Toward a Standardized Severity Assessment in Intestinal Behçet's Disease: Reflections on the Proposal of the <scp>SCIBD</scp> Criteria

Behçet's disease (BD) is a complex multi-organ inflammatory disorder characterized by recurrent oral aphthous ulcers, ocular lesions, genital ulcers, skin manifestations, and various systemic symptoms. Among its clinical manifestations, intestinal BD poses significant therapeutic challenges owing to its diverse symptoms, unpredictable disease course, and potential for serious complications, such as perforation and massive bleeding. Accurate and rapid assessment of disease severity is crucial to make effective treatment strategy decisions and predict patient prognosis. A recent multicenter study by Fukui et al. [1] represents an important step toward standardizing disease severity assessment. The authors proposed new severity criteria for intestinal Behçet's disease (SCIBD) based on five parameters: abdominal pain, abdominal tenderness, intestinal bleeding, serum C-reactive protein (CRP) levels, and endoscopic findings. They validated the clinical utility in a nationwide cohort comprising 14 institutions across Japan. This study represents the first attempt to integrate an objective endoscopic assessment of intestinal BD into a formal severity classification system, bridging the gap between clinical symptoms, biomarker values, and treatment decisions. The SCIBD criteria provide a framework for the clinical evaluation of intestinal BD. Although the conventional disease activity index for intestinal Behçet's disease (DAIBD) [2, pp. 605–613] is a useful tool for assessing disease activity, it is primarily symptom-based and lacks elements for endoscopic evaluation. Fukui et al. addressed this limitation by incorporating endoscopic ulcer grades into the definition of ulcer severity: grade 1 (aphthae and ulcers < 1 cm), grade 2 (well-demarcated shallow ulcers ≥ 1 cm), and grade 3 (deep [mining] ulcers). Deep [mining] ulcers, characteristic of intestinal-type BD, are key indicators of severe disease. This approach is critically important because it emphasizes direct visualization of mucosal lesions. This is because deep ulcers are known predictors of poor prognosis and complications such as perforation [3, pp. 635–640]. The main findings of this study were the consistent correlations between the severity classification based on the SCIBD and established inflammatory markers such as CRP, erythrocyte sedimentation rate, serum albumin, and DAIBD score. Importantly, the treatment patterns aligned with the defined severity based on the SCIBD. Anti-TNF-α therapy was more frequently used in severe cases (49.4%) than in moderate cases (20.8%), and surgical intervention was more common in patients classified as severe. These findings are consistent with current treatment guidelines that recommend more aggressive therapy for severe cases [4, pp. 679–700]. Furthermore, the multicenter retrospective study design involving 146 patients, including those with intestinal BD and simple ulcerative disease, addressed the challenges in conducting research in this field due to the rarity of the disease through collaborative clinical research. By establishing a consensus-based, data-driven severity assessment framework, the authors provided a foundation for future prospective studies, clinical registries, and international harmonization efforts. Although this study holds significant value, several conceptual and methodological considerations warrant further discussion. First, the retrospective study design inevitably introduced selection and recall biases. The inclusion of long-term cases (2006–2022) and variability in the timing of endoscopy and biomarker collection may have affected consistency. Furthermore, the study population primarily consisted of moderate-to-severe cases (approximately 60% classified as severe), potentially limiting the generalizability to patients in remission or with mild disease. Second, although SCIBD was correlated with DAIBD and treatment intensity, the agreement rate between SCIBD and DAIBD classifications was only 51%. This suggests that SCIBD and DAIBD may need to be recognized as separate disease interpretation measures and treated as complementary scores in future practice. Furthermore, the SCIBD was developed based on expert consensus rather than a formal scoring system using weighted parameters. Although expert consensus is valuable, a validated scoring system derived from advanced statistical modeling can offer higher quantitative accuracy and interobserver reliability. Third, caution should be exercised when relying solely on CRP levels as an indicator of disease activity. While elevated CRP levels reflect inflammatory burden, they are nonspecific and may be influenced by extraintestinal inflammation. The authors appropriately pointed out that severe disease should not be defined solely by elevated CRP levels and emphasized the need for multifaceted assessment. Fourth, although endoscopic lesion grading is a major strength, it involves subjectivity. The classification of ulcers as “deep” or “well-demarcated shallow ulcers of 1 cm or more” and the decision to omit endoscopy in severe cases for safety reasons may vary between institutions. Finally, a crucial point is that the SCIBD primarily focuses on ileocecal lesions, which are the typical and most common presentation of intestinal BD in Japan. However, gastrointestinal lesions in BD can occur not only in the ileocecal region but also in the esophagus, small intestine, and elsewhere, potentially presenting as atypical lesions. These clinically significant lesions are not captured by the current SCIBD framework. Therefore, in future revisions of the criteria, these factors should be incorporated into the SCIBD score as a cumulative measure of lesion extent, aiming to create a score that more accurately reflects the clinical condition. In summary, although SCIBD provides an important framework for standardizing disease assessment, its refinement requires prospective validation, clearer operational definitions, and a broader inclusion of atypical symptoms. From a clinical perspective, the SCIBD demonstrates the ability to reflect treatment responsiveness, supported by improvements in severity grade following corticosteroid or anti-TNF-α therapy, suggesting its utility as a response monitoring tool. Considering that mucosal healing predicts long-term prognosis in intestinal BD [5, pp. 2529–2535], a classification integrating endoscopic healing status may contribute to prognosis prediction and the development of individualized care plans. Furthermore, in rare diseases, such as intestinal BD, a consistent disease definition is essential for registry development, conducting multicenter studies, and harmonizing endpoints across trials. Therefore, the SCIBD represents a crucial step toward establishing a common language for disease activity in intestinal BD. However, the authors' findings also highlight that the need for global validation and adaptation remains unmet. Differences in disease phenotypes and management strategies observed between Japan and regions such as the Mediterranean and Middle East necessitate cross-cultural harmonization. Integrating the SCIBD framework with international consensus-building efforts led by the European Alliance of Associations for Rheumatology (EULAR) [6, pp. 808–818] could contribute to establishing a truly universal severity index. Furthermore, future improvements should address the exclusion of diseases outside the ileocecal region. As upper GI endoscopy, capsule endoscopy, and balloon-assisted enteroscopy enhance the detection of upper GI lesions (e.g., esophageal ulcers) and small bowel lesions, expanding the endoscopic field of view for SCIBD may broaden its clinical significance. Incorporating the number, distribution, and morphology of lesions throughout the GI tract may enable a more comprehensive understanding of disease burden. Finally, prospective validation studies are warranted. A longitudinal design evaluating SCIBD dynamics in response to treatment, the predictive value for recurrence and surgical outcomes, and interobserver reproducibility would further strengthen the clinical reliability. Because BD is a relapsing–remitting disease with systemic symptoms, incorporating extraintestinal domains, such as the four major signs, into a multidimensional composite score may ultimately enable a unified severity assessment framework for systemic BD. The multicenter collaborative study by Fukui et al. [1] represents a groundbreaking achievement in the evolution of disease assessment for intestinal BD. The proposed SCIBD, which integrates clinical, biochemical, and endoscopic parameters, offers a more objective and clinically consistent approach to define disease severity. However, its current form, which primarily focuses on ileocecal lesions and lacks formal scoring refinement, should be considered a foundational framework rather than a definitive one. Future research should aim to validate and refine the SCIBD through prospective multicenter studies, while expanding its application to atypical cases and upper gastrointestinal lesions. Through these efforts, the SCIBD has the potential to evolve into a universally accepted evidence-based standard for assessing the severity of intestinal BD and guiding individualized treatment. Teppei Omori drafted the first version of the manuscript, revised the manuscript, and approved the final version. The author has nothing to report. The author has nothing to report. The author has nothing to report. Teppei Omori received lecture fees from AbbVie GK., Takeda Pharmaceutical Co. Ltd., and KISSEI Co. Ltd. This article is linked to Fukui et al. papers. To view this article, visit https://doi.org/10.1111/den.70041.