Severe haematological involvement in children with systemic lupus erythematosus and clinical associations.

OBJECTIVES: To investigate the severe haematological involvement in children with SLE and assess its clinical associations, treatments, outcome and damage accrual. METHODS: The medical charts of children with SLE in whom haematological involvement was observed were reviewed. Severe haematological indices were defined as autoimmune haemolytic anaemia with a haemoglobin concentration < 8 g/dL, thrombocyte count < 30 000/µL, and neutrophil count < 500/µL. RESULTS: Among the 224 patients included, 102 (45.5%) displayed severe indices, predominantly at the initial involvement, and most frequently as severe anaemia in 54 (24.1%) and severe thrombocytopenia in 45 (20.1%). Disease activity did not differ according to the presence of severe disease indices. In addition, the presence of severe indices at initial involvement did not affect the damage accrual. However, a higher rate of damage (51.1% vs. 29.9%, p = 0.002) and steroid-induced damage (28.9% vs. 8.2%, p < 0.001) was evident in patients with flares of the haematological system. Regression analysis revealed that rituximab treatment during the initial episode (OR:4.5, p = 0.006) and the presence of anticardiolipin antibodies (OR:2.3, p = 0.014) significantly increases the odds for haematological system flare. However, severe indices at initial involvement did not increase the odds of a haematological flare. CONCLUSION: Severe haematological indices at onset are common but not related with disease outcomes. Prevention of flares is important to improve outcomes, and a more rigorous maintenance strategy would benefit most to children who display haematological indices refractory to conventional immunosuppressants and those with anti-cardiolipin antibodies.

Exploring factors for predicting colchicine responsiveness in children with PFAPA.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) are the most common autoinflammatory syndromes in children. This study aimed to evaluate the clinical and laboratory parameters that may predict colchicine responsiveness.This retrospective, multicenter, cross-sectional study involved nine pediatric rheumatology centers from our country., The patients diagnosed with PFAPA were compared on the basis of their responses to colchicine. In the 806 (42.3% female 57.7% male) patients, the most common clinical findings were fever (100%), exudative tonsillitis (86.5%), pharyngitis (80.9%), and aphthous stomatitis (50.5%). The mean attack frequency was 13.5 ± 6.8 attacks per year lasting for a mean of 3.9 ± 1.1 days. Colchicine treatment was attempted in 519 (64.4%) patients, with 419 (80.7%) showing a favorable response. In patients who underwent MEFV gene analysis (70.8%), the most common variant was M694V heterozygous (16.8%). The presence of pharyngitis (p = 0.03, 95% CI 0.885 to 0.994), the presence of arthralgia (p = 0.04, 95% CI 0.169 to 0.958), and having more frequent attacks (p = 0.001, 95% CI 0.028 to 0.748) were found to be associated with colchicine unresponsiveness, whereas the carriage of the M694V variant (p = 0.001, 95% CI 0.065 to 0.242) was associated with colchicine responsiveness. CONCLUSION: This study identified the presence of pharyngitis, arthralgia, and increased attack frequency in patients with PFAPA as factors predicting colchicine unresponsiveness, whereas the carriage of the M694V variant emerged as a predictor of colchicine responsiveness. Predicting colchicine response at disease onset may facilitate a more effective management of PFAPA. WHAT IS KNOWN: • Colchicine treatment can be used in the prophylaxis of PFAPA disease. • Having the MEFV variant is the most commonly known factor in predicting response to colchicine. WHAT IS NEW: • The presence of pharyngitis or arthralgia, and more frequent attacks in PFAPA disease were found to be independently associated with colchicine unresponsiveness. • Carrying the M694V variant was identified as the sole factor predicting colchicine responsiveness.

Endoscopic characterization of gastrointestinal manifestations in children with undifferentiated recurrent fever.

BACKGROUND AND STUDY AIMS: Systemic autoinflammatory diseases are characterized by recurrent or chronic inflammation, and monogenic forms are increasingly defined. However, a group of patients without genetic diagnosis is called the syndrome of undifferentiated recurrent fever (SURF). This study analyzed the clinical and endoscopic features of patients with SURF presenting with gastrointestinal (GI) symptoms. PATIENTS AND METHODS: Between 2019 and 2022, GI endoscopy were performed in patients with SURF who presented with GI symptoms. Clinical, genetic, laboratory, and endoscopy findings were analyzed. RESULTS: Fifteen patients were included in the study, eight (53.3 %) were girls. The mean age was 10.5 ± 5.80 years, and the median age at symptom onset was 4 (0.3-16) years. All patients experienced fever and abdominal pain. Thirteen patients (86.7 %) experienced diarrhea, 11 (73.3 %) reported myalgia, and 10 (66.7 %) had joint involvement. Lymphoid follicles in the terminal ileum mucosa were detected in 10 patients (66.7 %), and nodular lymphoid hyperplasia in the terminal ileum was the histopathological finding in 12 patients (80 %). CONCLUSIONS: The current study found that patients with SURF experiencing gastrointestinal symptoms have excessive lymph node formation in the terminal ileal mucosa due to an exaggerated inflammatory response. This may be the cause of their GI symptoms.

Retinal vessel density and choroidal flow changes in oligoarticular juvenile idiopathic arthritis with and without uveitis.

PURPOSE: This cross-sectional optical coherence tomography angiography (OCTA) study aimed to assess the macular and optic nerve head (ONH) vascular density, foveal avascular zone, and outer retina and choriocapillaris flow in oligoarticular juvenile idiopathic arthritis (oJIA). STUDY DESIGN: Prospective. METHODS: Twenty-two eyes of 22 oJIA patients with uveitis (oJIA-U), 20 eyes of 20 oJIA patients without uveitis (isolated oJIA), and 26 healthy volunteers of similar ages and sexes were investigated. The superficial capillary plexus (SCP) and deep capillary plexus (DCP), ONH, foveal avascular zone (FAZ) parameters, the flow area of the outer retina, and choriocapillaris were evaluated. RESULTS: Compared with the control group, both the oJIA-U group and isolated oJIA group showed significantly decreased vessel density of parafovea (p = 0.031 and p = 0.047, respectively) in DCP. Choriocapillaris flow area at 1 mm radius was significantly lower in the oJIA-U group compared to the control group (p = 0.001). Choriocapillaris flow area at 2- and 3-mm radius were significantly lower in the oJIA-U group compared to the control group (p < 0.001, for both) and isolated oJIA-U group compared to the control group (p = 0.008 and p = 0.001, respectively). The VD and thickness parameters of SCP and ONH, FAZ, and outer retina flow area were similar between the groups. CONCLUSIONS: oJIA patients with and without uveitis revealed a decreased vessel density in the deep parafoveal region and choriocapillaris flow. Our findings suggest that retinal choroidal microvascular changes could be evident in oJIA-U patients without posterior segment involvement as well as oJIA patients without uveitis.

Cardiac evaluation of patients with juvenile dermatomyositis.

BACKGROUND: The present study aims to evaluate possible cardiac involvement in juvenile dermatomyositis (JDM) patients by conventional methods and cardiac magnetic resonance imaging (MRI) along with a systematic review of the literature on cardiac features in JDM. METHODS: The study group consisted of JDM patients who underwent cardiac MRI. We conducted a systematic review of the published literature involving JDM patients with cardiac involvement. RESULTS: In the present study, although baseline cardiologic evaluations including electrocardiography and echocardiography were within normal limits, we showed late gadolinium enhancement on cardiac MRI in 3 of 11 JDM patients. In the literature review, we identified 25 articles related to cardiac involvement in JDM. However, none of them, except one case report, included cardiac MRI of JDM patients. CONCLUSION: Cardiac abnormalities have been reported among the less frequent findings in patients with JDM. Cardiovascular complications during the long-term disease course are a leading cause of morbidity and mortality in these patients. Early detection of cardiac involvement by cardiac MRI in patients with JDM and aggressive treatment of them may improve the clinical course of these patients. IMPACT: The myocardium in patients with JDM may be involved by inflammation. Myocardial involvement may be evaluated by using contrast-enhanced cardiac MRI. This is the first study evaluating cardiac involvement by cardiac MRI in JDM patients. MRI may show early cardiac involvement in patients whose baseline cardiologic evaluations are within normal limits. Early detection of cardiac involvement by cardiac MRI may improve the long-term prognosis of patients with JDM.

The Association of Behçet's Disease on the Quality of Life for Children and Their Parents.

Background and Aim Chronic diseases profoundly impact people's quality of life (QoL). Behçet's Disease (BD) is a multisystemic chronic disease characterized by vasculitis of various vessels. We aimed to assess QoL in pediatric BD patients and their parents. Methods We included pediatric BD patients meeting the pediatric BD classification criteria in a cross-sectional study conducted from June to December 2022. We recorded patients' clinical characteristics and assessed their QoL using PedsQL. Parents' QoL was evaluated using WHOQOL-Bref. Results The study involved 38 patients (60.5% girls, 39.5% boys) with a median age of 15.5 years (10-17) and a disease duration of 2 years (1-4) and their 38 parents. All patients exhibited oral aphthae, and many had other mucocutaneous findings: genital ulcers (78.9%), pseudofolliculitis (76.3%), and erythema nodosum (23.6%). Some patients had uveitis (13.1%), vascular (13.1%), neurological (10.5%), and gastrointestinal (5.2%) involvement. All patients were in remission under treatment during the study. Median PedsQL scores for total, physical health, and psychosocial health were 74.5(40-94.8), 76.5(43-100), and 75(25-92), respectively, with 14 patients scoring below the cut-off value. Girls had lower physical health scores than boys (p=0.004), and a negative correlation emerged between disease duration and PedsQL score (r=0.648, p=0.001). The median WHOQOL score among parents was 50(25-100), with 20 scoring below the cut-off value. Conclusion The QoL was low for one-third of children with pediatric BD and more than half of their parents.Similar to numerous chronic illnesses, factors such as the duration of the disease and gender were associated with the QoL in pediatric BD.

Retrospective evaluation of 130 cases with kawasaki disease follow-up in a tertiary care center in Turkey between 1999 and 2019: a 20-year experience.

OBJECTIVES: Kawasaki disease (KD), which is a medium vessel vasculitis, is common in Asian countries and is the most common cause of childhood-acquired heart diseases in developed countries. However, disease course and epidemiological data are limited in non-Asian developing countries like ours. We aimed to evaluate the clinical features and prognosis of patients with KD in our country and ethnicity, one of the referee centers of our country. METHODS: Patients with KD in our center for the last 20 years in the pre-COVID-19 pandemic era were included in the study. The clinical and laboratory findings, treatments, and follow-up findings were reviewed retrospectively in different age groups. RESULTS: Of the 130 patients, 82 (63%) were male. The median age at diagnosis was 2.97 years (2 months-11.5 years). Thirty-six (27.7%) patients were diagnosed with incomplete KD, and there was no significant laboratory difference between incomplete KD and complete KD patients. Thirty-three (25.3%) patients had coronary artery lesions (CAL), and it persisted in only 3 of 33 patients. One of 15 patients with IVIG resistance had CAL. The independent risk factors were days of illness at initial IVIG administration for CAL (p = 0.013, OR [95%CI] = 1.20 [1.04-1.38]) and low hemoglobin (p = 0.003, OR [95%CI] = 0.51 [0.33-0.79]) and low sodium for IVIG resistance (p = 0.012, OR [95%CI] = 0.81[0.69-0.95]). CONCLUSIONS: The rate of CAL is approximately three times higher in our results than in the Japanese data in recent years. We showed that the time of IVIG administration is the most critical factor for preventing CAL. Wide-ranging studies are needed to decently predict the disease process according to the age and region of patients.

Towards a standardized program of transitional care for adolescents with juvenile idiopathic arthritis for Turkey: a national survey study.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a prevalent childhood chronic arthritis, often persisting into adulthood. Effective transitional care becomes crucial as these patients transition from pediatric to adult healthcare systems. Despite the concept of transitional care being recognized, its real-world implementation remains inadequately explored. This study aims to evaluate the thoughts and practices of healthcare providers regarding transitional care for JIA patients. METHODS: A cross-sectional survey was conducted among pediatric and adult rheumatologists in Turkey. Based on the American Academy of Pediatrics' six core elements of transitional care, the survey included 86 questions. The respondents' demographic data, attitudes towards transitional care, and practical implementation were assessed. RESULTS: The survey included 48 rheumatologists, with 43.7% having a transition clinic. The main barriers to establishing transition programs were the absence of adult rheumatologists, lack of time, and financial constraints. Only 23.8% had a multidisciplinary team for transition care. Participants agreed on the importance of coordination and cooperation between pediatric and adult healthcare services. The timing of the transition process varied, with no consensus on when to initiate or complete it. Participants advocated for validated questionnaires adapted to local conditions to assess transition readiness. CONCLUSIONS: The study sheds light on the challenges and perspectives surrounding transitional care for JIA patients in Turkey. Despite recognized needs and intentions, practical implementation remains limited due to various barriers. Cultural factors and resource constraints affect the transition process. While acknowledging the existing shortcomings, the research serves as a ground for further efforts to improve transitional care and ensure better outcomes for JIA patients transitioning into adulthood.

Evaluation of endothelial dysfunction in hypertensive children and adolescents.

BACKGROUND: Atherosclerotic changes can be attributed to early endothelial damage in individuals with hypertension. We aimed to explore the relationship between endothelial dysfunction and hypertension in newly diagnosed children without end-organ damage, considering carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD), and functional capillaroscopy parameters. We also analyzed the differences between dipper and non-dipper patients. METHODS: In this cross-sectional study, 20 patients diagnosed with essential hypertension with no target organ damage, and 20 age and sex-matched healthy volunteers were enrolled. The patient group comprised newly diagnosed individuals not receiving antihypertensive treatment. Hypertensive patients were divided into two groups (dipper and non-dipper patients). The measurements of CIMT, brachial FMD, and functional capillaroscopy were performed before starting treatment. RESULTS: Among the patients, 11 were boys, and 9 were girls, with a median age of 16.0 (2.13) years. Of 20 hypertensive patients, 10 were dipper and 10 were non-dipper. Significant differences were observed between the hypertensive patients and controls in terms of CIMT (p = 0.04), brachial artery FMD (p = 0.02), and functional capillary density (p < 0.001). Hypertensive patients exhibited increased CIMT, reduced brachial artery FMD, and lower capillary density. However, there were no differences between dippers and non-dippers regarding age, sex, height SDS, weight SDS, CIMT SDS, brachial artery FMD, and capillary density. CONCLUSIONS: Understanding the vascular consequences associated with essential hypertension emphasizes the importance of early detection and management of hypertension. Herein, we have effectively highlighted significant endothelial changes through the analysis of three parameters in newly diagnosed children without apparent target organ damage.

Addressing the unmet needs of transitional care in juvenile idiopathic arthritis.

OBJECTIVES: We aimed to comprehensively analyse the available literature to identify the unmet requirements in transitional programs tailored specifically for patients diagnosed with JIA. METHODS: According to published guidance on narrative reviews, a systematic review of the literature on transitional care in rheumatology was conducted. Pertinent documents were collected from reputable databases, such as Web of Science, Scopus, and MEDLINE/PubMed. The search encompassed literature published from the inception of each database until January 2023. RESULTS: In this study, a comprehensive analysis of the findings of 34 studies was conducted. Among these, 12 studies focused on assessing the readiness of adolescents and young adults diagnosed with JIA. Additionally, 18 studies examined the effectiveness of structured transition programs in terms of adherence and satisfaction. Finally, 4 studies investigated disease-related outcomes in this population. CONCLUSION: The need for transitioning children with rheumatic diseases to adult rheumatology services for continued care is clearly evident. However, the absence of established best practice guidelines presents a challenge in facilitating this transition effectively. Although several scoring systems have been proposed to ensure organized and seamless transfers, a consensus has not yet been reached. Furthermore, the socio-economic and cultural variations across countries further complicate the development of universal guidelines for transitioning children with rheumatic diseases. To address these concerns, our objective in conducting this literature review was to emphasize the significance of this issue and identify the specific requirements based on the unmet needs in the transition process.

Is tear proteome profile a predictor of developing uveitis in ANA-positive patients with oligoarticular juvenile idiopathic arthritis?

PURPOSE: Although less than one-third of anti-nuclear antibody (ANA) positive patients with oJIA develop uveitis, ANA positivity is still the most well-known marker for assessing the risk of uveitis in oligoarticular JIA (oJIA). Therefore, novel biomarkers are needed to better assess the risk of developing uveitis. For this purpose, we performed a comparative tear proteome analysis of uveitis patients to reveal the identity of differentially regulated proteins. DESIGN: Tear samples were collected using the Schirmer strips in 7 oJIA and 7 oJIA patients with uveitis (oJIA-U). All oJIA-U patients had developed bilateral anterior uveitis and were inactive and topical treatment-free. METHODS: The nHPLC LC-MS/MS system was used for protein identification and label-free proteome comparisons. The PANTHER and STRING analyses were carried out using UniProt accession numbers of the identified proteins. RESULTS: Patient characteristics, e.g., age, gender, disease duration, and treatments were similar. For protein identification, three different databases were searched. Twenty-two, 147, and 258 database searches, respectively. Of these, 15 were common to all three proteome databases. Of these 15 proteins, 10 proteins were upregulated, and 2 were downregulated, based on the twofold regulation criteria. The upregulated proteins were, namely, cystatin-S, secretoglobin family 1D member, opiorphin prepropeptide, mammaglobin-B, lysozyme C, mesothelin, immunoglobulin kappa constant, extracellular glycoprotein lacritin, beta-2-microglobulin, and immunoglobulin J chain. The downregulated proteins were dermcidin and prolactin-inducible protein. Among the differentially regulated proteins, cystatin-S was the most regulated protein with an 18-fold upregulation ratio in tear samples from uveitis patients. CONCLUSION: Here, the identities and regulation ratios of several proteins were revealed when tear samples from uveitis patients were compared to patients without uveitis. These proteins are putative biomarkers for assessing uveitis risk and require further attention.

The effect of intra-articular steroid injection on the cartilage and tendon thicknesses in juvenile idiopathic arthritis.

BACKGROUND AND AIM: Intra-articular corticosteroid injection (IACI) is a safe first-line or adjunct therapy that can be used in any subtype of juvenile idiopathic arthritis (JIA). However, limited studies evaluated the effect of IACI on cartilage. As a result, our study aimed to examine the distal femoral cartilage thickness of patients with JIA who received IACI to the knee joint using ultrasound imaging. METHODS: We randomly selected JIA patients who performed IACI in the knee joint. Baseline bilateral joint cartilage and tendons thickness were measured. Then, the articulary fluid was aspirated, and intra articulary steroid was injected during the same period. Six months after injection, the exact measurements were repeated. Exclusion criterias were that patients had IACI past six months of the baseline measurement and more than one IACI during the study period.. Distal femoral cartilage thickness, quadriceps tendon thickness, and distal and proximal patellar tendon thicknesses were compared at baseline (before IACI) and six months after IACI. RESULTS: Thirty patients with JIA were included in the study, and 23 (76.7%) were female. The median age was 11 years (interquartile range (IQR), 6 to 14), and the median disease duration was 3.3 years (IQR, 5 months to 5 years). Subtypes of JIA were oligoarticular in 25 (83.3%), polyarticular in 2 (6.7%), enthesitis-related arthritis in 2 (6.7%), and juvenile psoriatic arthritis in 1 (3.3%). Distal femoral cartilage thickness was 2.96±0.79 mm at baseline and 2.85±0.70 mm at six months after IACI (p=0.35). Also, the tendon thicknesses were the similar at six months after baseline measurements. CONCLUSION: Our findings reveal that knee IACI in patients with JIA did not significantly change cartilage and tendons thicknesses. This observation could indicate that IACIs have no detrimental effects on the cartilage and the tendons.

Clinical usefulness of anti-nuclear antibody in childhood: real-world experience at a tertiary care center : Usefulness of ANA in pediatric autoimmune diseases.

We evaluated the reasons for requesting anti-nuclear antibody (ANA) analysis in clinical practice at a tertiary center and the performance of ANA in pediatric autoimmune diseases. Patients under 18 years of age who underwent ANA testing for various symptoms between 2013 and 2017 were included. We retrieved data from medical records, including demographic and clinical characteristics, diagnoses, ANA results, titers, and staining patterns. The performance assessment tools were calculated according to the ANA titer for autoimmune diseases. Risk factors for autoimmune diseases in ANA-positive patients were evaluated using logistic regression analysis. Changes in ANA titer and seroconversion were evaluated using repeated ANA analyses. A total of 3812 patients underwent ANA. Medical records of 3320 patients were obtained. The rate of ANA positivity was 27.4%. ANA was requested most frequently because of musculoskeletal findings in 1355 patients (40.8%). Juvenile idiopathic arthritis (n = 174, 20.2%) was the most common diagnosis in ANA-positive patients, followed by systemic lupus erythematosus (n = 52, 6%). For autoimmune diseases, a titer of ≥ 1:100, a sensitivity of 40.1%, and a specificity of 77.1% were observed. At a titer ≥ 1:1000, the sensitivity and specificity were 24.1% and 89%, respectively. Homogeneous staining was an additional risk factor for autoimmune diseases in ANA-positive patients by multivariate logistic regression analysis (OR [95% CI]: 4.562 [3.076-6.766], p < 0.001).    Conclusion: Our results revealed that the performance of the ANA test in diagnosing autoimmune diseases in pediatric clinical practice was poor. Therefore, clinical findings should be carefully evaluated before ANA testing is performed. What is Known: • ANA can be detected in systemic autoimmune rheumatic diseases. • The diagnostic role of ANA is controversial, especially in childhood. What is New: • One in four patients who requested the ANA test had an autoimmune disease. • Less than half of patients with an autoimmune disease had ANA positivity.

Neuropsychiatric involvement in juvenile-onset systemic lupus erythematosus: A multicenter study.

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

Effect of comorbid benign joint hypermobility and juvenile fibromyalgia syndromes on pediatric functional gastrointestinal disorders.

OBJECTIVES: Musculoskeletal pain has a considerable frequency in pediatric outpatients. Benign joint hypermobility (BJHS) and juvenile fibromyalgia syndrome (JFMS) are non-inflammatory causes of musculoskeletal pain. In these syndromes, pain is often accompanied by various symptoms such as fatigue, sleep difficulties, mood disorders, cognitive dysfunction, dizziness, headaches, abdominal pain, irritable bowel syndrome, and restless legs syndrome. Functional dyspepsia, functional vomiting, functional abdominal pain, functional constipation, and irritable bowel syndrome all together are termed functional gastrointestinal (GI) disorders. We aimed to evaluate the functional gastrointestinal disorders association of BJHS and JFMS. METHODS: Patients aged 10-18 years who were diagnosed with functional GI disorder in the pediatric gastroenterology department were included in the study. The findings of BJHS and JFMS were evaluated by the pediatric rheumatology department. Scales for anxiety, somatization, and depression were administered by a child psychiatrist. COMPASS 31 scoring was used in autonomic dysfunction. RESULTS: The prevalence of JFMS and BJHS was 64% and 32%, respectively in children with a functional GI disorder. Retrosternal chest pain, dysphagia, early satiation, nausea, vomiting, and regurgitation were common in JFMS (p = 0.007; p = 0.005; p = 0.018; p = 0.002, p = 0.013; p = 0.014, respectively). Gastrointestinal symptoms did not differ with BJHS. One hundred six (88.3%) and 99 (82.5%) had orthostatic intolerance and reflex syncope, respectively. One hundred three (85.6%) had anxiety symptoms, 101 (84.2%) had somatization symptoms, and 102 (85%) had depression symptoms. CONCLUSIONS: Functional GI disorders, JFMS, and BJHS are complex intertwined disorders influenced by emotional distress. Therefore, a multidisciplinary approach is necessary for the diagnosis and treatment process.

Analysis of Meibomian Glands in Juvenile Systemic Lupus Erythematosus Patients without Dry Eye Symptoms and Signs.

PURPOSE: To evaluate meibomian gland loss and its possible association with disease duration and activity in Juvenile Systemic Lupus Erythematosus (JSLE) patients' without dry eye symptoms or signs. STUDY DESIGN: Prospective clinical study. METHODS: Ten eyes of 10 JSLE patients were evaluated using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and 14 eyes of 14 healthy controls were also enrolled. Ocular Surface Disease Index (OSDI) questionnaire and Schirmer I test were performed. Lid margin score, meibum quality and expressibility scores were evaluated. Noninvasive first breakup time (NIF-BUT) and noninvasive average breakup time (NIAvg-BUT), meibomian gland dropout area (MGDA) and meibography scores were evaluated using non-contact meibography (Sirius; CSO). RESULTS: There was no significant difference between the JSLE patients and the healthy controls in the OSDI, NIF-BUT, NIAvg-BUT and Schirmer I tests. Also lid margin score, meibum quality and expressibility scores were not significantly different between the groups. However, JSLE patients had increased upper and lower lid MGDA and increased upper lid, lower lid and total meibography scores compared to the healthy subjects. Furthermore, the duration of JSLE showed a high positive correlation with upper and lower lid MGDA and meibography scores. CONCLUSION: Meibomian gland loss could be observed in JSLE patients with no clinical signs and symptoms of dry eye. Considering the longer life expectancy of children, the positive correlation of disease duration with the meibomian gland reveals the importance of routine eye examinations from the diagnosis of the disease.

Evaluation of liver elasticity with shear-wave elastography in juvenile idiopathic arthritis patients receiving methotrexate.

BACKGROUND: Methotrexate (MTX) is the first-choice disease-modifying drug in juvenile idiopathic arthritis (JIA) treatment. Methotrexate is metabolized in the liver and can cause liver toxicity and fibrosis with long-term use. Ultrasound shear wave elastography (SWE) is a non-invasive method and can detect liver fibrosis by evaluating the liver elasticity. The aim of this study was to assess liver stiffness and detect if there is an increase in liver stiffness or fibrosis findings with the non-invasive SWE method in JIA patients under MTX treatment. METHOD: The study included 49 JIA patients under MTX treatment and 48 healthy controls, matched for age and sex with a body mass index below the 95th percentile. The demographic data and clinical characteristics of patients were obtained from medical records. Liver function tests were evaluated, and liver tissue stiffness measurements were performed with SWE. RESULTS: Of the 49 patients, 67.35% were girls and the mean age was 10.69 (±4.33) years. The duration of MTX treatment was 23.00 (1-80) months, and the cumulative dose of MTX was 1,280.867 mg (±934.2) in the patient group. There was no statistically significant difference in liver stiffness between patients receiving MTX and healthy controls (P = 0.313). There was no relationship between MTX duration, cumulative dose, route of administration, and liver stiffness. Only gamma glutamyl transferase values were weakly correlated with liver stiffness (P = 0.029). CONCLUSIONS: We did not detect an increase in liver tissue stiffness in JIA patients using methotrexate in comparison with controls.

The remarkable characteristics of the children with colchicine-resistant familial Mediterranean fever in Turkey.

OBJECTIVES: Colchicine is the fundamental treatment of familial Mediterranean fever (FMF). Still, 5-10% of patients are not in remission with colchicine treatment. A consensus could not be established for the definition of colchicine resistance in FMF. This study aimed to determine factors that help to predict colchicine resistance in pediatric FMF patients. METHODS: Patients with FMF that age of diagnosis was under 18 years old were included in our study. Fifty colchicine responsive and 33 colchicine-resistant patients were stratified as groups 1 and 2, respectively. Patients' clinical and laboratory findings were evaluated. Logistic regression analysis was used to determine the risk factors of colchicine-resistant FMF. Receiver operating characteristic (ROC) curve analysis was used to identify and compare the predictive performances of colchicine-resistant FMF models. RESULTS: Homozygous exon 10 MEFV mutations were frequent in group 2 (Group 1: 34 (68%), group 2: 32 (97%), p = .013). Univariate analysis showed that the age of onset of symptoms, age of diagnosis, chronic arthritis, myalgia and diarrhea during attacks, and the number of attacks, high ISSF and Pras score, high C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values under colchicine treatment were risk factors for colchicine-resistant FMF. With multivariate analysis, the number of attacks (OR 1.418, CI (95%) 1.149-1.750, p = .001) and high ESR values (OR 1.129, CI (95%) 1.059-1.204, p<.001) were detected as independent risk factors for colchicine-resistant FMF. CONCLUSION: The predictive factors were determined for pediatric colchicine-resistant FMF in our study. The results will help to early diagnosis and treatment of chronic inflammation in FMF.

The clinical course of SARS-CoV-2 infection among children with rheumatic disease under biologic therapy: a retrospective and multicenter study.

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.

Adherence to best practice consensus guidelines for familial Mediterranean fever: a modified Delphi study among paediatric rheumatologists in Turkey.

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.