Etiology

Several inflammatory and/or infectious conditions of the colon may predispose patients to toxic colitis/toxic megacolon (TC/TM). Inflammatory bowel disease remains the most common etiology (46% to 51.6% reported from various retrospective studies) for hospital admission of patients with TC/TM.[4][8]Clostridium difficile colitis is the second most common cause, accounting for an additional 31% of toxic megacolon cases.[4][6][8] Other infectious agents including Salmonella, Shigella, Campylobacter, Yersinia, Entamoeba histolytica, and Cryptosporidium have been associated with toxic megacolon.[9][10][11][12][13] Cytomegalovirus is often associated with toxic megacolon in patients with HIV or AIDS; however, patients with ulcerative colitis or Crohn disease receiving immunosuppressants are also susceptible to cytomegalovirus infection and subsequent toxic megacolon.[14][15][16]

Toxic megacolon has also been reported as a consequence of ischemic colitis, obstructive colon cancer, diverticulitis, volvulus, and other inflammatory diseases such as Behcet disease.[7][17] In patients with underlying colitis, toxic megacolon may be triggered by electrolyte abnormalities, including hypokalemia and hypomagnesemia; discontinuation of aminosalicylates or corticosteroids; the use of narcotics; or the use of anticholinergics or antidiarrheals, which slow colonic motility.[17] Toxic megacolon may also present as a complication of immunosuppressive therapy for several underlying etiologies.[18][19][20]

Pathophysiology

Although the exact mechanisms leading to toxic megacolon are unknown, the most widely accepted hypothesis is of decreased mucosal blood supply from colonic distention leading to disruption of mucosal defenses, and subsequent increased translocation of bacteria and toxins into systemic circulation.

Inflammatory changes that are limited to the mucosa and superficial submucosa in uncomplicated colitis penetrate into the muscularis propria in the course of toxic megacolon. The extent of colonic dilation seems to correlate with the depth of inflammation and ulceration.[7][21][22] Nitric oxide released by neutrophils paralyzes muscle cells, leading to further colonic dilation.[7] The effect of damage to the myenteric plexus remains a matter of controversy. It has been suggested that soluble inflammatory mediators may inhibit colonic muscle tone, as well as leading to fever, tachycardia, hypotension, and other signs of sepsis.[22][23] In Clostridium difficile-associated infection, toxins A and B cause proinflammatory cytokine release, with a cascade of effects including increased vascular permeability and host cell necrosis. Other bacterial virulence factors trigger downstream cell-mediated immune pathways.[23]

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