Background: Familial Mediterranean Fever (FMF) is a common autoinflammatory disease in childhood, characterized by recurrent inflammatory attacks with heterogeneous clinical manifestations and variable attack frequency [1,2]. Various environmental and contextual factors have been suggested to influence attack occurrence; however, the role of specific triggers remains poorly understood [3]. In particular, the relationship between infectious symptoms and FMF attacks in children is not well defined, and existing data are limited by retrospective designs and recall bias [4]. A clearer understanding of potential triggers and attack patterns is needed to improve disease monitoring and patient counseling.

Objectives: To prospectively investigate the relationship between FMF attacks and potential triggering factors, using real-time patient-reported data collected through a purpose-built, study team–developed digital monitoring platform in children with FMF.

Methods: Children aged 8–18 years with a diagnosis of FMF according to the Eurofever/PRINTO classification criteria were prospectively enrolled starting in October 2025, and patients with a minimum follow-up duration of six months were included in the analysis. Real-time, longitudinal monitoring of FMF attacks, attack-related triggering factors (including stress, cold exposure, irregular sleep patterns, travel, seasonal changes, and menstruation), and treatment adherence (colchicine and antiIL-1 therapy) was conducted using FMFTrackR , a purpose-built, web-based mobile application developed by the study team. Prior to study entry, patients and caregivers received standardized training on the use of the application. Throughout the study period, patients or caregivers completed weekly structured questionnaires via the application. The FMFTrackR Platform has a three-layer architecture: (i) a patient/caregiver interface for structured weekly reporting of FMF attacks, potential triggers and treatments, with in-app reminders/notifications to support treatment adherence; (ii) a clinician (supervisor) dashboard enabling patient-level monitoring of reported attacks; and (iii) an analytical visualization layer providing a chronological timeline (time-series) view of events and symptom patterns to facilitate rapid clinical review. The clinician dashboard also displays engagement metrics (e.g., reporting frequency) to track completeness of follow-up. When features regarding infection were reported concurrently with FMF attacks, differentiation between infection-related manifestations and FMF attacks was performed based on physician clinical evaluation, including history and physical examination. An interim analysis was conducted after the first 10 weeks of follow-up to assess data completeness, feasibility of digital monitoring, and preliminary temporal patterns between FMF attacks and their potential triggers. The study was registered at ClinicalTrials.gov (NCT07212764).

Results: At the time of interim analysis, a total of 48 children with FMF (median age 14.2 years, 54.1% female) were enrolled, of whom 44 (91.7%) provided regular symptom reports during follow-up. All patients were receiving colchicine therapy, and three patients were additionally treated with antiIL-1. During the observation period, 32 FMF attacks were reported by 39 patients. Among the reported attacks, the most common clinical features were fever (87.5%), abdominal pain (59.3%), arthralgia/arthritis (28.1%), and chest pain (18.7%). Infection was the most frequently identified triggering factor, reported in 16 attacks, most commonly as upper respiratory tract infections (87.5%). Other reported potential triggering factors included stress (n=3), fatigue (n=1), and irregular sleep patterns (n=1). Caregivers reported the use of non-steroidal anti-inflammatory drugs (n=3) or rest and other supportive measures for attack management.

Conclusions: Using FMFTrackR , a purpose-built web-based mobile application, this prospective study provides real-time patient-reported data on FMF attacks and potential triggering factors and supports the feasibility of digital follow-up in pediatric FMF. As data collection is ongoing, final analyses will allow a more robust evaluation of the temporal relationship between infectious symptoms and FMF attacks and facilitate the identification of additional triggering factors in pediatric FMF.

REFERENCES: [1] Öztürk K, Coşkuner T, Baglan E, et al. Real-Life Data From the Largest Pediatric Familial Mediterranean Fever Cohort. Front Pediatr. 2022;9:805919. Published 2022 Jan 20. doi:10.3389/fped.2021.805919

[2] Ozen S, Sağ E, Oton T, et al. EULAR/PReS endorsed recommendations for the management of familial Mediterranean fever (FMF): 2024 update. Ann Rheum Dis. 2025;84(6):899-909. doi:10.1016/j.ard.2025.01.028

[3] Maggio, M. C., & Corsello, G. (2020). FMF is not always “fever”: from clinical presentation to “treat to target”. Italian Journal of Pediatrics , 46 (1), 1–5. https://doi.org/10.1186/S13052-019-0766-Z

[4] Yenokyan, G., & Armenian, H. K. (2012). Triggers for Attacks in Familial Mediterranean Fever: Application of the Case-Crossover Design. American Journal of Epidemiology , 175 (10), 1054–1061. https://doi.org/10.1093/AJE/KWR460

Acknowledgments: NIL.

Disclosure of Interests: None declared.