Toxic Megacolon 

Toxic megacolon is the clinical term for an acute toxic colitis with dilatation of the colon. The dilatation can be either total or segmental. A more contemporary term for toxic megacolon is simply toxic colitis, because patients may develop toxicity without megacolon. For the purposes of this article, the term toxic megacolon (toxic colitis), or TM (TC), is used, but either toxicity or megacolon can occur exclusively of each other.^[1]

The hallmarks of toxic megacolon (toxic colitis), a potentially lethal condition, are nonobstructive colonic dilatation larger than 6cm and signs of systemic toxicity. TM (TC) was recognized by Marshak and Lester in 1950.^[2] Jalan et al described the diagnostic criteria, which are as follows^[3] (see Presentation and Workup):

• Radiographic evidence of colonic dilatation - The classic finding is more than 6cm in the transverse colon
• Any 3 of the following - Fever (>101.5°F), tachycardia (>120 beats/min), leukocytosis (>10.5 x 10³/µL), or anemia
• Any 1 of the following - Dehydration, altered mental status, electrolyte abnormality, or hypotension

TM (TC) was first thought to be a complication only of ulcerative colitis. In fact, TM (TC) may complicate any number of colitides, including inflammatory, ischemic, infectious, radiation, and pseudomembranous.^{[4, 5]} Indeed, the incidence of TM (TC) is expected to increase due to the rising prevalence of pseudomembranous colitis (see the images below). (See Etiology.)

Colonic dilatation may be present in other conditions, such as Hirschsprung disease, idiopathic megacolon/chronic constipation, and intestinal pseudo-obstruction (Ogilvie syndrome). However, these patients do not develop signs of systemic toxicity and, therefore, do not fall into the category of having TM (TC) (see the image below). (See Etiology, Presentation, and Workup.)

Complications

The complication of TM (TC) one must constantly be alert for is perforation, even in the absence of colonic dilatation. Numerous studies have demonstrated that classic physical signs of peritonitis are absent in the majority of patients with free perforation, possibly because of the effects of steroids. (See Prognosis and Presentation.)

The classic etiologies of toxic megacolon (toxic colitis), or TM (TC), include the following inflammatory causes:

• Ulcerative colitis^[6]
• Crohn colitis
• Pseudomembranous colitis

The many causes of infectious colitis, including the following, may lead to TM (TC):

• Salmonella species
• Shigella species
• Campylobacter species
• Yersinia species
• Clostridium difficile^[7]
• Entamoeba histolytica
• Cytomegalovirus^[8]

TM (TC) may also be caused by the following:

• Radiation colitis
• Ischemic colitis
• Nonspecific colitis secondary to chemotherapy^[9]
• Rarely as a complication of collagenous colitis^[10]

Although the precise pathophysiology of TM (TC) is unproven, several factors may contribute to its development and precipitation. Signs and symptoms of acute colitis may be present for as long as 1 week before dilatation develops.

Often, triggering or predisposing factors can be identified. Although the risk of TM (TC) increases with the severity of colitis, rapid tapering or abrupt discontinuation of medications such as steroids, sulfasalazine, and 5-aminosalicylic acid may precipitate toxemia and dilatation.

Medications that negatively impact bowel motility also are implicated in the development of toxic megacolon. These include, but are not limited to, anticholinergics, antidepressants, loperamide, and opioids. Procedures such as barium enema or colonoscopy may cause distention, impair blood supply, or exacerbate a microperforation and cause subsequent toxemia.

In cases of uncomplicated colitis, the inflammatory response is confined to the mucosa. The microscopic hallmark of TM (TC) is inflammation extending beyond the mucosa into the smooth-muscle layers and serosa. Myenteric plexus involvement is not consistent and probably does not contribute to dilatation.

As inflammation progresses into the smooth-muscle layers of the colon, nitric oxide appears to be involved in the pathogenesis of TM (TC). Nitric oxide inhibits smooth-muscle tone and is generated by inflammatory cells such as neutrophils and macrophages in the inflamed portions of the colon.

Studies by Mourelle et al showed increased amounts of inducible nitric oxide synthetase in the muscularis propria of patients with toxic megacolon.^{[11, 12]} Inflammation and upregulated nitric oxide synthetase are thought to increase local nitric oxide, which inhibits colonic smooth muscle and causes dilatation.^{[11, 12, 13]}

The incidence of toxic megacolon (toxic colitis), or TM (TC), cited in the literature of depends on the etiology. The lifetime risk of TM (TC) in ulcerative colitis has been estimated to be 1-2.5%. In one series of 1236 patients admitted to the hospital over a 19-year period, toxic megacolon was present in 6% of patients, specifically 10% of ulcerative colitis admissions and 2.3% of Crohn disease admissions.^[14]

TM (TC) occurs in approximately 5% of severe attacks of ulcerative colitis. In pseudomembranous colitis, toxic megacolon is reported to occur in 0.4-3% of patients. This number is expected to increase in proportion to the increasing prevalence of pseudomembranous colitis, which is thought to be due to the increased use of broad-spectrum antibiotics.

Race-related demographics

In the United States, Jewish people are more prone to ulcerative colitis than are people who are not Jewish. In Israel, Ashkenazi Jewish people have a higher incidence of ulcerative colitis than do Sephardic Jewish people. No data exist regarding race and the incidence of TM (TC).

Sex-related demographics

Regarding ulcerative colitis, most studies demonstrate that both sexes are affected equally.

Age-related demographics

Young adults (aged 20-40 y), primarily, are affected by ulcerative colitis, but this disease may present at any age. With TM (TC), no predilection appears to exist for any particular age group. All ages may be affected. Many individuals present with TM (TC) during their first flare. The mean duration of disease has been reported to be 3-5 years.

A few studies have shown that the prognosis is poor with medical management of toxic megacolon (toxic colitis), or TM (TC). A study by Grant and Dozois followed the clinical course and ultimate outcome in 38 patients with TM (TC) who were successfully treated nonoperatively.^[15] Thirty-two patients had ulcerative colitis and 6 had Crohn disease, with complete follow-up ranging 3-22 years (average, 13 y). Eleven of 38 patients (29%) eventually suffered a second episode of fulminant acute colitis or recurrent TM (TC). Ultimately, a total of 18 patients (47%) underwent colon resection, which was performed on an emergency or urgent basis in 15 patients.^[15]

The survival prognosis of TM (TC) should be excellent in the absence of perforation. Indeed, the mortality rates for TM (TC) have improved substantially over the past few decades, from 20% in 1976 to 4-5% currently. The decrease is a result of earlier recognition, intensive medical management, early surgical consultation, and improved surgical technique and postoperative care. If perforation occurs, the mortality rate is approximately 20%.

In the case of ulcerative colitis, a proctocolectomy cures patients of the disease. In the case of Crohn disease, proctocolectomy does not necessarily cure the patient, because Crohn disease can occur in any portion of the gastrointestinal tract.

With the use of tumor necrosis factor (TNF)-alpha inhibitors, it is hoped that more cases can be managed medically in future. More studies are needed.

Educating the patient about toxic megacolon (toxic colitis), or TM (TC), is crucial. First, educate the patient about the causes of the disease. The most common cause of TM (TC) is inflammatory bowel disease. However, with the rising incidence of C difficile, pseudomembranous colitis must always be considered, even in patients with inflammatory bowel disease. Educate the patient about ulcerative colitis, Crohn disease, and indeterminate colitis.

The patient should be clearly informed that, if an operation is required for this acute problem, an ostomy likely will be the procedure needed, regardless of the cause.

Secondly, educate the patient about the operation. Patients require at least a temporary, and possibly a permanent, ostomy. Most patients require a thoughtful, compassionate discussion regarding this aspect of their treatment. The psychological aspects of dealing with an ostomy can be extremely difficult.

Finally, educate patients so that they understand that this disease is a process that may require several months to overcome if an operation is needed and that a 2- or 3-stage procedure is usually required.