- Clinical science
Crohn disease (CD) is an inflammatory bowel disease (IBD), the pathogenesis of which is not fully understood. The clinical presentation of CD may be similar to ulcerative colitis (UC), the other most common IBD. CD mostly affects young adults and adolescents between the ages of 15 and 35. It typically affects the terminal ileum, but can discontinuously affect the entire gastrointestinal tract and commonly leads to complications such as fistulas, abscesses, and stenosis. Clinical features include diarrhea, weight loss, and abdominal pain in the right lower quadrant (RLQ), as well as extraintestinal manifestations in the eyes, joints, or skin. Diagnosis is based on the patient's medical history, physical examination, lab tests, imaging (e.g., MRI), endoscopy, and serological testing. Acute episodes are treated with corticosteroids; immunosuppressants may be indicated in severe cases. Antibiotics and surgical intervention may be needed to help treat complications. As Crohn disease is not localized to a specific region of the GI tract, surgical resection is not a curative option (unlike in UC), and treatment instead focuses on limiting the progression and recurrence of inflammatory episodes.
- Prevalence: 200 cases per 100,000 population
- Incidence: ∼ 6 cases per 100,000 population per year 
- Sex: ♂ = ♀
- Typical age of onset: bimodal distribution with one peak at 15–35 years and another one at 55–70 years 
Populations with higher prevalence 
- Individuals of Northern European descent
- Individuals of Ashkenazi Jewish descent
Epidemiological data refers to the US, unless otherwise specified.
- Cause: Immune dysregulation and dysbiosis, which promotes chronic inflammation, the ultimate cause of which is not fully understood.
- Risk factors 
Nicotine consumption is the only (known) controllable risk factor for Crohn disease. Therefore, smoking cessation is especially important in patients with CD.
Definition: A validated score used to assess disease activity in Crohn disease calculated using the following variables, assessed over the course of one week:
- Number of liquid or soft stools per day
- Severity of abdominal pain
- General condition
- Presence of the following
- Use of antidiarrheal drugs
- Abdominal masses
- Percentage above or below standard weight
- 0–149: asymptomatic remission
- 150–220: low to moderate activity
- 221–450: moderate to high activity
- 451–1100: high activity, fulminant disease
Inflammation is most likely caused by immune dysregulation.
- Dysregulation of IL-23-Th17 signaling → unrestrained Th17 cell function → inflammation → local tissue damage (edema, erosions/ulcers, necrosis) → obstruction, fibrotic scarring, stricture, and strangulation of the bowel 
- There is evidence that mutations in the nucleotide oligomerization binding domain 2 (NOD2) protein are involved in the development of Crohn disease, but the exact mechanism is not fully understood. 
Abscess and fistula formation
Intestinal aphthous ulcers → transmural fissures and inflammation of the intestinal walls → adherence of other organs or the skin → penetration → microperforation and abscess formation → macroperforation into these structures → fistula formation
CD typically occurs episodically with a 30%-risk of recurring inflammation over the span of one year. If symptoms persist for six months, the disease is considered chronic. Without treatment, relapses and complications are to be expected.
Constitutional symptoms 
- Low-grade fever
- Weight loss
Intestinal symptoms 
- Chronic diarrhea, typically nonbloody
- Abdominal pain, typically in the RLQ
- (see “Signs of malabsorption” in “Complications” below)
- Palpable abdominal mass in the RLQ
- Enterocutaneous perianal fistulas, often associated with abscess formation 
- Oral aphthae
Perianal fistulas and abscesses are often the first signs of Crohn disease.
Extraintestinal symptoms 
- Joints: enteropathic arthritis (e.g., sacroiliitis, spondylitis, inflammation of peripheral joints)
- Liver/bile ducts: cholelithiasis
- Urogenital system: urolithiasis (mostly calcium oxalate stones)
- Associated with various conditions (e.g., , rheumatoid arthritis, and trauma)
- Manifests with very painful, rapidly-progressive, red spots that can change into purulent pustules or deep ulcerated lesions with central necrosis
- Commonly located at extensor side of the lower limbs
- Treated with immunosuppressants (e.g., corticosteroids, cyclosporine A)
Diagnosing CD requires the integration of clinical presentation, laboratory tests, and endoscopic, histologic, pathologic and radiologic findings.
- If a patient presents with symptoms suggestive of CD, conduct blood tests and stool tests (see “Laboratory tests” below) to rule out other possible causes for bowel inflammation/GI symptoms. 
- Confirm diagnosis with endoscopy and/or radiographic imaging and/or biopsy.
- Perform contrast radiological studies and/or ultrasonography to assess extent, severity, and complications (e.g., abscesses, fistulas, and stenoses)
- Blood work
- Serology: routine use to establish diagnosis is not recommended due to low sensitivity 
- Stool culture to rule out bacterial gastroenteritis
- Microscopy to examine presence of worm larvae or eggs (ova and parasites)
- Identification of bacterial toxins (e.g., toxin of Clostridium difficile)
- Detection of fecal calprotectin and/or fecal lactoferrin 
- Plain x-ray abdomen: may show bowel distention or pneumoperitoneum
Upper GI series with barium swallow and small bowel follow-through (enteroclysis): used to detect fistulas or stenoses, characteristic findings are:
- String sign: contrast-filled bowel segment that resembles a string on x-ray
Creeping fat: pathognomonic hyperplasia of adipose tissue that results in accumulation of mesenteric fat around the circumference of the intestine 
- May cover more than 50% of the inflamed bowel
- Correlates with severity of transmural inflammation
- Ultrasound findings
MR enterography: noninvasive, highly sensitive and specific imaging technique that involves the visualization of an oral contrast medium on MRI and is used in the diagnosis of IBD.
- Used to assess the extent and pattern of intestinal inflammation, detect perianal and pelvic disease, and to predict disease activity
- Characteristic findings are an edematous thickening of the intestinal wall and enlarged lymph nodes.
- Can be done as invasive MRI enteroclysis, during which contrast medium is applied via nasoduodenal tube and the small bowel is distended via an electric infusion pump.
Endoscopy confirms the diagnosis, assesses the extent of the disease, differentiates CD from other diseases (e.g., ulcerative colitis, peptic ulcers, etc.), and may also be used as a therapeutic tool (e.g., dilatation of ducts, intestinal loops).
Ileocolonoscopy: endoscopic examination of the rectum, colon, and terminal ileum that allows for direct visualization of the intestinal mucosa and sampling of tissue
- Procedure: ileocolonoscopy with biopsies at various locations throughout the terminal ileum, colon, and rectum
- Characteristic macroscopic findings
- Segmental/discontinuous pattern of involvement
- Snail trails: longitudinal ulcerations
- Pinpoint lesions: small, aphthous hemorrhagic mucosal defects
- Cobblestone sign: inflamed sections followed by deep ulcerations that resemble cobblestones
- Erythema and transmural inflammation (all mucosal layers of the intestinal wall are involved)
- Fissures, fistulas
- Video capsule endoscopy 
|Crohn disease and ulcerative colitis|
|Pathophysiology|| || |
|Frequency/type of defecation|| |
|Nutritional status|| || |
|Other complications|| |
|Cancer risk|| |
|Endoscopy and imaging|
|Pattern of inflammation|| || |
|Typical diagnostic findings|
|Surgery|| || |
To remember the most important features of Crohn disease (creeping fat, granuloma, skip lesions, rectal sparing, cobblestone sign), think: The crone and the fat granny skipped over the wrecked cobblestones.
Other differential diagnoses
- Infectious gastroenteritis/colitis
- Noninfectious colitis (ischemic, after radiation therapy, after ingestion of drugs, etc.)
- Malignant intestinal transformations
The differential diagnoses listed here are not exhaustive.
Therapy of CD is based on the following steps:
- Treating acute disease
- Inducing clinical remission
- Maintaining response/remission
- Patients should be stratified according to their specific prognostic risk factors.
- For optimal results, therapy should be as individually tailored as possible.
- Disease activity should be monitored regularly based on objective markers.
- Patients should be motivated to engage in lifestyle modifications (see below).
Treatment of Crohn disease can be approached in two different ways: step-up therapy and top-down therapy.
|Overview of pharmacotherapy for Crohn disease |
|Substance class|| |
|Acute episode|| |
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|Severe/fulminant disease|| |
|Maintenance therapy|| |
Corticosteroids should not be used for long-term maintenance therapy!
- Minimally-invasive resection of affected and nonfunctional intestinal loops while preserving as much intestinal length and function as possible
- Indicated when medical therapy fails or patient develops severe complications (e.g., obstruction, stricture, abscess)
- Balloon dilatation: to treat intestinal stenosis
- Percutaneous drainage: prevents retention of secretions and abscessation
- Surgical drainage: when application of percutaneous drainage fails
- A surgical procedure that opens up a bowel stricture without having to resect the bowel (bowel-sparing technique)
- Indicated after multiple resections
- Limited resection (e.g., proctocolectomy): in case of obstructions or strictures
Crohn disease is mainly treated with medication, but surgical interventions may be required to treat complications or if medical therapy fails.
Surgical intervention alone cannot cure Crohn disease and should therefore be considered as a last resort to avoid complications in which significant amounts of bowel are lost (e.g., short bowel syndrome)!
- Smoking cessation
- Avoiding certain drugs (e.g., NSAIDs )
- Minimizing stress
Management of complications and comorbidities
- Malabsorption syndrome: appropriate substitution of vitamins, calories, protein, zinc, calcium, and iron
- Bile acid diarrhea: administration of ion-exchange resins to bind bile acids (e.g., cholestyramine)
- Depression and anxiety: See “ ” and “ .”
Prevention of malignancies
- Individuals with CD have an increased risk of cancer (especially of the small intestine, colon , and lymphatics).
- Regular colonoscopies should be performed to minimize risk.
- People without major colonic involvement are managed according to the general screening guidelines (see ” ”)
- Colorectal cancer (especially in the case of pancolitis)
- Short bowel syndrome and associated issues after surgery
- Stenosis/strictures → bowel obstruction/(sub)ileus
- Intestinal perforation → peritonitis
- Impaired bile acid reabsorption
- Abscess formation/phlegmons: See below.
- Typically involve the terminal ileum and/or perianal region
- Recurrences are common
- See “ .”
- Inflammation → epithelial defects → epithelial-mesenchymal transition → deeper penetration of cell layers by epithelial cells → tissue damage that organizes as tubular structures that ultimately connect to other organs or the surface
- After surgery or percutaneous drainage: deficient anastomoses/sutures or improper healing following intervention (e.g., due to reduced organ blood flow) → leakage of intestinal contents → local infection → abscess formation and/or erosion → fistula formation
Clinical features: depend on location of the fistula
- Enterovesical/colovesical fistula → pneumaturia; (passing of urine together with air)/fecaluria; (passing of stool together with urine) → recurrent urinary tract infections (UTIs)
- Enterocutaneous fistula → drainage of intestinal content through the skin
- Gastrocolic fistula → abdominal pain, weight loss, foul‑smelling (feculent) belching
- Signs of malabsorption syndrome
We list the most important complications. The selection is not exhaustive.
- CD is a chronic disease that is currently not curable.
- Life expectancy is normal with proper treatment. 
- 70–90% of all patients will require surgery at some point during their lifetime.