Introduction
Isolated perianal Crohn’s disease (ipCD) remains a diagnostic challenge. The TOpCLASS criteria were developed to standardize diagnosis; however, their clinical applicability and prognostic value are uncertain. In particular, the relationship between criteria burden, biomarkers, and clinical outcomes remains unclear. This study aimed to evaluate the performance and clinical relevance of TOpCLASS criteria in a cohort of patients with suspected ipCD.
Aims & Methods
We conducted a retrospective, observational, single-center cohort study (2002–2025). Adult patients with complex and/or recurrent perianal fistulae and no diagnostic evidence of baseline luminal Crohn’s disease were included. Baseline workup included ileocolonoscopy, upper endoscopy, magnetic resonance (MRI) enterography, along with normal or only minor findings on small-bowel capsule endoscopy (SBCE). Patients with less than 12 months of follow-up were excluded. Clinical, laboratory, SBCE, and pelvic MRI data were collected, and patients were classified according to baseline TOpCLASS criteria.
Results
Thirty patients with suspected ipCD were included, 66.7% of whom were female. At baseline, 29 patients met ≥1 TOpCLASS criterion, but only 3 reached the diagnostic threshold, defined as a score ≥5. Overall, 36.7% (n=11) fulfilled ≥1 major criterion and 83.3% (n=25) ≥1 minor criterion. Mild/nonspecific SBCE abnormalities were observed in 33.3% of patients. Overall, mean fecal calprotectin (FC) was 492.1 µg/g (median 138.5 µg/g).
During follow-up, 11 patients initiated immunosuppressive and/or biologic therapy. Among these, 27.3% achieved combined clinical and radiological remission, and 18.2% had clinical remission, defined as Perianal Disease Activity Index [PDAI] ≤ 4.
Six patients developed luminal Crohn’s disease. At baseline, 66.7% had elevated FC (>150 µg/g) and 66.7% had minor SBCE findings. All received biologic therapy. In this group, although all had ≥1 TOpCLASS criterion, only 33.3% met ≥2 criteria.
Overall, among patients with perianal disease improvement, only 23% had baseline FC >150 µg/g. Notably, 94.3% of responders had ≥1 TOpCLASS criterion - though only 27.8% met ≥2 – and none reached the diagnostic threshold at baseline.
Surgical intervention was required in 53.3% of cases, all of whom maintained a strong clinical suspicion of ipCD despite the absence of histological confirmation.
Conclusion
In this real-world cohort, most patients fulfilled at least one TOpCLASS criterion, yet only a small minority reached the diagnostic threshold, highlighting a significant diagnostic gap in clinical practice. Patients in this “grey zone” constituted a clinically relevant group, frequently requiring immunosuppressive therapy or surgery despite the lack of formal diagnosis.
In this cohort, the burden of TOpCLASS criteria did not demonstrate prognostic value, as neither the number of criteria nor FC levels predicted treatment response or disease progression. A subset of patients progressed to luminal Crohn’s disease, suggesting that this population may represent an early or incomplete disease phenotype.
These findings raise questions about the applicability of current diagnostic thresholds in real-world settings and support the need for more flexible, clinically driven approaches to identify and manage suspected ipCD. Larger prospective studies are needed to refine diagnostic frameworks and improve risk stratification in this understudied population.
