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.

The aim of this study is to investigate the effect of anti-interleukin (IL)-1/-6 biologics on systemic juvenile idiopathic arthritis (sJIA)-associated macrophage activation syndrome (MAS). Demographic, clinical, and laboratory data of patients followed up with a diagnosis of sJIA-associated MAS assessed from sixteen pediatric rheumatology centers across the country. The clinical and laboratory features of MAS developing while on biological drugs were compared with those without this treatment. One hundred and sixty-two patients were included in the study. 45 of the MAS events were detected under the effect of anti-IL-1/-6 biologics, while the patients experiencing the remaining 155 events have not received biological treatment in the last three months. Platelet count [128 (72–232) vs 199 (130–371) 10⁹/l], ferritin level on admission [1107 (676–2050) vs 2863 (1193–9562) ng/ml], C-reactive protein level [15.4 (2.9–56) vs 90 (32–160) mg/l], erythrocyte sedimentation rate [13 (3–36) vs 43.5 (13–77) mm/h] and fever duration [5 (4–7.5) vs 10 (7–14.3) days] were found lower in the group under the impact of anti-IL-1/-6 biologics. Among patients treated with biologics, 26.6% did not meet the published 2016 MAS classification criteria at presentation. The rates of hepatomegaly and splenomegaly were relatively lower in the canakinumab-treated group when compared with those receiving other biologicals or to patients, not on biologicals. Anti-IL-1/-6 therapies can mask the clinical and laboratory features of MAS, and proposed guidelines for MAS classification criteria may not be met.

Objectives: This study aims to provide a multidimensional assessment of juvenile Sjögren’s disease (jSjD), focusing on diagnostic and management processes through various instrumental tests. Methods: A cross-sectional and retrospective study was conducted on 21 jSjD patients diagnosed between June 2016 and September 2023. In addition, 37 healthy children were included only for comparison of nailfold videocapillaroscopy (NVC) findings. Clinical data, parotid gland ultrasound (US), NVC, salivary gland biopsy, and Schirmer test results were analyzed. Results: Positive correlations were found between parotitis scores in parotid gland US and bizarre capillary, neoangiogenesis, and microhemorrhage scores in NVC (r = 0.35, 0.32, 0.52; p < 0.05). Diagnostic delay was associated with higher parotitis frequency and scores in US (p = 0.025) and increased dilated capillaries in NVC (p < 0.05). Clinically evident parotitis correlated with higher parotitis frequency in US (p = 0.009) and higher parotitis scores (r = 0.480, p = 0.051). Higher ESSDAI scores at diagnosis correlated with increased parotitis frequency and scores in US (p = 0.001), with higher scores in patients with high disease activity (p < 0.05). ENA-positive patients had higher parotitis scores in US (p = 0.022) and increased cross capillaries in NVC (p = 0.024). Capillary density was lower in the jSjD group compared to healthy controls (p = 0.021), with healthy children having higher median capillary density (p = 0.005). Dilated, bushy, bizarre capillaries, and microhemorrhages were significantly higher in the jSjD group (p < 0.001). Conclusion: Early and accurate diagnosis is crucial for managing jSjD. The integration of US and NVC provides a comprehensive framework for detecting glandular and microvascular abnormalities, emphasizing the need for multidimensional approach. Key Points • This study provides a multidimensional and comprehensive assessment of Juvenile Sjögren's disease (jSjD) by combining various instrumental tests used in the diagnosis and monitoring of Sjögren's disease.• It is the first study in the literature to demonstrate the connection between glandular and microvascular abnormalities in jSjD patients.• The comparison of nailfold videocapillaroscopy findings in healthy children highlights the pronounced microvascular abnormalities present in jSjD patients.• The results emphasize the importance of early diagnosis and intervention, offering critical insights into the systemic effects and clinical progression of the disease.

Objective: The aim of this study was to identify key parameters of a scoring system to be developed to predict the homozygous M694V genotype in patients clinically diagnosed with familial Mediterranean fever. Methods: This study was a cross-sectional analysis of 472 pediatric familial Mediterranean fever patients with a homozygous genotype on exon 10, followed at our tertiary pediatric rheumatology clinic between June 2016 and June 2023. The patients were categorized into 2 groups based on their genotypes: group 1 comprised 402 patients (85.2%) with the homozygous M694V genotype, whereas group 2 consisted of 70 patients (14.8%) with other homozygous genotypes. Demographic information, clinical manifestations, MEFV (Mediterranean fever) gene variant analysis, and treatment responses were recorded from the patients' medical charts. Results: The odds ratios for age at disease onset, arthritis, and chest pain were 0.892 (95% confidence interval [CI]: 0.832–0.958, p = 0.002), 2.565 (95% CI: 1.109–5.934, p = 0.028), and 2.351 (95% CI: 1.123–4.922, p = 0.023), respectively. A total of 60.7% of patients in group 1 had arthralgia, and 25% had erysipelas-like erythema, with these percentages were higher in group 1 compared with group 2 (p = 0.002, p = 0.001, respectively). Protracted febrile myalgia syndrome was detected in 1.5% of patients, all of whom had homozygous M694V genotype. Colchicine resistance was detected in 13.3% of patients, and all had homozygous M694V genotype. Conclusions: This preliminary evaluation identified key parameters for a scoring system designed to predict the homozygous M694V genotype. A multicenter national study will further refine these parameters and develop the scoring system, which will aid clinicians in disease prognosis and therapeutic decision-making.

Objective: To assess the phenotypic characteristics of the patients carrying variants of uncertain significance (VUS) in the Mediterranean fever (MEFV) gene. Methods: The study included patients carrying only VUS in the MEFV gene. Patients were excluded if they did not meet the paediatric criteria for familial Mediterranean fever (FMF). Patients were assigned to homozygous, compound heterozygous or heterozygous groups according to their genotype. Additionally, analyses were conducted based on specific genotypes. Results: A total of 2326 MEFV gene records were reviewed. Of these, 310 (F: 152/M: 158) met the inclusion criteria for analysis. The mean age at diagnosis and symptom onset was 7.51 ± 3.9 and 6.03 ± 3.86 years, respectively. Among the patients, 75.5% had a single variant, 17.1% were compound heterozygous, and 7.4% were homozygous. The common VUS alleles accounted for 93% of the cohort: E148Q (65.7%), P369S (15.6%), R408Q (7.6%) and A744S (4.1%). Most cases exhibited mild disease severity, while those with multiple variants were more likely to experience moderate disease severity. Patients with a homozygous allele had a higher mean number of annual attacks (11.2/year), a higher Pras severity score (5.86) and a greater proportion of moderate disease severity (56.5%). The most common clinical manifestations were abdominal pain (90.6%), fever (84.2%) and arthralgia (58.7%). Conclusion: Individuals with VUS variants in the MEFV gene may present with a classic FMF phenotype characterized by mild to moderate disease activity. Patients carrying various VUS genotypes in the MEFV gene exhibit comparable clinical features with some degree of variation.