A 26-year-old man with 3-year history of Crohn disease presents to the emergency department with postprandial abdominal pain and vomiting of 2 days’ duration. He has been receiving infliximab (Remicade) infusions at 5 mg/kg every 8 weeks for the past 8 months. Before that time, he had taken prednisone 40 mg/d for several weeks intermittently for treatment of disease exacerbation. Also, he had received Asacol (a 5-aminosalicylate [5-ASA] derivative), 2.4 g/d. The patient reports a 15-lb weight loss over the past 2 months. His past surgical history is significant for an appendectomy 4 years ago. On examination, his temperature is 38.0°C (100.4°F), pulse rate 95 beats/min, and blood pressure 130/70 mm Hg. His abdomen is moderately distended and tender in the right lower quadrant. There are no masses or peritonitis. A rectal examination reveals no perianal disease or abnormalities. The remaining results from the physical examination are unremarkable. The complete blood count revealed a white blood cell count of 14,000/mm3, and his hemoglobin level is 10.5 g/dL. The results from serum electrolyte studies and a urinalysis are within the normal range.
What is the most likely diagnosis?
What is the next step?
ANSWERS TO CASE 50: Crohn Disease
Summary: A 26-year-old man presents with a history of Crohn disease with disease exacerbation. Despite infliximab therapy, the patient’s symptoms have not improved. Currently, he has nausea, vomiting, abdominal pain and distention, and a low-grade fever and leukocytosis, which are suggestive of chronic small bowel obstruction and low-grade sepsis.
• Most likely diagnosis: Crohn disease, likely ileocolic, complicated by obstruction and possible intra-abdominal infection.
• Next step: The next step is to define the extent of disease involvement, the site of obstruction, and the possible presence of intra-abdominal abscesses. A computed tomography (CT) scan of the abdomen and pelvis, small bowel follow-through (SBFT) radiography, and colonoscopy are indicated.
1. Know the clinical features, diagnosis, and natural history of Crohn disease.
2. Be familiar with the medical therapies and the role of surgery in Crohn disease.
A 26-year-old man presents with a 3-year history of Crohn disease, refractory to maintenance therapy with a 5-ASA derivative. Exacerbations required steroid therapy in the past; however, he has now received several doses of infliximab. Despite this, he has progression of disease evidenced by weight loss, GI tract obstructive symptoms, and fever. This patient’s bowel obstruction is likely related to chronic fibrotic strictures rather than subacute inflammation. Obstruction from subacute inflammation can be resolved with anti-inflammatory and immunomodulator therapies. In contrast, fibrotic strictures cannot be resolved with medical management and generally require surgical therapy to relieve the obstruction. A CT scan is a useful initial imaging study for assessing the severity and extent of the disease and for detecting intra-abdominal abscesses. Crohn disease may involve both the small bowel and colon. Therefore, complete evaluation should include colonoscopy and an SBFT contrast study to visualize the location and severity of small bowel disease. Once the small bowel and colon have been evaluated, this patient should undergo exploratory laparotomy to relieve his bowel obstruction. Surgical options include resection of the obstructed bowel or stricturoplasty.
APPROACH TO: Crohn Disease
DISEASE ACTIVITY: Severity can be assessed by histology, endoscopy, radiography, symptoms, or surgical findings. Histologic, endoscopic, radiographic, and surgical criteria frequently do not correlate with clinical criteria and may not correlate with the physiologic impact of the disease on the patient. It is more important to know how the disease is affecting the patient. The histologic finding of granulomas is pathognomonic for Crohn disease.
DISEASE PATTERNS: Crohn disease can be intra-abdominal, perianal, or both. Intra-abdominal Crohn disease usually results in one of three predominant disease patterns: stricture, perforation, or inflammation. Perianal disease results in anal strictures, fistulas-in-ano, and abscesses.
MEDICAL THERAPY: Pharmacologic therapy can be generally categorized as maintenance therapy (to maintain disease remission) and therapy for active disease (for acute flare-ups).
STRICTUROPLASTY: A surgical option that may be effective for patients with intestinal strictures from Crohn disease. The strictured segment of bowel is divided longitudinally then reapproximated transversely, thus increasing the diameter of that segment without resection. This approach may help preserve bowel length and function for patients with involvement of multiple sites by fibrotic strictures.
Most patients with Crohn disease have distinct patterns of disease distribution: terminal ileum and right colon (35%-50%), ileum (30%-35%), colon (25%-35%), or stomach and/or duodenum (0.5%-4%). Anorectal involvement is frequently found in patients with small bowel Crohn disease and may be the initial manifestation in 10% of patients. Therefore, Crohn disease should be considered whenever recurrent or complex perianal abscesses and fistulas are encountered. The other symptoms related to Crohn disease are often nonspecific, including chronic abdominal pain, postprandial abdominal cramps, weight loss, or fever related to fistulizing disease. It is not uncommon for patients with Crohn disease to have symptoms for months to years before the diagnosis is established. The goals of management are to relieve symptoms and optimize the patient’s quality of life. Medical and surgical options should be viewed as complementary therapeutic options rather than competing modalities. Thus, when medical therapy becomes ineffective or significantly compromises the patient’s quality of life, surgical interventions should be implemented. Similarly, the role of surgery in Crohn disease is palliative and not curative; therefore, surgical goals should be directed toward symptom relief without exposing patients to excessive short- and long-term morbidity. Whenever an operative procedure is to be implemented, it is vital for the surgeon to coordinate with the gastroenterologist in formulating plans so that the patient will have the best possible outcome.
The etiology of Crohn disease remains unknown, but it is in part caused by stimulation of an intestinal immune cascade in genetically susceptible individuals. Severity of disease dictates medical therapy, and many gastroenterologists use a sequential approach, using more aggressive medications for more aggressive disease (“bottom-up approach”). Categories of disease severity include mild, moderate, severe, and fulminant (Table 50–1). Medical therapy can be broadly categorized as nutritional, antimicrobial, anti-inflammatory, immunomodulatory, and anti-TNF (tumor necrosis factor) (Table 50–2). Nutritional therapies include bowel rest with total parenteral nutrition (TPN), elemental feeding, or omega-3 fatty acid supplementation. Nutritional therapies produce improvement and cause remission in patients with active disease; however, because of the impact of nutritional therapy on a patient’s lifestyle, nutritional therapy has been limited to the short-term treatment of active disease.
Table 50–1 • DISEASE SEVERITY OF CROHN DISEASE
Table 50–2 • THERAPY FOR CROHN DISEASE
First-line therapy for mild to moderate disease is either antimicrobial or anti-inflammatory. Antimicrobial therapy with metronidazole or ciprofloxacin is effective in the resolution of active intestinal and perianal disease, and long-term metronidazole maintenance therapy is effective in preventing disease recurrence. The mechanisms of antimicrobial therapy are largely unknown and may be in part based on its immunosuppressive effects. Long-term metronidazole therapy is poorly tolerated because of multiple side effects, including nausea, metallic taste, disulfiram-like reactions, and peripheral neuropathy. Aminosalicylates (5-ASA) are effective in maintenance therapy and in the treatment of mild active disease. Limitations of 5-ASA derivatives include GI tract and systemic side effects, and hypersensitivity reactions.
Moderate to severe disease refractory to antimicrobials and anti-inflammatory agents is treated with corticosteroids. Corticosteroids are nonspecific anti-inflammatory agents effective in treating small bowel and ileocolic disease. Although beneficial for disease flare-ups, corticosteroids are not efficacious in maintenance therapy. Also, they are associated with many major side effects, including hyperglycemia, fluid retention, fat redistribution, acne, mood changes, and growth retardation in children. Budesonide is a newer agent that is more rapidly metabolized than prednisone and may lead to fewer side effects. However, it is most helpful in patients with mild to moderate disease.
In patients with moderate to severe disease who are in remission after a course of corticosteroids, immunomodulators are effective in maintaining remission. Several immunomodulators have been used in the treatment of Crohn disease. Azathioprine (AZT) and 6-mercaptopurine (6-MP) are most commonly used. The potential toxic effects of AZT and 6-MP include bone marrow suppression, nausea, fever, rash, hepatitis, and pancreatitis. Methotrexate is also effective in the treatment of active disease but associated with many side effects, including nausea, headache, stomatitis, bone marrow suppression, hepatitis, and pneumonitis. It is thus reserved for patients unable to take AZT or 6-MP.
Cyclosporin A (CSA) produces significant improvement in severe disease associated with fistulas; however, controlled trials in patients with moderate disease have not demonstrated significant benefits. CSA use is associated with severe side effects, including hypertension, hyperesthesias, tremors, and nephrotoxicity. Thus, it has been largely replaced by infliximab, the chimeric monoclonal antibody directed toward the TNF receptor. Infliximab is highly effective in the treatment of patients who are refractory to all other medical therapy. It can potentially delay the need for operative intervention in patients with severe disease. It is also an effective first-line therapy in patients with fistulizing perianal disease. Unfortunately, major drawbacks are associated with anti-TNF therapy, including opportunistic infections and B-cell lymphoma development.
Recently, there has been some debate within the gastroenterological circle regarding the optimal strategy in the medical management of Crohn disease. Some practitioners believe that the initial medical approach to patients with severe disease should involve earlier treatment with stronger medications such as the biologics and early surgery; this approach is described as the “top-down” approach. The “top-down” theory is based on the premise that the combination of biologic agents and early surgery may be more effective before the disease becomes refractory to multiple medical therapies.
There are two major roles of operative intervention in the management of Crohn disease. One is to relieve symptoms associated with Crohn disease refractory to medical therapy, namely pain, obstructive symptoms, and weight loss. Another is to improve the quality of life of patients who experience severe side effects from medical therapy (eg, growth retardation from corticosteroid therapy). Surgical options include bowel resection, stricturoplasty, and abscess drainage. Approximately 30% of patients may require another operation within 5 years after undergoing resection for Crohn disease. One of the potential long-term complications of repeated bowel resection is the development of short bowel syndrome, that is, malabsorption requiring permanent TPN therapy (approximately 1% of patients). In an effort to prevent this, stricturoplasty is performed whenever possible. Patients with multiple sites of disease involvement have a greater risk for disease recurrence. In addition, nonsteroidal anti-inflammatory drug use and tobacco smoking are linked to disease recurrences; therefore, patients should be counseled regarding these issues.
50.1 In the treatment of which of the following symptoms associated with Crohn disease may medical management be effective?
A. Partial bowel obstruction
B. Enterocolonic fistulas
C. Abdominal pain related to an inflammatory mass
D. Perianal disease
E. All of the above
50.2 A 22-year-old woman is newly diagnosed with Crohn disease of the terminal ileum. She complains of significant abdominal pain. Her temperature is 36.7°C (98°F), and HR 90 beats/min. Which of the following is the best management for this patient?
A. Exploratory celiotomy to assess for bowel perforation
B. Medical management and reassessment
C. Radionuclide-tagged leukocyte imaging study to assess location of disease
D. Intravenous morphine for pain control
E. Exploratory celiotomy and stricturoplasty
50.3 Four weeks following appendectomy for presumed acute appendicitis, a 23-year-old man returns to the emergency center with drainage of bile-stained fluid from his right lower quadrant surgical site. The patient is afebrile and has been tolerating a normal diet. Abdominal CT revealed postoperative inflammatory changes and no abscess. A review of the pathology report from his previous appendectomy specimen revealed involvement of the appendix with transmural inflammation and granulomatous changes. Which of the following is the most appropriate management at this time?
A. Exploratory laparotomy to identify and remove the segment of intestine responsible for the leakage of enteric contents
B. CT of the abdomen followed by CT-guided drainage
C. Cortical steroids
E. Exploratory celiotomy and cecectomy
50.1 E. Medical management may be effective for all these complications associated with Crohn disease. They can include obstruction, fistulas, and inflammation. Surgery is also indicated for all these complications if a patient does not respond to medications or if medications produce unacceptable side effects.
50.2 B. Medical management is the appropriate choice in a patient with uncomplicated and newly diagnosed Crohn disease. A CT scan of the abdomen should be performed to rule out the possibility of intra-abdominal abscess associated with Crohn disease and rule out alternative pathology such as appendicitis.
50.3 D. This patient’s clinical presentation is compatible with enterocutaneous fistula presumably related to his Crohn disease. Enterocutaneous fistula in the setting of Crohn disease does not always require surgical treatment. In this patient who appears to have a low-output fistula, absence of a septic picture, and no evidence of ongoing intra-abdominal septic focus, a trial of nonoperative management that includes the use of infliximab may be appropriate. Fistula closure rates reported with infliximab has ranged from 6% to 70%.
With the exception of the treatment of toxic colitis, emergency (unplanned) operative treatment for patients with Crohn disease is rare.
Fibrotic strictures cannot be resolved with medical management and generally require operative therapy to relieve the obstruction.
Crohn disease may involve both the small bowel and the colon; therefore, a complete evaluation should include colonoscopy and SBFT to visualize the location and severity of the small bowel disease.
Repeated resection of the GI tract can result in clinical short bowel syndrome requiring permanent TPN therapy in approximately 1% of patients with Crohn disease.
In general, the role of surgery in Crohn disease is to relieve symptoms refractory to medical therapy (pain, obstructive symptoms, weight loss) and to improve the quality of life of patients who experience severe medication side effects.
Whether the initial medical treatment strategy for patients with severe Crohn disease should be a “bottom-up” or “top-down” approach is currently controversial.
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