Description of the Characteristics of the Nailfold Capillary Structure in Healthy Children: A Multi-Centric Study.

BACKGROUND: Nailfold videocapillaroscopy (NVC) is the primary diagnostic tool for the assessment of microcirculation in the pediatric population. OBJECTIVE: To define and standardize age-specific normal NVC patterns in healthy children and adolescents. METHODS: A cross-sectional observational multicentric study was conducted in 564 participants aged 5-17 years. Dino-Lite CapillaryScope 200 Pro Model MEDL4N Pro was performed at 200× magnification. Quantitative and qualitative NVC parameters were analyzed separately for each age group and divided into 4 groups based on age categories. RESULTS: Of the 564 healthy participants, 54.9% were female. A total of 1184 images and 3384 capillaries were analysed. Positive correlations were observed between age and capillary density (p < 0.001, R = 0.450, CI95% 0.398-0.503). There was also a positive correlation between age and arterial/venous, loop diameter and capillary length, whereas there was a weak negative correlation between intercapillary distance. However, no correlation was found between age and capillary width. In addition, capillary density was significantly lower in 5-7 age group compared to the other patient groups. Arterial limb diameter was lower in 5-7 age group, while venous limb diameter was significantly wider in 15-17 age group compared to the other patient groups. Dilated capillaries (8.7%), capillary tortuosity (14.4%), crossed capillaries (43.1%), micro-haemorrhages (2.7%), avascular area (4.8%) were present in all age groups. Excellent intra- and interobserver ICC values were obtained for all parameters. CONCLUSION: These findings hold potential significance for future studies, aiding in the analysis and differentiation of children suspected of rheumatological diseases with potential microangiopathy.

Evaluation of clinical outcomes in systemic juvenile idiopathic arthritis patients treated with biological agents in Turkey: the TURSIS study.

OBJECTIVES: Biological drugs are one of the most effective treatment methods for systemic juvenile idiopathic arthritis (SJIA) and can significantly prevent morbidity and mortality. This study aimed to evaluate the efficacy and safety of biologics in patients with SJIA and provide real-life data that might help improve the outcomes. METHODS: TURSIS was a retrospective multicentre study carried out in patients with SJIA for whom a biological treatment had been initiated between 1st March 2013 and 30th December 2018. Data include patients' characteristics, laboratory-clinical results, outcomes, and safety-related variables. The 24-month follow-up data of the patients and the efficacy and safety of biological drugs were evaluated. RESULTS: 147 patients were enrolled. The clinical course of the disease was as follows; it was monocyclic in 38.1%, polycyclic in 49%, and persistent in 12.9% of patients. First-choice biologics were interleukin (IL)-1 blockers in the majority of patients (56.5%), followed by the anti-IL-6 (25.2%) and anti-TNF-alpha drugs (18.4%). Anakinra was the most preferred biologic agent in patients with macrophage activation syndrome (MAS), and tocilizumab was used more frequently in patients with persistent type (p=0.000 and p=0.003). The most frequent switch rate was seen in patients receiving anakinra (n=40/68, 58.8%), and it was most frequently switched to canakinumab (n=32/40, 80%). Better physician's global assessment scores were achieved in patients treated with anakinra in Month 3, compared to other treatments (p=0.04). CONCLUSIONS: The results of our study support the efficacy of biological drugs in particular anti-IL-1 and anti-IL-6 drugs, in the treatment of SJIA. These treatments resulted in improvement in activity of disease and provide a considerable decrease in the frequency of MAS.

Evaluation of pediatric rheumatologists' approach to rituximab use: a questionnaire study.

Rituximab (RTX) is a chimeric monoclonal antibody that targets the CD20 antigen on B cells and is used in various autoimmune disorders. In this study, we aimed to measure the awareness of pediatric rheumatologists about the use of RTX through a survey. Between February and March 2023, a 42-question survey was sent via email to pediatric rheumatology specialists in Turkey. The participants were questioned for which diagnoses and system involvement they preferred to use RTX, which routine tests they performed, vaccination policy, and adverse events that occurred during or after infusion. Forty-one pediatric rheumatologists answered the survey. They prescribed RTX most frequently for systemic lupus erythematosus (87.8%) and ANCA-associated vasculitis (9.8%). Prior to the administration of RTX, 95% of clinicians checked renal and liver function tests, as well as immunoglobulin levels. The most frequently tested hepatitis markers before treatment were HBsAg and anti-HBs antibody (97.6%), while 85.4% of rheumatologists checked for anti-HCV. Clinicians (31.4%) reported that they postpone RTX infusion 2 weeks following an inactivated vaccine. Sixty-one percent of rheumatologists reported starting RTX treatment 1 month after live vaccines, while 26.8% waited 6 months. The most frequent adverse events were an allergic reaction during RTX infusion (65.9%), hypogammaglobulinemia (46.3%), and rash (36.6%). In the event of hypogammaglobulinemia after RTX treatment, physicians reported that they frequently (58.5%) continued RTX after intravenous immunoglobulin administration. CONCLUSIONS: RTX has become a common treatment option in pediatric rheumatology in recent years. Treatment management may vary between clinician such as vaccination and routine tests. WHAT IS KNOWN: • During the course of rituximab therapy, clinicians should be attentive to specific considerations in pre-treatment, during administration, and in post-treatment patient monitoring. WHAT IS NEW: • There are differences in practice among clinicians in the management of RTX therapy. These practice disparities have the potential to impact the optimal course of treatment. • This study highlights that standardized guidelines are needed for RTX treatment in pediatric rheumatology, particularly for vaccination policies and routine tests.

Unveiling Cardiac Involvement in Juvenile Dermatomyositis Through Speckle-Tracking Echocardiography.

Early detection of cardiac involvement in Juvenile Dermatomyositis (JDM) is difficult due to the absence of clinical signs and symptoms, with systolic dysfunction often emerging in late stages and associated with a poor prognosis. This study aimed to employ two-dimensional speckle-tracking echocardiography (STE) for subclinical assessment of left ventricular (LV) systolic failure in JDM and explore potential associations between impaired LV systolic function (LV-GLS) and disease activity. A prospective study enrolled 20 healthy volunteers and 26 JDM patients (< 18 years old) without cardiac symptoms. Clinical data were collected from medical records, and echocardiograms were conducted by a pediatric cardiologist. Our study cohort demonstrated similar age to controls (13.5 ± .6 vs. 13.8 ± 4.7; p = 0.465). Median illness duration at echocardiography was 5 (1.5-17.5) years, and conventional echocardiography indicated normal LV ejection fraction (> 55%) in all participants. However, STE revealed lowered LV GLS in JDM patients (- 22.2 ± 4.1% vs. - 26.5 ± 5.3% p = 0.022). Pulse steroid users displayed lower GLS average values compared to non-users (ß = 4.99, 95% CI 1.34-8.64, p = 0.009). Negative correlations existed between LV-GLS and age at diagnosis (r = - 0.499; p = 0.011), diastolic parameters (E/E' ratio) and age at diagnosis (r = - 0.469; p = 0.018), as well as RV global strain and age at diagnosis (r = - 0.443; p = 0.024). Employing STE in JDM patients facilitated the identification of preclinical cardiac dysfunction. Given JDM patients' younger age, early myocardial damage detection through STE may impact treatment decisions and long-term cardiovascular prognosis.

Assessment of myelin oligodendrocyte glycoprotein antibodies and magnetic resonance spectroscopy in childhood-onset systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterised by the presence of various autoantibodies. Mild cognitive impairment developing in patients without significant neuropsychiatric (NP) symptoms was thought to be the result of immune-mediated myelinopathy. We aimed to determine the role of myelin oligodendrocyte glycoprotein antibody (MOG-Ab) in the neurological manifestations of childhood-onset SLE (cSLE) and if there is a correlation between various metabolite peaks in magnetic resonance spectroscopy (MRS) and myelinopathy. METHODS: MOG-Ab levels were studied in all healthy subjects (n=28) and in all patients with (NPSLE=9) and without (non-NPSLE=36) overt neuropsychiatric manifestations. Twenty patients (all had a normal-appearing brain on plain magnetic resonance) in non-NPSLE and 20 subjects in healthy group met the MRS imaging standards for evaluation in which normal appearing brain on plain MR. RESULTS: A total of 45 cSLE (36 non-NPSLE and 9 NPSLE) subjects and 28 healthy children were recruited to the study. The mean age of the SLE patients at study time was 16.22±3.22 years. MOG-Ab was not detected in cSLE or in healthy group. There was no significant difference between the non-NPSLE group and healthy subjects in terms of choline, N-acetyl aspartate (NAA), creatine, NAA/creatine, and choline/creatine. CONCLUSIONS: There was no association of MOG-Ab with cSLE, whether NP manifestations were present or not. A causal relationship between immune-mediated myelinopathy and cognitive impairment could not be suggested, since there has been no patient with positive MOG-Ab and there has been no difference in choline, choline/creatine between groups.

Gray zone in the spectrum of autoinflammatory diseases: familial Mediterranean fever accompanying periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome: single-center experience.

Despite the advanced knowledge concerning autoinflammatory diseases (AID), more data regarding the optimal treatment options and outcomes of the children who met the criteria of more than one AID are required. This study aimed to describe the demographic and clinical characteristics of children from familial Mediterranean fever (FMF)-endemic countries who meet both the FMF and the periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome criteria. Moreover, we aimed to measure the response rates to colchicine and tonsillectomy and evaluate the factors affecting the colchicine response in these patients. The study was conducted at pediatric rheumatology tertiary centre. A total of 131 patients (58 females; 73 males) who met both the modified Marshall and pediatric FMF criteria were included. The median age at onset was 18 months (1-77 months), and the mean age at diagnosis was 47 ± 21.88 months. The median interval between episodes was 21 (7-90) days. The median disease duration was 46 (6-128) months. Consanguineous marriage was detected in 17 (13%) of the patients. The most common clinical finding was fever (100%), followed by exudative pharyngitis (88.5%), abdominal pain (86.3%), arthralgia (61.8%), stomatitis (51.1%), adenitis (42%), myalgia (28.7%), chest pain (16%), maculopapular rash (12.2%), arthritis (8.4%), and erysipelas-like rash (4.6%). MEFV gene variants were identified in 106 (80.9%) patients. The most common variants were M694V heterozygous (29%). We found that patients with tonsillopharyngitis, aphthous stomatitis, and PFAPA family history were more likely to be colchicine-resistant and tonsillectomy responsive, while those with exon 10 MEFV gene mutations were more prone to have a favorable response to colchicine.     Conclusion: PFAPA syndrome patients with exon 10 MEFV gene mutation, showing typical FMF symptoms, should be treated with colchicine, even after tonsillectomy. In multivariate analysis, PFAPA family history and lack of exon 10 MEFV gene mutations were independent risk factors for colchicine resistance. Thus, tonsillectomy may be recommended as a possible treatment option for these patients. It has yet to be clarified when colchicine treatment will be discontinued in patients whose attacks ceased after tonsillectomy that was performed due to colchicine unresponsiveness. What is Known: • A certain number of patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome concomitantly fulfill the familial Mediterranean fever (FMF) criteria. • While colchicine is proposed as a first treatment choice in familial Mediterranean fever (FMF), corticosteroids are recommended as a first-line treatment in PFAPA syndrome patients. What is New: • In patients with concomitant PFAPA syndrome and FMF, PFAPA family history and lack of exon 10 MEFV gene mutation are predictive factors of colchicine resistance. • The presence of exon 10 MEFV gene mutations in patients with concomitant FMF and PFAPA syndrome has a favourable effect on response to colchicine treatment.

Long-term efficacy of tonsillectomy/adenotonsillectomy in patients with periodic fever aphthous stomatitis pharyngitis adenitis syndrome with special emphasis on co-existence of familial Mediterranean fever.

Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome is one of the most common autoinflammatory fever disorders in the childhood which may co-exists with familial Mediterranean fever (FMF) causing treatment complexity. As the role of surgery in PFAPA syndrome is still controversial, in this paper, our aim is to present our results of tonsillectomy/adenotonsillectomy in the treatment of PFAPA syndrome. Archives of a tertiary care hospital were investigated for patients who underwent tonsillectomy or adenotonsillectomy due to PFAPA Syndrome between 2010 and 2020. 344 patients were found but only 281 of them were accessible. Through phone call interview and chart review methods, preoperative and postoperative the number and severity of the attacks and general satisfaction after the operation were recorded and analyzed. Also, patients with concomitant FMF were analyzed separately. A total of 281 patients were included in the study. There was no improvement in 10 (3.55%) patients. Eight (2.84%) patients showed mild improvement, 29 (10.32%) patients had moderate improvement and 234 (83.27%) patients had full recovery after tonsillectomy. There were 266 PFAPA patients without FMF. No improvement, mild improvement, moderate improvement, and full recovery in this patient group were 5 (1.9%), 6 (2.3%), 25 (9.4%) and 230 (86.5%), respectively. FMF was present in 5.33% (15/281) of the patients. In PFAPA + FMF group 5 patients had no improvement (33.3%), 2 had mild improvement (13.3%), 4 had moderate improvement (26.7%) and 4 had full recovery (26.7%). Benefit of tonsillectomy was significantly lower in the patients with concomitant FMF when compared to the patients who did not have FMF (p < 0.001). Age of diagnosis, age of operation, severity of the disease, type of operation, and gender were found to have no significant relationship with the benefit from surgery (p < 0.05). According to the findings of this study, tonsillectomy is an effective long-term treatment for PFAPA syndrome with success rate of 83.27%. Also, preoperatively FMF should be considered in these patients, which dramatically reduces surgical efficacy.

The efficacy of a single-dose anakinra injection during disease attack in pediatric familial Mediterranean fever.

The aim of this retrospective study is to evaluate the efficacy of a single-dose anakinra during familial Mediterranean fever (FMF) attacks and its effect on the duration, severity, and frequency of attacks. The patients with FMF who had disease episode and received a single-dose anakinra during disease episode between December 2020 and May 2022 were included. Demographic characteristics, MEFV gene variants detected, concomitant medical conditions, demographics of recent and previous episodes, laboratory findings and length of hospital stay were recorded. A retrospective analysis of medical records revealed 79 attacks from 68 patients who met inclusion criteria. The patients had a median age of 13 (2.5-25) years. All patients reported that the average duration of their previous episodes lasted longer than 24 h. When the recovery time of attacks after subcutaneous anakinra application at the disease attack was examined, it was observed that 4 attacks (5.1%) ended in 10 min; 10 attacks (12.7%) in 10-30 min; 29 attacks (36.7%) in 30-60 min; 28 attacks (35.4%) in 1-4 h; 4 attacks (5.1%) in 24 h; and 4 attacks (5.1%) ended in more than 24 h. There was no patient who did not recover from their attack after a single dose of anakinra. Although the efficacy of a single-dose anakinra administration during FMF attacks in children needs to be confirmed by prospective studies, our results suggest that use of a single-dose anakinra during FMF attacks is effective in reduction of severity and duration of disease attacks.

Retrospective analysis of children diagnosed with Kawasaki disease.

BACKGROUND: The aim of our study was to evaluate the long-term impacts of Kawasaki disease on our patients regarding coronary involvement demographic characteristics, treatment regimens, and clinical course. METHODS: Our study included 104 patients diagnosed and hospitalized with Kawasaki disease in our center, from January 2004 to January 2019. In our study, patients were divided into three groups according to coronary artery involvement. Patients in group 1 had no echocardiographic findings, while the ones in group 2 had coronary artery dilatation and ones in group 3 had coronary artery aneurysm (CAA). RESULTS: Among 104 patients, the median age was 9.15 (3.0-22.0) years, and 61 of the patients were male while 43 of the patients were female. With a wide range of 1.50-16.50 years of follow-up time, the median diagnosis age of our patients was 31 months (3.0-164.0). Fever duration (median day 10 (5-21), p = 0.025) was statistically significantly higher in group 3. Blood C-reactive protein (CRP) levels, white blood cell (WBC) counts, and neutrophil counts were significantly higher in group 3. There was a statistically significant difference between patients in group 3 and group 2 in which the lowest strain deformation values were in the patients of group 3. In contrast to group 1, the time for initiation of IVIG therapy is significantly prolonged both in group 2 (median: 9.5 days, p = 0.028) and group 3 (median: 10 days, p = 0.036). DISCUSSION: In our study, serum CRP levels, WBC count, and neutrophil count were higher in patients with coronary artery abnormalities, in agreement with the previous studies. In the light of our results, we consider that the most important determining factor for the development of coronary artery aneurysm is the time of intravenous immunoglobulin (IVIG) administration.

Specific early signs and long-term follow-up findings of progressive pseudorheumatoid dysplasia (PPRD) in the Turkish cohort.

OBJECTIVES: Progressive pseudorheumatoid dysplasia (PPRD) is a spondyloepiphyseal dysplasia caused by biallelic variants in CCN6. This study aimed to describe the early signs and follow-up findings in 44 Turkish PPRD patients. METHODS: The patients with progressive stiffness of multiple joints, characteristic wide metaphysis of interphalangeal (IP) joints and platyspondyly were clinically diagnosed with PPRD. Fifteen patients who had first symptoms under 3 years of age were grouped as early-onset, while others were grouped as classical. CCN6 sequencing was performed in 43 patients. RESULTS: Thirteen pathogenic/likely pathogenic variants were identified, five were novel. c.156C>A(p.Cys52*) variant was found in 53.3% of the families. The initial symptom in the early-onset group was genu varum deformity, while it was widening of IP joints in the classical group. The median age of onset of symptoms and of diagnosis was 4 and 9.7 years, respectively. The mean follow-up duration was 5.6 years. The median age of onset of IP, elbow, knee and hip stiffness, which became progressive with growth was 5, 9, 9 and 12.2 years, respectively. Waddling gait occurred in 97.7% of the patients. A total of 47.7% lost independent walking ability at the median age of 12 years. In the early-onset group, waddling gait occurred earlier than in classical group (P < 0.001). Two patients had atypical presentation with late-onset and mild or lack of IP involvement. CONCLUSION: We observed that genu varum deformity before the age of 3 years was an early sign for PPRD and almost half of the patients lost walking ability at the median age of 12 years.

Genetic screening of early-onset patients with systemic lupus erythematosus by a targeted next-generation sequencing gene panel.

OBJECTIVE: In this study, we aimed to screen 31 genes (C1QA, C1QB, C1QC, C1R, C1S, C2, C3, TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, DNASE1, DNASE1L3, PRKCD, ACP5, SLC7A7, IFIH1, TMEM173, ISG15, CYBB, FAS, FASLG, KRAS, NRAS, MAN2B1, PEPD, PTPN11, RAG2, and SHOC2), that we have categorized under the umbrella term "monogenic lupus" using a targeted next-generation sequencing (NGS) panel in 24 individuals with early-onset (≤10 years of age) systemic lupus erythematosus (SLE) and in 24 patients with late-onset (>10 years of age) disease. METHODS: A total of 48 SLE patients (24 with disease onset ≤10 years of age and 24 with disease onset >10 years of age) were included. Patients with late-onset disease have been used as patient controls. Sequencing was carried out using 400 bp kit on the Ion S5 system. RESULTS: Among the 48 patients, three had one pathogenic variant and 45 patients had at least one rare variant classified as benign, likely benign or variant of unknown significance (VUS). In all three patients with a pathogenic variant, the onset of disease was before 10 years of age. Two patients (they were siblings) carried C1QA homozygote pathogenic allele (p.Gln208Ter, rs121909581), and one patient carried PEPD heterozygote pathogenic allele (p.Arg184Gln, rs121917722). CONCLUSION: We demonstrated a pathogenic variant in our target gene panel with a frequency of 9.52% in patients with a disease onset ≤10 years of age. All patients with early-onset SLE phenotype, irrespective of a positive family history for SLE or parental consanguinity, should be scanned for a single-gene defect by a targeted gene panel sequencing. With the discovery of many single-gene defects and ongoing efforts to identify novel genes in SLE, similar gene panels including even more genes will possibly become more necessary and practical in the future.

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.

Differences and similarities of multisystem inflammatory syndrome in children, Kawasaki disease and macrophage activating syndrome due to systemic juvenile idiopathic arthritis: a comparative study.

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.

Systolic and Diastolic Cardiac Functions in Juvenile Spondyloarthropathies.

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.

The role of Mediterranean fever gene variants in patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome.

This study was conducted to investigate the relationship between clinic features and Mediterranean fever gene (MEFV) variants in patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. In total, 167 patients with PFAPA syndrome were included in the study. Female:male ratio of the patients was 0.75 (72 females, 95 males). In total 59.9% of patients with PFAPA had at least one MEFV variant and the most common heterozygous variants were M694V in 29.3% of the patients (40/167), E148Q in 8.3% (14/167), and V726A in 7.1% (12/167). The median age at the disease onset was significantly higher and the median duration of the episodes was significantly lower in patient with variants in exon 10 comparing to the others (both p = 0.01). Similarly, the median age at the disease onset was significantly higher (p = 0.01) and the median duration of the episodes was significantly lower (p = 0.04) in patient with MEFV variants than in the remaining patients. There were no significant differences according to the genotypes of the patients in terms of both treatment response and the frequency of clinical findings.Conclusion: In PFAPA syndrome, MEFV variants may be a modifier for disease onset and attack duration. What is Known: • Due to periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome having clinical findings resembling familial Mediterranean fever (FMF), it can be difficult to distinguish PFAPA syndrome and FMF especially in endemic regions for FMF. • Underlying MEFV mutations could affect the periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome's clinical presentation and response to treatment. What is New: • Having one of the underlying MEFV variants is related to later disease onset and shorter episode duration in patients with PFAPA syndrome.

Psychosocial and clinical effects of the COVID-19 pandemic in patients with childhood rheumatic diseases and their parents.

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.

Tocilizumab therapy in juvenile systemic sclerosis: a retrospective single centre pilot study.

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.

Anti-nuclear antibody testing in children: How much is really necessary?

BACKGROUND: 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 effectiveness of ordering ANA testing in childhood. METHODS: Children referred to our department to be examined due to positive ANA findings 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 of positive ANA findings was 9.31 (1.3-17.86) years 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 positive ANA findings 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 only if there is a strong suspicion of autoimmune diseases or certain rheumatic conditions, such as systemic lupus erythematosus.

Effects of sense and functionality changes in the hands on activity and participation in patients with juvenile scleroderma.

OBJECTIVES: 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). METHODS: 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)'. RESULTS: 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 (p < .05). Over than half of patients with JSS (57.1%) and almost half of patients with JLS stated that their diseases obstructed them from doing any activity (p < .001). A significant percent of JSS patients (64.3%) had hand and wrist joint involvement. CONCLUSION: 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.

Decreased frequency of allergy in juvenile idiopathic arthritis: Results of a case-control study.

OBJECTIVES: To determine the frequency of Th2-mediated allergic diseases (AD) in mainly Th1-driven juvenile idiopathic arthritis (JIA) subtypes. METHODS: 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. RESULTS: Despite similar allergy risk factors, the frequencies of asthma and allergic rhinitis were lower in JIA group (all p ≤ .02). Allergic patients with JIA performed lower FEV1/FVC ratio, PEF, and FEF25-75 compared to the control group (all p ≤ .04). JADAS27 and sAPR were similar among JIA patients with and without AD. Two JIA patients were found to have hypogammaglobulinemia. CONCLUSION: The 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.