creation date: 2025-11-13 15:16
tags: Pathologies
Crohn’s Disease
Background
Definitions
Crohn’s disease is one of the two major disorders comprising inflammatory bowel disease (IBD), the other being ulcerative colitis.
Crohn’s disease is characterized by transmural inflammation of the GI tract ranging from the oral cavity to the perianal area.
Etiology and Pathogenesis
The exact etiology of Crohn’s disease is unknown but evidence suggests an inappropriate immune response to environmental antigens such as drugs, toxins, infections, or intestinal microbes in a genetically susceptible host.
Distribution of GI involvement varies but include:
- ~80% have small bowel involvement (usually distal ileum)
- ~50% have ileocolitis (both ileum and colon)
- ~20% have disease of just the colon, with half sparing the rectum
- ~1/3 of patients have perianal disease
- ~5-15% have mouth or gastroduodenal involvement
- Very few have esophageal and proximal small bowel involvement
In the initial stages of illness, excessive immune responses involve intestinal macrophages, neutrophils, and helper T-cells results in inflammation and non-specific systemic symptoms. Inflammation may give rise to abdominal pain and diarrhea.
Further damage to the terminal ileum may give rise to malabsorption and vitamin deficiencies. Blood loss or B12 insufficiency can result in anemia.
Systemic inflammation results in extraintestinal manifestations.
Clinical Presentation
Signs & Symptoms
Symptoms may present acutely or patients can have symptoms for many years before a diagnosis.
The cardinal symptoms of Crohn’s disease are:
- Abdominal pain (distal ileum limited disease may present with RLQ pain)
- Diarrhea (persistent but intermittent without gross blood)
- Systemic symptoms (fatigue, weight loss due to decreased intake or malabsorption)
Features of transmural inflammation include:
- Fistulas; manifestations depend on area of involvement (enteroenteric, enterovesical, enterovaginal, enterocutaneous)
- Inflammatory mass/abscess
- Perianal disease (first presentation may be perianal abscess)
Involvement of other sites of the GI tract may manifest as:
- Aphthous ulcers or pain in mouth and gums
- Odynophagia or dysphagia with esophagus
- Upper abdominal pain, nausea, and/or postprandial vomiting with gastroduodenal involvement
Extraintestinal manifestations include:
- Arthritis
- Eye involvement (uveitis, iritis, and episcleritis)
- Skin disorders (erythema nodosum and pyoderma gangrenosum)
- Primary sclerosing cholangitis
- Pulmonary involvement (bronchiectasis, chronic bronchitis, intersitital disease)
History & Physical Exam
History may elicit report of:
- Recurrent episodes of symptoms with asymptomatic periods lasting weeks to months
- Emotional or physical stress precipitating the flare-up
- Family history of IBD
History should also try to determine:
- Involvement of GI tract
- Extraintestinal symptoms
Examination of the abdomen, skin, eyes, oral cavity, and joints should be performed. Additionally, assessment of malnutrition and neurologic symptoms should be made. Goals of examination are:
- Identify active inflammation
- Assess severity
- Detect complications
Risk factors
Diagnosis
Criteria
Diagnosis of Crohn’s is made based on radiologic, endoscopic, and/or histologic findings that demonstrate segmental and transmural inflammation of the luminal gastrointestinal tract in addition to a compatible clinical picture.
Work-up
Laboratory studies
Lab testing is useful for assessing complications but cannot be used alone to diagnose disease.
Blood tests consist of:
- CBC
- Electrolytes and creatinine
- Liver function and enzyme tests
- Blood glucose
- Iron studies
- Vitamin D and B12 levels
- Serum albumin
- CRP (note: acute phase reactant used for differentiating IBS vs. IBD)
Stool studies can be used:
- Enteric pathogen if diarrhea
- Stool inflammatory markers (not routine)
Endoscopy
Colonoscopy with intubation of the terminal ileum is performed. Endoscopic features which support diagnosis include:
- Focal ulcerations adjacent to areas of normal mucosa in addition to nodular mucosal changes - results in cobblestone appearance
- Skip areas of involvement with segments of normal bowel with large areas of disease
- Pseudopolyps (hypertrophied masses of mucous membrane)
During colonoscopy, biopsies are obtained from the right colon, left colon, and rectum for histological evidence of inflammation.
Upper endoscopy with biopsy of the stomach and small bowel may be indicated for patients with upper gastrointestinal symptoms. Findings include:
- Esophageal ulceration
- Gastric inflammation
- Duodenal ulceration
- Inflammation
Imaging
Small bowel imaging is performed as the small bowels are not easily accessible by endoscopy. CT enterography (CTE) or magnetic resonance enterography (MRE) is routinely used for diagnosis and follow-up.
Findings include:
- Segmental, asymmetric wall thickening
- Wall enhancement
- Ulcerations
- Wall edema and decreased motility (on MRE)
- Luminal narrowing with upstream dilation
- Fistulas
- Inflammatory masses or abscess
Differential
Red Flags / Complications
While Crohn’s disease is often chronic, symptoms are typically intermittent. Some patients may have continuous and progressive course of disease.
Chronic bowel inflammation can lead to complications such as:
- Strictures
- Fistulas
- Abscesses
Complications associated with malabsorptions are also associated due to small intestine involvement. This includes:
- Vitamin deficiencies
- Kidney stones (calcium oxalate)
Risk factors for progressive disease include:
- Age <40
- Tobacco use
- Perianal or rectal involvement
- Glucocorticoid-requiring disease
Crohn’s also has a risk of requiring surgery and increases the incidence of cancers.
Management
Management of Crohn’s disease generally consist of an induction phase to achievement remission and a maintenance phase to prevent clinical and endoscopic relapse.
Mild / Low-risk Disease
Patients are considered low-risk by the American Gastroenterological Association (AGA) if patients have the following:
- No or mild symptoms
- Normal or minimal elevation in CRP and/or fecal calprotectin levels
- Diagnosis at age >30 years
- Limited distribution of bowel inflammation
- Superficial or no ulceration on colonoscopy
- Lack of perianal complications
- No prior intestinal resections
- Absence of penetrating or stricturing disease
A step-up approach is utilized for low-risk patients. For patients who are asymptomatic and diagnosed incidentally, a repeat ileocolonoscopy is performed after 6-12 months for observation in addition to clinical monitoring.
Induction
The goal of induction is to achieve remission demonstrated by complete mucosal healing. The exact regime depends on the distribution of involvement.
Ileum and/or proximal colon involvement:
- Budesonide (enteric-coated) 9 mg per day for 4-8 weeks; tapered 3 mg q2-4 weeks for total of 8-12 weeks of therapy
- Alternatives: prednisone, 5-aminosalicylate
Diffuse colitis or left colonic involvement:
- Prednisone PO 40 mg per day for 1 week; tapered 5-10 mg per week
- Sulfasalazine 3-6 g per day for 16 weeks
Maintenance
After clinical remission has been achieved, patients on glucocorticoid should have their treatment tapered and discontinued. A follow-up ileocolonoscopy in 6-12 months is recommended.
For patients who achieved remission with a 5-ASA or sulfasalazine, the agent can be used long-term with a follow-up ileocolonoscopy in 6-12 months.
Symptom management
In addition to first line medications, patients can consider:
- Loperamide prn in small doses
- Cholestryamine for patients with chronic watery diarrhea
- Dietary changes (eg. lactose avoidance)
It should be noted that antibiotics and probiotics do not have conclusive benefits.
Moderate-to-Severe Disease
Features that suggest high-risk / moderate-to-severe disease include:
- Diagnosis at a younger age (<30)
- History of active or recent tobacco use
- Elevated CRP and/or fecal calprotectin levels
- Deep ulcers on colonoscopy
- Long segments of small and/or large bowel involvement
- Perianal disease
- Extra-intestinal manifestations
- History of bowel resections
In-patient management
Hospitalization is required for patients with Crohn’s disease if they are actively ill from a complications:
- Partial small bowel obstruction
- Peritonitis
- Abscess
- Disease flare that doesn’t respond to outpatient therapy
Management involves treatment of complication, fluid and electrolyte repletion, antibiotics, and VTE prophylaxis.
Induction
Selection of induction regimen should be individualized and made through shared-decision making. Options typically consist of some combination of biologics and immunomodulator.
In patients naive to biologics or for patients with fistulizing disease, a common options is:
- Combination of anti-TNF (eg. infliximab) with immunomodulator (eg. azathioprine or methotrexate)
Options may vary based on response to biologics and other factors such as age.
Other treatments include:
- JAK inhibitors (if anti-TNF therapy not responsive)
- Glucocorticoids (for immediate symptom relief but not long-term)
Maintenance
Once remission is achieved, an ileocolonoscopy should be performed in 6-12 months.
Maintenance typically consist of continuing long-term anti-TNF monotherapy. The choice to maintain immunomodulator use is individualized and depends on the severity of disease and risk of adverse events related to immunomodulators.