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

Objectives: This study aimed to explore the influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic among patients with juvenile systemic sclerosis (JSS). Patients and methods: Twenty-seven patients (22 females, 5 males; mean age: 20 years; range, 17 to 22 years) diagnosed with JSS and followed up at the department of pediatric rheumatology were included in the cross-sectional study. A web-based survey was performed by focusing on patients' complaints, accessibility to health care, and compliance with routine treatment from January 1, 2021, to January 10, 2021. Results: Five (18.5%) patients had deterioration of the disease, while six (22.2%) patients reported irregular usage of their routine scleroderma treatment during the last six months. Nine (33.3%) patients had missed their routine clinic control since the proclamation of the SARS-CoV-2 pandemic. Seven (25.9%) patients had household contact with coronavirus disease 2019 (COVID-19). Four (14.8%) patients were diagnosed with COVID-19, and only one (3.7%) was hospitalized. Nine patients were under biological treatment (tocilizumab); however, only one of them was diagnosed with COVID-19. Conclusion: The COVID-19 pandemic has not significantly disrupted the medical care of JSS patients. Telemedicine could be an acceptable option for JSS patients disenabled to come to the hospital. [ABSTRACT FROM AUTHOR]

Possible interactions of the neuropeptide oxytocin and the sex hormone estradiol may contribute to previously observed sex-specific effects of oxytocin on resting-state functional connectivity (rsFC) of the amygdala and hippocampus. Therefore, we used a placebo-controlled, randomized, parallel-group functional magnetic resonance imaging study design and measured amygdala and hippocampus rsFC in healthy men (n = 116) and free-cycling women (n = 111), who received estradiol gel (2 mg) or placebo before the intranasal administration of oxytocin (24 IU) or placebo. Our results reveal significant interaction effects of sex and treatments on rsFC of the amygdala and hippocampus in a seed-to-voxel analysis. In men, both oxytocin and estradiol significantly decreased rsFC between the left amygdala and the right and left lingual gyrus, the right calcarine fissure, and the right superior parietal gyrus compared to placebo, while the combined treatment produced a significant increase in rsFC. In women, the single treatments significantly increased the rsFC between the right hippocampus and the left anterior cingulate gyrus, whereas the combined treatment had the opposite effect. Collectively, our study indicates that exogenous oxytocin and estradiol have different region-specific effects on rsFC in women and men and that the combined treatment may produce antagonistic effects. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to investigate the possible relationship between the serum S100A12 and Toll‐like receptor 4 (TLR4) levels, and the activity of familial Mediterranean fever (FMF) and juvenile idiopathic arthritis (JIA) in accordance with the routine biochemical parameters. Furthermore, the effectiveness of these 2 biomarkers in distinguishing FMF from JIA has been evaluated. Method: Sixty‐nine children with FMF, 68 children with JIA, and 35 healthy children were included in this study. S100A12 and TLR4 levels were measured by the sandwich enzyme‐linked immunosorbent assay technique. Results: In the FMF patient group, serum S100A12 level was found to be significantly higher than in both the JIA and control groups (P =.000 and P =.000, respectively). Although S100A12 levels were higher in the attack period compared to the attack‐free period, this increase was not statistically significant (P >.05). TLR4 levels were statistically significantly higher in the attack period compared to the attack‐free period in children with FMF (P <.05). Although there was no relationship between S100A12 levels and disease activity, there is a clear correlation between S100A12 and the Auto‐Inflammatory Disease Activity Index in attack‐free FMF patients (r = 0.612 P =.000). Conclusion: Serum S100A12 levels were not found to be a potentially valuable biomarker for assessing disease activity in either FMF or JIA. However, TLR4 levels were found to be a valuable biomarker for assessing disease activity in children with FMF. Further research which includes serial monitoring of S100A12 and TLR4 levels in a large cohort will provide detailed information about accuracy of these 2 potential biomarkers in both patients group. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This paper contains results from ichthyofaunal research of freshwater fish in Bosnia and Herzegovina during 20th and at the beginning of twenty-first century. We found presence of more than 100 parasitic species from different groups in 52 freshwater fish species from Black Sea and Adriatic basins and some breeding ponds. Detected parasites belong to Trematoda – 25 species, Monogenea – 15, Cestoda – 16, Nematoda – 15, Acanthocephala - 11, Oligohymenophorea - 5, Phyllopharyngea - 3, and Copepoda – 2 species. Other detected parasite groups are Kinetoplastea, Trepomonadea, Myxosporea, Myxoza, Ichthyostraca, Clitellata and Bivalvia with one species each. This study shows the necessity of research of complete parasitic fauna of freshwater fish in Bosnia and Herzegovina. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 consanguinity of his parents, a cousin with similar clinical features and early disease onset led to suspicion of deficiency of adenosine deaminase type 2 (DADA2) diseases. DADA2 was established by demonstration of decreased ADA2 enzyme activity and a homozygous G47R mutation in the CECR1 gene. The diagnosis of DADA2 is challenging because of the overlapping manifestations with PAN and other periodic fever syndromes. DADA2 should be considered in the differential diagnosis of PAN. Raised IgG levels (usually low in DADA2) should be sought in future cases. Abbreviations: CECR1, cat eye syndrome chromosome region candidate 1; DADA2, deficiency of adenosine deaminase type 2; MEFV, Mediterranean fever; PAN, polyarteritis nodosa [ABSTRACT FROM AUTHOR]

Familial Mediterranean fever (FMF) is A common periodic fever syndrome. The causative gene of the FMF is named Mediterranean Fever gene (MEFV). Increased inflammation in FMF may play a role as a trigger for the development of some diseases. The objective of the study is to evaluate the frequency of comorbid disorders in children followed up with diagnosis of FMF. Additionally, we aimed to assess the association between FMF and other inflammatory conditions in a large pediatric FMF cohort. A total of 686 FMF patients were included in the cross-sectional study. A questionnaire including questions about characteristics of fever episodes, presence of arthralgia, arthritis, abdominal pain, chest pain during and co-existence of any other disease diagnosed by a physician was filled out by face-to-face interviews with patients or their parents. Female–male ratio was 0.85. Median age at the time of study, age at disease onset and at the time of diagnosis were 12.9 (1.7–22.3), 3 (0.08–17), and 6 (0.75–17) years, respectively. In 130 (18.9%) FMF patients we detected co-existing inflammatory condition. The most common co-existing diseases were: juvenile idiopathic arthritis 42 (6.1%), asthma/reactive airway disease 29 (4.2%), Henoch–Schönlein purpura 20 (2.9%), uveitis 12 (1.7%) and inflammatory bowel disease 10 (1.4%). Except for asthma/reactive airway disease and inflammatory bowel disease, there was no significant difference regarding the type of MEFV gene mutation. We have reported increased frequencies of various inflammatory conditions and decreased frequency of asthma in patients with FMF. [ABSTRACT FROM AUTHOR]

The periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an auto-inflammatory condition characterized by recurrent episodes of fever accompanied by aphthosis, cervical adenitis, and pharyngitis. Diagnosis of PFAPA could be challenging due to clinic overlap with familial Mediterranean fever (FMF). An international consensus has been established recently, to define a new set of classification criteria for PFAPA syndrome. We aimed to evaluate the performance of recently proposed PFAPA criteria, to assess their utility in FMF regions. Patients diagnosed with PFAPA syndrome, FMF, and juvenile idiopathic arthritis (JIA) were included. Two investigators blindly evaluated all of patients for the newly proposed PFAPA criteria. A total of 542 patients (322 with PFAPA syndrome, 118 FMF and 102 JIA) were evaluated. Mean age of patients was 6.6 ± 2.81, 12.75 ± 3.9, and 12.42 ± 4.8 years for PFAPA, FMF, and JIA, respectively. We found quite high sensitivity (89.7%) but insufficient specificity of newly proposed PFAPA criteria (69.5%). When applied to control patients separately, specificity was found to be 61% and 79.4% for FMF and JIA patients, respectively. Positive predictive value was 81%, while negative predictive value was 82%. Recently proposed PFAPA criteria have satisfactory sensitivity, but its specificity is still under expectation. There is a need for a distinctive criterion between PFAPA syndrome and FMF, in FMF endemic regions, e.g., cryptic tonsillitis rapidly responsive to single dose of glucocorticoids. Further studies with higher patients' number in different regions are needed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Pediatric Rheumatology is an emerging specialty in Turkey with increasing number of available centers and specialists all over the country. In this paper, we sought to provide an overview on pediatric rheumatology service in our country, as well as to assess the principle published literature from Turkey in this field. A systematic literature search has been performed to achieve the significance and the impact of this manuscript. The most relevant used databases (PubMed/MEDLINE, Web of Science, SCOPUS) for peer-reviewed studies and reviews in English language published during the last 5 years were screened. In the first part of the manuscript, we tried to give more details on the history of pediatric rheumatology in Turkey. In further text, we put an accent over the most common rheumatologic conditions among children in Turkey, including Familial Mediterranean fever, juvenile idiopathic arthritis, juvenile spondyloarthropathies, and childhood vasculitides. Despite the considerable literature from Turkey on pediatric rheumatic diseases, a need for unique strategies that would guide the management of rheumatic diseases in childhood remains open. The cultural and historical inheritance together with geographical position make the Turkey a suitable ground for investigations in filed of auto-inflammation and all other inflammatory conditions. Prospective, multicentric studies especially among rheumatologic conditions common in this part of the world would give us more relevant data and open new horizons in diseases' management. International collaborations and databases should be highly encouraged and supported, to make the care of pediatric rheumatic disease uniform. [ABSTRACT FROM AUTHOR]

Autoinflammatory diseases are characterized by fever attacks of varying durations, associated with variety of symptoms including abdominal pain, lymphadenopathy, polyserositis, arthritis, etc. Despite the diversity of the clinical presentation, there are some common features that make the differential diagnosis of the autoinflammatory diseases challenging. Familial Mediterranean fever (FMF) is the most commonly seen autoinflammatory conditions, followed by syndrome associated with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA). In this review, we aim to evaluate disease characteristics that make a diagnosis of FMF and PFAPA challenging, especially in a regions endemic for FMF. The ethnicity of patient, the regularity of the disease attacks, and the involvement of the upper respiratory systems and symphonies could be helpful in differential diagnosis. Current data from the literature suggest the use of biological agents as an alternative for patients with FMF and PFAPA who are non-responder classic treatment options. More controlled studies are needed to evaluate the efficacy and safety of this strategy. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to evaluate the demographic and clinical features, laboratory data, treatment modalities, and outcomes of juvenile systemic sclerosis (JSS) and juvenile localized scleroderma (JLS) patients at a referral pediatric rheumatology center in Turkey. Patients and methods: Medical records of a total of 57 patients, including 29 with JSS (1 male, 28 females; mean age 18.3±3.2 years; range 14 to 27 years) and 28 with JLS (6 males, 22 females; mean age 14.4±4.8 years; range 6 to 23 years), diagnosed betweenJanuary 2006 and Mart 2015 and followed-up for at least six months were evaluated in this retrospective longitudinal study. All medical records were retrospectively analyzed for demographic, clinical, and laboratory findings. Results: Mean age at disease onset was 9.9±4.2 years and 7.7±3.9 years for JSS and JLS, respectively. Mean ages at diagnosis and at the time of study were lower in JLS: 9.1±3.5 years vs. 11.7±3.7 years and 14.4±4.8 years vs. 18.3±3.2 years, respectively. Mean disease duration was 7.8±5.2 years and 8.0±4.3 years for JSS and JLS, respectively. Among JSS patients, interstitial lung disease was seen in eight (27%), pulmonary hypertension in three (10%), and arrhythmia in one (3%). One JSS patient (3%) died as a consequence of cardiac sclerosis. Corticosteroids with methotrexate were used in 29 JSS patients (100%) and in 21 JLS patients (75%). Patients with vasculopathy were treated with nifedipine (n=18, 62%) and bosentan (n=12, 41%). Internal organ involvement was treated with high-dose cyclophosphamide (n=10, 34%) or biological agent (n=3, 10%). Conclusion: Close monitoring of internal organ involvement is of great importance in preventing disease-related complications in JSS and JLS. Although rare, vital organ involvement has a devastating effect on prognosis. Biological agents represent an option for patients resistant to standard immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Deficiency of adenosine deaminase type 2 (DADA2) is a rare form of autoinflammatory disorder with limited reported cases. In this paper, we have presented the clinico-immunological, radiological and genetic characteristics of five surviving and three deceased childhood-onset DADA2 patients. We aimed to compare surviving and deceased patients in terms of clinical features and treatment modalities. Moreover, we have evaluated the causes of death in our DADA2 subjects together with the previously reported cases. Demographic features, clinical characteristics, imaging findings, mutations and pharmacological treatments of DADA2 subjects were noted from patient records of pediatric and adult rheumatology clinics in a retrospective and longitudinal nature. Eight patients from seven families were enrolled. While five of them were surviving, three of them had died due to various reasons. Median age of the patients at disease onset and diagnosis was 7 years (range 0.5-13 years) and 14 years (range 5-27 years), respectively. The main clinical manifestations were cutaneous findings (7/8), recurrent low-grade fever (6/8), neurological involvement (6/8) and gastrointestinal involvement (5/8). All patients had increased acute phase reactants at presentation and also during the disease flares. Until the diagnosis of DADA2 was confirmed, five patients have been followed-up with the diagnosis of PAN: two patients both with PAN and FMF, and one patient with CAPS and vasculitis. Demographic, clinical, neurological features and genetic mutations did not differ in surviving and deceased DADA2 patients. Deceased and surviving subjects differed in terms of treatment modalities after the diagnosis of DADA2. Anti-TNF alpha treatment has been initiated in five surviving patients as soon as the diagnosis of DADA2 was established. However, three patients who have died were not able to use sufficient doses of anti-TNF alpha treatment; in one case due to reluctance of patient and in two cases due to establishment of the definite diagnosis by genetic analysis at the same time with the last fatal DADA2 episode. Despite limited number of patients, this case series for the first time compares the phenotypic, genotypic and medication differences between surviving and deceased DADA2 patients. Anti-TNF alpha treatment seems to be efficient and lifesaving in DADA2 patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We aimed to assess the frequency of celiac disease (CD) in patients with Familial Mediterranean Fever (FMF). This prospective study was carried out from October 2015 to March 2016 and included 303 patients with FMF. We used 98 sex- and age-matched healthy subjects as a control group. Levels of total IgA and tissue transglutaminase (tTG) IgA antibody were measured in all groups. Those with increased level of tTG IgA were tested for anti-endomysium IgA antibodies (EMA). Patients with positive EMA underwent gastro-duodenoscopy and intestinal biopsy for a definite diagnosis of CD. Only 9 of 303 patients (2.9%) were positive for tTG IgA. Patients positive for tTG IgA were then tested for EMA and only one of them (0.3%) had a positive result. This patient underwent gastro-duodenoscopy. The pathological report was compatible with Marsh 0 classification score for the diagnosis of CD. Two subjects from the control group were positive for tTG IgA but none of them had positive EMA antibodies. We did not find CD in the large cohort of childhood FMF patients. The prevalence of CD did not show association with presence of childhood FMF in this study and CD would not be a considerable complication of childhood FMF. [ABSTRACT FROM AUTHOR]

Objectives Childhood-onset systemic lupus erythematosus (cSLE) is a multisystemic autoimmune disease characterized by inflammatory organ damage by means of vasculitis. Pentraxin-3 (PTX3) is expressed locally at the sites of inflammatory processes, predominantly from endothelial cells. In adult studies, PTX3 has shown to be an indicator of active vasculitis both in large-vessel and small-vessel vasculitides, as well as in SLE. Moreover, in SLE it has found to be correlated with disease activity, and with some of the clinical manifestations and laboratory parameters. We aimed to ascertain if PTX3 might be a significant mediator in cSLE and if it might indicate active vasculitis during the course of the disease. Methods Serum PTX3 levels were measured in 76 patients with cSLE and 41 healthy subjects. We have investigated its relation with disease activity, damage, clinical features, laboratory parameters and medications. Results Serum levels of PTX3 were found to be increased in cSLE compared to healthy controls (mean ± SD; 10.6 ± 8.2 ng/mL vs 2.7 ± 1.3 ng/mL, p < 0.001). PTX3 concentrations were also in correlation with SLEDAI-2K (r = 0.57, p < 0.001). When viewed from the clinical perspective, serum PTX3 levels were significantly higher only in patients with active vasculitis (p < 0.001), Raynaud phenomenon (p = 0.006) and mucocutaneous manifestations (p < 0.001). However, an association between PTX3 and age, age at disease onset, disease duration, complement levels, PedSDI score (pediatric version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), ESR, CRP, procalcitonin levels, anti-ds DNA antibody, anticardiolipin antibodies was not detected. Conclusions Patients with cSLE have increased levels of serum PTX3 compared to healthy controls. Thus, serum PTX-3 level might be a significant mediator in cSLE. Apart from these, the results support that PTX3 reflects active cutaneous vasculitis in cSLE and correlates with disease activity. [ABSTRACT FROM AUTHOR]

Juvenile idiopathic arthritis is the most common chronic rheumatic disease of unknown aetiology in childhood and predominantly presents with peripheral arthritis. The disease is divided into several subgroups, according to demographic characteristics, clinical features, treatment modalities and disease prognosis. Systemic juvenile idiopathic arthritis, which is one of the most frequent disease subtypes, is characterized by recurrent fever and rash. Oligoarticular juvenile idiopathic arthritis, common among young female patients, is usually accompanied by anti-nuclear antibodie positivity and anterior uveitis. Seropositive polyarticular juvenile idiopathic arthritis, an analogue of adult rheumatoid arthritis, is seen in less than 10% of paediatric patients. Seronegative polyarticular juvenile idiopathic arthritis, an entity more specific for childhood, appears with widespread large- and small-joint involvement. Enthesitis-related arthritis is a separate disease subtype, characterized by enthesitis and asymmetric lower-extremity arthritis. This disease subtype represents the childhood form of adult spondyloarthropathies, with human leukocyte antigen-B27 positivity and uveitis but commonly without axial skeleton involvement. Juvenile psoriatic arthritis is characterized by a psoriatic rash, accompanied by arthritis, nail pitting and dactylitis. Disease complications can vary from growth retardation and osteoporosis secondary to treatment and disease activity, to life-threatening macrophage activation syndrome with multi-organ insufficiency. With the advent of new therapeutics over the past 15 years, there has been a marked improvement in juvenile idiopathic arthritis treatment and long-term outcome, without any sequelae. The treatment of juvenile idiopathic arthritis patients involves teamwork, including an experienced paediatric rheumatologist, an ophthalmologist, an orthopaedist, a paediatric psychiatrist and a physiotherapist. The primary goals of treatment are to eliminate active disease, to normalize joint function, to preserve normal growth and to prevent long-term joint damage. Timely and aggressive treatment is important to provide early disease control. The first-line treatment includes disease-modifying anti-rheumatic drugs (methotrexate, sulphasalazine, leflunomide) in combination with corticosteroids, used in different dosages and routes (oral, intravenous, intra-articular). Intra-articular application of steroids seems to be an effective treatment modality, especially in monoarthritis. Biological agents should be added in the treatment of unresponsive patients. Anti-tumour necrosis factor agents (etanercept, infliximab, adalimumab), anti-interleukin-1 agents (anakinra, canakinumab), antiinterleukin-6 agents (tocilizumab) and T-cell regulatory agents (abatacept) have been shown to be safe and effective in childhood patients. Recent studies reported sustained reduction in joint damage with even complete clinical improvement in paediatric patients, compared to previous data. [ABSTRACT FROM AUTHOR]

Abstract: Finding a common factor of two multivariate polynomials with approximate coefficients is a problem in symbolic–numeric computing. Taking a tropical view of this problem leads to efficient preprocessing techniques, applying polyhedral methods to the exact exponents and numerical techniques to the approximate coefficients. With Maple we will illustrate our use of tropical algebraic geometry. [Copyright &y& Elsevier]

Atypical hemolytic uremic syndrome (aHUS) is mostly linked to defects in the regulation of alternative complement pathway, but a rare form is caused by an inherited defect of cobalamin 1 metabolism. Cobalamin C (cblC) deficiency is an autosomal recessive disorder of vitamin B12 metabolism that results from mutations in methylmalonic aciduria and homocysteinuria ( MMACHC). The most severe form of cblC deficiency and the associated high mortality rate are mostly observed in neonates or in infants <6 months of age. Early diagnosis of cblC deficiency leads to early treatment and an improved prognosis. We describe the case of a 6-year-old girl with cblC disorder, who presented with severe multiorgan involvement at the age of 5 months and who was successfully treated with vitamin B12, betaine, coenzyme Q10 and l-carnitene, and who had a new homozygous mutation of MMACHC. [ABSTRACT FROM AUTHOR]

Artificial intelligence algorithms, with roots extending into the past but experiencing a resurgence and evolution in recent years due to their superiority over traditional methods and contributions to human capabilities, have begun to make their presence felt in the field of pediatric rheumatology. In the ever-evolving realm of pediatric rheumatology, there have been incremental advancements supported by artificial intelligence in understanding and stratifying diseases, developing biomarkers, refining visual analyses, and facilitating individualized treatment approaches. However, like in many other domains, these strides have yet to gain clinical applicability and validation, and ethical issues remain unresolved. Furthermore, mastering different and novel terminologies appears challenging for clinicians. This review aims to provide a comprehensive overview of the current literature, categorizing algorithms and their applications, thus offering a fresh perspective on the nascent relationship between pediatric rheumatology and artificial intelligence, highlighting both its advancements and constraints. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Increased frequency of autoimmune thyroid disease, particularly Hashimoto's thyroiditis (HT) was reported several studies in the literature, in individuals with childhood-onset systemic lupus erythematosus (cSLE). Our study aimed to investigate the prevalence and contributing factors of thyroid dysfunction and HT among cSLE patients. Methods: Thyroid function tests were obtained cross-sectionally from cSLE patients. Demographic, clinical, and laboratory characteristics and activity scores were collected from medical records. Patients diagnosed with cSLE were compared to the healthy control group for the frequency of thyroid dysfunction. The Mann-Whitney U, independent samples t test, and the Chi-square or Fisher's exact test were used to compare study groups. A p -value below 0.05 was considered statistically significant. Results: Out of 73 cSLE patients, 14 (19.1%) had subclinical hypothyroidism, 9 (12.3%) had clinical hypothyroidism, 12 (16.4%) were diagnosed with HT, and 12 (16.4%) had a family history of HT. Thyroid USG was performed in 5 euthyroid patients and 1 borderline subclinical hypothyroid patient with positive thyroid autoantibody and reported as diffuse heterogeneous echogenicity enlargement in the thyroid gland. There were no significant differences in clinical and laboratory data or medication used between the groups with and without HT; however, patients with HT had a higher frequency of clinical hypothyroidism and family history of HT. Cumulative prednisolone dose was significantly lower in patients diagnosed with HT. The frequency of HT was considerably higher in patients with cSLE compared to the healthy control group. Conclusion: The results demonstrate an increased incidence of HT in cSLE patients, even if they are euthyroid, and recommend that cSLE patients be screened more frequently. [ABSTRACT FROM AUTHOR]

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. In this retrospective cohort study, we aimed to assess the effects of various MEFV genotypes on the clinical characteristics of the patients, with a special focus on the joint involvement. In total, 782 patients with FMF were categorized into 3 groups according to the MEFV mutation; Group 1: Patients homozygous for M694V; Group 2: Patients carrying other pathogenic MEFV variants in exon 10 in homozygous or compound heterozygous states; and Group 3: FMF patients with other variants or without mutations. Clinical and demographic findings were compared between groups. Among the 782 FMF patients, total frequency of arthritis was 237 (30.3%): 207 (26.4%) were acute monoarthritis and 67 (8.5%) were chronic arthritis. Both the frequency of arthritis (acute and/or chronic) (40.4% vs. 24.8% vs. 26.7%; p:0.001) and acute monoarthritis (35.4% vs. 20% vs. 23.7%; p:0.001) were significantly higher in Group 1 than in the other groups. FMF patients with chronic arthritis showed a distinct juvenile idiopathic arthritis (JIA) distribution pattern with a more frequent enthesitis-related arthritis (ERA) subtype (43.2%). HLA-B27 was positive in 24% of the ERA patients. Conclusion: Homozygous M694V mutation is associated with a more frequent and longer acute monoarthritis comparing to other MEFV genotypes. In addition, the risk of chronic arthritis seems not related to the MEFV mutations. However, FMF patients with chronic arthritis show a distinct ILAR JIA distribution pattern with a more frequent ERA and undifferentiated arthritis subtype. What is known: • Homozygous M694V mutation is associated with a more frequent and longer acute monoarthritis What is new: • FMF patients with chronic arthritis show a distinct ILAR JIA distribution pattern with a more frequent ERA subtype • ERA patients with negative HLA-B27 antigen should also be assessed for polyserositis episodes of FMF, especially in countries with high FMF carrier frequency [ABSTRACT FROM AUTHOR]

Objective: Transitional care is essential to maintain the continuity of care in younger patients with rheumatic diseases. In this study, we aimed to assess the transition readiness of rheumatology patients who had already transferred from pediatric to adult care using a questionnaire. Materials and Methods: We included young adult rheumatology patients who had already transferred to adult rheumatology care. The Transition Readiness Assessment Questionnaire (TRAQ) was used in the adult rheumatology clinic to assess the patients’ readiness; a retrospective chart review was conducted to include diagnosis, age at diagnosis, age at transfer, and current age. Results: Three hundred and ten patients (184 female and 126 male) participated in this study. The mean age at diagnosis, the mean age at transfer, and the mean age at the time of the study were 10.7 ± 4.29, 21.1 ± 1.69, and 24.0 ± 2.26 years, respectively. Most of the patients had familial Mediterranean fever, followed by arthritis, connective tissue disorders, and other diseases. Tracking health issues was the lowest-scored domain. Females scored significantly higher than males in the tracking health issue domain (P = .006) and managing health issue domain (P = .028) but not in the overall TRAQ score (P = .053). Patients in different diagnosis and transfer age groups scored similarly across the domains. Conclusion: In this study, females performed better than males in 2 domains of the TRAQ questionnaire. Diagnoses or transfer age groups were not associated with TRAQ outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Amaç: Pulmoner vasküler hastalık ve interstisyel akciğer fibrozisi, jüvenil sistemik sklerodermada (jSS) morbidite ve mortaliteyi belirleyen en önemli tablolardır. Bu komplikasyonların hastalığın sinsi ve hızlı seyrine etkisi, akciğer tutulumunun de- ğerlendirilmesini önemli kılmıfltır. Altı dakika yürüme testi (6DYT) kardiyopulmoner hastalıklarda egzersiz kapasitesinin ve tedavi yanıtının belirlenmesinde kullanılan prognostik öne me sahip bir testtir. Eriflkin sistemik skleroderma tanılı hastalarda kullanılabilirliğine dair yapılan çalıflma sonuçları çeliflkiliyken, çocukluk çağı sistemik sklerodermada bu konuyla ilgili çalıflmalara ihtiyaç duyulmaktadır. 6DYT'ni jSS tanılı hastalara uygulayarak, egzersiz kapasitelerini belirlemeyi ve vital fonksiyonları nın değiflimlerini gözlemlemeyi hedefledik. Yöntem: Çalıflmaya jSS tanısıyla izlenen 25 hastanın yanı sıra, 27 jüvenil sistemik lupus eritematozus (JSLE) tanılı ve 30 sağlıklı çocuktan oluflan kontrol grubu dahil edildi. 6DYT uygulanmasında Amerikan Göğüs Derneği tarafından oluflturulmufl ve 2002 yılında standardize edilmifl kılavuz kuralları esas alındı. Yorgunluk ve dispne düzeylerinin belirlenmesinde Borg Skalası kullanıldı. Bulgular: Çalıflmaya alınan 25 jSS (22 kız/3 erkek), 27 jSLE (21 kız/6 erkek) ve 30 sağlıklı kontrolden (16 kız/14 erkek) oluflan 82 çocuğa 6DYT uygulandı. Demografik veriler Tablo 1 PS-117'de gösterilmifltir. Ortalama yürüme mesafesi jSS tanılı hastalarda 480.18±47.22 metre, jSLE tanılı hastalarda 513.66±51.70 metre, sağlıklı grupta 553.21±41.65 metre saptandı. jSS hastaların kontrol grubuna göre az mesafe yürüdüğü görüldü (p<0.001). jSS grubunda ortalama oksijen satürasyonu (%SpO2) test öncesi %98.0±0.9; test sonrası %97.5±1.6 saptanırken, iki bağımlı değiflkenin karflılafltı rılmasında anlamlı fark elde edildi (p=0.01). 6DYT sonuçları Tablo 2 PS-117'de gösterilmifltir. jSS grubunda akciğer tutulumu olanlar (ortalama yürüme mesafesi 476.08±47.13 metre), olmayanlara göre (ortalama yürüme mesafesi 483.96± 48.89 metre) daha az yürüdü. Ancak istatistiksel fark gözlenmedi (p=0.68). Bacak ağrısı olan jSS hastaları (ortalama 460.20±40.29 metre), olmayanlara göre (ortalama 498.61±46.94 metre) daha az yürüdü (p=0.038). Sonuç: jSS tanılı hastaların yürüme mesafeleri kısıtlıdır. Ancak akciğer tutulumu tek baflına egzersiz kapasitesini etkilememektedir. 6DYT'nin jSS takibindeki yeriyle ilgili arafltırma sayısı sı- nırlı olduğundan, elde ettiğimiz sonuçların sonraki çalıflmalara ıflık tutacağı inancındayız. [ABSTRACT FROM AUTHOR]

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 (β = 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. [ABSTRACT FROM AUTHOR]

Objective: 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. Materials and Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Objective: 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. Methods: 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. Results: 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. Conclusion: 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. Key points: • 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Autoinflammatory diseases are characterized by recurrent fevers and clinical findings of impaired natural immunity and can involve various organ systems. The concept of autoinflammatory disease emerged after the definition of familial Mediterranean fever and tumor necrosis factor receptor-associated periodic syndrome. This new disease group was considered to differ from the standard concept of autoimmune diseases, which is relatively better known in terms of basic features, such as defects in innate immunity and the absence of antibodies. A better understanding has been achieved regarding the genetic and pathogenetic mechanisms of this relatively new disease group over the past 20 years since they were first diagnosed, which have led to some changes in the concept of autoinflammatory diseases. The recent definition classifies autoinflammatory disease to be a wide range of diseases with different clinical features, mainly accompanied by changes in innate immune and rarely in humoral immunity. The spectrum of autoinflammatory diseases is rapidly expanding owing to recent developments in molecular sciences and genetics. This review article discusses the clinical features, classification criteria, treatment options, and long-term prognosis of periodic fever, aphthous stomatitis, pharyngitis, adenitis syndrome, and other common autoinflammatory diseases in the light of current literature. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Behçet's Disease was first described by a Turkish dermatologist, Hulusi Behçet, 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 Behçet'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. [ABSTRACT FROM AUTHOR]

Background/Objectives: The aim of the study is to assess the effect of juvenile idiopathic arthritis (JIA) and biologic disease-modifying anti-rheumatic drugs (bDMARDs) on ovarian reserve in children. Materials and Methods: A cross-sectional study was performed from March 2021 to March 2022 and included 81 patients with JIA and 49 healthy children. Serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol levels were analyzed using electrochemiluminescence methods. Results: The mean of current age (13.5 ± 3.2 vs. 14.4 ± 2.4 years), height standard deviation score (SDS) (− 0.35 ± 1.18 vs. − 0.44 ± 0.94), body mass index SDS (0.12 ± 1.33 vs. 0.25 ± 1.28), and the median weight SDS (− 0.13 (− 2.27–3.23) vs. − 0.52 (− 3.4–3.3)) were similar in JIA patients and controls (p > 0.05). Patients with JIA were divided into two groups according to their treatment regimens: treated with methotrexate (MTX) (biologic naive) (n = 32) and treated with MTX plus bDMARDs (n = 49). No significant differences were detected between the 3 groups regarding menarche age, menstrual cycle length, and flow duration (for all p > 0.05). The median serum concentration of AMH was 2.94 (1.12–7.88) ng/ml in the control group, 3.02 (0.36–8.54) ng/ml in the biologic naïve group, and 3.01 (0.99–8.26) ng/ml in the MTX plus bDMARD group. There were no significant differences between 3 groups according to serum AMH, FSH, LH, and estradiol levels (p > 0.05). Conclusion: Biologic DMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment. Prospective studies with larger sample sizes are needed to confirm our findings and to evaluate the impact on the future fertility of patients. Key Points • Although biologic disease-modifying anti-rheumatic drugs (bDMARDs) are being game-changing treatment options in juvenile idiopathic arthritis, their effect on fertility and ovarian reserve is one of the most discussed issues. • In addition to treatment used, autoimmune diseases might also have a negative effect on fertility. • In this cross-sectional study, we found that anti-Mullerian hormone level of patients who were on bDMARDs, patients who were on methotrexate, and healthy controls were similar. • Our results suggest that bDMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment. [ABSTRACT FROM AUTHOR]

Objective: Mercury poisoning is a condition with multiple-organ dysfunction that has effects on the central nervous system, gastrointestinal system, cardiovascular system, skin, lungs, and kidneys. It can be fatal or may result in sequelae such as neurological disturbances, if treated late or left untreated. The endocrinological effects of mercury exposure are not well-known. We aimed to evaluate patients with mercury poisoning. Materials and Methods: A total of 6 cases of mercury poisoning from 3 families were included in the study. Clinical, laboratory, and follow-up data were recorded. Results: Thyroid dysfunction was presented as high thyroid hormones and normal thyrotropin level (unsuppressed) in 5 cases (83.3%). On the other hand, pheochromocytoma-like syndrome was detected in 5 cases (83.3%) with hypertension. The 4 cases were the first to use methimazole for mercury poisoning due to tachycardia and hypertension despite antihypertensive treatment due to catecholamine excess and thyroid dysfunction. Hyponatremia was detected in 3 cases (50%). Conclusion: Mercury poisoning is difficult to diagnose because it is rare and presents with nonspecific physical and laboratory findings. Early diagnosis and providing appropriate treatment are essential in order to prevent sequelae. Mercury poisoning should be considered in patients with unexplained hypertension and tachycardia suggesting the involvement of thyroid hormones and catecholamines. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to investigate the frequency of celiac disease (CD) in patients with juvenile systemic lupus erythematosus (JSLE) and the potential association of JSLE and CD. Methods: This was a cross-sectional study performed from October 2015 to October 2017. A total of 50 patients with JSLE were included in the study. The levels of total IgA and tissue transglutaminase (tTG) IgA antibody were measured in all patients. Subjects with increased tTG were further evaluated for anti-endomysial antibodies (EMAs). Gastroduodenoscopy and intestinal biopsy were performed in those with increased EMA levels to confirm the diagnosis of CD. Results: The study included 44 (88.0%) female and 6 (12.0%) male patients. Of the 50 patients, 30 (60.0%) received corticosteroids, and only 4 (8.0%) received no therapy at the time of the study. Only 3 (6.0%) patients were positive for tTG IgA. Patients with positive tTG IgA were then tested for EMA IgA antibodies, and none of them had a positive result. Conclusion: We did not find CD in children with systemic lupus erythematosus. Studies with more patients with JSLE are needed to conclude a more precise result. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to investigate the frequency of celiac disease (CD) in patients with juvenile systemic lupus erythematosus (JSLE) and the potential association of JSLE and CD. Methods: This was a cross-sectional study performed from October 2015 to October 2017. A total of 50 patients with JSLE were included in the study. The levels of total IgA and tissue transglutaminase (tTG) IgA antibody were measured in all patients. Subjects with increased tTG were further evaluated for anti-endomysial antibodies (EMAs). Gastroduodenoscopy and intestinal biopsy were performed in those with increased EMA levels to confirm the diagnosis of CD. Results: The study included 44 (88.0%) female and 6 (12.0%) male patients. Of the 50 patients, 30 (60.0%) received corticosteroids, and only 4 (8.0%) received no therapy at the time of the study. Only 3 (6.0%) patients were positive for tTG IgA. Patients with positive tTG IgA were then tested for EMA IgA antibodies, and none of them had a positive result. Conclusion: We did not find CD in children with systemic lupus erythematosus. Studies with more patients with JSLE are needed to conclude a more precise result. [ABSTRACT FROM AUTHOR]

Introduction: 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.Methods: Patients on biologic treatment regimen were examined by the pediatric infectious disease specialist in every 2 months during 1-year long.Results: 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 < 0.001). The total rate of infection development after 1-year period was lowest for etanercept; it was highest for the patients on infliximab treatment (p < 0.001).Conclusion: We comment that the altered immune system of JIA can be responsible from the serious infections irrespective of immunosuppressive therapy. Biologic agents can be safely used in JIA evaluating the loss and benefit statement. [ABSTRACT FROM AUTHOR]

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 < 0.001). jSSc patients with lung involvement walked less than those without lung involvement [463.2 (418-565) m vs. 491.5 (415-580) m], but without a significant difference (p = 0.82). The frequency of lower extremity pain during and after the test was significantly higher in the jSSc cohort compared to both control groups (p = 0.001). Patients with myalgia were found to walk less than those without myalgia [446.5 (415-538) m vs. 493.5 (428-580) m] (p = 0.04). Patients with jSSc have limited walking distances. Despite the decreased walking distance among jSSc patients with ILD and/or PAH, the limited number of patients makes the results inappropriate for interpretation. Low extremity pain influences the walking capacity of jSSc patients. [ABSTRACT FROM AUTHOR]

An obituary for Hans-Dietrich Genscher, former foreign minister and German Minister of the Interior, is presented.