The prediagnostic period of Behçet's disease: a nationwide population-based study.

During the five years before diagnosis, future Behçet's disease (BD) patients had markedly higher rates of oral aphthosis than matched controls.

• Oral aphthosis was documented in 36.2% of future BD patients vs 3.0% of controls (OR 18.2, P<0.001).
• The study included 218 patients who later developed BD and 1,090 matched controls (1:5 matching by sex, age, socioeconomic category and year of first observation).
• Cases were identified by manual chart review and met International Criteria for Behçet's Disease or International Study Group criteria.

Panuveitis, inflammatory polyarthritis and venous thromboembolism were each more common in the prediagnostic period among future BD patients.

• Panuveitis: 4.6% vs 0.1% (OR 52.4, P<0.001).
• Inflammatory polyarthritis: 7.3% vs 0.6% (OR 14.3, P<0.001).
• Venous thromboembolism: 4.6% vs 0.2% (OR 26.2, P<0.001).

Over the entire available record, oral aphthosis was documented much more often in BD patients than in controls.

• Oral aphthosis was documented in 61.0% of BD patients vs 11.8% of controls.
• Manifestations over the entire available record were analyzed separately from the five-year prediagnostic window.

Autoimmune serology was frequently requested in the prediagnostic period but remained largely negative.

• The abstract describes serology as 'frequently requested but... largely negative'.
• Diagnostic investigations recorded in the five years before diagnosis were compared between groups.

Monocyte count and neutrophil-to-lymphocyte ratio (NLR) showed a biphasic trajectory: lower than controls at the early prediagnostic assessment and higher near diagnosis.

• Early absolute monocyte count: 0.40 vs 0.44 ×10^9/L (P = 0.009); early NLR: 1.45 vs 1.49 (P = 0.023).
• Near diagnosis monocyte count: 0.64 vs 0.58 ×10^9/L (P = 0.025); NLR: 2.44 vs 2.09 (P = 0.003).
• Early and late laboratory measurements within the prediagnostic period were analyzed to assess temporal trends.

The shift toward higher monocytes and NLR coincided with rising systemic inflammatory markers, with persistently lower mean corpuscular volume.

• CRP, ESR, platelet count and globulin levels rose over the transition.
• Mean corpuscular volume was persistently lower in future BD patients than in controls.

IgA was consistently higher in future BD patients at both early and late assessments, whereas IgG and IgM were comparable to controls.

• Early IgA: 247 vs 189 mg/dL (P = 0.009).
• Late IgA: 256 vs 189 mg/dL (P = 0.012).
• IgG and IgM remained comparable between groups.

The authors conclude BD is preceded by a clinically and biologically active prediagnostic phase with a distinct inflammatory multisystem footprint.

• The study was a nationwide retrospective matched case-control study using Leumit Health Services electronic health records.
• Clinical diagnoses, diagnostic investigations, laboratory measurements and medication dispensing were compared across the five years before diagnosis.