Diagnostic Timelines and Referral Patterns in the Hamilton Health Sciences Systemic Autoinflammatory Disease (HHS SAID) Registry

Objectives The study aimed to assess diagnostic timelines and completeness of referrals in the Hamilton Health Sciences Systemic Autoinflammatory Disease (HHS SAID) Registry and identify factors contributing to delays in the referral-to-diagnosis pathway.

Methods The HHS SAID registry was established to describe and follow patients with systemic autoinflammatory diseases at Hamilton Health Sciences. Patients enrolled in the registry from February 2023 to April 2025 (N=94) were stratified by consultation clinic (Autoinflammatory Clinic [AC] or Pediatric Rheumatology Clinic [PRC]) and by diagnosis (Periodic fever, Aphthous stomatitis, Pharyngitis, and Adenitis [PFAPA]; Syndrome of Undifferentiated Recurrent Fever [SURF]; Familial Mediterranean Fever [FMF]; Other Monogenic Autoinflammatory Syndromes [OMAS]; and systemic Juvenile Idiopathic Arthritis [sJIA]). Descriptive statistics were generated using an available-case approach to summarize demographic, referral, and time-interval data. Group differences were assessed using chi-square or Fisher’s exact tests for categorical variables and Mann-Whitney U or Kruskal-Wallis tests with post hoc pairwise comparisons for continuous variables.

Results Ninety-four participants were included (50 male, 44 female). Sixty pediatric participants were seen through PRC (median age=5.2yr, IQR=6.0yr) and 24 pediatric and adult participants were seen through AC (median=15.4yr, IQR=33.8yr) (p=0.000). Diagnosis stratification amounted to 39 PFAPA (41.5%), 21 FMF (22.3%), 14 OMAS (14.9%), 13 SURF (13.8%), and 7 sJIA (7.5%). Besides sJIA, all other groups had similar referral to consultation times (median range=3.0-4.1mo, p>0.05). From consultation to diagnosis, PFAPA (median=0.0mo) and sJIA (median=0.1mo) showed near-immediate diagnosis, unlike FMF (median=3.0mo, IQR=5.3mo), SURF (median=4.6mo, IQR=14.1mo), and OMAS (median=12.8mo, IQR=33.1mo) (p=0.000). From symptom onset to diagnosis, OMAS (median=47.5mo, IQR=21.7mo, p=0.002), SURF (median=26.2mo, IQR=39.5mo, p=0.001) and PFAPA (median=14.8mo, IQR=18.9mo, p=0.014) had the longest durations (Table 1). Referrals lacked key information in 91.7% (22) of AC and 74.6% (44) of PRC cases. Within the AC, missing information on fever/episode duration (OR=4.5, p=0.003) and symptom onset (OR=3.3, p=0.047) were significantly higher vs the PRC. OMAS was the only group predominantly referred by other specialists (64.3%, p=0.005). All disease groups showed high missing referral information rates on symptom onset, episode duration, and frequency: lowest in PFAPA (61.5%) and >90% in others.

Conclusion Except for sJIA, all autoinflammatory diseases had long referral, consultation, and diagnostic intervals, most notably SURF and OMAS, reflecting diagnostic uncertainty and referral inefficiencies. High rates of missing referral details may have contributed to these diagnostic delays. Standardized referral templates and clinician education on diverse autoinflammatory presentations may help reduce diagnostic latency and improve timely specialist care.