Toxic Megacolon

Updated: Nov 20, 2016
  • Author: Brian Lin; Chief Editor: Burt Cagir, MD, FACS  more...
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Overview

Background

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 6 cm 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 6 cm in the transverse colon
  • Any 3 of the following - Fever (>101.5°F), tachycardia (>120 beats/min), leukocytosis (>10.5 x 10 3/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.)

A 22-year-old man presented with abdominal pain, p A 22-year-old man presented with abdominal pain, passage of blood and mucus per rectum, abdominal distention, fever, and disorientation. Findings from sigmoidoscopy confirmed ulcerative colitis. Abdominal radiographs obtained 2 days apart show mucosal edema and worsening of the distention in the transverse colon. The patient's clinical condition deteriorated over the next 36 hours despite steroid and antibiotic therapy, and the patient had to undergo a total colectomy and ileostomy.
Gross pathology specimen from a case of pseudomemb Gross pathology specimen from a case of pseudomembranous colitis demonstrating characteristic yellowish plaques.
Computed tomography scan from a patient with pseud Computed tomography scan from a patient with pseudomembranous colitis demonstrating the classic accordion sign.

Colonic dilatation may be present in other conditions, such as Hirschsprung disease, [6] 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.)

A 72-year-old woman presented with vomiting and ab A 72-year-old woman presented with vomiting and abdominal distention. The supine (right) and erect (left) plain abdominal radiographs show gross dilatation of the colon with multiple air-fluid levels. On further questioning, the patient revealed that she was taking diuretics for hypertension. Blood biochemical tests revealed markedly lowered potassium levels. After potassium replacement therapy, the patient's pseudo-obstruction completely resolved.

Complications

The dreaded complication of TM (TC) 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.)

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Pathophysiology

Although the precise pathophysiology of toxic megacolon/colitis TM (TC) is unproven, several factors may contribute to its development and precipitation. 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. Whereas the typical ulcerative colitis inflammatory response is limited to the mucosa, toxic megacolon is characterized by severe inflammation extending into the smooth muscle layer, thus paralyzing the colonic smooth muscle and leading to dilatation. The extent of dilatation seems to be correlated with the depth of inflammation and ulceration. [7]

Studies by Mourelle et al showed significantly increased amounts of inducible nitric oxide synthetase in the muscularis propria of patients with toxic megacolon, particularly in the more dilated colonic segments. [8, 9]  Inflammation and upregulated nitric oxide synthetase are thought to increase local nitric oxide levels, which inhibits colonic smooth muscle and causes dilatation. [8, 9, 10]

As inflammation progresses into the smooth-muscle layers of the colon, nitric oxide and local inflammatory modulators appear to be involved in the pathogenesis of TM (TC).  In toxic megacolon, neutrophils also invade the muscle layer and directly damage muscle cells by the release of proteolytic enzymes, cytokines, and leukotriene B4. [7]  Systemic uptake of cytokines and other inflammatory mediators leads to fever, tachcardia, hypotension, and other signs of systemic toxicity. Nitric oxide is generated by inflammatory cells such as neutrophils and macrophages in the inflamed portions of the colon, inhibiting smooth-muscle tone and leading to colonic dilatation.

Myenteric plexus involvement is not consistent and likely does not contribute to colonic dilatation. Hypokalemia and other electrolyte disturbances probably do not contribute to dilatation in most patients. [7]

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Etiology

Inflammatory causes of toxic megacolon (toxic colitis), or TM (TC), include the following:

  • Ulcerative colitis [11]
  • Crohn colitis
  • Pseudomembranous colitis

Infectious causes of TM (TC) include:

  • Salmonella species
  • Shigella species
  • Campylobacter species
  • Yersinia species
  • Clostridium difficile [12, 13, 14]
  • Entamoeba histolytica
  • Cryptosporidium [15]
  • Cytomegalovirus [16]
  • Rotavirus [17]
  • Invasive aspergillosis [18]

In a murine model, spread of type 1 herpes simplex virus infection from the sensory nervous system to the autonomic ganglia of the colonic enteric nervous system has been associated with toxic megacolon and lethality, primarily via viral gene transcription, pathologic inflammatory responses, and neutrophil-mediated destruction of the enteric neurons. [19] The use of laxatives prevented lethality in the mice following genital HSV-1 infection.

TM (TC) may also be caused by:

  • Radiation colitis
  • Ischemic colitis
  • Nonspecific colitis secondary to chemotherapy [20, 21]
  • Rarely as a complication of collagenous colitis [22, 23]
  • Behçet syndrome - Patients with this syndrome can rarely develop TM (TC) as a complication [24, 25]
  • Kaposi's sarcoma [7]
  • Methotrexate therapy induced pseudomembranous colitis

Often, triggering or predisposing factors can be identified. Signs and symptoms of acute colitis may be present for as long as 1 week before dilatation develops. 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.

A retrospective study by Tschudin-Sutter et al indicated that the incidence of TM (TC) is higher in pediatric patients with community–associated, rather than healthcare facility–associated, C difficile infection. The study involved 202 pediatric patients with C difficile infection, including 38 with community–associated infection, 144 with healthcare facility–associated infection, and 20 with an indeterminate source of infection. Compared with the healthcare facility–associated group, children with a community–associated infection had a higher rate not only of TM (TC) but also of toxic shock and recurrence. (They were less likely, however, to have comorbidities than were children with healthcare facility–associated infection.) [26]

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Epidemiology

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. [27]

TM (TC) has been reported to occur in approximately 5% of severe attacks of ulcerative colitis. In pseudomembranous colitis, toxic megacolon  occurs 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-, sex-, and age-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).

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

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.

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Prognosis

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. [28] 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. [28]

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.

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Patient Education

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.

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