What is Crohn's disease?

Crohn's Disease: Definition, Diagnosis, and Management

Crohn's disease is a chronic inflammatory bowel disease characterized by transmural inflammation that can affect any part of the gastrointestinal tract from mouth to anus, with the terminal ileum and colon being the most commonly affected sites. 1, 2

Definition and Pathophysiology

• Crohn's disease is a chronic inflammatory disease that mainly affects the gastrointestinal tract, with a prevalence of approximately 145-157 per 100,000 people in the UK 1
• The disease is characterized by transmural granulomatous inflammation that can affect the entire GI tract, including the mouth and perianal region 1
• Crohn's disease runs a long-term course that includes periods of clinical remission and intercurrent exacerbations 1
• The disease results from a complex interplay between genetic susceptibility, environmental factors, altered gut microbiota, and dysregulated immune responses 3

Clinical Presentation

• Common presenting symptoms include abdominal pain, diarrhea, weight loss, and fatigue 1, 4
• Severe disease may present with at least 10 loose stools/day, daily abdominal pain, anorectal symptoms (pain, urgency, incontinence), and significant impact on activities of daily living 1
• Up to one-third of patients present with complicated behavior (strictures, fistula, or abscesses) at diagnosis 5
• Perianal disease occurs in 15-25% of patients and is a characteristic feature of Crohn's disease 2
• Extraintestinal manifestations may include arthritis, cutaneous lesions, and ocular inflammation 2

Disease Classification

• The Montreal Classification categorizes Crohn's disease as stricturing, penetrating, inflammatory (non-stricturing and non-penetrating), and perianal disease 1
• Each phenotype can present with a range in severity from mild to severe disease 1
• Three main disease phenotypes are recognized: inflammatory, structuring, and penetrating 5

Diagnostic Approach

• Diagnosis is based on a combination of clinical, laboratory, endoscopic, histological, and imaging findings 1
• Ileocolonoscopy with biopsies from both inflamed and uninflamed segments is required for initial diagnosis 2
• Key endoscopic features include discontinuous (skip) lesions throughout the GI tract, presence of strictures and fistulae, perianal involvement, and transmural inflammation 2
• Stool specimens should be obtained to exclude common pathogens and specifically tested for C. difficile toxin 2
• Cross-sectional imaging (preferably MR enterography) is essential for evaluating small bowel involvement beyond the reach of endoscopy 1, 2
• Upper GI endoscopy may reveal specific findings such as bamboo-joint-like appearance in the gastric cardiac region and notch-like appearance in the duodenum, which are highly specific for Crohn's disease 6

Laboratory and Biomarkers

• C-reactive protein and fecal calprotectin are useful for assessing disease activity 2
• Serological markers (pANCA and ASCAs) may support diagnosis but have limited accuracy 2
• Complete blood count may reveal anemia, which is a marker of severe disease 1

Treatment Approach

• The goal of treatment is to improve or completely resolve symptoms, improve quality of life, avoid hospitalization, and promote endoscopic mucosal healing 1
• Treatment strategies aim for deep and long-lasting remission to prevent complications and block disease progression 4
• A treat-to-target approach with frequent monitoring of inflammation and therapy adjustment is recommended 2

Induction Therapy

• For first presentation or single inflammatory exacerbation in a 12-month period, conventional glucocorticosteroids (prednisolone, methylprednisolone, or IV hydrocortisone) are recommended 1
• For moderate to severe Crohn's disease, biologic agents are often required 7, 8
• Infliximab is indicated for reducing signs and symptoms, inducing and maintaining clinical remission in adults and pediatric patients (≥6 years) with moderately to severely active Crohn's disease who have had inadequate response to conventional therapy 7
• Adalimumab is indicated for treatment of moderately to severely active Crohn's disease in adults and pediatric patients 6 years and older 8

Maintenance Therapy

• Long-term immunosuppression is often required to maintain remission 9
• Thiopurines are important in steroid-sparing maintenance therapy 9
• Anti-TNF agents play a fundamental role, especially in fistulizing Crohn's disease 9
• Regular monitoring with clinical indices, blood tests (CRP, CBC), fecal calprotectin, endoscopic evaluation, and cross-sectional imaging is essential 2

Disease Complications and Outcomes

• Without adequate control, Crohn's disease can lead to substantial morbidity 1
• Historically, approximately 20% of patients were hospitalized annually, with surgery required in 24% within one year, 36% by five years, and 47% by 10 years of diagnosis 1
• Outcomes have improved in recent years due to earlier diagnosis, increasing use of biologics, therapy escalation based on disease severity, and endoscopic management 1
• Despite advances in medical therapy, most patients will eventually require surgery, which is not curative 5

Special Considerations

• Up to one-third of people with Crohn's disease are diagnosed before the age of 21 1
• Pediatric patients are more likely to have upper GI and colonic involvement compared to adults 2
• There is a high incidence of psychological morbidity in both children and adults with Crohn's disease 1
• Treatment discussions should address concerns about body image, living with a chronic illness, and impact on education or work 1

Crohn's disease requires lifelong management with a combination of medical therapies, regular monitoring, and sometimes surgical interventions. Early aggressive treatment and tight control of inflammation are key to preventing disease progression and complications.