Management of Acute Toxic Colitis and Megacolon

Introduction

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.

Pathophysiology

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.