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Insulin resistance (IR) has been described in adults with systemic lupus erythematosus (SLE), though its mechanism has not been fully clarified. In this study, it was aimed to investigate insulin sensitivity for the first time in children with juvenile SLE (jSLE) by considering the effect of the already known contributing factors of IR.This is a cross-sectional study including 43 patients with jSLE and the same number of healthy controls matched for age, gender, pubertal stage, body mass index, and physical activity level. IR, as calculated by both homeostatic model assessment for insulin resistance (HOMA-IR) and a relatively new method, triglyceride glucose (TyG) index, was compared between the patients and their matched controls, also among the patients stratified by disease duration, corticosteroid use, and disease activity.Insulin resistance in the patient group was higher than the controls according to both HOMA-IR and TyG index (p 0.001 for both). In the patient group, no significant effect of disease duration, corticosteroid use, disease activity, and levels of anti-dsDNA, anti-cardiolipin IgM, anti-cardiolipin IgG, C3, and C4 on IR was demonstrated.Children with jSLE were found to have higher IR even after neutralizing the effects of the contributing factors which are expected to aggravate IR. This elevation in IR in jSLE seems not to be associated with corticosteroid use, disease duration, disease activity, or autoantibody levels. Thus, the presence of IR in jSLE cannot be explained solely with neither the already known contributing factors nor the increased inflammation of the disease. Key Points • In this study, insulin sensitivity was investigated for the first time in children with jSLE. • Children with jSLE have higher insulin resistance than healthy ones. • Insulin resistance in children with jSLE is independent of corticosteroid use, disease duration, disease activity or autoantibody, and complement levels.

The effects of biological disease-modifying antirheumatic drugs (bDMARDs) in the clinical course of COVID-19 on children with underlying rheumatologic diseases have not been fully demonstrated. To evaluate the course of COVID-19 infection in patients with rheumatic disease receiving bDMARD treatment. This was a retrospective, multicenter study conducted in pediatric patients infected by SARS-CoV-2 and under bDMARDs therapy. The study population consisted of 113 patients (72 female/41 male). The mean age of the patients was 12.87 ± 4.69 years. The primary diagnosis of the cohort was as follows: 63 juvenile idiopathic arthritis, 35 systemic autoinflammatory diseases, 10 vasculitides, and five cases of connective tissue diseases. The mean duration of the primary disease was 4.62 ± 3.65 years. A total of 19 patients had additional comorbid diseases. Thirty-five patients were treated with canakinumab, 25 with adalimumab, 18 with etanercept, 10 with infliximab, nine with tocilizumab, six with rituximab, four with anakinra, three with tofacitinib, and one with abatacept. The median exposure time of the biological drug was 13.5 months. Seventy-one patients had symptomatic COVID-19, while 42 were asymptomatic. Twenty-four patients required hospitalization. Five patients presented with MIS-C. The hospitalized patients were younger and had a shorter duration of rheumatic disease compared to ambulatory patients, although the difference was not statistically significant. Steroid usage, presence of fever, and dyspnea were more common among the hospitalized patients. A worsening in the course of both COVID-19 and current disease was not noticed under bDMARDs, however, to end with a strong conclusion multicentric international studies are required. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Aim To compare childhood-onset (c-TAK) versus adult-onset Takayasu arteritis (a-TAK) patients for vascular involvement, disease activity, damage, and treatment. Methods Patient charts from two tertiary-care centers of a pediatric and adult rheumatology clinic were reviewed. Adult patients diagnosed before the age of 18 years were included in the childhood-onset group. The activity was assessed with the physician's global assessment (PGA) and Indian Takayasu Clinical Activity Score (ITAS). The damage was evaluated with Takayasu Arteritis Damage Score (TADS) and Vasculitis Damage Index (VDI). Results Twenty-four c-TAK (follow-up duration: 53 months) and 117 a-TAK patients (follow-up duration: 68 months) were analyzed. Aorta involvement was more prevalent (79% vs. 33%), and the median PGA score was higher in the c-TAK group (9 vs. 7), whereas the mean Indian Takayasu Arteritis Score was similar (14 vs. 13) among both groups. Median VDI score was lower for c-TAK patients (4 vs. 5), whereas TADS was similar for children and adults (8 vs. 8). Higher incidence of glucocorticoid related side-effects, a longer time to diagnosis and upper extremity claudication seemed to account for higher VDI scores in adults. Conclusion Aorta involvement was more common among children with TAK, whereas upper extremities were relatively spared. Biologic agents were used more commonly among children which may be explained by higher rates of aortic involvement. However, c-TAK patients did not have greater cumulative damage.

This study aimed to evaluate the psychological symptoms of children and adolescents with rheumatological diseases (RD) and their parents during the outbreak. A web-based questionnaire survey was conducted in a cross-sectional design in RD patients and healthy controls. The Hospital Anxiety and Depression Scale was used to evaluate parental psychiatric status; while the State-Trait Anxiety Inventory for Child was used for children. Four hundred and fifty-nine patients with RD and their parents completed the present study, as well as 336 healthy peers. The age and gender of the children were similar across groups. Under 12 years of age, the trait anxiety of the children and the psychological symptoms of parents were similar across groups; while over 13 years of age, anxiety and depression scores of the parents, as well as trait anxiety of the children were higher than the control groups' (7.3 +/- 3.4 vs 6.3 +/- 3.8, p = 0.006 for parental anxiety; 6.6 +/- 3.8 vs. 5.3 +/- 3.9, p < 0.001 for parental depression; 36.1 +/- 8.7 vs. 33.3 +/- 7.9, p = 0.002 for child trait anxiety). In patient group, there were no differences in scale scores according to variables such as rheumatological disease diagnosis, the consulting of doctor for treatment, thinking that RD increases the risk of COVID-19, the history of rheumatic disease attack during the pandemic process, and the use of biological agents. The children's trait anxiety was positively correlated with their parents' anxiety (r = 0.414, p < 0.001) and depression (r = 0.300, p < 0.001) scores. These findings suggest that clinicians should pay attention to the psychiatric symptoms of both children with RD and their parents during the pandemic.

Humanity has recently gained a novel foe named coronavirus disease 2019. Although data so far mostly suggest that children are more likely to have a favorable disease course, new concerns have been raised because of recently reported pediatric cases with hyperinflammatory conditions resembling Kawasaki disease, toxic shock syndrome, and macrophage activation syndrome/hemophagocytic lymphohistiocytosis. Because the increasing evidence suggests that this recent hyperinflammatory condition emerged in the coronavirus disease 2019 era is a distinct clinical picture, the Centers for Disease Control and Prevention named this novel disease multisystem inflammatory syndrome in children. Even if this novel disease is rare, it seems to be highly fatal. Therefore, it is urgent to understand the pathogenesis of the disease to be able to establish the appropriate treatment regimes. Concerns regarding the diagnostic process and the management of the disease have been raised even among pediatricians. Therefore, we aimed to clarify this newly occurring enigma based on the current literature and our clinical insights.

To evaluate the efficacy and safety of anti-interleukin (IL)-6 receptor antibody tocilizumab (TCZ) as a treatment option of juvenile systemic sclerosis (JSS). Nine JSS patients were assigned to a TCZ, additionally to conventional treatment (steroids, methotrexate, mycophenolate-mofetil). The modified Rodnan skin score (mRSS), carbon-monoxide diffusion capacity (DLCO), thorax high-resolution tomography (HRCT), patient global assessment (PGA) and Juvenile Systemic Sclerosis Severity (J4S) score were used to explore the efficacy of treatment. Nine JSS patients were treated with TCZ with a median treatment duration of 10 (1-21) months. Nine patients (77.8%) had radiologically confirmed improvement on thorax HRCT, 7 (77.8%) had decreased PGA (mean pre-treatment PGA 3.7 vs. 2.3 post-treatment PGA 2), 6 (66.7%) had increased DLCO (mean pre-treatment DLCO 69.14% vs. post-treatment DLCO 79.50%) after the TCZ treatment. In all patients mRSS and the J4S decreased: 26.1 vs. 19.7 and 8.2 vs. 4.7, respectively. Changes in mRSS, DLCO, PGA and J4S were statistically significant: p = 0.012, 0.04, 0.026 and 0.007, respectively. All patients tolerated well TCZ treatment. JSS is a rare condition characterized with skin fibrosis and internal organ involvement. Tocilizumab represents a potential treatment option for patients unresponsive to conventional treatment. Long-term prospective studies with higher number of patients are needed to provide more relevant data.

Juvenile spondyloarthropathy is an umbrella term for a group of childhood rheumatic diseases that can cause chronic arthritis extending to the axial skeleton before the age of 16. Although ankylosing spondylitis has aortic involvement as one of its most important effects, this relationship has not been extensively studied in children with juvenile spondyloarthropathy. Here, a cross-sectional study of the elastic properties of the aorta of 43 patients with juvenile spondyloarthropathy and 19 healthy controls is reported. Aortic stiffness assessed by echocardiography was used to predict the presence of aortitis, supplemented by pulsed-wave tissue Doppler indices. The right ventricular fractional area change was found to be significantly lower in the patients with juvenile spondyloarthropathy than in the healthy controls; aortic strain and distensibility were also significantly lower, and aortic stiffness index β was significantly higher; and the aortic root diameter change was significantly lower. According to HLA-B27 positivity, there was no difference in the stiffness parameters between the two groups. There was a significant correlation between juvenile Ankylosing Spondylitis Disease Activity Index and aortic diameter change, between juvenile Ankylosing Spondylitis Disease Activity Index and aortic stiffness. Thus, juvenile spondyloarthropathy is linked to high aortic stiffness parameters.

To determine the frequency of Th2-mediated allergic diseases (AD) in mainly Th1-driven juvenile idiopathic arthritis (JIA) subtypes.Ninety-nine JIA patients and 128 control subjects were enrolled in a prospective case-control study. All subjects were assessed with standard allergy questionnaire, complete blood cell count, and total serum immunoglobulin (sIg) E. sIgs G, A, M, Juvenile Arthritis Disease Activity Score-27 (JADAS27), and serum acute phase reactants (sAPR) were obtained in JIA. In the presence of allergic symptoms, skin prick (SPT) and pulmonary function tests (PFT) were performed.Despite similar allergy risk factors, the frequencies of asthma and allergic rhinitis were lower in JIA group (allThe frequencies of AD, asthma, and allergic rhinitis may decrease in Th1-mediated JIA subtypes although the coexistence does not appear to affect the severity of arthritis whereas allergic symptoms may resolve after immunosuppressive treatment. PFTs should be obtained periodically in JIA. JIA patients may have an underlying primary immunodeficiency (ID) or immunosuppressive drugs may cause secondary ID.KEY POINTSCompared to the population, the frequency of Th2-mediated allergic diseases is lower in oligoarthritis and RF-negative polyarthritis that are primarily driven by a Th1 activity.The coexistence of allergic diseases in juvenile idiopathic arthritis does not affect the severity of arthritis.Pulmonary function tests can be thought to be obtained periodically in juvenile idiopathic arthritis.Immunological workup should be considered in atypically or severely presented patients with juvenile idiopathic arthritis before the initiation of immunosuppressive therapy to differentiate primary and secondary immunodeficiency.

As it is known, we are all in a pandemic situation due to a novel coronavirus, officially named “Severe Acute Respiratory Syndrome Coronavirus 2” and the disease caused by the virus named “Coronavirus disease-2019”. The virus seems to has propensity to infect older male individuals with underlying disease. The clinical features were on a large scale that varies from being an asymptomatic carrier to acute respiratory distress syndrome and multiorgan dysfunction. Fever, dry cough and fatigue are the most common symptoms. Not only, the disease seems to be rare and have a milder course in pediatric age but also respiratory failure, multiorgan dysfunction, and death are extremely rare. Although several comorbidities such as hypertension, diabetes and cardiovascular diseases are defined as a risk factor for developing the acute respiratory syndrome and need for intensive care; immune-compromised situations such as rheumatic disease which require immunosuppressive treatment strikingly are not found to be a risk factor for more severe disease course. However, there is a lack of data regarding the effects of “Coronavirus disease-2019” on pediatric patients with rheumatic diseases. Additionally, there are three controversial circumstances that patients with rheumatic diseases are believed to be more likely to have viral infections like “Severe Acute Respiratory Syndrome Coronavirus 2”, on the other hand, antirheumatic drugs may have a protective and therapeutic role in Coronavirus disease-2019 and children are more unlikely to have serious disease course. Therefore, we aimed to have a contributor role for explaining this conundrum and present a bird’s eye view regarding this equivocal issue in this review. In December 2019, a cluster of acute viral pneumoniae cases with unknown origin emerged in Wuhan, Hubei province, China (1). Most of the cases had a common exposure to the Huanan wholesale seafood market (2). Several days later, causative viral agent was analyzed with deep sequencing and indicated as a novel coronavirus, officially named 2019 novel coronavirus (2019 nCoV) (3). Coronavirus Study Group (CSG) of the International Commission on Virus Classification named this novel coronavirus “Severe Acute Respiratory syndrome Coronavirus 2 (SARS-CoV-2)” on February 11, 2020 and on the same day, the World Health Organization (WHO) named the disease caused by SARS-CoV-2, “Coronavirus disease-2019 (COVID-19)” (4). In a couple of weeks, severe COVID-19 cases were all over the world, and on the basis of disease severity and spread, finally WHO characterized the COVID-19 situation as a pandemic on March 11th, 2020 (5). In the past two decades, addition to this current pandemic, we experienced two different coronavirus outbreaks, and previous two were named “Severe Acute Respiratory Syndrome Coronavirus” (SARS-CoV) and “Middle East Respiratory Syndrome Coronavirus” (MERS-CoV) (6). Bats are known to be reservoir hosts for SARS-CoV and MERS-CoV (7). Given the findings of genomic analyze of SARS-CoV-2, bats are assumed to be origin of also COVID-19 pandemic (8). Although intermediary animals between bats and humans are uncertain, pangolin and snakes seem to be leading suspects (2).

Mercury is the only metal that remains in liquid form at the room temperature. It is a very toxic metal and even short-term exposure can lead to poisoning. Mercury intoxication can affect many systems such as skin, cardiovascular, genitourinary, central and peripheral nervous, respiratory, and musculoskeletal system. Consequently, the diagnosis of mercury intoxication can be challenging due to its non-specific and multisystemic presentation. Herein, we report five pediatric cases with mercury intoxication from two families that were initially misdiagnosed as rheumatic disorders. We also performed a literature review about pediatric cases with mercury intoxication to investigate the clinical findings in children, the source of intoxication, and the current treatment preferences. As in our cases, reported patients were previously misdiagnosed as various infectious and/or rheumatic diseases before the diagnosis of mercury intoxication was established. A delay in diagnosis and treatment can cause serious morbidities and even mortality. We report this case series to emphasize the multisystemic presentation of mercury intoxication, and to remind and provide clues for physicians to recognize this rare toxicologic syndrome.

OBJECTIVE: Utilizing data obtained from a prospective, international, juvenile systemic sclerosis (SSc) cohort, the present study was undertaken to determine if pulmonary screening with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) is sufficient to assess the presence of interstitial lung disease (ILD) in comparison to high-resolution computed tomography (HRCT) in juvenile SSc. METHODS: The juvenile SSc cohort database was queried for patients enrolled from January 2008 to January 2020 with recorded pulmonary function tests (PFTs) parameters and HRCT to determine the discriminatory properties of PFT parameters, FVC, and DLco in detecting ILD. RESULTS: Eighty-six juvenile SSc patients had both computed tomography imaging and FVC values for direct comparison. Using findings on HRCT as the standard measure of ILD presence, the sensitivity of FVC in detecting ILD in juvenile SSc was only 40%, the specificity was 77%, and area under the curve (AUC) was 0.58. Fifty-eight juvenile SSc patients had both CT imaging and DLco values for comparison. The sensitivity of DLco in detecting ILD was 76%, the specificity was 70%, and AUC was 0.73. CONCLUSION: The performance of PFTs in juvenile SSc to detect underlying ILD was quite limited. Specifically, the FVC, which is one of the main clinical parameters in adult SSc to detect and monitor ILD, would miss ~60% of children who had ILD changes on their accompanying HRCT. The DLco was more sensitive in detecting potential abnormalities on HRCT, but with less specificity than the FVC. These results support the use of HRCT in tandem with PFTs for the screening of ILD in juvenile SSc.

The purpose of this study is to share our experience about clinical findings, natural course, and treatment response rates of a large cohort of patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome.Medical records of patients who were diagnosed with PFAPA syndrome between January 2010 and May 2021 at Istanbul University-Cerrahpasa Cerrahpasa Medical Faculty pediatric rheumatology department were reviewed retrospectively.A total of 607 patients (females: 277, males: 330) with PFAPA syndrome were included. The median duration of episodes was 3 (1-15; interquartile range (IQR) 3-5) days, and the median interval between episodes was 20 days (5-120; IQR 15-30). The median age at the last attack and median disease duration were 66 (24-168; IQR 48-84) months and 40 (4-132; IQR 27.5-60) months, respectively. Fever (100%) was the most common clinical finding, followed by pharyngitis/exudative tonsillitis in 594 (97.9%), aphthous stomatitis in 308 (50.7%), cervical lymphadenopathy in 278 (45.8%), abdominal pain in 249 (41%), and arthralgia in 228 (37.6%) of the patients. Among the clinical findings, there was no statistical difference according to gender, except for cervical lymphadenitis being higher in males (P.001). Of the patients who were given steroids during attacks, 94.6% were responsive. Colchicine was effective in 93 (63.7%) patients. The disease episodes ceased in 313 (95.4%) of patients who had tonsillectomy/adenoidectomy.Clinicians should be alert for additional symptoms such as abdominal pain, arthralgia, and headache apart from the cardinal signs. Although tonsillectomy is highly effective, its use is controversial. Colchicine may be a good alternative for prophylaxis.

Considerable evidence supports sex differences in autobiographical and episodic memory which may translate to heightened vulnerability to stress- and trauma-related disorders in women. The hormones estradiol and oxytocin both affect episodic memory, but possible sex-specific effects and hormonal interactions have not been systemically tested in humans. We conducted a randomized, placebo-controlled, parallel-group functional magnetic resonance imaging (fMRI) study involving healthy women (n = 111) and men (n = 115). Participants were scanned under four experimental conditions: 1. estradiol gel (2 mg) and intranasal oxytocin (24 IU), 2. placebo gel and intranasal oxytocin, 3. estradiol gel and placebo spray, 4. placebo gel and placebo spray. During fMRI, participants viewed positive, neutral and negative scenes. A surprise recognition task three days later was used to classify encoding trials as remembered or forgotten. Under placebo, women showed a significantly better recognition memory and increased hippocampal responses to subsequently remembered items independent of the emotional valence compared to men. Separate treatments with either estradiol or oxytocin significantly diminished this mnemonic and hippocampal sex difference, whereas the combined treatment produced no significant effect. Collectively, our results suggest that estradiol and oxytocin play a crucial role in modulating sex differences in episodic memory. Furthermore, possible antagonistic interactions between estradiol and oxytocin could explain previously observed opposing hormonal effects in women and men.

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.

Background Juvenile idiopathic arthritis (JIA), is the most common pediatric rheumatologic disorder with unknown etiology. Currently, no population-based data are available regarding the distribution of categories and frequency of uveitis in patients with JIA in Turkey. The purpose of this study was to evaluate the frequency of JIA-associated uveitis (JIAU) and distribution of JIA categories in a Turkish JIA cohort. Methods This was a retrospective study of 500 randomized patients in four pediatric rheumatology clinics in Turkey. Results Oligoarticular JIA (oJIA) was the most common JIA disease category in this study cohort (38.8%). The frequencies of the other categories were as follows: enthesitis-related arthritis (ERA), 23.2%; rheumatoid factor (RF)–negative polyarthritis, 15.6%; systemic arthritis, 12.2%; juvenile psoriatic arthritis, 5.2%; undifferentiated arthritis, 2.8%; and RF-positive polyarthritis, 2.2%. JIA-associated uveitis was observed in 6.8% of patients at a mean (Standard Deviation, SD) age of 9.1 (3.8) years over a mean JIA disease duration of 4 (1.9) years. Uveitis developed after joint disease, with a mean (SD) duration of 1.8 (1.9) years. Patients with oJIA had the highest rate of uveitis (12.9%) followed by patients with ERA (5.2%) and polyarticular RF-negative disease (3.8%). Compared with persistent oJIA, the extended oJIA category had a > 3-fold higher risk of uveitis (11.3% vs 27.7%; odds ratio, 3.38 [95% Confidence Interval, 1.09–10.4]). The most frequently administered drug after development of uveitis was tumor necrosis factor–alpha inhibitors (38.2%). Five patients (14.7%) had uveitis-related complications that required surgical intervention. Conclusions Turkish pediatric patients with JIA experience a lower frequency of oJIA and higher frequency of ERA than their white European counterparts; the occurrence of uveitis is also somewhat lower than expected. Geographic and ethnic factors may affect these differences and need further investigation.

Krebs von den Lungen-6 (KL-6) has been described as a promising biomarker in the diagnosis and determining the severity of interstitial lung disease in adults with connective tissue disease. This study was performed to determine whether the serum KL-6 level is useful as a biomarker for detecting the interstitial lung disease (ILD) in pediatric cases of connective tissue disease (CTD). In total, 88 patients [36 patients with systemic juvenile idiopathic arthritis (sJIA), 27 patients with juvenile systemic lupus erythematosus (JSLE), 14 patients with juvenile dermatomyositis (JDM), and 11 patients with juvenile systemic sclerosis (JSSc)] and 68 healthy controls were included in this study. Age, sex, and duration of CTD and ILD (if any) were recorded. Blood samples from all the patients and controls were examined by ELISA. Eleven of the 88 patients with CTD (12.5%) had ILD and all of them were symptomatic. Subgroup analysis indicated that eight patients had JSSc, two had JSLE, and one had systemic JIA. The median serum KL-6 level was 1450.5 U/mL (interquartile range (IQR) 742.9–2603.2) in the CTD with ILD group, 415.9 U/mL (IQR 233.4–748.4) in the CTD without ILD group, and 465.9 U/mL (IQR 273.6–1036) in the control group. KL-6 levels were significantly higher in the CTD with ILD group than the CTD without ILD group and the control group (p = 0.003). At a cut-off of 712.5 U/ml identified by ROC curve, serum KL-6 yielded a sensitivity of 81% and specificity of 72% for CTD with ILD group. There was no significant difference in serum KL-6 level among the disease subgroups (sJIA, JSLE, JSSc, JDM), in either the CTD with ILD group or the CTD without ILD group (p > 0.05). In conclusion, KL-6 is a useful biomarker of CTD with ILD in pediatric patients.

Aim Systemic juvenile idiopathic arthritis (sJIA) is a distinctive subtype of JIA characterized by systemic features and poor outcome. We aimed to investigate demographic and clinical features, long-term treatment response and disease complications in a large sJIA cohort. Methods Patients diagnosed with sJIA followed up at a pediatric rheumatology outpatient department from January 2003 to December 2017 were included. Demographic and clinical features, long-term treatment response and disease complications were retrospectively collected. Results A total of 168 sJIA patients (51.8% female, 48.2% male) were included: 31.5% with monocyclic, 13.7% polycyclic and 54.8% with persistent clinical course. Corticosteroids were initially used in all patients. Methotrexate was used in 75% and cyclosporine A was used in 17.3% patients. Biological drugs were used in 42.8% patients; etanercept in 29.7%, anakinra in 16%, canakinumab in 16%, tocilizumab in 10% patients. Remission off medication was achieved in 82 (48.8%). Macrophage activation syndrome (MAS) was present in 11.9%, growth retardation in 11.3% patients. Eight percent (4/50) of patients had low bone mineral density. Three patients (1.78%) died due to MAS secondary multiorgan insufficiency and infection. Conclusion The disease is characterized with diverse clinical presentation and possibly severe complications. MAS complicated with multiorgan insufficiency is the major mortality factor. Corticosteroids represent the mainstay of the initial treatment. In patients resistant to classic treatment, biological drugs should be timely introduced.

A 9.5-year-old boy was referred with a 2-year history of recurrent fever, myalgia, abdominal pain and various neurological manifestations associated with increased acute phase reactants and IgG level. During the recent episode, severe hypertension and right-sided hemiparesis developed and angiography demonstrated irregularities and stenosis in renal and mesenteric artery branches. Although these manifestations were consistent with polyarteritis nodosa (PAN), the

Objectives: Multi-system inflammatory syndrome in children (MIS-C) is a less understood and a rare complication of coronavirus disease-2019 (COVID-19). Given the scarce data regarding this novel disease, we aimed to describe the clinical features and outcomes of our patients with MIS-C and to evaluate the associated factors for the pediatric intensive care unit (PICU) admission. Methods: The MIS-C patients under 18 years old diagnosed and treated in three referral centers between July 2020 and March 2021 were included. Data of the patients were retrospectively obtained from their medical records. Results: Overall, 76 subjects (24 females) with a mean age of 8.17 ± 4.42 years were enrolled. Twenty-seven (35.5%) patients were admitted to the PICUs. The two most common systemic involvement patterns were cardiac and gastrointestinal. There was only one lethal outcome in a patient with underlying acute lymphoblastic leukemia. Those with higher procalcitonin levels at admission were found to stay longer in the hospital (r = 0.254, p = 0.027). The risk of PICU admission increased with age (aOR: 1.277; 95% CI: 1.089–1.498; p = 0.003) and with decreased initial serum albumin levels (aOR: 0.105; 95% CI: 0.029–0.378; p = 0.001). Conclusion: Although there is a wide clinical variability among the patients with MIS-C, we suggest that those with older age and lower initial serum albumin levels merit close monitoring due to their higher risk for PICU admission.Key Points• Although there is a wide variability regarding the management process among clinicians, MIS-C is a rare, severe, less understood complication of COVID-19 that may cause rapid clinical deterioration in the patients.• Clinicians should be aware of this condition in children with persistent fever and a family history of COVID-19.• Older age and low serum albumin levels are the independent predictors for the pediatric intensive care unit admission among MIS-C patients. © 2021, International League of Associations for Rheumatology (ILAR).

Objective To evaluate the baseline clinical characteristics of juvenile systemic sclerosis (SSc) patients in the international juvenile SSc inception cohort, and to compare these characteristics between the classically defined juvenile diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) subtypes and among those with overlap features. Methods A cross-sectional study was performed using baseline visit data. Information on demographic characteristics, organ system evaluation, treatment, and patient- and physician-reported outcomes was extracted and summary statistics applied. Comparisons between juvenile dcSSc and lcSSc subtypes and patients with and without overlap features were performed using chi-square and Mann-Whitney U tests. Results At data extraction, 150 juvenile SSc patients were enrolled across 42 centers; 83% were White, 80% were female, juvenile dcSSc predominated (72%), and 17% of the cohort had overlap features. Significant differences were found between juvenile dcSSc and juvenile lcSSc regarding modified Rodnan skin thickness score, the presence of Gottron's papules, digital tip ulceration, results of the 6-minute walk test, and composite pulmonary and cardiac involvement. All of these were more frequent in dcSSc except for cardiac involvement. Juvenile dcSSc patients had significantly worse scores for physician-rated disease activity and damage. A significantly higher occurrence of Gottron's papules and musculoskeletal and composite pulmonary involvement, and a significantly lower frequency of Raynaud's phenomenon, were seen in those with overlap features. Conclusion Results from a large international juvenile SSc cohort demonstrate significant differences between juvenile dcSSc and juvenile lcSSc patients, including more globally severe disease and increased frequency of interstitial lung disease in juvenile dcSSc patients, while those with lcSSc have more frequent cardiac involvement. Those with overlap features had an unexpected higher frequency of interstitial lung disease.

Behçet's Disease (BD) is a systemic vasculitis firstly described as a disorder causing aphthous lesion in oral and genital mucosae and uveitis. The disease has an extremely unique distribution characterized by the highest incidence in communities living along the historical Silk road. Although our understanding of the etiopathogenesis of BD has expanded over time, there are still lots of unidentified points in the underlying mechanisms of the disease. The accepted opinion in the light of the current knowledge is that various identified and/or unidentified infectious and/or environmental triggers can take a role as a trigger in individuals with genetic susceptibility. Although the disease usually develops in young adulthood, it is reported that about 15–20% of all Behçet's patients develop in childhood. Pediatric BD differs from adult BD not only with the age of onset but also in the frequency and distribution of clinical findings, disease severity and outcome. While gastrointestinal system involvement, neurological findings, arthralgia and positive family history are more common in children, genital lesions and vascular lesions are more common in adult patients. In addition, a better disease outcome with lower severity score and activity index has been reported in children. The diagnosis of the disease is made according to clinical findings. It can be challenging to diagnose the disease due to the absence of a specific diagnostic test, and the long time interval from the first finding of the disease to the full-blown disease phenotype in pediatric cases. Therefore, many classification criteria have been proposed so far. The widely accepted ones are proposed by the International Study Group. The new sets of classification criteria which is the only one for pediatric BD were also developed for pediatric cases by the PEDBD group. The primary goal for the treatment is preventing the organ damages by suppressing the ongoing inflammation and forestalling the disease flares. The treatment of the BD can be onerous due to its multisystemic nature and a multidisciplinary approach is essential for the management of the patients. In this review article, the definition, clinical findings, epidemiology, etiopathogenesis, and treatment will be discussed.

Background Juvenile dermatomyositis associated interstitial lung disease, rarely seen in pediatric age groups, has adverse effects on survival. Anti-melanoma differentiation associated gene 5, one of the identified autoantibodies in juvenile dermatomyositis, preferentially affects the lung tissue and may cause rapidly progressive interstitial lung disease. It is a major cause of mortality in juvenile dermatomyositis. In this case report, we present a pediatric patient diagnosed with juvenile dermatomyositis without anti-melanoma differentiation associated gene 5 antibody positivity. Case A six-year-old male patient admitted to the Pediatric Intensive Care Unit with symptoms of respiratory failure, 1.5 months after the diagnosis of juvenile dermatomyositis. Thorax computed tomography examination revealed pneumomediastinum, a trace of left-sided pneumothorax, atelectasis on the left posterior lung region, ground-glass opacity, minimal subpleural patchy consolidation, and subcutaneous emphysema especially on the sides of the chest wall. Broad-spectrum antibiotics were started. His nasal swab sample was positive in terms of influenza B; therefore, oseltamivir was added to the treatment. Autoimmune myositis antibodies panel was examined but all of them including anti-melanoma differentiation associated gene 5 antibody resulted as negative. There was no notable reduction in lung infiltrations with the patient`s current treatment regimen. On the 12 th day of Pediatric Intensive Care Unit admission, thorax computed tomography scan revealed progressed radiological lung findings compatible with rapidly progressive interstitial lung disease secondary to juvenile dermatomyositis. Despite intensive medical and extracorporeal treatments such as pulse steroid, intravenous immunoglobulin, methotrexate, cyclophosphamide, rituximab, therapeutic plasma exchange and, extracorporeal membrane oxygenation, the patient died on the 35 th day. Conclusions Juvenile dermatomyositis patients should be carefully monitored for the development of interstitial lung disease. Rapidly progressive interstitial lung disease with a high mortality may develop shortly after diagnosis, even if the anti-melanoma differentiation associated gene 5 antibody is negative.

Preliminary data have suggested that children have milder COVID-19 disease course compared to adults. However, pediatric cases with severe clinical findings caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) are being reported since April 2020. These children have been presented with significant hyperinflammatory states resembling Kawasaki disease, toxic shock syndrome, and macrophage activation syndrome. However, they had several distinct features, as well. Therefore, this novel condition was considered a unique disease and named Multi-inflammatory syndrome in children (MIS-C). Thus, new concerns have been raised regarding the vulnerability of the children. However, it has been realized that this condition is extremely rare. Nonetheless, considering that it is a life-threatening disease and may cause devastating consequences, clinicians should be aware of MIS-C while evaluating children with persistent fever and history of COVID-19 contact or active infection.

BACKGROUND/OBJECTIVE Juvenile spondyloarthropathies (JSpAs) are a group of inflammatory diseases characterized by asymmetric peripheral arthritis (especially in lower extremities), axial skeleton involvement, and enthesitis. Although cardiovascular findings of inflammatory diseases such as juvenile systemic lupus erythematosus (SLE) and juvenile scleroderma (SD) are well documented, there are only a few studies assessing the cardiovascular consequences of JSpA in the literature. METHODS Forty patients with JSpA and 20 healthy controls were included into this cross-sectional study. Cardiac functions of the participants were evaluated by conventional echocardiography and pulse-wave (PW) tissue Doppler. RESULTS The patients with JSpA had higher mitral lateral S (p = 0.005) and E' wave (p < 0.001), tricuspid A' wave (p = 0.03), ejection fraction (p = 0.03) and shortening fraction (p = 0.01) than the control patients. In contrast, the patients with JSpA had lower left ventricle MPI (p = 0.01) and the ratio of tricuspid E'/A' waves (p = 0.05). Patients with enthesitis detected on magnetic resonance imaging had lower ejection fraction (p = 0.05), the ratio of E/A waves (p = 0.03) and had higher Mitral lateral A' wave (p = 0.01) than those without. There was a significant inverse correlation between the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and PW transmitral A velocity (r = -0.256, p = 0.03), the BASDAI score and tricuspid annular plane systolic excursion (r = -0.301, p = 0.04), the BASDAI score and the ratio of E/E' waves (r = -0.276, p = 0.02), and the Juvenile Spondyloarthritis Disease Activity Index and PW transmitral A velocity (r = -0.246, p = 0.04). CONCLUSIONS In this study, we report the possible early signs of RV diastolic dysfunction and possible association between magnetic resonance imaging-confirmed enthesitis and lower LV systolic functions. Early identification of cardiac dysfunctions can help with prevention of long-term cardiovascular complications.

Background In the pediatric age, anti-nuclear antibody (ANA) testing is most commonly ordered by general pediatricians to evaluate children with musculoskeletal system complaints. Given the limited utility of the test, we aimed to estimate the effectivity of ordering ANA testing in childhood. Methods Children referred to our department to be examined due to ANA positivity between 2008 and 2020 were included in the study. Those with less than one-year follow-up period, those with previously known rheumatic or autoimmune disease, and those diagnosed as an autoimmune and/or rheumatic disease at the first visit were excluded. Data were obtained from their medical records, retrospectively. The parents of all of the patients were called via phone, data were verified, and missing information was collected. Results Three hundred and fifty-eight patients (230 females) were eligible for the study. The median age at ANA positivity was found is 9.31 (1.3-17.86) years old and the median follow-up duration was 4.85 (1-11.91) years. Most of the patients had no underlying disease (n=337, 94.1%). The most common reason for ordering ANA testing was to evaluate musculoskeletal system symptoms (n=225, 62.8%). None of our patients referred to us due to ANA positivity developed any autoimmune conditions or ANA associated rheumatic disease. Hypermobility syndrome is the most common final diagnosis among our ANA-positive patients CONCLUSION: We suggest that instead of using it as a screening tool, ANA testing should be performed if only there is a strong suspicion of autoimmune diseases or certain rheumatic conditions such as systemic lupus erythematosus.

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is a polygenic disease with unknown etiology. In this retrospective cohort study, we aimed to evaluate the risk factors for the resolution of PFAPA syndrome within 4 years after the onset.In total, 466 patients with PFAPA syndrome that are being followed up our department were included into the study. Between May 2020 and September 2020, medical charts of the patients were reviewed retrospectively.The median age of the patients at the time of the study and at disease onset were 8.6 (2.9-20.5; IQR 6.9-10.6) years and 18 (1-84; IQR 11-31) months. On univariate analysis age at disease onset (p = 0.003), positive family history of PFAPA syndrome (p = 0.04), absence of myalgia (p = 0.04), and absence of headache (p = 0.003) were all associated with the resolution of PFAPA syndrome within 4 years after the onset. Multivariate logistic regression analysis revealed that age at disease onset (OR 1.04, 95% CI 1.01-1.07, p = 0.002), positive family history of PFAPA syndrome (OR 2.69, 95% CI 1.12-6.48, p = 0.02), and absence of headache (OR 0.2, 95% CI 0.05-0.74, p = 0.01) were independent risk factors for the resolution of PFAPA syndrome within 4 years after the onset.We report later age of disease onset, positive family history of PFAPA syndrome, and absence of headache as independent risk factors for resolution of PFAPA syndrome within 4 years after the onset.• Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is a multifactorial disease with unknown etiology. • Although, PFAPA syndrome usually resolves within 3-5 years after the disease onset, it can persist for years and even continue into adulthood. With our current knowledge, there is no clue to predict which patients will have a long disease course and which patients will not. • Later age of disease onset, positive family history of PFAPA syndrome and absence of headache as independent risk factors for resolution of PFAPA syndrome within 4 years after the onset.

The purpose of the study was to examine the effects of sense and functionality changes in the hands on activity and participation in patients with juvenile scleroderma (JS).Sixteen patients with juvenile localized scleroderma (JLS), 14 patients with Juvenile Systemic Sclerosis (JSS), and 30 healthy controls were included. Light touch-deep pressure sensation was assessed by Semmes-Weinstein monofilament test (SWMT). Localization sensation testing was performed by lightly stroking the patient's skin. The hand joint range of motion was measured with a goniometer, hand grip strength with Dynomometer, the pinch gripping force with pinch meter, and the hand mobility with modified Hand Mobility in Scleroderma (mHAMIS). Children completed their activity and participant performance status with 'Childhood Health Assessment Questionnaire (CHAQ)' and 'Jebson Taylor Hand Function Test (JTHFT)' questionnaire tests. The quality of life was evaluated using the 'Scleroderma Health Assessment Questionnaire (SHAQ)'.There were significantly differences among evaluated three groups in light of touch-deep pressure sensation, sense of touch localization, range of motion, mHAMIS scores, JTHFT scores, all CHAQ scores, and almost all SHAQ score (Sensory and functional disorders caused by hand involvement in JS patients result in limitation of daily living activities and affect negatively the effective usage of the hand. Approximately half of the JS patients had disabilities in performing pinch motor skills of hands. The assessment of sensory symptoms that affect the functionality, activity level and participation of JSS and JLS patients should be considered during the routine clinical examination. We suggest the sensory therapies as an important factor in increasing the effectiveness of rehabilitation.

Objective Over the last 2 decades, the usage of biological agents in the treatment of juvenile idiopathic arthritis (JIA) has been a successful and promising approach in controlling disease activity and preventing chronic sequelae. However, there are ongoing concerns about the long-term safety data and side-effect profile. We aimed to present preliminary data on the incidence of malignancy in patients with JIA treated with biological agents versus the general population rates in Turkey. Method A single-center hospital-based cohort study was performed to analyze cancer occurrence among JIA patients treated with biologic agents during the observation period between January 2004 and May 2019. As reference data for direct standardization, age, gender, and calendar year-specific incidence rates from the Turkish cancer registry were used. The standardized incidence ratio (SIR, ratio of cancers observed to expected) was generated with 95% confidence intervals. Results The study sample consisted of 1023 JIA patients who had been treated with biologic or non-biologic agents. In the biologic-experienced group (n = 656), the mean age (at the study) was 16.7 ± 5.6 years. The mean length of follow-up was 9.9 ± 5.0 years. One cancer was detected within the observation period (SIR: 1.3, 95% CI: 0.06-6.3). The patient was an 18-year-old male who had previously received etanercept and tocilizumab until the diagnosis of the hematologic malignancy (SIR: 2.5, 95% CI: 0.1-12.6). Conclusion Patients treated with biologic agents appeared to have an increased rate of incident hematologic malignancy versus the general population in Turkey. However, before mentioning a clear causal relationship, other potential contributing factors should be taken into consideration.

YILDIZ, Mehmet/0000-0002-7834-4909; Sahin, Sezgin/0000-0002-5365-3457; Kasapcopur, Ozgur/0000-0002-1125-7720; Haslak, Fatih/0000-0002-6963-9668; Barut, Kenan/0000-0001-8459-2872 WOS:000548231000002 PubMed ID: 32661928 Concerns regarding the comorbidity as a significant risk factor for Coronavirus Disease-2019 (COVID-19), gave rise to an urgent need for studies evaluating patients with chronic conditions such as autoinflammatory diseases (AIDs). We prepared a web-based survey investigating the clinical findings and contact histories among pediatric patients with AIDs. Confirmed COVID-19 cases, patients with contact history and those with symptoms which were highly suggestive of COVID-19 were called via phone or recruited to a video or face to face appointment. Data of AIDs were obtained from their medical records, retrospectively. Laboratory and screening findings were confirmed by our national health registry website. There were 404 patients (217 female) eligible for the enrollment. During pandemic, 375 (93%) were on colchicine treatment and 48 (11.8%) were receiving biologic treatment. Twenty-four out of 404 patients were admitted to hospital due to COVID-19 suspicion. Severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) was identified through rhinopharyngeal swabs in seven patients, six of whom were only on colchicine treatment. Only one patient with no finding of any severe respiratory complications was hospitalized. All of seven patients recovered completely. Among patients on biologic drugs, neither a symptom nor a positive polymerase chain reaction test for COVID 19 was detected. In conclusion, pediatric patients with AIDs, those receiving biologic treatment and/or colchicine, may not be at increased risk for neither being infected nor the severe disease course.

Although it is well-known that autoimmune thyroid diseases are more common in most of the autoimmune connective tissue diseases, the relationship between autoinflammatory diseases and autoimmune thyroid diseases has not well-evaluated yet and still remains unclear. The aim of this study was to investigate the frequency of autoimmune diseases of the thyroid gland and to evaluate thyroid function tests in children with familial Mediterranean fever. Thyroxine, thyroid-stimulating hormone, and thyroid autoimmune markers such as thyroid peroxidase and thyroglobulin antibodies, and thyroid ultrasound findings of 133 patients with familial Mediterranean fever and 70 healthy controls were evaluated. Serum levels of thyroid-stimulating hormone, free thyroxine, and thyroid autoimmunity markers were similar in patients with familial Mediterranean fever compared with healthy controls. There was no relationship between the duration of the disease and thyroid-stimulating hormone, free thyroxine, anti-thyroid peroxidase, and anti-thyroglobulin levels. This study revealed that incidence of thyroid dysfunction and autoimmunity is not increased in patients with familial Mediterranean fever. In conclusion, routine screening of serum thyroid function tests and thyroid antibody levels is not required in patients with familial Mediterranean fever in the absence of clinical symptoms or family history. Key Points • It is well-known that autoimmune thyroid diseases are common in autoimmune diseases. • The relationship between autoimmune thyroid diseases and autoinflammatory diseases like familial Mediterranean fever is still unclear. • In this study, we report the similar frequency of the autoinflammatory thyroid diseases in patients with familial Mediterranean fever and healthy controls. • A routine screening of serum thyroid function tests and thyroid antibody levels may not be required in patients with familial Mediterranean fever in the absence of clinical symptoms or family history.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. The disease is divided in different subtypes based on main clinical features and disease course. Emergence of biological agents targeting specific pro-inflammatory cytokines responsible for the disease pathogenesis represents the revolution in the JIA treatment. Discovery and widespread usage of biological agents have led to significant improvement in JIA patients’ treatment, with evidently increased functionality and decreased disease sequel. Increased risk of infections remains the main discussion topic for years. Despite the slightly increased frequency of upper respiratory tract infections reported in some studies, the general safety of drugs is acceptable with rare reports of severe adverse effects (SAEs). Tuberculosis (TBC) represents the important threat in regions with increased TBC prevalence. Therefore, routine screening for TBC should not be neglected when prescribing and during the follow-up of biological treatment. Malignancy represents a hypothetical complication that sometimes causes hesitations for physicians and patients in its prescription and usage. On the other hand, current reports from the literature do not support the increased risk for malignancy among JIA patients treated with biological agents. A multidisciplinary approach including a pediatric rheumatologist and an infectious disease specialist is mandatory in the follow- up of JIA patients. Although the efficacy and safety of biological agents have been proven in different studies, there is still a need for long-term, multicentric evaluation providing relevant data.

Since concerns have been raised that comorbidity is a significant risk factor for Coronavirus Disease-2019 (COVID-19), there is an urgent need to perform studies which evaluate patients with chronic diseases such as autoinflammatory diseases (AIDs). We prepared a web-based survey investigating the clinical findings and contagion histories. Patients with AIDs, were included in the study. Confirmed COVID-19 cases, patients with contact history and patients with symptoms which were highly suggestive of COVID-19 were called via phone or recruited to a video or face to face appointment. Data of AIDs were obtained from their medical records, retrospectively. Laboratory and screening findings were confirmed by using our national health registry website and they were re-examined, if required. There were 404 patients (217 female) eligible for the enrollment. During pandemic, 375 (93%) were on colchicine treatment, and 48 (11.8%) were receiving biologic treatment. 24 out of 404 patients had admission to hospital due to COVID-19 suspicion. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were identified through rhino-pharyngeal swabs in 7 patients, 6 of whom were only on colchicine treatment. Only one patient with no finding of any severe respiratory complications has been hospitalized. All of them recovered completely. Among patients on biologic drugs, neither a symptom nor a positive polymerase chain reaction test was detected that would have been suggestive of COVID-19. In conclusion, pediatric patients with AIDs, those receive either biologic treatment or colchicine may not be at increased risk for either being infected or having worse disease course.

Spondyloenchondrodysplasia (SPENCD) is a rare skeletal dysplasia characterized with platyspondyly and metaphyseal lesions of the long bones mimicking enchondromatosis, resulting in short stature. SPENCD often coexists with neurologic disorders and immune dysregulation. Spasticity, developmental delay and intracranial calcification are main neurologic abnormalities. Large spectrum of immunologic abnormalities may be seen in SPENCD, including immune deficiencies and autoimmune disorders with autoimmune thrombocytopenia and systemic lupus erythematosus as the most common phenotypes. SPENCD is caused by loss of tartrate-resistant acid phosphatase (TRAP) activity, due to homozygous mutations in ACP5, playing a role in non-nucleic acid-related stimulation/regulation of the type I interferon pathway. We present two siblings, 13-year-old girl and 25-year-old boy with SPENCD, from consanguineous parents. Both patients had short stature, platyspondyly, metaphyseal changes, spastic paraparesis, mild intellectual disability, and juvenile-onset SLE. The age at disease-onset was 2 years for girl and 19 years for boy. Both had skin and mucosa involvement. The age at diagnosis of SLE was 4 years for girl, and 19 years for boy. The clinical diagnosis of SPENCD was confirmed by sequencing of ACP5 gene, which revealed a homozygous c.155A > C (p.K52T), a variant reported before as pathogenic. Juvenile-onset SLE accounts for about 15–20% of all SLE cases. But, the onset of SLE before 5-years of age and also monogenic SLE are rare. Our case report and the literature review show the importance of multisystemic evaluation in the diagnosis of SPENCD and to remind the necessity of investigating the monogenic etiology in early-onset and familial SLE cases.

OBJECTIVE The use of tumor necrosis factor inhibitors (anti-TNF) has a risk of activating latent tuberculosis infection (LTBI). This study was performed to investigate LTBI according to tuberculin skin test (TST) size and to determine the frequency of tuberculosis (TB) in bacillus Calmette-Guerin (BCG)-vaccinated children receiving anti-TNF treatment for rheumatological disease. MATERIALS AND METHODS The study consisted of 559 children. Information on demographics, anti-TNF agents, TST size, and isoniazid (INH) prophylaxis was recorded. Patients (n = 254) with TST size ≥5 mm were divided into three groups according to TST size and INH prophylaxis: group 1, TST size 5 to 9 mm and no INH prophylaxis; group 2, TST size 5 to 9 mm with INH prophylaxis; and group 3, TST size ≥10 mm with INH prophylaxis. RESULTS The 559 patients comprised 314 (56.3%) females and 245 (43.6%) males; they had a mean age of 13.1 ± 4.1 years. The mean TST size in all patients was 4.2 ± 4.7 mm. Group 1 consisted of 76 (29.9%) patients, group 2 consisted of 88 (34.6%) patients, and group 3 consisted of 90 (35.4%) patients. The mean TST sizes for the three groups were 6.8 ± 3.1 mm, 7.2 ± 3.2 mm, and 13.9 ± 2.8 mm, respectively. New TB was diagnosed in only two (0.35%) patients. Both of them were in group 3. CONCLUSIONS A TST size of ≥10 mm in BCG-vaccinated children receiving anti-TNF treatment may distinguish children at high risk for reactivation of LTBI.

Objectives This study aims to determine the prevalence of Fabry disease (FD) among patients with juvenile systemic lupus erythematosus (SLE). Patients and methods This cross-sectional study included 76 juvenile SLE patients (12 males; 64 females; mean age 16±3.3 years; range, 8 to 23.5 years) who were diagnosed according to 1997 update of the 1982 American College of Rheumatology revised criteria for classification of SLE. Since the majority of patients were female, alpha-galactosidase A gene was investigated for mutations resulting in FD. Lysosomal accumulation of globotriaosylsphingosine (lyso-Gb3) was further evaluated in mutation positive subjects by using dried blood spot testing. Results Alpha-galactosidase A gene screening did not yield any positive mutation in our 74 subjects. However, a heterozygous p.D313Y mutation was found in two females. These subjects were further investigated for lyso-Gb3 levels in dried blood spot samples and the levels of lyso-Gb3 being normal lead to exclusion of FD in these two patients. Conclusion We do not suggest routine screening of FD in patients with juvenile SLE; however, prospective studies with larger sample sizes are needed for further analysis.

Behcet's Disease was first described by a Turkish dermatologist, Hulusi Behcet, in 1937 as a triple symptom complex; aphthous stomatitis, genital ulcers, and uveitis. Today, in light of current trials and experiments, we know that the disease may have a wider involvement with a multisystemic recurrent course, causing significant morbidity and mortality. However, there are still unanswered questions, particularly about Pediatric Behcet's Disease. Although several immunological and genetic associations have been demonstrated, the real etiologic mechanism of the disease is unclear. The diagnosis is difficult due to its rarity in childhood, the lack of validation of the diagnostic criteria obtained from adult studies, and the inadequacy of large case-controlled studies. Also, the management is challenging and controversial due to the various geographic distribution of clinical spectrum. New therapeutic options under development in light of pathogenetic hypothesis seem to be promising.

Background/aim: The aim of this study is to evaluate the effect of biologic drugs on the tuberculin skin test in patients with juvenile idiopathic arthritis.Materials and methods: A total of 234 biologic drug-using juvenile idiopathic arthritis patients and 45 healthy controls were enrolled in the study. The tuberculin skin test results of the patients, which had been routinely provided during follow-up, were obtained from the patient files. Tuberculin skin test values of ≥ 5 mm were considered to be positive. Results: The mean diameter of tuberculin skin test induration was 4.99 ± 6.84 mm (IQR: 0-10 mm) and 7.83 ± 3.47 mm (IQR: 0-16 mm) in patients and controls, respectively (P < 0.05). Tuberculin skin test positivity (≥5 mm) was found in 96 (41%) and 38 (84.4%) of patients and controls, respectively (P < 0.001). There was no induration in 125 (53.4%) patients and 3 (6.6%) healthy controls, respectively (P < 0.001).Conclusion: In the patients with juvenile idiopathic arthritis who were using biologic drugs, tuberculin skin test induration was significantly lower compared to the control group. Tuberculin skin tests alone seem inadequate for recognition of latent tuberculosis in juvenile idiopathic arthritis patients on anti-TNF therapy.

The most effective and concurrently the safest treatment regimen selection is important to provide early control of juvenile idiopathic arthritis (JIA) and to have an acceptable quality of life. The effectivity of biologic agents as well as standard disease-modifying drugs is well documented in treatment of JIA. In spite of their high benefit, these drugs have the risk of serious infections. Herein, we conducted a prospective study to investigate the infectious complications of biologic agents in patients diagnosed with JIA. Patients on biologic treatment regimen were examined by the pediatric infectious disease specialist in every 2 months during 1-year long. Throughout the study period, 57% (n:175) of the patients developed infection and 43% (n:132) of them completed this period without any infection. Upper respiratory tract infections which were treated in outpatient clinic were the most common infection. Only three serious infections (two pneumonia, one pleural effusion), which required hospitalization, developed. The infection rate was highest in systemic JIA and lowest in enthesitis-related arthritis (p

The objective is to evaluate the walking distance and oxygen desaturation during the six-minute walk test and to establish correlations between the test results and other clinical findings so to assess the reliability of the test for evaluation of children with juvenile systemic sclerosis (jSSc). A total of 25 jSSc, 27 juvenile systemic lupus erythematosus (jSLE), and 30 healthy controls were included. The test is conducted according to the guidelines recommended by the American Thoracic Society, standardized in 2002. Median values of walking distances were 470 (415–580) m in jSSc; 518 (376–618) m in jSLE; and 562 (493.5–618) m in healthy controls. jSSc patients walked significantly less distance comparing to controls (p

Introduction: Juvenile systemic sclerosis is an orphan disease. Currently, the majority of juvenile systemic sclerosis cohort studies are retrospective in design without standardized assessment. This study was conducted prospectively to investigate the difference in manifestations of limited cutaneous juvenile systemic sclerosis and diffuse cutaneous juvenile systemic sclerosis subtypes. An additional aim was to compare these data to other juvenile systemic sclerosis cohorts and a large adult systemic sclerosis cohort. Methods: Patients fulfilling the Paediatric Rheumatology European Society juvenile systemic sclerosis classification criteria were included. Clinical characteristics and patient-related outcomes were assessed. Results: In all, 88 patients with a mean disease duration of 3.5 years were enrolled, 72.5% with diffuse cutaneous juvenile systemic sclerosis with a mean modified Rodnan Skin score of 18 and 27.5% with limited cutaneous juvenile systemic sclerosis with mean modified Rodnan Skin score of 9. The mean age at the onset of Raynaud’s and first non-Raynaud’s symptoms was similar in both groups, approximately 9 and 10.5 years. Active digital tip ulcerations were present in 29% diffuse cutaneous juvenile systemic sclerosis and none in the limited cutaneous juvenile systemic sclerosis subjects (p = 0.005). Of those with cardiopulmonary testing, 3% of diffuse cutaneous juvenile systemic sclerosis and 23% of limited cutaneous juvenile systemic sclerosis group had cardiac involvement (p = 0.015), and 41% diffuse cutaneous juvenile systemic sclerosis and 22% of the limited cutaneous juvenile systemic sclerosis group had pulmonary involvement (p = 0.009). Physician global disease damage assessment was higher in the diffuse cutaneous juvenile systemic sclerosis group compared to the limited cutaneous juvenile systemic sclerosis group: 35 and 15 (p = 0.021). Discussion: The majority of this international juvenile systemic sclerosis cohort had diffuse cutaneous juvenile systemic sclerosis (72.5%) with more frequent vascular and pulmonary involvement compared to the limited cutaneous group, who had increased cardiac involvement. Our cohort reflects prior findings of published juvenile systemic sclerosis cohorts and emphasizes a difference in the presentation compared to adult-onset systemic sclerosis.

Objectives This study aims to evaluate the levels of serum endocan in children with juvenile idiopathic arthritis (JIA). Patients and methods Sixty-seven children with JIA (30 males, 37 females; mean age 10.4±4.9 years; range 2 to 18 years) and a sex- and age- matched healthy control group of 39 children (16 males, 23 females; mean age 9.3±4.1 years; range 1 to 17 years) were recruited. Patients with JIA were divided into two groups as the clinically active JIA group (n=27) and inactive JIA group (n=40). Results The median serum endocan level in patients with JIA was significantly higher than in the control group (633.75 ng/L vs. 379.76 ng/L, p

Aim Familial Mediterranean fever is an inherited condition that is more prevalent in some regions of Turkey. Juvenile idiopathic arthritis is the most common chronic arthritis of childhood. There is lack of studies on the frequency of mentioned conditions across different regions of Turkey. We aimed to compare the Familial Mediterranean fever and juvenile idiopathic arthritis patients according to their family origin. Material and methods Patients with diagnosis of familial Mediterranean fever and juvenile idiopathic arthritis followed up at the Division of Pediatric Rheumatology were assessed. Data regarding the family origin of patients were noted from their medical records. Both groups were compared according to their origins. Results A total of 704 patients with Familial Mediterranean fever, 204 patients with juvenile idiopathic arthritis were enrolled. The main age of the patients at the study time was 12.3±4.4 years and 12.1±4.8 years, respectively. The frequency of familial Mediterranean fever was significantly higher in subjects with the origin of Black Sea and Central Anatolia regions (z score 2.69, and 3.69, respectively). Juvenile idiopathic arthritis was significantly more common in subjects from Marmara and Southeastern Anatolia regions (z score -4.11 and -2.54, respectively). Conclusion The familial Mediterranean fever is more common among subjects from the Black Sea and Central Anatolia regions of Turkey, especially Kastamonu, Sivas and Tokat provinces. Whereas, patients with juvenile idiopathic arthritis more commonly originate from Marmara and Southeastern Anatolia regions of Turkey.

Objectives This paper aims to assess in a retrospective fashion the clinical and laboratory features, severity and outcome of juvenile systemic lupus erythematosus (jSLE) from a referral center in Turkey. Methods We have included all jSLE patients ( n = 92) diagnosed according to the revised American College of Rheumatology 1997 criteria between January 2004 and January 2017. Results The most prevalent clinical feature in our cohort was mucocutaneous manifestations (97.8%), followed by constitutional (81.5%), hematological (59.8%) and musculoskeletal manifestations (56.5%). Renal involvement was observed in 38% ( n = 35) of the patients, whereas biopsy-proven lupus nephritis was detected in 29.3% ( n = 27) of the cohort. Neurologic involvement was seen in 15 (16.3%) individuals. Among the patients positive for anticardiolipin IgM and/or IgG ( n = 11, 12%), only three developed antiphospholipid antibody syndrome. The mean SLEDAI-2K scores at disease onset (10.5 ± 4.8) showed a substantial decrease at last visit (4.3 ± 4.6). One-quarter of the patients (26.1%, n = 24) had damage according to the PedSDI criteria with a mean score of 0.45 ± 1.0 (range 0–7). When the PedSDI damage items were evaluated individually, growth failure was the most frequent damage criterion ( n = 6), followed by seizure ( n = 5). Two patients died during the designated study period of end-stage renal disease. The five-year and 10-year survival rate of our cohort was 100% and 94.4%, respectively. Conclusions Given the lower frequency of nephritis and central nervous system disease and lower basal disease activity and damage scores, we could conclude that children with jSLE in Turkey have a more favorable course compared to Asian and African American children, as expected from Caucasian ethnicity.

Juvenile spondyloarthropathies (JSpA) are a group of rheumatologic diseases with a disease onset before 16; characterized with enthesitis, lower extremity oligoarthritis, involvement of the axial skeleton and HLA B27 positivity. The diversity of classification criteria along with the phenotype heterogeneity makes the classification of JSpA challenging. The aim of our study was to evaluate the performance of the pre-determined and recently proposed classification criteria for JSpA. The study group consisted of 113 patients with JSpA and 150 patients with juvenile idiopathic arthritis (JIA). Eligible criteria for JSpA were applied to all of the enrolled patients. The analysis of sensitivity, specificity and the kappa index were used to verify the performance of the JSpA criteria. The Amor criteria showed the highest sensitivity (98.2%) while the ASAS criteria for the axial SpA had highest specificity (100%). The sensitivity and specificity of the remaining criteria were: 93.8 and 63.8% for ESSG, 95.6 and 62.7% for Garmisch-Partenkirchen, 91.2 and 75.3% for ASAS criteria for peripheral SpA, respectively. Criteria proposed by our group showed the high sensitivity, specificity and kappa value: 90.3, 90.7, 0.843%, respectively. We suggest that criteria proposed by us could be used in the classification of JSpA. However, neither the pre-determined nor the new criteria are totally adequate and efficacious for the classification and diagnosis of this disease. The evaluation of the validity and reliability of proposed criteria in multicentric studies are mandatory, to increase its utility in routine clinical practice.

Cardiac manifestations in juvenile scleroderma or systemic sclerosis (JSSc) have poor prognosis, begin in early stages of the disease, and remain clinically asymptomatic. New echocardiography modalities, such as 2D/3D speckle tracking (STE, strain analysis for regional and global ventricular functions), can detect cardiac involvement in early stages. We assessed 21 JSSc patients and 19 controls using 2D/3D STE. The left ventricular end diastolic volume, end systolic volume, and ejection fraction of the patient and control groups were significantly different (99.2 ± 23.8 vs. 52 ± 23.8, 40.6 ± 16.0 vs. 20.2 ± 17.4 and 59.2 ± 7.5 vs. 65.6 ± 5.2, respectively). Global longitudinal strain (GLS) and global circumferential strain (GCS) were lower in the patient group (18.4 ± 4.7 vs. 22.4 ± 3.7, 26.4 ± 5.8 vs. 31.4 ± 3.5), as were the peak systolic strain values of the right ventricular longitudinal strain (RVLS) septum and RVLS free wall (18.1 ± 6.8 vs. 24.8 ± 6.0 and 22.8 ± 5.9 vs. 28.0 ± 6.9, respectively). 3D measurements of RVEDV, RVESV, and RVSV were higher in the patient group (88.2 ± 31.3 vs. 50.8 ± 23.5, 43.1 ± 17.6 vs. 19.0 ± 12.2, and 45.0 ± 16.2 vs. 31.7 ± 12.6). RVLS freewall results were lower in the JSSc patients with interstitial lung fibrosis, arthritis, muscle weakness, weight loss, and anti-scl 70 antibodies than in the JSSc patients without these variables. We found that a GCS of

There is no documentation about the association between peer victimization, psychological status, and quality of life (QOL) in children and adolescents with systemic lupus erythematosus (SLE). The aim of this study was to evaluate the association between peer victimization, psychological symptoms, and QOL in a cohort of children and adolescents with SLE. Forty-one patients (aged 9-18 years) participated in this study. The control group (n = 49) was composed of healthy children and adolescents from local community. Questionnaires were used to evaluate the peer victimization, psychological status, and QOL of children and adolescents with and without SLE. No significant difference was found between the study and control groups for peer victimization, depression, state and trait anxiety, and QOL scores. The peer victimization, depression, anxiety, and self-esteem scores were negatively correlated with psychosocial and total subscale scores of QOL in the study group. According to regression analyses, trait anxiety had a negative predictive effect on the physical health domain scores of QOL, whereas trait anxiety and peer victimization had a negative effect on the psychosocial domain and total scores of QOL in the SLE patients. This study suggests that trait anxiety and peer victimization are risk factors for poor QOL in adolescents with SLE.

Speckle-tracking echocardiography is a recently developed technique for the evaluation of myocardial deformation or strain. Our objective was to examine strain through a mid-term follow-up of patients with Kawasaki disease.MethodsWe explored left ventricular mechanics using speckle-tracking echocardiography in 35 patients with a history of Kawasaki disease at least 6 months after the acute phase. We also included 30 healthy children as controls. Strain data sets were acquired for the quantification of left ventricular global strain, segmental strain, and left ventricular ejection fraction.ResultsThe mean age of our patients was 25.6±15.4 months. At a median follow-up of 57.5 months (16.5–98.2), although both values were in the normal range, the mean left ventricular ejection proportion of patients (57.3%) was a little lower than that of controls (p⩽0.05). Patient strain values at the basal inferoseptal (20.0), basal anterolateral (19.5), apical septal (23.3), and apical inferior (24.0) segments were lower compared with controls. In all, seven patients had coronary aneurysms during follow-up. Kawasaki disease patients with pyuria had lower left ventricular strain at the mid anterior, mid anteroseptal, apical anterior, and apical inferior segments and global longitudinal strain compared with patients with no pyuria (p⩽0.05).ConclusionIn children with a history of Kawasaki disease, impairment of left ventricular mechanics occurs especially within the left anterior descending artery territories.