家族性地中海熱

OBJECTIVES: To determine the time from symptom onset to diagnosis in Familial Mediterranean Fever (FMF) patients, identify the clinical characteristics associated with diagnostic delay, and evaluate the effect of age at symptom onset on the time to diagnosis. METHODS: Medical records of FMF patients aged 0 to 18 years followed at a tertiary pediatric rheumatology center between 2013 and 2024 were retrospectively analyzed. Patients fulfilling the 2019 Eurofever/PRINTO criteria were included. Clinical, genetic, treatment data and disease severity assessed by the International Severity Scoring System for FMF (ISSF) were evaluated. RESULTS: A total of 1259 FMF patients were included. The median time from symptom onset to diagnosis was 17 (IQR 10 to 36) months. Patients were categorized into 2 groups based on the elapsed time from symptom onset to diagnosis (≤12 months, n = 469 and >12 months, n = 790). Those with a longer diagnostic delay had a younger age at symptom onset but higher ages at referral and diagnosis (P < 0.001). Fever (P = 0.007), abdominal pain (P = 0.006), and erysipelas-like erythema (P = 0.017) were more frequent in the delayed group, whereas a positive family history was linked to shorter diagnostic intervals (P = 0.012 for parents, P < 0.001 for siblings). No significant differences were found in MEFV variant distribution (P = 0.972) or ISSF scores (P = 0.151). Age at symptom onset was negatively correlated with time to diagnosis (ρ = -0.210, P < 0.001). CONCLUSION: Diagnostic delay remains common in pediatric FMF, especially among young children with early and nonspecific symptoms. Increasing awareness among primary and secondary care physicians may help shorten diagnostic intervals and improve outcomes.

OBJECTIVES: Familial Mediterranean fever (FMF) shows marked phenotypic variability depending upon age at symptom onset. This study compared clinical characteristics, genetic variants, and disease severity of paediatric FMF patients according to age at symptom onset. METHODS: This study included 1203 paediatric FMF patients followed 2015 through 2025. Patients were classified into two groups based on age at symptom onset: <10 or ≥10 years. Demographic, clinical, genetic, and treatment-related variables were compared between groups. Multivariate logistic regression analysis identified factors independently associated with age at symptom onset ≥10 years. RESULTS: Symptoms began at <10 years in 1043 patients (86.7%) and at ≥10 years in 160 patients (13.3%). Patients with later onset had shorter diagnostic delay (P < 0.05). Fever and abdominal pain were more common in patients with onset <10 years (P < 0.001), whereas chest pain (29.3% vs. 21.5%, P = 0.029) and arthritis (25.6% vs. 14.5%, P < 0.001) were more frequent in those with onset ≥10 years. M694V homozygosity was significantly less frequent in the ≥10 group (13.1% vs. 26.9%, P = 0.004). In multivariate analysis, age at symptom onset ≥10 years was independently associated with lower fever frequency (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.22 to 0.46) and higher chest pain frequency (OR 1.63, 95% CI 1.07 to 2.49). CONCLUSION: Age at symptom onset is closely related to clinical phenotype in paediatric FMF. Adolescent-onset FMF is more frequently characterized by chest pain. These findings highlight the importance of considering FMF in adolescents with recurrent chest pain, even without typical febrile attacks.

Chronic multilevel central venous occlusion (CVO) in young adults is uncommon and presents major challenges in establishing reliable vascular access. Patients with recurrent thrombosis develop extensive collateral formation and progressive loss of venous access. Although familial Mediterranean fever (FMF) is primarily an autoinflammatory disease, emerging evidence suggests an increased risk of thromboembolic events mediated by chronic endothelial inflammation and dysfunction. Endovascular recanalization using conventional and sharp techniques is well described for complex long-segment occlusions; reports specifically describing this approach in a young patient with FMF and recurrent venous thromboembolism, however, remain limited. We report a 23-year-old woman with type 1 diabetes mellitus, hypothyroidism, epilepsy, asthma, and FMF (MEFV E148Q variant), with 3 prior ischemic strokes and approximately 30 venous thromboembolic events despite anticoagulation, in whom an extended inherited thrombophilia workup, including whole-exome sequencing and JAK2 testing, was negative. She presented with chest and abdominal pain, palpitations, dizziness, and limb swelling. Imaging revealed extensive multilevel CVO involving the axillary, subclavian, brachiocephalic, internal jugular, and external iliac veins with prominent collateral formation, and repeated attempts at peripheral and central venous access had failed. Endovascular recanalization was performed under sedation. Conventional wire-and-catheter technique crossed most occlusions; sharp recanalization with a 0.018-inch guidewire was required for the left subclavian vein. Subsequently, sequential balloon angioplasty and stent placement were followed by bilateral placement of 5-French dual-lumen peripherally inserted central catheters (PICCs). Finally, postprocedure venography demonstrated satisfactory recanalization with no major complications. Combined conventional and sharp recanalization restored central venous patency and enabled venous access in extensive multilevel CVO. Both PICC lines remained functional without complication over 7 months of follow up. However, the patient required escalating anticoagulation with an unexplained subtherapeutic anti-Xa level, and CT at 4.5 months showed the subclavian stent in situ without acute pulmonary embolism but persistent chronic left brachiocephalic stenosis with extensive collaterals. This case illustrates both the technical feasibility of endovascular recanalization in this setting and the durability challenge posed by an ongoing, incompletely controlled inflammatory and thrombotic state.

Amyloidosis is a systemic clinical condition characterised by the extracellular deposition of misfolded proteins in various organs, most frequently involving the heart, kidneys, gastrointestinal tract, and bone marrow. Among its types, AA amyloidosis accounts for approximately 15% of cases and is mainly secondary to chronic infectious or inflammatory conditions. The association between Familial Mediterranean Fever (FMF) and AA amyloidosis is well-established, with the MEFV gene's M694V mutation being the most recognised risk factor. However, the role of other genetic variants often remains underestimated. This case series presents a spectrum of AA amyloidosis patients harbouring various MEFV gene variants. By emphasizing the clinical presentations and diagnostic challenges encountered, this report aims to highlight the clinical significance of heterozygous and less common variants that are frequently overlooked in the progression to AA amyloidosis.

Background/Objectives: Autoinflammatory syndromes are defined by episodes of recurrent fever driven by innate immune dysregulation, yet their long-term organ consequences remain largely underestimated, mostly in children. Renal AA amyloidosis represents the most perilous complication of sustained, even subclinical, inflammation, capable of progressing silently to irreversible renal failure. In pediatric cohorts, the interval between autoinflammatory disease onset and amyloidosis diagnosis spans nearly a decade, an actionable window that current surveillance frameworks have not adequately addressed. This review examines the pathophysiological continuum linking chronic cytokine overproduction to renal amyloid deposition in children with autoinflammatory syndromes, evaluates emerging subclinical biomarkers of early renal injury, identifies relevant diagnostic pitfalls, and proposes a structured renal surveillance framework for at-risk pediatric populations. Materials and Methods: This comprehensive review has been conducted analyzing studies reporting renal outcomes, biomarker data, or therapeutic interventions in pediatric patients with monogenic or polygenic autoinflammatory conditions. No date restriction was applied, with emphasis placed on publications from 2015 onward reflecting contemporary treatments and diagnostic standards. Results: An overproduction of interleukin (IL)-1β and IL-6 drives serum amyloid-A accumulation that may persist measurably during intercritical periods, preceding overt proteinuria by years in most young patients with autoinflammatory syndromes. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is significantly elevated in attack-free children with familial Mediterranean fever (FMF) compared to healthy controls, representing an early and sensitive marker of tubular stress. Shear wave elastography has demonstrated measurable increases in renal tissue stiffness in pediatric FMF patients, correlating with subclinical inflammatory activity. Critically, nutcracker syndrome has emerged as the leading cause of proteinuria in colchicine-treated FMF cohorts, accounting for up to 67.5% of proteinuria cases and representing a clinically significant confounder. IL-1 inhibition with either anakinra or canakinumab has demonstrated histological regression of established amyloid deposits in different cohorts of pediatric patients, reinforcing the potential therapeutic value of earlier identification and intervention before overt irreversible glomerular damage comes out. Conclusions: Renal amyloidosis in autoinflammatory syndromes is a plausibly preventable outcome when subclinical injury is identified and treated within the pre-amyloid window in the pediatric age. Conventional reliance on 'proteinuria' as the primary surveillance threshold is potentially misleading. A biomarker-guided monitoring approach incorporating serum amyloid-A, urinary NGAL, and renal elastography might offer a clinically actionable pathway toward earlier nephrology referral and targeted IL-1 blockade, with the potential to improve renal prognosis of these children.