Crohn Disease

Essentials of Diagnosis

• Insidious onset

• Intermittent bouts of low-grade fever, diarrhea, and right lower quadrant pain

• Right lower quadrant mass and tenderness

• Perianal disease with fistulas, fissures, and abscesses

• Radiographic or endoscopic evidence of ulceration, stricturing, or fistulas of the small intestine or colon

General Considerations

• Crohn disease is a transmural process

• Crohn disease may involve

  • Small bowel only, most commonly the terminal ileum (ileitis) in ~33% of cases

  • Small bowel and colon, most often the terminal ileum and adjacent proximal ascending colon (ileocolitis) in ~50%

  • Colon alone in 20%

• Chronic illness with exacerbations and remissions

• One-third of patients have associated perianal disease (fistulas, fissures, abscesses)

• Less than 5% of patients have symptomatic involvement of the upper intestinal tract

• Smokers are at increased risk

• Treatment is directed both toward improving the symptoms and controlling the disease process

Symptoms and Signs

• Abdominal pain

• Liquid bowel movements

• Abdominal tenderness or abdominal mass

Chronic inflammatory disease

• Malaise, loss of energy

• Diarrhea, nonbloody, intermittent

• Cramping or steady right lower quadrant or periumbilical pain

• Focal tenderness, right lower quadrant

• Palpable, tender mass in the lower abdomen

Intestinal obstruction

• Postprandial bloating, cramping pains, and loud borborygmi

• Narrowing of the small bowel may occur as a result of inflammation, spasm, or fibrotic stenosis

Fistulization with or without infection

• Sinus tracts and fistulas can result in intra-abdominal or retroperitoneal abscesses manifested by fevers, chills, tender abdominal mass, and leukocytosis

• Fistulas can occur

  • Between the small intestine and the colon and commonly are asymptomatic but can cause

    • Diarrhea

    • Weight loss

    • Bacterial overgrowth

    • Malnutrition

  • Between the small intestine and the bladder or vagina and can cause

    • Recurrent urinary tract infections

    • Recurrent vaginal infections

  • Between the small intestine and the skin and can cause

    • Cutaneous fistulas

    • Perianal abscesses

    • Anal fissures

    • Skin tags

Extraintestinal manifestations

• Arthralgias, arthritis

• Iritis or uveitis

• Pyoderma gangrenosum

• Erythema nodosum

• Oral aphthous lesions

• Gallstones

• Nephrolithiasis with stones

Differential Diagnosis

• Ulcerative colitis

• Irritable bowel syndrome

• Appendicitis

• Yersinia enterocolitica enteritis

• Mesenteric adenitis

• Intestinal lymphoma

• Segmental colitis due to ischemic colitis, tuberculosis, amebiasis, chlamydia

• Diverticulitis or appendicitis with abscess

• Nonsteroidal anti-inflammatory drug–induced colitis

• Perianal fistula due to other cause

Laboratory Tests

• Obtain complete blood count, erythrocyte sedimentation rate or C-reactive protein, serum albumin

  • Anemia may be due to chronic inflammation, blood loss, iron deficiency, or vitamin B₁₂ malabsorption

  • Leukocytosis occurs with abscesses

  • Sedimentation rate or C-reactive protein elevated

• Fecal calprotectin

  • An excellent noninvasive test

  • Elevated levels are correlated with active inflammation as seen on ileocolonoscopy or radiologic CT or MR enterography

• Stool specimens are sent for examination for routine pathogens and Clostridioides difficile toxin by microscopy, culture, and toxin assay or by rapid multiplex polymerase chain reaction (PCR) diagnostic assessment

Imaging Studies

• CT or MR enterography

  • Suggestive findings include ulcerations, strictures, and fistulas

  • May identify bowel wall thickening and vascularity, mucosal enhancement, and fat stranding

• Capsuled (video) imaging of small intestine

• Barium upper gastrointestinal series with small bowel follow through should no longer be performed except where CT or MR enterography is unavailable

Diagnostic Procedures

• Colonoscopy

• Biopsy of intestine reveals granulomas in 25%

Medications

Symptomatic treatment of diarrhea

• Antidiarrheal agents

  • Loperamide (2–4 mg), diphenoxylate with atropine (one tablet), or tincture of opium (5–15 drops) four times daily as needed

  • Should not be used in patients with active severe colitis

• Cholestyramine 2–4 g, colestipol 5 g, or colesevelam 625 mg one to two times daily before meals to bind the malabsorbed bile salts

Treatment of exacerbations

• Early introduction of biologic therapy should be strongly considered in patients with risk factors for aggressive disease, including young age, perianal disease, stricturing disease, or need for corticosteroids

• 5-Aminosalicylic acid agents

  • Sulfasalazine is recommended in current treatment guidelines

    • Dosage: 1.5–3 g orally twice daily

    • Appears effective in improving symptoms and inducing remission in patients with mild Crohn disease involving the colon (not small intestine)

  • Mesalamine

    • Commonly is used in clinical practice as initial therapy for the treatment of mild to moderately active colonic and ileocolonic Crohn disease

    • However, current treatment guidelines recommend against its use for inducing or maintaining remission

• Ileal-release budesonide

  • Dosage: 9 mg once daily orally for 8–16 weeks initially induces remission in 50–70% of patients with mild to moderate Crohn disease involving the terminal ileum or ascending colon

  • If disease remission has been achieved, budesonide is tapered over 2–4 weeks in 3 mg increments

  • Patients with disease relapse may be treated again followed by initiation of immunomodulator therapy (azathioprine, mercaptopurine or methotrexate) to maintain long term remission

  • Preferred over systemic corticosteroids

• Corticosteroids

  • Prednisone or methylprednisolone, 40–60 mg/day, is administered to patients with

    • Mild to moderate Crohn disease involving the colon

    • Mild to moderate ileocolonic disease that has not responded to budesonide

    • Moderate to severe Crohn disease (in any location) in patients in whom the need for biologic therapy remains uncertain

  • Remission or significant improvement occurs in > 80% of patients after 8–16 weeks of therapy

  • After improvement at 2 weeks, tapering proceeds at 5 mg/wk until a dosage of 20 mg/day is being given

  • Thereafter, slow tapering by 2.5 mg/wk is recommended

  • Use of long-term low corticosteroid doses (2.5–10 mg/day) should be avoided because of associated complications

• Immunomodulatory drugs

  • Three main indications for use in Crohn disease are

    • After induction therapy with corticosteroids to allow their withdrawal (particularly in patients who are corticosteroid-dependent) and to maintain remission

    • For the induction of remission, in combination with anti-TNF therapy, in patients with moderate to severe active Crohn disease

    • In combination with biologic agents to reduce the likelihood of neutralizing antibody formation

  • Do not appear to be effective as monotherapy for induction of remission and are not recommended in guidelines

• Anti-TNF therapies: infliximab, adalimumab, and certolizumab are used to induce and maintain remission in moderate to severe Crohn disease as well as to treat extraintestinal manifestations (except optic neuritis)

  • Induction therapy

    • Infliximab: three-dose regimen of 5 mg/kg intravenously at 0, 2, and 6 weeks

    • Adalimumab: 160 mg subcutaneously at week 0, 80 mg at week 2, and 40 mg every 2 weeks beginning at week 5

    • Certolizumab: 400 mg subcutaneously at weeks 0, 2, and 4

  • Maintenance therapy

    • Infliximab: 5 mg/kg intravenously every 8 weeks

    • Adalimumab: 40 mg subcutaneously every 1–2 weeks

  • Loss of efficacy is due to low anti-TNF levels, the development of antibodies to the anti-TNF agent, or inflammation that is unresponsive to anti-TNF therapy

    • Patients with antibodies to the anti-TNF agent should be switched to another anti-TNF agent

    • Patients with low serum anti-TNF trough levels and absent drug antibodies should receive increased anti-TNF dosing (infliximab 10 mg/kg; adalimumab 80 mg) or decreased dosing intervals (infliximab every 6 weeks; adalimumab every week)

• Anti-integrins

  • Vedolizumab

    • Approved for the treatment of moderate to severe Crohn disease

    • Used primarily in patients in whom anti-TNF therapy has failed or is not tolerated

    • One-quarter (26.6%) of patients treated with vedolizumab (300 mg intravenously at weeks 0 and 2) were in clinical remission at week 10 compared to 12.1% of placebo-treated patients

    • More than one-third (39%) of patients treated with long-term vedolizumab (300 mg every 8 weeks) were in remission at 1 year compared to 21.6% of patients given placebo

    • May be less effective than anti-TNF or ustekinumab in the treatment of fistulous disease

• Ustekinumab, an anti-IL-12/IL-23 antibody, is approved by the FDA for moderate to severe Crohn disease that has not responded to or are intolerant of conventional therapies

Surgery

• At least one surgical procedure is required by > 50% of patients

• Indications for surgery

  • Intractability to medical therapy

  • Intra-abdominal abscess

  • Massive bleeding

  • Obstruction with fibrous stricture

• Incision and drainage of abscess

• Surgical resection of the stenotic area or stricturoplasty in small bowel obstruction

Therapeutic Procedures

• Percutaneous drainage of abscess

• Nasogastric suction and intravenous fluids for small bowel obstruction

• Well-balanced diet

• Avoid lactose-containing foods since lactose intolerance is common; use lactose supplements (eg, Lactaid) with first bite of meal if avoidance is impossible

• Fiber supplementation for patients with colonic involvement

• Low-roughage diet for patients with obstructive symptoms

• Low-fat diet for patients with fat malabsorption

• Vitamin B₁₂ 1000 mcg subcutaneously every month if prior terminal ileal resection

• Total parenteral nutrition

  • Used short term in patients with active disease and progressive weight loss or in malnourished patients awaiting surgery

  • Used long term in subset of patients with extensive intestinal resections resulting in short bowel syndrome with malnutrition

Complications

• Abscess

• Small bowel obstruction

• Fistulas

• Perianal disease

• Carcinoma

• Hemorrhage (unusual)

• Malabsorption

• Short bowel syndrome (following extensive surgery)

Prognosis

• With proper medical and surgical treatment, most patients are able to cope with this chronic disease and its complications

• Few patients die of Crohn disease

Prevention

• Annual colonoscopy screening to detect dysplasia or cancer is recommended for patients with a history of 8 or more years of Crohn colitis

When to Refer

• For expertise in endoscopic procedures or capsule endoscopy

• For follow-up of any patient requiring hospitalization

• When patients with moderate to severe disease are being considered for therapy with immunomodulators or biologic agents

• When surgery may be necessary

When to Admit

• An intestinal obstruction is suspected

• An intra-abdominal or perirectal abscess is suspected

• A serious infectious complication is suspected, especially in patients who are immunocompromised due to concomitant use of corticosteroids, immunomodulators, anti-tumor necrosis factor, or anti-integrin agents

• Patients with severe symptoms of diarrhea, dehydration, weight loss, or abdominal pain

• Patients with severe or persisting symptoms despite treatment with corticosteroids