Ayşe Tanatar

1. Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood and may lead to substantial morbidity due to persistent inflammation and irreversible joint damage i...

Colchicine is the cornerstone of treatment in familial Mediterranean fever and is generally recommended as lifelong therapy. However, a subset of pediatric patients may experience a milder disease course, raising questions about the feasibility and safety of colchicine discontinuation. Evidence guiding this decision remains limited, and no consensus exists on patient selection criteria or monitoring strategies. The objective of this study was to evaluate long-term outcomes after colchicine discontinuation in a large pediatric familial Mediterranean fever cohort and to identify clinical and genetic factors associated with sustained colchicine-free remission. We retrospectively analyzed medical records of 2316 pediatric patients diagnosed with familial Mediterranean fever and followed at the Pediatric Rheumatology Unit of Istanbul University, Istanbul Faculty of Medicine, Istanbul, Türkiye. Patients fulfilling at least one of the Tel-Hashomer or Eurofever/Pediatric Rheumatology International Trials Organization (PRINTO) classification criteria and carrying at least one pathogenic or likely pathogenic MEFV (Mediterranean fever) gene mutation were eligible. Colchicine was discontinued in 127 patients (5.48%), who were classified into two groups: Group 1 (n = 31), patients who required colchicine re-initiation because of recurrent attacks, and Group 2 (n = 96), patients who maintained sustained colchicine-free remission during follow-up. A contemporaneous comparator group of 118 patients who continued colchicine therapy without any attempt at discontinuation (Group 3) was included to provide clinical and genetic context. Demographic, clinical, genetic, and disease severity characteristics were compared across groups. Sustained colchicine-free remission was maintained in 96 of 2316 patients (4.14%; Group 2). Among all patients who discontinued colchicine (Groups 1 and 2 combined), the median duration of colchicine treatment before discontinuation was 3.85 years (interquartile range 1.84-7.10), and the median follow-up after cessation was 4.91 years (interquartile range 1.92-7.23). Baseline clinical, demographic, and genetic characteristics were largely similar between Group 1 and Group 2, and no robust independent predictor of sustained remission was identified. Biallelic pathogenic exon 10 MEFV variants were significantly more prevalent in Group 3 (32.2%) compared with Group 1 (12.9%) and Group 2 (3.1%), reflecting a progressive genetic gradient across the three groups. Patients in Group 3 also exhibited higher frequencies of fever, chest pain, arthritis, arthralgia, erysipelas-like erythema, and exercise-induced leg pain compared with the discontinuation groups. Fulfillment of Eurofever/PRINTO classification criteria was significantly lower in Groups 1 (54.8%) and 2 (54.2%) than in Group 3 (87.3%), consistent with a milder phenotypic profile in patients considered for discontinuation. No patient in the discontinuation cohort developed amyloidosis during follow-up. Colchicine discontinuation is achievable in a small but consistent subset of patients with pediatric familial Mediterranean fever (4.14% of the total cohort), the majority of whom maintain sustained remission over a long-term follow-up. While patients requiring continuous therapy exhibit a more severe clinical and genetic profile, no robust baseline predictor reliably distinguishes those who will remain in remission from those who will relapse. These findings highlight the need for individualized withdrawal decisions guided by rigorous longitudinal monitoring, and underscore the importance of prospective studies incorporating emerging biomarkers of subclinical inflammation.

Introduction: Juvenile spondyloarthropathies (JSpA) are a group of chronic inflammatory diseases that differ in their clinical features and course from adult spondyloarthropathies and other subtypes of juvenile idiopathic arthritis (JIA). Therefore, defining disease inactivity in JSpA requires specific criteria. This Delphi study aimed to establish a national consensus on its core clinical, laboratory, and radiological domains. Methods: A total of 27 pediatric rheumatologists participated in the Delphi survey, conducted in two rounds. Participants were asked multiple‐choice and Likert‐type questions regarding their preferences for using domains including anamnesis, laboratory findings, imaging methods, and predefined disease activity scores for assessing inactivity. At the end of each round, the study coordinators determined the “strong consensus” items based on a power analysis of these parameters. Results: The absence of “pain or tenderness in the peripheral joints, lower back and entheseal regions” in anamnesis domain and “tenderness in the peripheral joints, entheseal areas, and hip examination”; “swelling in the peripheral joints; tenderness on sacroiliac compression testing”; and “no reduction in hip RoM examination” in physical examination domain received the highest scores and were accepted as strong consensus. Furthermore, normalization of MRI findings of SIJ and hip/peripheral joint and “physician global score = 0” reached the specified thresholds, resulting in strong consensus following the second round. Conclusions: This Delphi study highlights the need for a multidimensional approach that integrates clinical, radiological, and physician assessments to define disease inactivity in patients with JSpA. The resulting consensus provides a more specific assessment on inactivity defining JSpA patients and reflects a national consensus.

Objectives: The role of neutrophil extracellular traps (NETs) in IgA vasculitis (IgAV) pathogenesis is emerging, with NETosis-associated markers potentially linked to disease activity. This study aimed to explore the relationship between NETosis biomarkers and IgAV disease phases. Methods: A longitudinal study involving 33 paediatric IgAV patients and 26 healthy controls was conducted. Blood and urine samples were collected from healthy controls and patients during active and inactive disease phases. NETosis markers, including cell-free DNA (cf-DNA), neutrophil elastase, MPO and citrullinated histone H3 (cit-H3) were measured using ELISA kits. Statistical analyses were conducted to compare differences for NETosis markers between groups and to evaluate correlations among variables using appropriate statistical tests. Results: There was no significant difference in gender and age between the patient and control groups. The serum cf-DNA level was significantly higher in the active patient group compared with the control and inactive patient groups (P = 0.04; P = 0.04, respectively). In urine, MPO levels were significantly lower in the active phase of patients than controls (P = 0.009), while cit-H3 levels were higher in both active and inactive phases compared with controls (P = 0.01 and P = 0.03, respectively). A cf-DNA threshold of 935 ng/ml was identified, which achieved a sensitivity of 93% (correctly identifying 93% of active patients) and a specificity of 72% (correctly identifying 72% of healthy controls). Conclusion: Elevated serum cf-DNA and urine cit-H3 suggest a potential role for NETosis in IgAV activity, highlighting these markers as potential indicators for disease monitoring. Further studies are warranted to establish standardized protocols for NETosis marker assessment in IgAV.

Objectives: This study aimed to evaluate the predictability of the homozygous M694V genotype in paediatric FMF patients and to develop a clinical scoring system to enhance disease management strategies. Methods: This nationwide, multicentre, cross-sectional study included 3981 paediatric FMF patients with biallelic pathogenic variants in exon 10 of the Mediterranean fever gene. Patients were divided into two groups: group 1 (homozygous M694V) and group 2 (other variants). Data were collected from 37 paediatric rheumatology and/or nephrology clinics across Türkiye, covering patients followed between 2014 and 2023. Results: Group 1 had significantly earlier symptom onset (≤3 years: 49.8% vs 43.9%, P < 0.001) and diagnosis (median age: 5 years vs 5.8 years, P < 0.001) compared with group 2. A higher prevalence of family history of FMF was observed in group 1 (P < 0.001). Clinical manifestations, including arthritis (27.5%), erysipelas-like erythema (ELE) (20.3%) and protracted febrile myalgia syndrome (PFMS) (3.6%), were significantly more frequent in group 1 (P < 0.001 for all). Colchicine resistance was also higher in group 1 (18.1% vs 5.1%, P < 0.001). Logistic regression analysis showed that ≤3 years of age at symptom onset, family history, arthritis, myalgia, PFMS, ELE and splenomegaly were independent predictors of the homozygous M694V genotype. A clinical scoring system was proposed based on these findings. Conclusion: This study provides valuable insights into the clinical predictors of the homozygous M694V genotype in paediatric FMF. The proposed scoring system will support clinicians in prognosis assessment and treatment planning, contributing to improved patient outcomes.

Background: This study sought to analyze patients to identify risk factors for scrotal involvement with childhood immunoglobulin A vasculitis (IgAV), evaluate its association with other systemic involvements, and discuss a tertiary center treatment experience with the literature. Methods: The medical records of male patients diagnosed with IgAV between January 2013 and January 2024 and regularly followed for at least 6 months in two pediatric rheumatology centers in Türkiye were reviewed retrospectively. Demographic, clinical, laboratory, radiological, and treatment data were collected from the medical records. Results: A total of 339 male pediatric patients with IgA vasculitis were included in this study. The median age of the patients at diagnosis was 8.1 years (range: 2–17). The median follow-up period was one year (6 months to 12 years). Palpable purpura was present in all patients. Gastrointestinal (GI) involvement was observed in 75 (22.1%) patients, joint involvement in 61 (18%), and renal involvement in 50 (14.7%). Scrotal involvement was observed in 36 (10.6%) patients. In the group with scrotal involvement, the rates of GI system involvement, recurrence, and steroid use were statistically significantly higher compared to those without scrotal involvement (p = 0.004, p = 0.011, p < 0.001, respectively). Conclusion: This study showed that scrotal involvement was more prevalent in patients with GI system involvement and those with younger age at diagnosis. Furthermore, patients with scrotal involvement required more frequent steroid treatment and experienced more recurrences. Therefore, detailed scrotal evaluation is essential in younger male patients with GI system involvement, and close monitoring for recurrences is crucial.

Background: The present study aimed to describe the differences between patients with and with-out ELE in patients with Familial Mediterranean Fever (FMF) and to determine the relationship between erysipelas-like erythema (ELE) and demographic, clinical, genetic and treatment character-istics of the patients. Materials and Methods: The medical files of patients who were followed up with a diagnosis of FMF in the Pediatric Rheumatology Department of Gaziantep City Hospital between October 2023 and October 2024 were retrospectively analysed. Results: Of 409 patients with FMF, 205 (50.1%) were male. The median age at diagnosis was 6 (min-imum:1-maximum:18) years. FMF attack was accompanied by fever in 325 (79.5%), abdominal pain in 302 (73.8%), arthralgia in 121 (29.6%), arthritis in 56 (13.7%), chest pain in 62 (15.6%) and ELE in 55 (13.4%) patients. When comparing patients with ELE to those without, the frequencies of chest pain, arthralgia, and arthritis were significantly higher in the ELE group (p=0.014, p<0.001, p<0.001, respectively). Pathological mutations were significantly more common in FMF with ELE than those without one (p<0.001). Additionally, among FMF patients, the use of anti-interleukin-1 (anti-IL-1) treatment combinations due to colchicine resistance was significantly higher in those with ELE (p<0.001). Conclusions: The present study showed that ELE may be associated with subclinical inflammation, arthritis, colchicine resistance, pathogenic mutations, and severe disease scores in FMF patients. Based on these findings and existing literature, we believe that the presence of ELE in FMF patients is significant in terms of diagnosis, prognosis, and predicting the course of the disease.