are present. Serum amyloid A testing at each visit is recommended in patients resistant to colchicine, with subclinical inflammation and family history of amyloidosis. Consensus was reached on both the definition of colchicine resistance and starting biologic in resistant cases. Cost, efficiency, ease of use, treatment adherence, accessibility and emergence of adverse events are the factors affecting the choice of biologic agents. In patients without any attack and evidence of subclinical inflammation within the last 6 months following initiation of biologics, treatment dose intervals can be prolonged. Conclusion A consensus was achieved regarding the routine diagnosis and screening and treatment of FMF patients. The definition of colchicine resistance was made and a protocol was created for prolongation of treatment intervals of biologic agents. We anticipate that the results of the study reveal real-life data on the approach to patients in clinical practice. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-020-04776-1.

Objectives To determine the rate of achieving The Lupus Low Disease Activity State (LLDAS) in children with systemic lupus erythematosus (SLE) for tracing pertinent treatment modalities. Methods A total of 122 juvenile-onset SLE (jSLE) patients from six pediatric rheumatology centers in Turkey were enrolled in the study. LLDAS-50 was defined as encountering LLDAS for at least 50% of the observation time. According to the achievement of LLDAS-50, clinical features, immunological profiles, and treatments of patients with jSLE have been revealed. Results LLDAS of any duration was achieved by 82% of the cohort. Although only 10.8% of the patients achieved remission, 68.9% reached LLDAS-50. A significant difference was found between patients who reached LLDAS-50 and those who did not, in terms of the time to reach low-dose corticosteroid treatment ( p = 0.002), the presence of subacute cutaneous findings ( p = 0.007), and the presence of proteinuria ( p = 0.002). Both of the groups were under similar treatment approaches. However, the number of patients being treated with corticosteroids at the last visit was found to be significantly higher in patients who achieved LLDAS-50 ( pConclusion Targeting LLDAS in jSLE, even with long-term, low-dose corticosteroid use, seems to be an achievable goal in clinical practice.

To compare the clinical and laboratory findings of multisystem inflammatory syndrome in children (MIS-C), patients with Kawasaki disease (KD) and with macrophage activating syndrome due to systemic juvenile idiopathic arthritis (sJIA-MAS) on real-life data. Patients diagnosed with MIS-C, KD, and sJIA-MAS from 12 different centers in Turkey who were followed for at least 6 months were included in the study. Demographic, clinical, and laboratory findings of all patients were analyzed. A total of 154 MIS-C, 59 KD, and 31 sJIA-MAS patients were included. The median age of patients with MIS-C were higher than those with KD while lower than those with sJIA-MAS (8.2, 3, 12 years, respectively). Myalgia (39.6%), cardiac (50.6%), gastrointestinal (72.7%), and neurological (22.1%) involvements were more common in patients with MIS-C compared to others. MIS-C patients had lower levels of lymphocyte (950 vs 1700 cells/µl) and thrombocyte (173,000 vs 355,000 cells/µl) counts and higher pro-BNP (1108 vs 55 pg/ml) levels than KD. Ferritin levels were higher in patients with MIS-C compared to patients with KD while they were lower than patients with sJIA-MAS (440, 170, 10,442 ng/ml, respectively). Patients with MIS-C had a shorter duration of hospitalization than sJIA-MAS (p = 0.02) while they required intensive care unit admission more frequently (55 vs 8 patients, p < 0.001). The median MAS/sJIA score of MIS-C patients was ? 1.64 (? 5.23 to 9.68) and the median MAS/sJIA score of sJIA-MAS patients was ?2.81 ([? 3.79] to [? 1.27]). MIS-C patients displayed certain differences in clinical and laboratory features when compared to KD and sJIA-MAS. Definition of the differences and similarities between MIS-C and the other intense inflammatory syndromes of childhood such as KD and MAS will help the clinicians while making timely diagnosis. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

To define the demographic, clinical and genetic features of familial Mediterranean fever (FMF) patients with early disease onset and to compare them with late-onset FMF patients.Patients were divided into two groups according to the age of disease onset: group 1 includes the patients who had their first attack ≤3 years of age; group 2 consisted of patients who had their first attack3 years of age. Furthermore, we compared the proportion of patients fulfilling the three diagnostic criteria among two groups.Of 1687 patients, 761 had first FMF attack at ≤3 years of age while 926 patients presented with their first manifestation of FMF at3 years. Delay in diagnosis, fever and peritonitis were significantly higher in group 1. Frequency of arthritis, erysipelas-like erythema, non-nephrotic proteinuria, incomplete attacks, chronic arthritis, arthralgia and mean colchicine dose were significantly higher in group 2. Mean Pras score was higher and the presence ofAlthough patients with early disease onset seem to have more severe disease course, they are more likely to have a delay in diagnosis. To avoid the diagnostic delay, clinicians should be aware of the findings of FMF in early age.

Parenteral treatments (either subcutaneous or intravenous) are frequently used in rheumatology practice. In this study, drug side effects in patients who were followed up with a rheumatic disease and treated with parenteral administration methods were evaluated. The drug side effects in children who were followed up with a rheumatic disease and treated with parenteral treatments between 2010 and 2019 were recorded, retrospectively. All parenteral treatments are applied by a clinical nurse specialist (CNS) who is experienced in pediatric rheumatology for 10 years. Four hundred and thirteen patients were evaluated in this study. The mean age was 12.09 ± 5.05 years. Most of them were diagnosed with juvenile idiopathic arthritis (n = 317) and colchicine-resistant familial Mediterranean fever (n = 57). Among the patients, 287 was treated with methotrexate, 130 with etanercept, 90 with adalimumab, 71 with anakinra, 64 with canakinumab, 55 with tocilizumab, seven with rituximab, six with infliximab, and four with abatacept. Two of the patients had a history of drug allergy (ceftriaxone = 1, ranitidine = 1). The most common adverse reactions were as follows: nausea-vomiting in 52, rash in 11, itching in three, chest tightening in two, bruising in two, headache in two, and abdominal pain in one of the patients. Drug side effects were observed after an average of three (1-4) administrations. Antihistaminic and steroids (tocilizumab = 3, infliximab = 1, methotrexate = 1) were administered to five patients due to hypersensitivity reactions. Considering the possible side effects and preparation protocols of parenteral treatments, experienced physicians and nurses are required in the field.

Isotretinoin is the mainstay treatment in severe acne; however, its musculoskeletal adverse effects such as lower-back pain can be disabling. Herein, we present four cases of isotretinoin-induced sacroiliitis with variable severity. We also present a review of the literature of isotretinoin-induced sacroiliitis. All our cases were male and human leukocyte antigen (HLA)-B27 negative. Sacroiliitis was detected a median of 55 (10-120) days after isotretinoin initiation. Two patients were responsive to baseline sulfasalazine and indomethacin treatment, while the other two patients required more intensive treatments: adalimumab in one and methotrexate in the other. We also identified 15 articles describing 33 patients (17 of whom were female) with isotretinoin-induced sacroiliitis. Most of them were responsive to low-to-medium doses of systemic steroids or non-steroidal anti-inflammatory drugs (NSAIDs). Our patients illustrate that severity of isotretinoin-induced sacroiliitis varies from patient to patient.

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.

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.

Objectives: The aim of this study was to demonstrate the frequency of macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis (sJIA) cases, to compare the laboratory tests at...

To determine the capability of serum amyloid A (SAA) in differentiating attacks of familial Mediterranean fever (FMF) from acute febrile upper respiratory tract infections.Children diagnosed with FMF during febrile attacks were recorded as the patient group. The control group consisted of children with febrile upper respiratory tract infections. Complete blood count, serum amyloid A (SAA), C-reactive protein (CRP), and erythrocyte sedimentation rate were recorded in both groups during febrile episodes.The cohort consisted of 28 children with FMF attack and 28 previously healthy children with acute febrile infection. While CRP and SAA levels were elevated in both groups, elevations during FMF attacks were significantly higher in the FMF group than in the control group. Median CRP was 85 mg/L in the FMF attack group and was 36 mg/L in the control group (p = 0.001). Median SAA was 497.5 mg/L in the FMF attack group and was 131.5 mg/L in the control group (p 0.001). Correlation analyses showed that SAA and CRP were positively correlated in the FMF attack group (r = 0.446, p = 0.01). The best cut-off value for SAA in differentiating FMF attack from an acute febrile infection was 111.5 mg/L (sensitivity 100%, specificity 65.1%, area under curve (AUC) = 0.78, confidence interval 0.66-0.90, p 0.001).Serum amyloid A is a sensitive but not specific marker for demonstrating inflammation in FMF. SAA levels rise substantially in febrile upper respiratory tract infections.Key Points• SAA levels rise substantially in febrile upper respiratory tract infections.• SAA is a sensitive but not specific method for demonstrating inflammation.• SAA cut-off value for discriminating FMF attacks from febrile infection is 111.5 mg/L (sensitivity 100%, specificity 65.1%).

Objectives This study aims to investigate the etiologic spectrum, demographic features, and long-term follow-up results of children with noninfectious uveitis (NIU). Patients and methods Files of patients with NIU were reviewed between May 2010 and September 2017. The cohort consisted of 54 juvenile uveitis patients (26 males, 28 females; mean age 7.7 years; interquartile range [IQR] 9.2 years) with 93 affected eyes. Location of uveitis, laterality, age at onset of uveitis, complications of uveitis, duration of follow-up, associated systemic diseases, pertinent laboratory tests, medications used, and status of uveitis at the time of enrollment were recorded from the files. All patients had final systemic and ocular examination at the last month of enrollment. Results Twenty-seven patients (50.0%) had juvenile idiopathic arthritis (JIA), 17 (31.4%) had idiopathic uveitis, six (11.1%) had Behcet disease (BD), and four (7.5%) had tubulointerstitial nephritis and uveitis (TINU) syndrome. Median duration of follow-up for uveitis was 16 (IQR: 15) months. Anterior uveitis was seen in 81.4% of the patients (65.9% had bilateral and 34.1% had unilateral anterior uveitis). Bilateral intermediate uveitis was observed in 11.2% and bilateral panuveitis in 7.4% of the patients. At the time of enrollment, 45 uveitis patients (83.3%) were under remission. Complications of uveitis were observed in 18.5% of the patients. Conclusion Patients with JIA and BD should be regularly checked for uveitis. It is challenging to find an etiology in uveitis patients referred from ophthalmologists if initial questioning and examination do not reveal an overt rheumatologic disease. However, a simple urine test may help in establishing the diagnosis of TINU syndrome.

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.

Objective To define the characteristics of children expressing the FMF phenotype under colchicine until it was ceased and to compare the clinical features of patients requiring colchicine again with the patients who did not need colchicine. Methods Sixty-four of 1786 children with FMF in whom colchicine was stopped by the physician or patients/parents were enrolled. These patients were grouped as children who were in need of colchicine due to attacks and/or elevated acute phase reactants after cessation of colchicine (group 1) and children in whom colchicine was not necessary and not restarted (group 2). Results Colchicine was stopped in 59.4% by the physician and in 40.6% by the patient/parents. It was ceased at a median of 10.6 years of age (range 2.1–20.5) and attack- and inflammation-free periods of 18.2 months (range 6–148). The median follow-up of 64 patients after colchicine cessation was 37.4 months (range 6.4–154.7). It was restarted in 17 patients due to attacks (n = 11) or elevated acute phase reactants (n = 6). The age at cessation of the colchicine was lower (P = 0.04) and the duration of colchicine treatment until its cessation was shorter (P = 0.007) in group 1 compared with group 2. Conclusion Life-long colchicine treatment may not be required in all FMF patients. There are no current guidelines to determine in which patients it is safe to stop colchicine. We found that younger age during cessation and shorter duration of colchicine treatment lead to a higher risk of needing to restart colchicine.

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

The primary aim of the treatment of juvenile idiopathic arthritis (JIA) is complete remission and minimizing the development of complications. Though biologic agents (BAs) provide better disease control, data related to BA switching patterns in JIA patients are scarce. This study aimed to determine the BA switching patterns in JIA patients. The study included children with JIA that received ≥ 1 BAs. Disease activity was evaluated based on the juvenile arthritis disease activity score 71 (JADAS71). Demographic data, clinical and laboratory findings, BA switching patterns, and the rationales for BA switching were recorded. The study included 177 (82 female and 95 male) JIA patients that received ≥ 1 BAs. Mean age at diagnosis of JIA was 9.1 ± 4.9 years. BAs were prescribed a median of 14 months (range: 3–66 months) after diagnosis. Among the 177 patients, 31 (17.5%) required BA switching a median 10.5 months (range: 3–38 months) after initiation of the first BA. Among all the BAs that were switched to after administration of the first BA, tocilizumab was the most commonly switched (n = 15). The most common reason for BA switching was inadequate response (n = 29). BAs were switched 2 times in 5 patients and 3 times in 1 patient. When patients that switched BAs 1 time were compared to those that switched 2 and 3 times there were not any differences in terms of JIA types, whereas those that switched 2 and 3 times had a higher active joint count and JADAS71 score after 6 months of initiation of the first BA. As some of the JIA patients could not achieve remission despite using the prescribed BA, BA switching was required. Herein, we provide data on both BA switching patterns and requirements, which may improve the management of JIA patients.

Objective: Takayasu arteritis is a rare granulomatous chronic vasculitis that affects the aorta and its main branches. Neurologic manifestations can accompany the disease; however, there is no study on neuroimaging in children with Takayasu arteritis. Therefore, we aimed to evaluate cranial magnetic resonance imaging (MRI) in pediatric Takayasu arteritis patients. Materials and Methods: Demographic, clinical, and laboratory data were obtained retrospectively. Results: The study included 15 pediatric Takayasu arteritis patients. All patients presented with constitutional symptoms. Additionally, 6 patients suffered from headache, 2 had syncope, 1 had loss of consciousness, and 1 had convulsion. All patients underwent cranial and diffusion MRI a median 12 months after diagnosis. Cranial MRI findings were normal in 12 patients, whereas 3 patients had abnormal findings, as follows: stenosis in the M1 and M2 segments of the left middle cerebral artery (n = 1); diffuse thinning of the right internal carotid, middle cerebral, and right vertebral and basilar artery (n = 1); as a sequela, areas of focal gliosis in both the lateral ventricular and posterior periventricular regions (n = 1). Among these 3 patients, 1 had no neurologic complaints. Conclusion: Abnormal MRI findings can be observed in pediatric Takayasu arteritis patients, even those that are asymptomatic; therefore, clinicians should carefully evaluate neurologic involvement in all pediatric Takayasu arteritis patients.

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.

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: We aimed to evaluate the patients who were referred to the pediatric rheumatology outpatient clinic with suspicious laboratory test results. METHODS: All patients who were referred to our outpatient clinic with suspicious laboratory test results between March 2018 and March 2019 were evaluated. RESULTS: A total of 273 new patients who were referred with suspicious laboratory test results were evaluated. Among them; 48% were girls and 52% were boys and they were referred mostly from the clinics of child health and diseases (70.3%). The most frequent indications for referrals were anti-streptolysin O (ASO) elevation (n=86) and anti-nuclear antibody (ANA) positivity (n=47), while 66% of the patients were not diagnosed with rheumatic disease. None of the patients without complaints but with suspicious laboratory test results (n=49) were diagnosed with rheumatic disease. While 64.6% of those diagnosed with rheumatic diseases had periodic fever syndrome, 17.1% had juvenile idiopathic arthritis, 8.5% had postinfectious arthritis, and the remaining 9.8% had connective tissue diseases, vasculitis and uveitis. DISCUSSION AND CONCLUSION: Laboratory findings alone in childhood rheumatic diseases are not significant in patients without complaints. The diagnosis of rheumatic diseases should be made with the patient’s complaints, history, family history and physical examination findings and supported by laboratory findings. With the rational use of laboratory tests; unnecessary health expenses can be prevented and referrals of patients with nonrheumatic diseases to pediatric rheumatology outpatient clinics can be prevented.

Objective: We aimed to evaluate the hearing status of children with Behçet’s Disease (BD). Materials and Method: It is a prospective, cross-sectional, controlled study. Pure-tone audiometry including high-frequencies and distortion product otoacoustic emission (DPOAE) were performed in 15 children with BD and 13 healthy controls. Results: Although both groups had normal hearing levels, the pure tone average of the study group was higher than the healthy controls. Hearing thresholds at 500 Hz and 4000 Hz were statistically significantly higher in children with BD. There was a significant difference in DPOAE levels at 1000 Hz and 4000 Hz. Children with BD had lower levels at these frequencies. Conclusion: In spite of the statistical differences in pure tone audiometry between the two groups, the delta was about 5 dB, which might not have clinical importance. However, this is the first study in children, and further studies are required., Amaç: Behçet Hastalığı (BH) olan çocukların işitme durumunu araştırmayı amaçladık. Gereç ve Yöntem: Bu çalışma prospektif, kesitsel, kontrollü bir çalışmadır. On beş BH olan ve 13 sağlıklı çocuğa yüksek frekansları içeren saf ses odyometrisi ve distorsiyon ürünü otoakustik emisyon (DPOAE) uygulanmıştır. Bulgular: Her iki grup da normal işitme seviyelerine sahip olmasına rağmen, çalışma grubunun saf ses ortalaması sağlıklı kontrollerden daha yüksekti. 500 Hz ve 4000 Hz’de işitme eşikleri BH’li çocuklarda istatistiksel olarak anlamlı derecede daha yüksekti. 1000 Hz ve 4000 Hz’de DPOAE seviyelerinde önemli fark vardı. BH olan çocuklar bu frekanslarda daha düşük seviyelere sahipti. Sonuç: İki grup arasındaki saf ses odyometrisindeki istatistiksel farklılıklara rağmen, delta yaklaşık 5 dB idi ve bunun klinik önemi olmayabilir. Ancak bu çocuklarda yapılan ilk çalışmadır ve daha fazla çalışmaya ihtiyaç vardır.

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.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.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.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.

Henoch-Schönlein Purpura (HSP) is the most common self-limiting vasculitis of childhood. Both serious gastrointestinal and renal complications may be observed during the disease course. The aim of this study was to evaluate the role of hematological markers in predicting the likely complications of the disease.The demographic findings, clinical features, organ involvements and laboratory findings including white blood cell count (WBC), neutrophil, lymphocyte and platelet counts, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), mean platelet volumes (MPV), MPV/platelet count ratio (MPR) were evaluated retrospectively from the charts of the patients with HSP and all these parameters were compared with the same parameters of healthy children.A total of 376 patients with HSP and age- and sex-matched 233 healthy children were evaluated. Mean age at the diagnosis was 7.5 ± 3.5. All patients had palpable purpura, 46% had arthritis, 56.1% GIS involvement and 21.3% had renal involvement. While platelet counts, neutrophil counts, NLR, and PLR were higher, lymphocyte counts, MPV, and MPR were lower in patients with GIS involvement. NLR was the sole biomarker that was higher in patients with renal involvement.This study had shown that platelet counts, neutrophil counts, NLR, and PLR were increasing and lymphocyte counts, MPV, and MPR were decreasing when the patients had GIS involvement. However, these parameters were not relevant in distinguishing severe and mild GIS involvement. When patients had renal involvement NLR was the unique elevated parameter.

Objective: The aim of the research was to further broaden current knowledge of whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) entails a risk for children with rheumatic diseases regarding immunosuppressive treatment.Methods: Telephone-survey was administered by conducting interviews with the parents. A message containing a link to the actual questionnaire was sent to their phones simultaneously. The medical records of the patients were reviewed for gathering information about demographic data, clinical follow-up, and treatments.Results: Patients who were followed up with immunosuppressive treatment (n=439) were attempted to be contacted between 1 May 2020 and 15 May 2020. The diagnostic distribution of patients who were accessible and eligible for the study was as follows; juvenile idiopathic arthritis (JIA) (n=243, 58.7%), autoinflammatory diseases (n=109, 26.3%), autoimmune connective tissue diseases (n=51, 12.3%) and vasculitis (n=11, 2.7%). In the entire cohort, the mean age was 12 ± 4.7 years, and 54.1% (n=224) of the patients were female. One patient with seronegative polyarticular JIA, previously prescribed methotrexate and receiving leflunomide during pandemic has been identified to be diagnosed with COVID-19. None of the patients, including the patient diagnosed with COVID-19, had any severe symptoms. More than half of the patients with household contacts required hospitalization as they were asymptomatic.Conclusion: Although circumstances such as compliance in social distancing policy, transmission patterns, attitude following contact may influence the results, immunosuppressive treatment does not seem to pose additional risk in terms of COVID-19.

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.

Background and objectives The aim of this observational retrospective cohort study was to demonstrate indications and response rates of the patients with pediatric rheumatic diseases that used canakinumab. Method The files of the patients that used canakinumab between December 2012 and July 2017 were reviewed. Canakinumab was used in 29 patients. Diagnosis of the patients were; colchicine resistant familial Mediterranean fever (crFMF) (19 cases), hyperimmunoglobulin D syndrome-mevalonate kinase deficiency (HIDS-MKD) (3 cases), cryopyrin-associated periodic syndrome (3 cases), systemic juvenile idiopathic arthritis (sJIA) (2 cases), idiopathic recurrent pericarditis (1 case) and pyoderma gangrenosum (1 case). Results Canakinumab was used for 21.8 ± 15.8 months (6-54 months). crFMF patients had a female predominance; 16 girls and 3 boys. Mean age at the first symptoms of FMF was 2.8 ± 2.2 years. Mean number of attacks per year before colchicine was 18.7 ± 6.9 (10-36), after colchicine was 8.2 ± 2.7 (6-12) and after biologic agent the number dropped to 0.1 ± 0.3 (0-1). Canakinumab led to resolution of attacks in 3 HIDS-MKD cases. Two familial cold autoinflammatory syndrome patients were using canakinumab for 13 months with total remission. Chronic infantile neurological cutaneous articular syndrome patient did not show dramatic response to standard doses of IL-1 blockers and remission was achieved with high doses of canakinumab. Canakinumab led to the resolution of all systemic and articular manifestations in one sJIA case but the other sJIA case developed polyarticular joint involvement under canakinumab treatment. A severe pyoderma gangrenosum patient that failed dapson and anakinra, also failed canakinumab treatment that was used for 9 months. We have successfully treated a case of idiopathic recurrent pericarditis with canakinumab. Canakinumab was discontinued due to inefficacy only in two cases. Conclusion Overall efficacy of canakinumab was 93.1% in this study. No major adverse event was observed under canakinumab treatment. Canakinumab seems to be effective and safe in children with rheumatic diseases.

Autoinflammatory periodic fever syndromes are a group of diseases mostly presenting in childhood and characterized by recurrent fever and inflammation attacks as a result of an innate immune system activation. Familial Mediterranean fever (FMF) is the most common periodic fever syndrome in Mediterranean countries such as Turkey. Other hereditary autoinflammatory periodic fever syndromes are classified as rare diseases. In this review, the clinical features, recommended classification criteria and treatment options of FMF, tumor necrosis factor (TNF) receptorassociated periodic fever syndrome (TRAPS), mevalonate kinase (MVK) deficiency, cryopyrin-associated periodic fever syndrome (CAPS), and periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome were evaluated.

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.

Familial Mediterranean fever (FMF) is the most common type of monogenic periodic fever syndromes and characterized by recurrent self-limited attacks of fever and polyserositis. Musculoskeletal signs and symptoms are not uncommon and manifested as arthritis and myalgia. Myalgia may be spontaneous or exercise-induced that mostly affects lower limbs and spontaneously resolves in 2–3 days. Protracted febrile myalgia syndrome (PFMS) is another form of rare and severe muscle involvement in FMF. PFMS affects all muscle groups and lasts for several weeks. Herein we present a pediatric case of PFMS that presented as the first manifestation of FMF, not responded to prednisolone at all but showed dramatic improvement with anakinra. Our case has a few distinctive points. She did not have a diagnosis of FMF and also she did not have any previous complaints compatible with FMF. Thus, PFMS was the first sign of FMF in this patient. Most of the cases of PFMS show dramatic response to corticosteroids, but our case did not respond at all to high-dose corticosteroids and anakinra resulted in rapid resolution of the symptoms. Protracted febrile myalgia syndrome may be the first manifestation of FMF. It should be suspected in cases with prolonged and unexplained fever, severe myalgia, and high acute phase reactants.

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.

Sacroiliitis has been scarcely reported in patients with systemic lupus erythematosus (SLE). In this article, we presented a pediatric case with coexis- tence of juvenile SLE and juvenile spondyloarthropathy (SpA) and discussed the clinical and laboratory findings by the literature review. A 16-year- old female patient with a diagnosis of SLE was referred to our outpatient clinic with inflammatory low-back pain for two months. Sacroiliac magnetic resonance imaging confirmed the presence of bilateral active sacroiliitis. She was finally diagnosed with juvenile SpA. She achieved remission with subcutaneous methotrexate and non-steroid anti-inflammatory drugs. To the best of our knowledge, this is the first pediatric case with SLE and SpA. This case provides further implication about atypical presentation of a well-known disorder.

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.