INTRODUCTION AND EPIDEMIOLOGY
Crohn's disease is a chronic granulomatous inflammatory disease of the gastrointestinal tract of unknown origin. Crohn's disease can involve any part of the gastrointestinal tract from the mouth to the anus. The ileum is involved in the majority of cases. In 20%, the disease is confined to the colon, making differentiation from ulcerative colitis difficult. The terms regional enteritis, terminal ileitis, granulomatous ileocolitis, and Crohn's disease are all used to describe the same disease process.
The peak incidence of Crohn's disease occurs between 15 and 22 years of age, with a secondary peak from 55 to 60 years. It is more common in women. The incidence is increasing, especially in children.35 The disease is four times more common among Jews than non-Jews and is more common in whites than blacks, Asians, or Native Americans. A family history of inflammatory bowel disease is present in 10% to 15% of patients, particularly with early onset of disease. Ulcerative colitis as well as Crohn's disease may be present in other family members, and siblings of patients with Crohn's disease have a higher incidence of the disease. Smoking, oral contraceptive use, and the use of nonsteroidal anti-inflammatory agents worsen the course of the disease.
The most important pathologic feature of Crohn's disease is the involvement of all the layers of the bowel and extension into mesenteric lymph nodes. The disease is discontinuous, with normal areas of bowel ("skip areas") located between one or more involved areas. Longitudinal, deep mucosal ulcerations are characteristic. If ulcerations penetrate the bowel wall, fissures, fistulas, and abscesses result. Late in the disease, a cobblestone appearance of the mucosa results from the criss-crossing of ulcers with intervening normal mucosa.
The clinical course of Crohn's disease varies and in the individual patient is unpredictable. Abdominal pain, anorexia, diarrhea, and weight loss are present in most cases. Chronic abdominal pain, fever, and diarrhea may be present for several years before definitive diagnosis is established. Perianal fissures or fistulas, hematochezia, abscesses, or rectal prolapse can develop, particularly with colonic involvement.36,37 Patients may also present with complications of the disease, such as obstruction with vomiting, crampy abdominal pain, and obstipation, or an intra-abdominal abscess with fever, abdominal pain, and a palpable mass.
In 10% to 20% of patients, the extraintestinal manifestations of arthritis, uveitis, or liver disease may be presenting symptoms. Crohn's disease should also be considered in the differential diagnosis of patients with fever of unknown etiology.
The clinical course and manifestations of the disease appear to be related to its anatomic distribution: in 30% the disease involves only the small bowel, in 20% only the colon is involved, and in 50% both the small bowel and colon are involved. A small percentage of patients present with disease involving the mouth, esophagus, and stomach. Crohn's disease of the stomach may demonstrate symptoms of peptic ulcer disease.
Extraintestinal manifestations are seen in up to 40% of patients with Crohn's disease (Table 73-4),38 and the incidence and types of extraintestinal complications are similar in patients with Crohn's disease and ulcerative colitis.
TABLE 73-4Common Extraintestinal Manifestations of Inflammatory Bowel Disease ||Download (.pdf) TABLE 73-4 Common Extraintestinal Manifestations of Inflammatory Bowel Disease
|Manifestation ||Description |
|Peripheral arthritis ||Migratory monoarticular or polyarticular pain in peripheral joints (hip, knee, ankle, wrist) with effusion |
|Ankylosing spondylitis ||Pain and stiffness of spine, hips, neck, and rib cage with limitation in truncal motion, loss of lumbar lordosis; decreased chest expansion and forward cervical flexion in advanced disease |
|Sacroiliitis ||Low back pain with morning stiffness, relieved by exercise; progressive joint sclerosis |
|Episcleritis ||Eye burning or itching without visual changes or pain; scleral and conjunctival hyperemia |
|Uveitis ||Acute blurring of vision, photophobia and pain; perilimbic scleral injection |
|Erythema nodosum ||Painful, red, raised nodules on extensor surfaces of arms or legs |
|Pyoderma gangrenosum ||Ulcerative lesions with a necrotic center and violaceous skin typically found in pretibial region or trunk |
|Cholelithiasis ||Varies from asymptomatic stones to right upper quadrant pain, fever, vomiting |
|Fatty liver ||Mild right upper quadrant pain; hepatomegaly |
|Pericholangitis ||Mild elevation in serum alkaline phosphatase, asymptomatic |
|Chronic active hepatitis ||Autoimmune elevation of liver aminotransferase enzymes, may progress to cirrhosis |
|Primary sclerosing cholangitis ||Pruritus progressing to jaundice, fatigue, and lethargy; laboratory findings vary from mild elevations of alkaline phosphatase to cirrhosis, portal hypertension, and liver failure; male predominance |
|Cholangiocarcinoma ||Extrahepatic biliary mass, evidence of biliary obstruction, jaundice, right upper quadrant pain, fever, malaise |
|Pancreatitis ||Varies from painless elevation of serum amylase to clinically apparent central abdominal pain radiating to back; may be associated with drugs such as azathioprine, 6-mercaptopurine, sulfasalazine, mesalamine, olsalazine, metronidazole |
|Thromboembolic disease ||Symptoms of deep venous thrombosis and pulmonary emboli; portal vein, mesenteric vein, and hepatic venous thrombosis reported |
|Malnutrition ||Fatigue, malaise, muscular wasting, cachexia |
|Chronic anemia ||Fatigue, malaise, pallor, dyspnea; may be microcytic (blood loss), macrocytic (B12 deficiency), or autoimmune hemolytic |
|Nephrolithiasis ||Flank pain, nausea, vomiting, hematuria; stones result from increased dietary oxalate absorption (calcium oxalate stones) and dehydration (urate stones) |
In most patients, the definitive diagnosis of Crohn's disease is established months or years after symptom onset. A provisional diagnosis of appendicitis or pelvic inflammatory disease may change to Crohn's disease after imaging or at the time of surgery. A detailed history asking about previous bowel symptoms that preceded the onset of acute right lower quadrant pain provides clues to the correct diagnosis.
ED evaluation focuses on determining the severity of the attack; identifying significant complications such as obstruction, intra-abdominal abscess, life-threatening hemorrhage, or toxic megacolon; and eliminating other possible causes of the patient's complaints.
Laboratory evaluation should include a CBC, serum electrolytes, BUN, creatinine, and a type and cross-match where appropriate. C-reactive protein levels can monitor disease activity.39 Fecal markers of inflammation (calprotectin and lactoferrin) are other markers of disease activity.40
Plain radiographs of the abdomen may demonstrate obstruction, perforation, or toxic megacolon. Abdominal CT scanning with PO and IV contrast identifies bowel wall thickening, segmental narrowing, destruction of the normal mucosal pattern, mesenteric edema, fistulas, and abscesses, which suggest the diagnosis of Crohn's disease. Extraintestinal complications such as gallstones, renal calculi, sacroiliitis, and osteomyelitis can also be seen on CT scan. Diagnosis is confirmed by colonoscopy.
The differential diagnosis of Crohn's disease includes lymphoma, ileocecal amebiasis, sarcoidosis, deep chronic mycotic infections involving the gastrointestinal tract, gastrointestinal tuberculosis, Kaposi's sarcoma, Campylobacter enteritis, and Yersinia ileocolitis. Fortunately, most of these are uncommon conditions and can be differentiated by appropriate laboratory tests. Yersinia ileocolitis and Campylobacter enteritis may cause chronic abdominal pain and diarrhea similar to Crohn's disease, but can be diagnosed by appropriate stool cultures. It is not uncommon that a bout of acute bacterial diarrhea may uncover a diagnosis of inflammatory bowel disease.41 Acute ileitis should not be confused with Crohn's disease. Young patients with acute ileitis usually recover without sequelae and should not undergo surgery. When Crohn's disease is confined to the colon, ischemic bowel disease (particularly in the elderly) and pseudomembranous colitis as well as ulcerative colitis must be included in the differential diagnosis.
The aim of therapy for this incurable disease includes relief of symptoms, induction of remission, maintenance of remission, prevention of complications, optimizing timing of surgery, and maintenance of nutrition.42,43
Initial treatment (Table 73-5) consists of adequate fluid resuscitation and restoration of electrolyte balance. Place a nasogastric tube for obstruction, peritonitis, or toxic megacolon. Administer broad-spectrum antibiotics for fulminant colitis or peritonitis. Patients with severe disease should receive IV steroids such as hydrocortisone 300 milligrams per day or an equivalent dose of methylprednisolone (48 milligrams per day) or prednisolone (60 milligrams per day).
TABLE 73-5Treatment of Fulminant Colitis ||Download (.pdf) TABLE 73-5 Treatment of Fulminant Colitis
Restore fluid and electrolyte balance
Nothing by mouth
Nasogastric suction for
Piperacillin-tazobactam 4.5 grams IV four times a day OR
Ampicillin 2 grams IV four times a day + metronidazole 500 milligrams IV three times a day + levofloxacin (Levaquin®) 750 milligrams IV once a day
Observe for complications
Outpatient management (nontoxic patients)
Sulfasalazine 3 to 5 grams per day is for mild to moderate Crohn's disease. Sulfapyridine is a byproduct of the colonic breakdown of sulfasalazine. Many of the toxic side effects of sulfasalazine (vomiting, anorexia, nausea, headache, diarrhea, epigastric distress, etc.) are attribuTable to sulfapyridine.
The active moiety in sulfasalazine is mesalamine. Many of the newer 5ʹ-acetyl salicylic acid drugs feature a derivative of mesalamine without the sulfapyridine component. Pentasa®, Asacol®, Claversal®, Salofalk®, and Lialda® are mesalamine derivatives. Olsalazine (Dipentum®) and balsalazide (Colazide®) are 5-aminosalicylic molecules. The mesalamine formulations are most effective in patients with colonic disease and particularly in those with mild disease.
Oral glucocorticoids such as prednisone (40 to 60 milligrams per day) have traditionally been reserved for more severely affected patients but are now used as induction therapy. An ileal-released form of budesonide (9 milligrams per day) may be beneficial in patients with ileal and right colon disease. Glucocorticoids are not preferred for maintaining remission because of their complications and concerns about effectiveness.
Immunosuppressive drugs such as 6-mercaptopurine, azathioprine, and thioguanine are useful in maintenance, as steroid-sparing agents, in healing fistulas, and in patients in whom there are serious contraindications to surgery.44 Both agents have been associated with leukopenia, fever, hepatitis, and pancreatitis, necessitating the need for close follow-up, particularly during the initial phase of therapy. The response to immunosuppressives should not be expected before 3 to 6 months following the initiation of therapy. Parenteral methotrexate (15 to 25 milligrams per week) is considered third line and has been used following steroid and thiopurine metabolite failure.
Antibiotics are first-line agents for perianal disease and help induce remission. Ciprofloxacin (1.0 to 1.5 milligrams/kg per day) induces remission with rates (55%) similar to those in patients treated with mesalamine (4 grams per day).45 Metronidazole (10 to 20 milligrams/kg per day) is also effective for perianal complications and fistulous disease. Combination therapies with antibiotics and biologic agents (see next section) have produced dramatic improvements in response.46 Rifaximin is a broad-spectrum antibiotic that is not absorbed from the gastrointestinal tract. Rifaximin 800 milligrams twice daily for 12 weeks is effective for mild to moderate disease.45 However, antibiotics raise concerns about precipitating C. difficile colitis infection.
Patients with medically resistant moderate to severe Crohn's disease may benefit from the antitumor necrosis factor antibody, infliximab (Remicade®) or adalimumab (Humira®).45,47,48 All biologics increase the risk of infections, especially those caused by intracellular pathogens such as tuberculosis. Concern about the emergence of lymphomas and progressive multifocal leukoencephalopathy has limited the long-term use of these agents.
Maintenance therapy and the effectiveness of various therapeutic agents in Crohn's disease are variable. Glucocorticoids are not used for maintaining a remission because of the lack of sufficient evidence of their efficacy and the potential for long-term complications. A reduced dose of 5-aminosalicyclic acid derivatives is used for the maintenance of remission of colonic disease. The addition of sulfasalazine, azathioprine, and 6-mercaptopurine to prednisone does not improve the response rate and increases side effects. Infliximab or adalimumab and an immunosuppressive (azathioprine, 6-mercaptopurine, and methotrexate) can maintain remission.45
Diarrhea can be controlled by loperamide (Imodium®) 4 to 16 milligrams per day, diphenoxylate (Lomotil®) 5 to 20 milligrams per day, and in some cases, cholestyramine (Questran®) 4 grams one to six times a day. The mechanism of action of cholestyramine is binding bile acids and eliminating their known cathartic action.
More than three out of four patients with Crohn's disease will require surgery within the first 20 years of the onset of initial symptoms. Abscess and fissure formation is common. Abscesses can be characterized as intraperitoneal, visceral, retroperitoneal, interloop, or intramesenteric. Signs and symptoms are worsening abdominal pain and tenderness, fever, and possibly a palpable mass. Retroperitoneal abscesses may cause hip or back pain and difficulty ambulating.
Fistulas are the result of extension of the intestinal fissures seen in Crohn's disease into adjacent structures. The most common sites are between the ileum and the sigmoid colon, the cecum, another ileal segment, urinary bladder, vagina, or the skin. Suspect an internal fistula when there are changes in the patient's symptom complex, such as bowel movement frequency, amount of pain, or weight loss.
Obstruction is the result of both stricture formation due to the inflammatory process and of edema of the bowel wall. The distal small bowel is the most common site of obstruction. Symptoms include crampy abdominal pain, distention, nausea, and bloating.
Perianal complications include perianal or ischiorectal abscesses, fissures, fistulas, rectovaginal fistulas, and rectal prolapse. These are more commonly seen in patients with colonic involvement.
Major gastrointestinal bleeding is rare. Bleeding results from erosion into a vessel in the bowel wall. Toxic megacolon is also uncommon, but is associated with massive gastrointestinal bleeding in over half the cases.
When bowel symptoms are present, malnutrition, malabsorption, hypocalcemia, and vitamin deficiency can be severe. In addition to the complications of the disease itself are complications associated with the treatment of the disease with mesalamine, steroids, immunosuppressive agents, and antibiotics. These include leukopenia, thrombocytopenia, fever, infection, profuse diarrhea, pancreatitis, renal insufficiency, and liver failure.
The incidence of malignant neoplasm of the gastrointestinal tract is three times higher in patients with Crohn's disease than for the general population.
Patients with colitis, peritonitis, or complications such as obstruction, significant gastrointestinal hemorrhage, severe dehydration, or fluid/electrolyte imbalance should be hospitalized. Hospital admission should be considered in less severe cases that cannot be managed successfully with outpatient management. Surgical intervention is indicated in those patients with complications of the disease, including intestinal obstruction or hemorrhage, perforation, abscess or fistula formation, toxic megacolon, and perianal disease.
Before discharging patients with Crohn's disease, discuss alterations in the therapeutic regimen with the gastroenterologist. Assure close follow-up after discharge.