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.

A clinical overview of paediatric sarcoidosis: Multicentre experience from Turkey.

OBJECTIVES: We aimed to outline the demographic data, clinical spectrum, and treatment approach of sarcoidosis in a large group of patients and sought to figure out the variations of early-onset (EOS) and late-onset paediatric sarcoidosis (LOS). METHODS: The study followed a retrospective-descriptive design, with the analysis of medical records of cases diagnosed as paediatric sarcoidosis. RESULTS: Fifty-two patients were included in the study. The median age at disease onset and follow-up duration were 83 (28.2-119) and 24 (6-48) months, respectively. Ten (19.2%) cases had EOS (before 5th birthday) and 42 (80.7%) cases had LOS. The most common clinical findings at the time of the disease onset were ocular symptoms (40.4%) followed by joint manifestation (25%), dermatological symptoms (13.5%), and features related to multi-organ involvement (11.5%). Anterior uveitis was the most common (55%) one among ocular manifestations. Patients with EOS displayed joint, eye, and dermatological findings more commonly than patients with LOS. The recurrence rate of disease in patients with EOS (5.7%) and LOS (21.1%) were not statistically different (P = .7). CONCLUSIONS: Patients with EOS and LOS may present with variable clinical features and studies addressing paediatric sarcoidosis cases in collaboration between disciplines will enhance the awareness of this rare disease among physicians and assist early diagnosis with lesser complications.

Do the features of juvenile psoriatic arthritis change according to age? A comprehensive evaluation of the PeRA Research Group Registry.

OBJECTIVES: To describe the clinical features and treatment outcomes of children with juvenile psoriatic arthritis (JPsA) and to compare the distinct patterns of the disease between early-onset and late-onset age groups. METHODS: Patients with JPsA followed regularly for at least 6 months between 2010-2020 in 7 pediatric rheumatology centers in Turkey were included in the study. The demographic features, clinical manifestations, treatment strategies, and outcomes of the patients were evaluated retrospectively. RESULTS: Eighty-seven (46 male/41 female) patients were included in the study. The mean age at diagnosis was 11.9 ± 4.5. Fifty-seven (65.5%) patients had psoriasis at the time of diagnosis, arthritis preceded psoriasis in 10 (11.5%) patients. Thirty (34.5%) patients had dactylitis, 28 (32.2%) had nail pitting, 36 (41.4%) had involvement of the small joints, 20 (23%) had enthesitis. Sacroiliitis was detected in 11 (12.6%) patients by magnetic resonance imaging. Anti-nuclear antibodies (ANA) were positive in 35 (40.2%) patients. Twelve children (%13.8) were in the early-onset (<5 years) group. Uveitis and ANA positivity were more common in the early-onset group. Active joint counts and activity scores of our patients showed significant improvement at 6th month and at the last control compared with baseline. CONCLUSION: About one-third of patients with JPsA do not have psoriasis at the time of diagnosis. In some patients, no skin lesion is seen during the course of the disease. Children with psoriatic arthritis seem to display two different phenotypes. Younger children have female predominance, ANA positivity, and uveitis, while older children have more axial involvement.

NLRP12-associated autoinflammatory disease: much more than the FCAS phenotype.

OBJECTIVES: NLRP12-associated autoinflammatory disease (NLRP12-AID) is a rarely seen periodic fever syndrome also known as familial cold autoinflammatory syndrome-2 (FCAS2), caused by autosomal dominant inherited mutations in the NLRP12 gene. We aimed to present our clinical experience constituting one of the largest paediatric NLRP12-AID cohort. METHODS: The patients with preliminary diagnosis of systemic autoinflammatory disease (SAID) other than familial Mediterranean fever (FMF) and PFAPA syndrome were evaluated with the next-generation-sequence (NGS) genetic-panel analysis between January-2016 and January-2022. Among children carrying NLRP12-variant, patients with recurrent episodes of autoinflammatory disease manifestations were diagnosed with NLRP12-AID. Demographic, clinical and laboratory data, treatments and outcomes of patients were presented. RESULTS: Seventeen patients were diagnosed with NLRP12-AID. The mean age at diagnosis was 114.7±69.5 months. The most frequently seen clinical manifestations were respectively; fever (100%), arthritis/arthralgia (58.8%), rash (52.9%), abdominal pain (52.9%), diarrhoea (41.2%), myalgia/fatigue (53.2%) and, conjunctivitis (11.7%). Clinical manifestations were triggered by cold exposure in three patients (17.6%). Seven patients had pathogenic, one had likely pathogenic, seven had VUS, and two had novel heterozygous variants. The most common defined variant in the NLRP12 gene was R352C. Complete response was achieved in 5 patients and partial response was in 6 with colchicine treatment. Attacks were prevented with anti-IL-1 treatments in 6 patients unresponsive to colchicine. CONCLUSIONS: In conclusion, the disease can cause effects on various tissues, especially the musculoskeletal and gastrointestinal systems, apart from FCAS symptoms. We think that a patient who can be defined as syndrome of undifferentiated recurrent fever should also be evaluated genetically in terms of NLRP12 previously.

Chronic recurrent multifocal osteomyelitis: A multidisciplinary experience of 22 pediatric cases with a mean follow-up of 27 months.

BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO) is not a well known disorder among nonpediatricians. The aim of this study is to retrospectively evaluate the clinical outcomes of twenty-two CRMO patients presenting to two referral centres. METHODS: This retrospective study included twenty-two children (12 males, 10 females; mean age 13 years; range 7-17 years). The diagnosis was based on clinical, radiological, and pathological findings. Data were retrieved from hospital charts. RESULTS: The mean delay in diagnosis was 26 months (range, 0-96 months). The mean follow-up after diagnosis was 27.4 months (range, 6-47 months). Symptoms included pain, limping, local swelling, morning stiffness, and fever. 18 patients had multifocal and 4 patients had unifocal disease. Bone lesions were detected with whole-body or local MRI (Magnetic Resonance Imaging). The mean number of bone lesions was 2.5 (range, 1-8). Ten cases underwent biopsy to exclude malignancy and infection. Prior to diagnosis, cast immobilization or curettage was erroneously performed in four patients. One patient suffered from vertebral compression fracture. There is no growth disturbance or deformity in any patient. CONCLUSION: This study demonstrated that early recognition of the disease can be improved by using Bristol criteria which should be evaluated by a multidisciplinary team rather than one single specialist. In this way, the reliability of these criteria is improved and the treatment could be given earlier with decreased delay in diagnosis. This multidisciplinary approach is also important for decision for biopsy, timely aggressive medical treatment, and follow-up of the disease to minimise possible complications.

Cluster analysis of paediatric Behçet's disease: Data from The Pediatric Rheumatology Academy-Research Group.

OBJECTIVES: Behçet's disease (BD) is a systemic vasculitis affecting many organ systems, with the involvement of all-sized arteries and veins. The study aims to determine the main characteristics of paediatric BD patients and also analyse the clustering phenotypes. METHODS: Demographic data, clinical manifestations, laboratory features, treatment schedules, and disease outcomes were achieved from patients' charts retrospectively. A cluster analysis was performed according to the phenotype. RESULTS: A total of 225 (109 male/116 female) patients with BD were enrolled in the study. The median ages of disease onset and diagnosis were 131 (36-151) and 156 (36-192) months, respectively. According to cluster analysis, 132 (58.6%) patients belonged to the mucocutaneous-only cluster (C1), while 35 (15.6%) patients fitted to articular type (C2), 25 (11.1%) were in the ocular cluster (C3), 26 (11.6%) were in the vascular cluster (C4), and 7(3.1%) belonged to the gastrointestinal cluster (C5). Ocular and vascular clusters were more common in boys (p < .001), while girls usually presented with the mucocutaneous-only cluster. The disease activity at the diagnosis and the last control was higher in ocular, vascular, and gastrointestinal clusters. CONCLUSIONS: These identified juvenile BD clusters express different phenotypes with different outcomes Our analysis may help clinicians to identify the disease subtypes accurately and to arrange personalized treatment.

PREDICT-crFMF score: A novel model for predicting colchicine resistance in children with familial Mediterranean fever.

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

Clinical characteristics and predictors for recurrence in chronic nonbacterial osteomyelitis: a retrospective multicenter analysis.

Background/aim: Chronic nonbacterial osteomyelitis (CNO) is a rare disease of unknown etiology and most commonly occurs during childhood or adolescence. The purpose of this study is to collect data on the clinical features, outcomes, and management of the disease and to identify the factors affecting recurrence. Materials and methods: This is a retrospective multicenter cross-sectional study of pediatric patients diagnosed with CNO. A total of 87 patients with a diagnosis of CNO followed for at least 6 months in 8 pediatric rheumatology centers across the country between January 2010 and December 2021 were included in this study. Results: The study included 87 patients (38 girls, 49 boys; median age: 12.5 years). The median follow-up time was 20 months (IQR: 8.5-40). The median time of diagnostic delay was 9.9 months (IQR: 3-24). Arthralgia and bone pain were the most common presenting symptoms. Multifocal involvement was detected in 86.2% of the cases and a recurrent course was reported in one-third of those included in the study. The most commonly involved bones were the femur and tibia. Vertebrae and clavicles were affected in 19.5% and 20.6% of cases, respectively. The erythrocyte sedimentation rate (ESR) values of 60.9% of the patients were above 20 mm/h and the C-reactive protein values of 44.8% were above 5 mg/L. The remission rate was 13.3% in patients using nonsteroidal antiinflammatory drugs and 75.0% in those using biological drugs. Vertebral and mandibular involvement and high ESR values at the time of diagnosis were associated with recurrence. Conclusion: In this multicenter study, CNO with vertebral and mandibular involvement and high ESR at diagnosis were associated with recurrence.

Hepatitis B vaccination response of treatment-naive patients with juvenile idiopathic arthritis.

To evaluate the vaccine response of treatment-naive juvenile idiopathic arthritis (JIA) patients who were fully vaccinated against Hepatitis B Virus (HBV) and then compare their antibody status with healthy controls. In this multicenter study, initial visit hepatitis B surface antigen (HbsAg) and anti-hepatitis B surface antibody (anti-Hbs) titers of 262 treatment-naive JIA patients who were followed up regularly between May 2015 and October 2019 were evaluated retrospectively from patients' medical records and compared with 276 healthy peers. Both HbsAg and anti-Hbs antibody titers were tested by the ELISA technique. Anti-HBs titers ≥ 10 IU/L were considered as reactive indicating seroprotection against HBV. In the JIA group, seropositivity rate was 59.1% while 72.9% of the control group were immune against HBV (p = 0.002). The median titer for anti-Hbs was 14 (range: 0-1000) IU/L in the patient group and 43.3 (range: 0-1000) IU/L in the control group (p = 0.01). Neither JIA patients nor healthy controls were positive for HbsAg. Patients with JIA vaccinated according to the national vaccination schedule were evaluated at their first visit in pediatric rheumatology outpatient clinics for anti-Hbs presence and it was found that they have lesser seroprotectivity than their age and sex-matched routinely vaccinated, healthy peers. So, to complete missing vaccines and booster vaccine doses, assessing the immune status of the patients at the time of diagnosis against HBV should be in the check-list of physicians dealing with pediatric rheumatic diseases.

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

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

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.

Low disease activity state in juvenile-onset systemic lupus erythematosus.

OBJECTIVES: To determine the rate of achieving The Lupus Low Disease Activity State (LLDAS) in children with systemic lupus erythematosus (SLE) for tracing pertinent treatment modalities. METHODS: A total of 122 juvenile-onset SLE (jSLE) patients from six pediatric rheumatology centers in Turkey were enrolled in the study. LLDAS-50 was defined as encountering LLDAS for at least 50% of the observation time. According to the achievement of LLDAS-50, clinical features, immunological profiles, and treatments of patients with jSLE have been revealed. RESULTS: LLDAS of any duration was achieved by 82% of the cohort. Although only 10.8% of the patients achieved remission, 68.9% reached LLDAS-50. A significant difference was found between patients who reached LLDAS-50 and those who did not, in terms of the time to reach low-dose corticosteroid treatment (p = 0.002), the presence of subacute cutaneous findings (p = 0.007), and the presence of proteinuria (p = 0.002). Both of the groups were under similar treatment approaches. However, the number of patients being treated with corticosteroids at the last visit was found to be significantly higher in patients who achieved LLDAS-50 (p<0.001). CONCLUSION: Targeting LLDAS in jSLE, even with long-term, low-dose corticosteroid use, seems to be an achievable goal in clinical practice.

Hematological involvement in pediatric systemic lupus erythematosus: A multi-center study.

Introduction: Systemic lupus erythematosus (SLE) may present with features of several systems, including hematological manifestations. In this study, we aimed to evaluate the characteristics of hematological involvement and assess possible associations and correlations in pediatric SLE patients. Method: This is a retrospective multi-center study. The medical records of pediatric SLE patients followed between January 2000 and June 2020 were analyzed. All children fulfilled the criteria of the Systemic Lupus International Collaborating Clinics. Results: The study included 215 children with SLE, 118 of whom had hematological manifestations. Concomitant renal involvement and low C3 levels were significantly more frequent in patients with hematological involvement (p = 0.04, p = 0.008, respectively). Also, anti-cardiolipin, anti-beta-2-glycoprotein I (anti-ß2 GP1), and anti-Sm antibody positivity, and the presence of lupus anticoagulant were more common in the group with hematological findings (p = 0.001 for anti-cardiolipin antibody positivity and p < 0.001 for the positivity of anti-ß2 GP1 antibody, anti-Sm antibody, and lupus anticoagulant). The most common hematologic abnormality was anemia (n = 88, 74.5%), with autoimmune hemolytic anemia constituting the majority (n = 40). Corticosteroids followed by IVIG were the mainstay of treatment. In patients resistant to corticosteroid and IVIG treatments, the most preferred drug was rituximab. Low levels of C3, high SLEDAI score, high incidence of renal involvement, and positive antiphospholipid antibodies were associated with hematological involvement in the univariate analysis. The presence of antiphospholipid antibodies and high SLEDAI score were independently associated with hematological involvement in multivariate analysis (OR: 4.021; 95% CI: 2.041-7.921; p < 0.001 and OR: 1.136; 95% CI: 1.065-1.212; p < 0.001). Conclusion: Hematological abnormalities are frequently encountered in pediatric SLE. Positive antiphospholipid antibodies and high SLEDAI scores were associated with hematological involvement.

Drug survival of the infliximab biosimilar (CT-P13) in paediatric patients with non-infectious uveitis.

OBJECTIVES: Paediatric non-infectious uveitis (NIU) is an important cause of significant long-term complications and blindness in children. Infliximab (IFX) is a chimeric human/murine monoclonal antibody against TNF-α that is effective in NIU resistant to conventional therapies. In this study, we aimed to determine the efficacy and safety of an IFX biosimilar (CT-P13) in paediatric patients with NIU. METHODS: This was a non-interventional and retrospective study that included paediatric patients with NIU who received IFX biosimilar CT-P13 treatment between January 2016 and January 2020. Demographic data pertaining to patients and their disease were collected. The efficacy and safety of the IFX biosimilar were evaluated. RESULTS: Twenty-six patients (44 eyes) were enrolled in this study. The median age (interquartile range) at the diagnosis of uveitis was 9.41 (5-12.3) years. The most common site of involvement was anterior uveitis, and bilateral involvement was more commonly seen in the older age group (p=0.32). The primary diagnosis of 16 patients was juvenile idiopathic arthritis, three had Behçet's disease, six had idiopathic disease and one had sarcoidosis. All patients were treated with CT-P13 (22 patients were biologic-naïve, and four switched from adalimumab). The median follow-up time on IFX was 14 months (range 4-48). Complete recovery was achieved in 95.4% of eyes with active uveitis, while inactive disease was not achieved in two of them. We observed a reduction in the number of flares in all patients during the follow-up period (4.5±2.2 vs. 0.89±1, p=0.01). Treatment-emergent adverse events occurred in 26.9% of patients. CONCLUSIONS: To our knowledge, this is the first study to assess the impact of CT-P13 treatment adherence on disease activity in children with NIU. The IFX biosimilar CT-P13 is remarkably safe and effective for the long-term treatment of paediatric NIU.

The feasibility of withdrawing canakinumab in paediatric colchicine-resistant familial Mediterranean fever patients.

OBJECTIVES: To determine the feasibility of withdrawing canakinumab (CAN) in a large cohort of paediatric patients with colchicine-resistant familial Mediterranean fever (crFMF). METHODS: This retrospective observational cohort study included paediatric crFMF patients that received CAN treatment for ≥6 months. Patient data were recorded at treatment onset (baseline), and at 1, 3, 6, 12, 18, and 24 months after initiation of treatment. RESULTS: The study included 114 patients that were followed-up for 2736 person-months. During the 24-month follow-up period, the CAN dose interval remained unchanged in 44 patients. The dose interval was extended in 58 patients within a median 6 months (range: 3-18 months) of treatment initiation. In all, 4 of these 58 patients had a new attack of crFMF after the dose interval was extended. CAN was withdrawn in 12 patients (in 5 at month 12 month and in 7 at month 18), of which 2 had a new attack within 3 months of withdrawal. In these 2 patients CAN was re-initiated with a dose interval of 8 weeks. The remaining 10 patients in which CAN was withdrawn did not report any symptoms throughout the remainder of the 24-month follow-up period. The median attack-free period in those treated with CAN was 669 d (95% CI: 644-696). CONCLUSIONS: The present findings show that it may be feasible to withdraw CAN or extend its dose interval in paediatric crFMF patients. Based on the present findings, we think that as the quantity of real-life data increases, standard CAN protocols may be developed.

The same mutation in a family with adenosine deaminase 2 deficiency.

The deficiency of adenosine deaminase 2 (DADA2) has recently been defined as a monogenetic autosomal recessive autoinflammatory disease. DADA2 is mainly characterized by high fever, livedo racemose, early-onset stroke, mild immunodeficiency and clinically polyarteritis nodosa (PAN)-like symptoms. Mutations in CECR1 (cat eye syndrome chromosome region, candidate 1) are responsible for DADA2. Livedoid racemose, lacunar infarct due to involvement in small vessel of the central nervous system, peripheral neuropathy, digital ulcers and loss of fingers are predominantly seen in the disease which could progress to end-stage organ failure and death in some patients. A wide spectrum of severity in phenotype as well as in the age of onset has been reported in the literature. This phenotypic variability is also found in our clinical practice even in patients with the same mutation. Here, we present a family diagnosed with DADA2, with the previously reported p.Gly47Arg mutation in CECR1.

Evaluation of Dental Status and Temporomandibular Joint in Children With Generalized Joint Hypermobility.

OBJECTIVE: The aim of this study was to evaluate the dental status and temporomandibular diseases (TMDs)-related symptoms in children with generalized joint hypermobility (GJH) and compare them with healthy controls (HCs). METHODS: This is a cross-sectional, observational study carried out between September 2016 and April 2017. A total of 124 children with GJH (n = 62) and HC (n = 62) were enrolled. The GJH was assessed with the Beighton hypermobility score. The subjects were screened for dental status and TMD-related symptoms. The assessment included the index for "decayed," "missing," and "filled teeth" (DMFT, dmft); plaque; gingival bleeding; tooth mobility; and temporomandibular joint (TMJ) evaluation. RESULTS: The mean Beighton hypermobility score was 6.3 ± 1.2 in the GJH group. Visible plaque index and gingival bleeding index scores were found to be significantly higher in children with GJH then in the HC (p = 0.031, p = 0.023). No differences were found regarding the DMFT scores between the groups (p = 0.16). Temporomandibular disorder-related symptom frequencies were significantly higher in children with GJH (p < 0.001). The most common clinically determined sign of TMD was clicking with a maximum active mouth-opening. Combined TMJ symptoms and TMD were observed in approximately one third of the children with GJH. CONCLUSIONS: The presence of GJH in a child may be indicative of future dental or TMJ problems, and it may cause dental problems due to increased gingival bleeding index and visible plaque index scores. Therefore, children with GJH require preventive dental and TMJ care.