Toxic colitis and megacolon fall within the spectrum of inflammatory bowel disease (IBD). Toxic colitis, also referred to as acute, fulminant, or severe colitis, is a potentially life-threatening form of IBD. Patients display gastrointestinal symptoms in conjunction with signs of systemic toxicity. In its rare, extreme manifestation—toxic megacolon—toxic colitis is accompanied by radiographic evidence of nonobstructive colonic dilatation in excess of 6 cm. Systemic toxicity distinguishes toxic megacolon from nontoxic causes of colonic distention such as acute colonic pseudo-obstruction (Ogilvie syndrome) or Hirschsprung disease. Even in the current era of enhanced medical management and surgical technique, toxic colitis and megacolon are associated with considerable morbidity and mortality. Successful treatment of these patients requires the close collaboration of surgeons and gastroenterologists. In this chapter we review the latest thoughts on management of toxic colitis and megacolon.
Epidemiology and Etiology
The incidence of toxic colitis and megacolon has decreased as the options for medical treatment of IBD have expanded. Toxic colitis affects approximately 10% of patients with ulcerative colitis (UC) and 6% of those with Crohn colitis. The incidence of toxic megacolon is 1.6% to 13% in patients with UC and 2.3% for patients with Crohn disease. Both toxic colitis and megacolon are more likely to afflict patients early in their disease course, sometimes as the initial presentation of the disease. In the absence of a prior diagnosis of IBD, toxic colitis must be differentiated from other conditions such as an infectious or ischemic colitis. Patients with well-established IBD may also experience toxic colitis or megacolon at any time during their disease. Toxic colitis and megacolon show no affinity for a particular age or gender.
Recently, infection has surpassed IBD as the most frequent cause of toxic megacolon ( Table 37-1 ). Although the most common infectious source— Clostridium difficile –related pseudomembranous colitis—is associated with a 0.4% to 4.3% incidence of toxic megacolon, its toxicity is due to the toxins produced by the bacteria themselves. This mechanism is different from the toxicity of the inflammatory process in the bowel wall that is the feature of toxic UC or Crohn disease. Among other infectious causes of toxic megacolon are bacterial infections such as Salmonella, Escherichia coli , and Campylobacter; viral infections such as cytomegalovirus (CMV); and parasitic infections such as cryptosporidium. Behçet disease, ischemic colitis, and colonic lymphoma have also been associated with toxic megacolon. A review of patients who underwent surgery for toxic megacolon from 1985 to 2004 determined that the underlying causes consisted of UC in 46%, infectious colitis in 34%, ischemic colitis in 11%, chemotherapy in 3%, and Crohn disease in 2%. However, in the second half of the study period, infections eclipsed UC as the origin of toxic megacolon (from 14% vs. 30% to 39% vs. 14%, respectively). The incidence of C. difficile infections, in particular, is rising as a result of increased antibiotic use, an aging population, and more virulent strains. Patients with human immunodeficiency virus and acquired immunodeficiency syndrome are particularly susceptible to toxic megacolon from C. difficile, as well as CMV infections.
|Inflammatory||Behçet disease |
Escherichia coli 0157 (hemolytic-uremic syndrome)
|Ischemic colitis |
|Cancer-related causes||Chemotherapy |
Obstructive colorectal cancer
Stem cell transplantation
The pathophysiology of toxic colitis and megacolon has not yet been well defined. A link between colonic inflammation and diminished smooth muscle contractility has been well established, and toxic megacolon is more common in patients with pancolitis. Whereas uncomplicated UC is characterized by inflammation confined to the mucosa and submucosa, UC-associated toxic megacolon is defined by inflammation that has spread into the muscularis propria. Moreover, the severity of the colonic distension is directly related to the extent of the transmural inflammatory process. Apparently the myenteric plexus has no role in the disease process, but enzyme-inducible nitric oxide synthase, which produces the nonadrenergic, noncholinergic neurotransmitter nitric oxide, has been shown to be more active in patients with UC and, to a greater degree, with UC-associated toxic megacolon. Synthesized by macrophages and smooth muscle cells, nitric oxide promotes smooth muscle relaxation in the colon, an effect that is magnified by its overproduction in the inflamed bowel. By inhibiting enzyme-inducible nitric oxide synthase in animal and in vitro models, improvements were achieved in colonic distention and pressure. In addition to nitric oxide, groups have studied hydrogen peroxide (H 2 O 2 ) and interleukin (IL)-1β as potential contributors to the genesis of toxic megacolon by promoting smooth muscle relaxation. Colonic motility may also be adversely impacted by inflammation-induced changes in neuromuscular signaling.
Patients with the acute onset of severe bloody diarrhea, abdominal pain, malaise, and anorexia should be suspected of having toxic colitis, especially if IBD has previously been diagnosed. Toxic megacolon should be considered in a patient with symptoms of severe colitis—particularly bloody diarrhea—in addition to increasing abdominal distention. The symptoms of severe colitis that are refractory to treatment are usually present for 1 week before toxic megacolon develops.
In a patient presumed to have toxic colitis and/or megacolon, a thorough history should be obtained ( Figs. 37-1 and 37-2 ). Questions should focus on the cause of the condition, differentiating between infectious and inflammatory conditions, especially with de novo presentations. Inquiries are directed to a previous diagnosis of IBD and a history of exacerbations, and extraintestinal manifestations such as arthritis, iritis, or liver disease also should be sought. If IBD has not been previously diagnosed, then pre-existing symptoms that could signal an undiagnosed IBD are important: abdominal pain, diarrhea, bloody stools, vomiting, or weight loss. The possibility of exposure to a gastrointestinal pathogen via close contacts, the environment, or travel should be explored. Current or recent use of medications—particularly antibiotics, anticholinergic agents, narcotics, or antidiarrheal agents—that could incite the episode of toxic colitis and/or megacolon is documented. Other factors include a recent barium enema or colonoscopy, hypokalemia, antiinflammatory medications, antidepressants, CMV infection, or an overly rapid or abrupt cessation of steroids, sulfasalazine, or 5-ASA medications. Also, ongoing use of certain medications such as opiates and steroids could blunt the symptoms and signs of systemic toxicity at the initial presentation. It is important to note if the patient is immunocompromised as a result of human immunodeficiency virus, malignancy, or chemotherapy.
The severity of UC is gauged by criteria proposed by Truelove and Witts ( Table 37-2 ). A patient who satisfies a greater number of these criteria at the time of admission has a higher risk of urgent colectomy—48% for three or more criteria. The clinical criteria for toxic megacolon, as submitted by Jalan and colleagues, incorporate physical signs of toxicity with evidence of colonic dilatation ( Table 37-3 ). Although a colonic diameter of 6 cm confirms a diagnosis of toxic megacolon, a lesser degree of dilatation does not arbitrarily exclude this diagnosis. Another sign of toxic dilation is a gas pattern that shows distended transverse colon for the entire length of the segment. Overall, though, it is the physician’s clinical impression that best distinguishes the patient with toxic colitis or megacolon.
|Criterion||Mild Disease||Severe Disease||Fulminant Disease|
|Stools per day||<4||>6||>10|
|Blood in stool||Infrequent||Frequent||Continuous|
|Temperature, ° C||Normal||>37.5||>37.5|
|Heart rate, beats per minute||Normal||>90||>90|
|Hemoglobin||Normal||<75% of baseline||Transfusion required|
|Erythrocyte sedimentation rate, mm/hr||<30||>30||>30|
|Abdominal radiograph||—||Edema||Dilatation <6 cm|
|Clinical signs||—||Abdominal tenderness||Abdominal tenderness and distention|