Crohn’s Disease: Causes, Pathophysiology, Imaging, Treatment, and Prognosis

Introduction

Crohn’s disease (CD) is a chronic, idiopathic inflammatory bowel disease (IBD) that primarily affects the gastrointestinal (GI) tract but can manifest with systemic and extraintestinal symptoms. It is characterized by transmural inflammation, skip lesions, and a propensity to cause strictures, fistulas, and abscesses. The disease most commonly involves the terminal ileum, though any segment from the mouth to the anus may be affected.

This article provides a comprehensive expert-level review of Crohn’s disease, covering its etiology, pathophysiology, epidemiology, clinical presentation, imaging features, treatment strategies, and prognosis. Figures and imaging findings are integrated from the provided case of a 23-year-old male presenting with abdominal pain and bloody diarrhea.

By the end of this column, readers will also find quiz questions with explanations to test their knowledge.

Etiology and Cause

The exact etiology of Crohn’s disease remains unknown, but it is widely accepted that it results from a complex interplay between:

Genetic susceptibility – Genome-wide association studies (GWAS) have identified mutations in NOD2/CARD15, ATG16L1, and other loci that influence innate immunity and autophagy.
Immune dysregulation – Dysregulated T-cell-mediated immune response, particularly an overactive Th1/Th17 pathway, promotes uncontrolled inflammation.
Environmental triggers – Smoking, diet, use of oral contraceptives, and exposure to antibiotics in childhood have been associated with increased risk.
Microbiome alterations – A loss of commensal microbial diversity and pathogenic colonization (dysbiosis) may act as triggers.

Together, these factors promote a chronic, relapsing-remitting cycle of intestinal inflammation and mucosal injury.

Pathophysiology

The hallmark of Crohn’s disease is transmural inflammation of the bowel wall. Unlike ulcerative colitis (UC), which is limited to the mucosa and submucosa, CD penetrates deeply into the muscularis propria and serosa.

Key mechanisms include:

Mucosal ulceration – leading to skip lesions separated by normal bowel.
Granulomatous inflammation – noncaseating granulomas may be found in 30–50% of biopsies.
Fistula formation – due to penetrating ulcers that breach the bowel wall, forming enteroenteric, enterovesical, or perianal fistulas.
Fibrotic strictures – chronic inflammation leads to fibrotic narrowing, causing bowel obstruction.

The most commonly affected site is the terminal ileum, as observed in [Figure 1].

Epidemiology

Age of onset: Peak incidence in the 2nd–3rd decade of life. Our case features a 23-year-old man, typical of Crohn’s demographics.
Sex distribution: No significant gender predilection.
Prevalence: Up to 16 per 100,000 population, though higher in Western countries.
Family history: First-degree relatives and monozygotic twins have an increased risk.

Recent studies suggest an increasing incidence in Asia and the Middle East, likely due to lifestyle westernization.

Clinical Presentation

The classic triad of Crohn’s disease includes:

Abdominal pain (often right lower quadrant).
Chronic diarrhea (sometimes bloody).
Weight loss and malnutrition.

Other features:

Extraintestinal manifestations – skin rashes (erythema nodosum, pyoderma gangrenosum), arthritis, uveitis, and kidney stones.
Systemic signs – fever, fatigue, and elevated inflammatory markers (C-reactive protein, ESR).
Perianal disease – fissures, fistulas, and abscesses, which occur in up to 30% of patients.

Our case demonstrates a patient with bloody diarrhea and abdominal pain, consistent with classical Crohn’s symptoms.

Imaging Features

Computed Tomography (CT)

[Figure 1: Coronal Contrast-Enhanced Abdominal CT]
Findings: Marked thickening and edema of the terminal ileum with engorged vasa recta and prominent mesenteric fat (“creeping fat”).

CT findings include:

Bowel wall thickening with stratified enhancement (“target sign”).
Mesenteric hyperemia (comb sign).
Creeping fat wraps around the diseased bowel segment.
Skip lesions – diseased bowel interspersed with normal bowel.
Complications: strictures, fistulas, abscesses.

Magnetic Resonance Imaging (MRI)

[Figure 2: Coronal Bright-Blood MR Image]
Findings: Hyperintense bowel wall signal corresponding to edema and active inflammation. MR was performed to reduce radiation exposure in this young patient.

MRI features:

Identical to CT but with improved tissue contrast.
Diffusion-weighted imaging helps detect subtle early inflammation.
Useful for perianal fistula assessment.
Preferred in young patients requiring serial follow-up.

Diagnosis

The gold standard remains colonoscopy with biopsy, which allows direct visualization of ulcers, cobblestoning, and granulomas. Imaging is complementary, particularly in evaluating complications and disease extent.

Differential diagnoses include:

Appendicitis
Infectious colitis (bacterial/parasitic)
Ileal tuberculosis
Mesenteric adenitis
Malignancy
Ulcerative colitis

Treatment

The therapeutic goal is to induce and maintain remission while preventing complications.

Medical therapy
- Corticosteroids – for induction of remission in moderate-to-severe disease.
- 5-Aminosalicylic acid (5-ASA) – limited role compared to UC but sometimes used.
- Immunomodulators – azathioprine, 6-mercaptopurine, methotrexate.
- Biologics – anti-TNF (infliximab, adalimumab), anti-integrin (vedolizumab), anti-IL-12/23 (ustekinumab).
- Antibiotics – for abscesses and perianal disease.
Surgical intervention
- Required in up to 70% of patients during their lifetime.
- Indications: strictures, perforation, fistulas, and refractory disease.
- Seton placement for perianal fistulas.

Prognosis

Crohn’s disease is chronic and incurable, but long-term management can greatly improve quality of life.

Relapse rate: 50–70% within 5 years.
Complications: strictures, fistulas, colon cancer risk (after >10 years).
Mortality: Slightly increased compared to the general population, but largely dependent on severity and treatment access.

Early diagnosis, optimized therapy, and close monitoring are crucial in reducing morbidity.

Quiz Section

1. Where is the most prominent imaging finding located in [Figure 1]?

(A) Bone

(B) Terminal ileum

(D) Bladder

2. Which statement is correct regarding bright-blood MR imaging in [Figure 2]?

(A) Fluids appear dark

(B) Field inhomogeneity increases artifacts

(D) Acquisition requires several minutes per image

3. What is the best next step after the findings in this case?

(A) IV antibiotics

(B) Colonoscopy

(D) Surgical resection

Answer & Explanation

1. Answer: (B) Terminal ileum. Explanation: The CT clearly demonstrates bowel wall thickening and mesenteric fat changes at the terminal ileum, a hallmark location for Crohn’s disease.

2. Answer: (C) Flowing blood is bright, while stagnant blood is dark. Explanation: Bright-blood sequences highlight flowing blood as bright, making them ideal for vascular and GI tract inflammation assessment.

3. Answer: (B) Colonoscopy. Explanation: While imaging is strongly suggestive, colonoscopy with biopsy is required for definitive diagnosis of Crohn’s disease.

References

[1] A. Furukawa, T. Saotome, M. Yamasaki, et al., “Cross-sectional imaging in Crohn disease,” Radiographics, vol. 24, no. 3, pp. 689–702, 2004, doi:10.1148/rg 243035120.

[2] F. F. Guglielmo, S. A. Anupindi, J. G. Fletcher, et al., “Small bowel Crohn disease at CT and MR enterography: Imaging atlas and glossary of terms,” Radiographics, vol. 40, no. 2, pp. 354–375, 2020, doi:10.1148/rg.. 2020190091.

[3] G. Roda, S. Chien Ng, P. G. Kotze, et al., “Crohn’s disease,” Nat Rev Dis Primers, vol. 6, no. 22, pp. 1–20, 2020, doi:10.1038/s41572-020-0156-2.

[4] J. Torres, S. Mehandru, J. F. Colombel, and L. Peyrin-Biroulet, “Crohn’s disease,” Lancet, vol. 389, no. 10080, pp. 1741–1755, 2017.

[5] D. C. Baumgart and W. J. Sandborn, “Crohn’s disease,” Lancet, vol. 380, pp. 1590–1605, 2012.

[6] S. C. Ng, H. Y. Shi, N. Hamidi, et al., “Worldwide incidence and prevalence of inflammatory bowel disease,” Lancet, vol. 390, no. 10114, pp. 2769–2778, 2018.

[7] J. Cosnes, C. Gower-Rousseau, P. Seksik, and A. Cortot, “Epidemiology and natural history of Crohn’s disease,” Gastroenterology, vol. 140, no. 6, pp. 1785–1794, 2011.

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