Clinical-Endoscopic-Histologic Discrepancies in Inflammatory Bowel Disease: An Expert Perspective with Special Focus on Crohn's Disease

Vol. 31, Issue 1 (March 2026)

Atteyat Aboelmaged Semeya, MD
Consultant of hepato-Gastroenterology
Benha Teaching Hospital
Benha, Egypt
 

Rehab Ahmed, MD
Consultant of Hepatology and Gastroenterology
National Hepatology and Tropical Medicine Research Institute
Cairo, Egypt
 

Raafat Saad Abdelrehim, MD
Lecturer of Internal Medicine
Damanhour Medical National Institute
Damanhour, Egypt
 

Introduction

The assessment of disease activity in inflammatory bowel disease (IBD), particularly Crohn’s disease (CD), represents a complex clinical challenge that extends beyond traditional symptom-based evaluation. A growing body of evidence demonstrates significant and often clinically meaningful discrepancies between patient-reported symptoms, endoscopic findings, and histological inflammation. This phenomenon, often termed “clinical-endoscopic dissociation” or “histologic-endoscopic discrepancy,” has profound implications for therapeutic decision-making, disease monitoring, and long-term outcomes.

The modern paradigm of IBD management has evolved from symptom-control toward objective measures of mucosal healing, driven by compelling evidence that endoscopic remission predicts superior long-term outcomes including reduced hospitalization, surgery, and disease progression.¹ However, the relationship between clinical symptoms, endoscopic appearance, and microscopic inflammation is far from linear, creating diagnostic and therapeutic dilemmas that clinicians face regularly in practice.

The Spectrum of Discrepancies

Clinical Remission with Endoscopic Activity

Perhaps the most clinically significant discrepancy occurs when patients report symptomatic improvement or complete clinical remission while harboring ongoing endoscopic inflammation. Studies consistently demonstrate that 30-45% of patients with Crohn’s disease in clinical remission have active endoscopic disease, and up to 60-70% demonstrate persistent histological inflammation despite clinical quiescence.

Figure 1

This dissociation carries substantial prognostic implications. Patients with persistent endoscopic activity despite clinical remission have significantly higher rates of clinical relapse within 12-18 months compared to those achieving both clinical and endoscopic remission. A landmark study by Frøslie et al.¹ demonstrated that mucosal healing, defined as the absence of ulceration on endoscopy, was the strongest predictor of sustained clinical remission over five years, surpassing clinical indices in prognostic value.

Several mechanisms underlie this discrepancy. First, symptom generation in IBD is multifactorial and not exclusively related to active inflammation. Factors including visceral hypersensitivity, altered gut motility, bile salt malabsorption, bacterial overgrowth, and psychological factors contribute to symptom experience independent of inflammatory burden.

Second, the threshold for symptom generation varies considerably between individuals, with some patients remaining asymptomatic despite moderate endoscopic inflammation while others experience significant symptoms with minimal visible disease.

Third, anatomical factors play a crucial role. Inflammation in bowel areas with less sensory innervation (such as the terminal ileum) may produce fewer symptoms than disease in more sensitive areas (such as the rectum). Stricturing disease may cause minimal inflammation but significant symptoms through mechanical obstruction, while active inflammation in a capacious segment may produce little symptom burden.

Endoscopic Remission with Persistent Histological Activity

The advent of treat-to-target strategies emphasizing mucosal healing^{2, 3} has highlighted another important discrepancy: the presence of histological inflammation despite endoscopic remission. Recent studies employing systematic biopsy protocols have revealed that 30-40% of patients with endoscopic mucosal healing in Crohn’s disease demonstrate persistent microscopic inflammation on histology.

This histologic activity in the absence of endoscopic lesions is not merely an academic observation. Emerging evidence suggests that histological remission predicts more durable clinical remission than endoscopic healing alone.^{4, 5} Patients achieving both endoscopic and histological remission have lower rates of clinical relapse and disease progression compared to those with endoscopic healing but persistent microscopic inflammation.

Figure 2

The pathophysiological basis for this discrepancy relates to the resolution kinetics of inflammation. Macroscopic healing occurs relatively rapidly with effective therapy, as ulceration epithelializes and gross mucosal architecture improves.⁶ However, complete resolution of microscopic inflammation—including normalization of crypt architecture, elimination of basal plasmacytosis, and resolution of lamina propria inflammatory infiltrates—occurs more slowly and may lag endoscopic improvement by months.

Furthermore, endoscopic assessment, even with high-definition technology, has inherent limitations in detecting subtle mucosal abnormalities. Mild erythema, granularity, or villous blunting may be endoscopically unapparent yet histologically significant. Sampling error also contributes to discrepancy, as random biopsies may miss patchy microscopic inflammation in areas appearing endoscopically normal.

Active Symptoms with Minimal Endoscopic Findings

A particularly challenging clinical scenario occurs when patients report significant symptoms despite minimal or absent endoscopic inflammation. This pattern is increasingly recognized in IBD and raises important differential diagnostic considerations.

Several mechanisms account for this discrepancy. Irritable bowel syndrome (IBS)-like symptoms are common in IBD patients in remission, occurring in up to 40-50% of cases. These symptoms reflect visceral hypersensitivity, altered gut-brain signaling, and microbiome dysbiosis rather than active inflammation. Distinguishing between IBS-type symptoms and true disease activity remains challenging, as clinical indices like the Crohn’s Disease Activity Index (CDAI)13 do not differentiate between inflammatory and functional symptoms.

Small bowel inflammation beyond the reach of colonoscopy represents another important cause. Standard colonoscopy with ileoscopy examines only the terminal ileum, missing proximal small bowel disease in approximately 20-30% of Crohn’s disease patients. Video capsule endoscopy and magnetic resonance enterography20-22 have revealed that many symptomatic patients with normal colonoscopies harbor active jejunal or proximal ileal diseases.

Microscopic inflammation, as discussed above, may produce symptoms despite endoscopically normal mucosa. Additionally, non-inflammatory complications of IBD—including strictures, fistulae, bile salt diarrhea, bacterial overgrowth, and pancreatic insufficiency—can produce symptoms mimicking active disease without endoscopic inflammation.

Extraintestinal manifestations, particularly arthralgia and fatigue, frequently cause symptom burden unrelated to intestinal inflammation. These manifestations may persist or even worsen despite intestinal mucosal healing, contributing to clinical-endoscopic dissociation.

Note on Healthcare Disparities and Specialist Gaps

An important consideration in evaluating clinical-endoscopic discrepancies is the availability of specialized expertise. A lack of IBD specialists, experienced endoscopists, and histopathologists creates significant gaps in the accurate evaluation of disease severity. This challenge is particularly pronounced in middle- and low-income countries (MLICs), where limited access to advanced diagnostic techniques and specialist training may lead to under recognition of subclinical inflammation or misattribution of symptoms.

In many MLICs, the scarcity of dedicated IBD centers means that patients are often managed by generalists who may not be familiar with the subtle endoscopic or histological markers of disease activity. Furthermore, the high cost of advanced imaging (like MRE) and the lack of standardized histological reporting further widen the gap between clinical perception and objective disease state. Addressing these disparities through targeted education, international collaboration, telemedicine, and capacity-building initiatives is essential for improving IBD care and ensuring that “treat-to-target” strategies are feasible globally.

Specific Considerations of Crohn's Disease

Crohn’s disease presents unique challenges regarding clinical-endoscopic-histologic correlation due to several distinctive features.

Transmural and Discontinuous Nature

The transmural inflammatory pattern characteristic of Crohn’s disease means that significant inflammation may exist in deeper bowel wall layers while the mucosa appears relatively normal endoscopically. Cross-sectional imaging with MRI or CT enterography^20-22 often reveals wall thickening, edema, and inflammatory changes invisible to endoscopy. This transmural disease can produce significant symptoms including pain, obstruction, or systemic inflammation despite reassuring endoscopic findings.

The discontinuous, skip-lesion pattern of Crohn’s disease creates sampling challenges. Unlike ulcerative colitis, where disease extent can be reliably determined by endoscopy, Crohn’s disease may spare examined segments while actively involving areas beyond endoscopic reach. The rectum is spared in approximately 50% of Crohn’s colitis cases, and isolated small bowel disease occurs in 30-40% of patients.

Location-Specific Discrepancies

The anatomical distribution of Crohn’s disease significantly influences clinical-endoscopic correlation. Terminal ileal disease, the most common pattern, produces fewer symptoms per unit of endoscopic inflammation compared to colonic disease. Patients may have extensive ileitis with minimal symptoms, while limited colonic involvement produces prominent symptoms.

Upper gastrointestinal Crohn’s disease presents particular diagnostic challenges. Esophageal, gastric, and duodenal involvement often produces atypical symptoms including dyspepsia, nausea, and epigastric pain that may be attributed to other causes. Standard colonoscopy misses this disease entirely, and upper endoscopy is not routinely performed in all Crohn’s patients.

Figure 3

Perianal disease represents another dissociation point. Patients may have quiescent intestinal inflammation but active perianal complications, or conversely, healed perianal disease with active luminal inflammation. Perianal findings require dedicated examination and imaging and do not correlate with proximal disease activity.

Penetrating and Stricturing Complications

The progression of Crohn’s disease from inflammatory to penetrating or stricturing phenotypes creates important clinical-endoscopic discrepancies. Fistulae and abscesses may produce minimal endoscopic findings at their intestinal origin, yet cause significant symptoms and systemic inflammation. Strictures may be endoscopically impassable, preventing assessment of proximal inflammation, or may appear as subtle narrowing while causing significant obstructive symptoms.

Cross-sectional imaging is essential in these scenarios but adds another layer of complexity to assessment. MRI findings of bowel wall thickening, enhancement, and fat wrapping may indicate active inflammation, chronic fibrosis, or both—distinctions that are clinically critical but often difficult to make radiologically.^20-22

Impact of Prior Surgery

Postoperative Crohn’s disease presents unique assessment challenges. Anastomotic inflammation may represent recurrent disease, surgical trauma, or non-specific reactive changes. The endoscopic Rutgeerts score,¹⁶ used to assess postoperative recurrence, demonstrates variable correlation with symptoms. Many patients with high Rutgeerts scores remain asymptomatic, while others with low scores report significant symptoms.

Surgical alterations in anatomy, including ileocecal valve resection and bypassed segments, complicate both clinical and endoscopic assessment. Bacterial overgrowth is common after ileocecal resection and produces symptoms indistinguishable from active Crohn’s disease but without endoscopic inflammation.

Diagnostic Tools and Their Limitations

Clinical Activity Indices

The Crohn’s Disease Activity Index (CDAI),¹³ while historically the standard for clinical trials, demonstrates poor correlation with endoscopic findings. The CDAI assigns substantial weight to subjective symptoms and functional parameters unrelated to inflammation, including stool frequency (which may reflect bile salt diarrhea or bacterial overgrowth), abdominal pain (which may be functional), and general well-being (influenced by numerous non-inflammatory factors).

Studies show that fewer than 50% of patients with CDAI scores indicating clinical remission have endoscopic remission, and conversely, some patients with active endoscopic disease have CDAI scores below 150.¹³ The Harvey-Bradshaw Index, a simplified clinical score, demonstrates similar limitations in correlating with objective inflammation.

Figure 4

Endoscopic Scoring Systems

Multiple endoscopic scoring systems have been developed for Crohn’s disease, including the Crohn’s Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for Crohn’s Disease (SES-CD).¹⁴ While more objective than clinical indices, these systems have limitations. They assess only colonoscopically accessible bowel, missing small bowel disease in a significant proportion of patients. Inter-observer variability exists even among experienced endoscopists, particularly for subtle findings.

The definition of mucosal healing lacks standardization. Some definitions require complete absence of ulceration, while others accept minor erosions or erythema. This variability impacts research interpretation and clinical decision-making. Additionally, endoscopic scores may not capture functionally significant complications like strictures or fistulae that lack active inflammation.

Histological Assessment

Histological evaluation, while providing detailed assessment of microscopic inflammation, faces its own challenges. Sampling error is substantial, as biopsies represent less than 1% of mucosal surface area. Patchy inflammation may be missed entirely or underestimated. Optimal biopsy protocols remain debated, with some experts advocating for systematic sampling of multiple segments regardless of endoscopic appearance.

Histological scoring systems for Crohn’s disease are less well-validated than those for ulcerative colitis. The Geboes score and the Nancy Histological Index have shown promise but require specialized pathology expertise and are not universally employed. Interobserver variability exists, and distinguishing active inflammation from chronic architectural changes or treatment effects can be challenging.

The clinical significance of specific histological features remains incompletely understood. While features like basal plasmacytosis, crypt architectural distortion, and granulomas indicate chronic inflammation, their prognostic value varies.⁹ Some histological changes may persist indefinitely despite clinical and endoscopic remission, raising questions about the realistic goals of histological healing.

Biomarkers

Serum and fecal biomarkers provide non-invasive assessment of inflammation but demonstrate imperfect correlation with endoscopic findings. C-reactive protein (CRP) elevation correlates better with extensive disease than limited inflammation and may be normal in up to 25% of patients with active endoscopic disease.^{23, 24} Genetic polymorphisms affect CRP production, further limiting its sensitivity.

Fecal calprotectin shows better correlation with endoscopic activity than clinical indices but has limitations.^{10, 12} Elevated calprotectin may reflect non-IBD pathology including infections, medications (particularly NSAIDs), and functional disorders. Conversely, isolated small bowel disease may produce normal calprotectin levels. Thresholds for defining remission vary, and discrepancies between calprotectin levels and endoscopic findings occur in 20-30% of cases.

Newer biomarkers including fecal lactoferrin, serum interleukins, and microRNA profiles show promise but require validation.^{11, 12} No biomarker perfectly predicts endoscopic activity, and combinations of biomarkers with clinical assessment provide better correlation than any single measure.

Figure 5

Clinical Implications and Management Strategies

Treat-to-Target Approach

The recognition of clinical-endoscopic discrepancies has driven the treat-to-target paradigm in IBD management. This strategy emphasizes objective treatment targets—primarily endoscopic remission—over symptom control alone. The STRIDE II consensus recommendations³ advocate for endoscopic healing as a primary treatment target, acknowledging that clinical remission alone is insufficient.

However, implementing treat-to-target requires balancing multiple considerations. Endoscopic assessment is invasive, costly, and carries small but definite risks. The optimal frequency of endoscopic monitoring remains debated, with most guidelines recommending reassessment 6-12 months after treatment initiation or modification, then less frequently if remission is achieved.

For patients in clinical remission with elevated biomarkers, endoscopic assessment is generally warranted to detect subclinical disease. Conversely, patients with persistent symptoms despite normal biomarkers present a dilemma. In these cases, distinguishing inflammatory disease from functional symptoms is crucial to avoid unnecessary treatment escalation.

Role of Cross-Sectional Imaging

MRI enterography has become essential in Crohn's disease management, particularly for evaluating small bowel disease beyond colonoscopic reach. MRI findings of active inflammation—including mural enhancement, wall thickening, edema, and mesenteric inflammation—may explain symptoms in patients with normal colonoscopy. Additionally, MRI detects penetrating complications like abscesses and fistulae that may be endoscopically occult.

However, MRI-endoscopy correlation is imperfect. MRI may show wall thickening and enhancement in areas that appear normal endoscopically, representing either transmural inflammation with mucosal sparing or fibrotic changes without active inflammation. Diffusion-weighted imaging and quantitative MRI parameters show promise in distinguishing inflammation from fibrosis but require standardization.

The integration of MRI findings into treatment decisions requires clinical judgment. Not all MRI abnormalities mandate treatment intensification, particularly if patients are clinically well and biomarkers are normal. Conversely, transmural inflammation despite mucosal healing may justify continued or escalated therapy to prevent complications.

Managing Discrepancies in Clinical Practice

When faced with clinical-endoscopic dissociation, a systematic approach is essential.

For patients with symptoms but no objective inflammation:

• Exclude infection with stool studies including Clostridioides difficile, enteric pathogens, and Giardia.
• Assess for small bowel disease with capsule endoscopy or MRI enterography.
• Evaluate for IBD complications, including strictures, fistulae, bile salt diarrhea, and bacterial overgrowth.
• Consider functional overlay and employ Rome IV criteria to diagnose superimposed IBS.
• Assess medication side effects, particularly from opiates or antidepressants.
• Screen for and address extraintestinal manifestations.
• Avoid unnecessary treatment escalation that exposes patients to therapy risks without addressing the true cause of symptoms.

For patients in clinical remission with objective inflammation:

• Reassess and optimize medical therapy, potentially escalating treatment.
• Consider therapeutic drug monitoring to ensure adequate drug exposure.
• Evaluate for treatment resistant mechanisms.
• Discuss treatments goals and shared decision-making, as some patients may prioritize life over aggressive treatment.
• Monitor closely for disease progression and complications.
• Recognize that endoscopic remission provides better long-term outcomes than clinical remission alone.^{1, 4, 5}

For patients with endoscopic remission but histological activity:

• The approach remains controversial given limited prospective data.
• Consider histological findings in the context of clinical trajectory.
• In patients with frequent relapses or high-risk features, histological remission may justify continued aggressive therapy.
• In stable patients with mild histological activity, observation may be reasonable.
• Further research is needed to define optimal management strategies.⁹

Figure 6

Special Populations

Pediatric patients with Crohn’s disease demonstrate particularly significant clinical-endoscopic dissociation. Children may minimize or fail to report symptoms, and growth failure or delayed puberty may be the only manifestation of ongoing inflammation. Consequently, pediatric guidelines emphasize objective disease monitoring with regular endoscopy and biomarker assessment.

Elderly patients present opposite challenges. Multiple comorbidities, polypharmacy, and age-related symptoms confound assessment. Functional limitations may prevent reliable symptom reporting. Additionally, the risks of endoscopy and aggressive immunosuppression are higher, requiring careful risk-benefit analysis.

Pregnant patients require special consideration. Clinical symptoms may be attributed to pregnancy rather than disease activity, while concerns about fetal safety limit investigation. Noninvasive monitoring with biomarkers and ultrasound is emphasized, with endoscopy reserved for specific indications.

Emerging Concepts and Future Directions

Histological Remission as a Treatment Target

Growing evidence supports histological remission as an important treatment endpoint. Multiple studies now demonstrate that histological healing predicts more durable remission than endoscopic healing alone.^{4, 5, 9} The concept of “deep remission”— encompassing clinical, endoscopic, and histological remission—is gaining traction as the optimal treatment goal.

However, challenges remain in implementing histological targets. Standardized scoring systems and systematic biopsy protocols are needed. The optimal histological definition of remission requires clarification—should any inflammation be accepted, or should complete normalization be the goal? The feasibility and cost-effectiveness of routine histological monitoring need evaluation.

Prospective studies examining whether treatment adjustment based on histological findings improves outcomes are ongoing. Until such data are available, histological assessment should complement but not replace endoscopic evaluation in treatment decisions.

Molecular and Advanced Imaging Techniques

Novel technologies may improve clinical-endoscopic correlation. Confocal laser endomicroscopy and endocytoscopy allow real-time microscopic imaging during endoscopy, potentially detecting inflammation invisible to conventional endoscopy. However, these techniques require expertise, are time-consuming, and have not yet demonstrated clinical utility beyond research settings.

Molecular markers of inflammation, including mucosal cytokine profiles and gene expression signatures, may provide more precise inflammation assessment than histology alone. Mucosal healing biomarkers measured in biopsy specimens could guide treatment decisions. Machine learning algorithms analyzing multiple data types—clinical, endoscopic, histological, biomarker—may improve disease activity prediction.

Artificial intelligence applications in endoscopy show promise for standardizing disease assessment and reducing interobserver variability. Computer-assisted systems can calculate endoscopic scores in real-time and may detect subtle mucosal changes that human observers miss. However, validation in diverse populations and practice settings is needed before routine implementation.

Personalized Treatment Targets

The recognition that clinical-endoscopic correlation varies between individuals suggests that personalized treatment targets may be optimal. Some patients achieve excellent quality of life with mild residual inflammation, while others require complete histological remission to prevent progression. Patient phenotype, genotype, disease history, and preferences should inform individualized treatment goals.

Risk stratification algorithms incorporating clinical, genetic, serological, and microbiological data may identify patients who benefit from aggressive treat-to-target strategies versus those for whom symptom control is sufficient. Pharmacokinetic and pharmacodynamic monitoring can optimize drug exposure and predict treatment response, allowing personalized therapy.

The emerging concept of precision medicine in IBD emphasizes matching patients to optimal therapies based on molecular signatures. As predictive biomarkers improve, treatment algorithms may evolve beyond trial-and-error approaches toward mechanistically guided therapy selection.

Patient-Reported Outcomes and Quality of Life

While objective inflammation assessment is critical, patient-centered outcomes remain paramount. Patients prioritize symptom control, quality of life, and functional status over endoscopic scores. Discordance between patient priorities and physician-focused outcomes can lead to dissatisfaction and non-adherence.

Validated patient-reported outcome measures that distinguish inflammatory symptoms from functional overlay are needed. Shared decision-making where treatment goals are established collaboratively, considering both objective disease activity and patient values, improves satisfaction and outcomes. Some patients may reasonably choose to accept mild endoscopic activity to avoid treatment-related risks or burdens.

The integration of patient-reported outcomes with objective measures in composite endpoints represents an important evolution. Treatment success should encompass both mucosal healing and meaningful improvement in quality of life, functionality, and patient-defined goals.

Conclusion

The discrepancies between clinical symptoms, endoscopic findings, and histological inflammation in inflammatory bowel disease, particularly Crohn’s disease, represent a fundamental challenge in disease assessment and management. These dissociations arise from the complex, multifactorial nature of symptom generation, the limitations of assessment tools, and the unique pathophysiological features of Crohn’s disease including its transmural, discontinuous nature and propensity for complications.

Recognition of these discrepancies has transformed IBD management toward objective treat-to-target strategies emphasizing mucosal healing.^{2, 3} However, implementation requires judicious use of endoscopy, cross-sectional imaging, biomarkers, and histology while maintaining focus on patient-centered outcomes. No single assessment modality perfectly captures disease activity, and integrated, multimodal evaluation provides the most accurate assessment.

References

1. Frøslie KF, Jahnsen J, Moum BA, Vatn MH. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007;133(2):412-422.
2. Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015;110(9):1324-1338.
3. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: an update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology. 2021;160(5):1570-1583.
4. Baert F, Moortgat L, Van Assche G, et al. Mucosal healing predicts sustained clinical remission in patients with early- stage Crohn's disease. Gastroenterology. 2010;138(2):463-468.
5. Colombel JF, Rutgeerts P, Reinisch W, et al. Early mucosal healing with infliximab is associated with improved long- term clinical outcomes in ulcerative colitis. Gastroenterology. 2011;141(4):1194-1201.
6. Neurath MF, Travis SP. Mucosal healing in inflammatory bowel diseases: a systematic review. Gut. 2012;61(11):1619-1635.
7. Mosli MH, Feagan BG, Zou G, et al. Development and validation of a histological index for UC. Gut. 2017;66(1):50- 58.
8. Marchal-Bressenot A, Salleron J, Boulagnon-Rombi C, et al. Development and validation of the Nancy histological index for UC. Gut. 2017;66(1):43-49.
9. Bryant RV, Winer S, Travis SP, Riddell RH. Systematic review: histological remission in inflammatory bowel disease. Is 'complete' remission the new treatment paradigm? An IOIBD initiative. J Crohns Colitis. 2014;8(12):1582-1597.
10. D'Haens G, Ferrante M, Vermeire S, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis. 2012;18(12):2218-2224.
11. Vermeire S, Van Assche G, Rutgeerts P. Laboratory markers in IBD: useful, magic, or unnecessary toys? Gut. 2006;55(3):426-431.
12. Sipponen T, Karkkainen P, Savilahti E, et al. Correlation of faecal calprotectin and lactoferrin with an endoscopic score for Crohn's disease and histological findings. Aliment Pharmacol Ther. 2008;28(10):1221-1229.
13. Sostegni R, Daperno M, Scaglione N, Lavagna A, Rocca R, Pera A. Review article: Crohn's disease: monitoring disease activity. Aliment Pharmacol Ther. 2003;17 Suppl 2:11-17.
14. Daperno M, D'Haens G, Van Assche G, et al. Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc. 2004;60(4):505-512.
15. Mary JY, Modigliani R. Development and validation of an endoscopic index of the severity for Crohn's disease: a prospective multicentre study. Groupe d'Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). Gut. 1989;30(7):983-989.
16. Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the postoperative course of Crohn's disease. Gastroenterology. 1990;99(4):956-963.
17. Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019;68(Suppl 3):s1-s106.
18. Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. ACG Clinical Guideline: management of Crohn's disease in adults. Am J Gastroenterol. 2018;113(4):481-517.
19. Torres J, Bonovas S, Doherty G, et al. ECCO guidelines on therapeutics in Crohn's disease: medical treatment. J Crohns Colitis. 2020;14(1):4-22.
20. Rimola J, Ordás I, Rodriguez S, et al. Magnetic resonance imaging for evaluation of Crohn's disease: validation of parameters of severity and quantitative index of activity. Inflamm Bowel Dis. 2011;17(8):1759-1768.
21. Rimola J, Rodriguez S, García-Bosch O, et al. Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn's disease. Gut. 2009;58(8):1113-1120.
22. Panes J, Bouzas R, Chaparro M, et al. Systematic review: the use of ultrasonography, computed tomography and magnetic resonance imaging for the diagnosis, assessment of activity and abdominal complications of Crohn's disease. Aliment Pharmacol Ther. 2011;34(2):125-145.
23. Peyrin-Biroulet L, Reinisch W, Colombel JF, et al. Clinical disease activity, C-reactive protein normalisation and mucosal healing in Crohn's disease in the SONIC trial. Gut. 2014;63(1):88-95.
24. Solem CA, Loftus EV Jr, Tremaine WJ, et al. Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease. Inflamm Bowel Dis. 2005;11(8):707-712.
25. De Vos M, Dewit O, D'Haens G, et al. Fast and sharp algorithm: how to manage endoscopic postoperative recurrence in Crohn's disease. Gut. 2012;61(11):1455-1459.