Overdiagnosis of Behçet Syndrome May Result From Broad Classification Criteria

The application of classification criteria alone to diagnose Behçet syndrome may lead to under- or overdiagnosis of the condition in low prevalence regions.

The application of the International Criteria for Behcet’s Disease (ICBD) may result in overdiagnosis of the disease in low prevalence areas, according to research results published in British Society for Rheumatology.

Researchers aimed to analyze the differential diagnosis spectrum in areas with a low prevalence for Behçet syndrome. 

Researchers conducted a retrospective study at 2 referral centers (Hamburg, Germany, and Amsterdam, Netherlands) that specialize in the care of Behçet syndrome. Data collected included multisystem manifestations, according to ISG and ICBD criteria. Manifestations that were not clearly defined by ISG and ICBD criteria were classified, according to recent literature, including ocular, gastrointestinal and neurologic findings. Patients’ origin were divided into endemic and nonendemic. Clinical diagnosis was based on fulfilling ISG criteria or scoring more than 5 points on ICBD criteria.  

In total, 384 patients were examined for the presence of Behçet syndrome, of whom182 were diagnosed with Behçet syndrome; the remaining 202 were included in the study.

Using an ICBD cutoff score of 4, sensitivity and specificity were 93.5% and 75.7%, respectively. When applying a cutoff score of 5 points, sensitivity and specificity were 75.8% and 97.2%, respectively. In 75 patients (37.1%), ICBD criteria were fulfilled using a score of 4 or more points.

[O]ur work should remind clinicians in low prevalence settings not to rely solely on the diagnostic and classification criteria (ICBD and ISG criteria) when diagnosing BS…

A total of 58 patients (28.7%) were categorized as “probable Behçet syndrome,” and remaining patients were classified into 10 differential diagnostic categories: 57 (28.2%) patients with skin disease, 26 (12.9%) with chronic pain syndrome, 14 (6.9%) with eye disease, 11 (5.4%) with spondyloarthropathy, 9 (4.5%) with gastrointestinal disease, 7 (3.5%) with neurologic disease, 4 (2.0%) with arthritis, 3 (1.5%) each with autoinflammatory diseases and connective tissue diseases, 10 (5.0%) with miscellaneous disorders. Human leukocyte antigen (HLA)-B51-positivity was present in 55 (27.2%); if only the tested patients were considered, the percentage rose to 41.6%. Excluding the diagnosis of “probable Behçet syndrome,” 24.2% of patients still fulfilled the ICBD criteria. 

Study limitations included limited recruitment in 2 centers, which may not have been relevant in different settings, as well as the lack of a longitudinal analysis, which excluded the evaluation of patients with a “probable Behçet syndrome” diagnosis. 

The study authors concluded, “Taken together, our results underline the difficulty of applying diagnostic/classification criteria in clinical practice and our work should remind clinicians in low prevalence settings not to rely solely on the diagnostic and classification criteria (ICBD and ISG criteria) when diagnosing [Behçet syndrome], especially in the presence of isolated [orogenital aphthosis]. Furthermore HLA-B51 should not be used as a diagnostic criterion”. 


Lötscher F, Kerstens F, Krusche M, et al; EULAR Study Group on MHC-I-opathy. When it looks like Behçet’s syndrome but is something else: differential diagnosis of Behcet’s syndrome: a two-centre retrospective analysisRheumatology (Oxford). Published March 2, 2023. doi:10.1093/rheumatology/kead101