Chronic Megacolon 

Updated: Sep 25, 2019
Author: David Manuel, MD; Chief Editor: BS Anand, MD 

Overview

Background

Megacolon, as well as megarectum, is a descriptive term. It denotes dilatation of the colon that is not caused by a mechanical obstruction.[1, 2] Although the definition of megacolon has varied in the literature, most researchers use the measurement of greater than 12 cm for the cecum as the standard. Because the diameter of the large intestine varies, the following definitions would also be considered: greater than 6.5 cm in the rectosigmoid region and greater than 8 cm for the ascending colon.

Megacolon can be divided into the following three categories:

  • Acute megacolon (pseudo-obstruction)

  • Chronic megacolon, which includes congenital, acquired, and idiopathic causes

  • Toxic megacolon

This article is devoted to chronic (noncongenital) megacolon.

Pathophysiology

The pathophysiology of chronic megacolon is incompletely understood. It likely represents an amalgam of primary disorders involving muscular and nervous systems of the intestine. Much basic science work has been performed in this area.[3, 4]

For example, with respect to the large bowel reacting to its luminal contents, fatty acids appear to reduce the volume of the proximal large bowel. Opiate narcotics, on the other hand, reduce the propensity of the colon to contract.

Control of colonic contractility is through a complex interaction of intrinsic colonic nerves, splanchnic nervous control, and central nervous system input. The final common pathway of intrinsic nervous control of colonic motility is via the postganglionic nerves: stimulatory cholinergic nerves and inhibitory nitric oxide-releasing nerves. Evidence suggests that excessive production of nitric oxide may be the mechanism for toxic megacolon in ulcerative colitis; as yet, there is no evidence for a possible role of nitric oxide in chronic megacolon unrelated to inflammatory bowel disease.

Studies in mouse models and in children with chronic colonic pseudo-obstruction show abnormalities involving the number and function of the interstitial cells of Cajal (intestinal pacemaker cells). Inherited disorders likely involve abnormal maturation and function of these cells, whereas acquired disorders demonstrate decreased numbers of them.

Animal studies show that the splanchnic nerves can dramatically affect colonic motility, both to contract and relax the colon. Extrinsic adrenergic nerves seem mainly to act by reducing acetylcholine release from intrinsic postganglionic nerves, although a direct action on the smooth muscle cells cannot be excluded. At this time, the respective roles of the intrinsic and splanchnic nerves in inducing megacolon have yet to be clarified.

Wallukat et al reported their experience in distinguishing distinct patterns of autoantibodies against G-protein-coupled receptors in Chagas cardiomyopathy and megacolon.[5] The investigators measured beta1-autobodies, beta2-autoantibodies, and muscarinergic2 autoantibodies, generally considered to be involved in the pathogenesis of Chagas cardiomyopathy and megacolon, from asymptomatic Chagas patients and those with cardiomyopathy and/or megacolon.

Autoantibodies were found in almost all patients with Chagas cardiomyopathy and/or megacolon; beta1 autoantibodies and muscarinergic2 autoantibodies were predominant in those with Chagas cardiomyopathy, whereas beta2 autoantibodies and muscarinergic2 autoantibodies were predominant in those with Chagas megacolon.[5] Of the 34% of asymptomatic patients who demonstrated similar patterns of autoantibodies, 84% of these individuals also had levels of beta1 autoantibody that are typical for Chagas cardiomyopathy, which the authors stated mirrored the epidemiologic situation in Latin America: clinical manifestations develop in approximately 30% of Chagas patients and cardiomyopathy in about 90% of them.[5]

Wallukat et al concluded that measuring the levels of beta1-autobodies, beta2-autoantibodies, and muscarinergic2 autoantibodies may be useful for potentially identifying patients at high risk of developing life-threatening complications of Chagas disease, but they cautioned further studies are needed.[5]

In another study, Sanchez-Mejias et al examined the potential roles of the EDNRB and EDN3 genes in the pathogenesis of Hirschsprung disease in 196 Spanish patients.[6] The investigators found several novel mutations in both genes as well as a truncating mutation in alternative isoform of EDNRB. In addition, an overrepresentation of a specific EDN3 haplotype was present in affected patients compared with control subjects.[6]

Sanchez-Mejias indicated that their findings suggest "the isoform EDNRB Delta 3 might be playing an essential role in the formation of enteric nervous system" and "based on the haplotype distribution, EDN3 might be considered as a common susceptibility gene for sporadic Hirschsprung disease in a low-penetrance fashion."[6]

Some experts believe it is common practice to separate the disorders associated with chronic megacolon into the following: (1) colonic inertia (eg, generalized delayed transit), and (2) rectosphincteric dyssynergy (eg, functional outlet obstruction).

Etiology

Causes of acquired megacolon

Neurologic diseases include the following:

  • Chagas disease

  • Parkinson disease

  • Myotonic dystrophy

  • Diabetic neuropathy

  • Spinal cord injury

  • Paraneoplastic neuropathy

  • Amyloidosis

Systemic diseases include the following:

  • Scleroderma

  • Dermatomyositis/polymyositis

  • Systemic lupus erythematosus

  • Mixed connective tissue disease

Metabolic diseases include the following:

  • Hypothyroidism

  • Hypokalemia

  • Porphyria

  • Pheochromocytoma

Medication-induced conditions can cause acquired megacolon.

Idiopathic causes include the following:

  • Nonfamilial visceral neuropathy (sporadic hollow visceral neuropathy or chronic idiopathic intestinal pseudo-obstruction)

  • Results from damage to the myenteric plexus from drugs or viral infections

The most common nonmechanical cause of acquired megacolon is infection with T cruzi (Chagas disease).[2] This infection results in the destruction of the enteric nervous system.[7, 8, 9] Although this disease was originally confined to South America, recent estimates indicate that 350,000 people in the United States are seropositive, one third of whom are thought to have chronic Chagas disease.

Causes of congenital megacolon

Enteric neuropathies include the following:

  • Hirschsprung disease (congenital aganglionosis)[2, 10] : It is caused by a single gene mutation of the RET proto-oncogene on band 10q11.2. The defect occurs in 1 in 5000 live births. Some cases are familial, with an overall incidence of 3.6% among siblings of index cases.[11]

  • Waardenburg-Shah syndrome (piebaldism, neural deafness, megacolon)

  • Multiple endocrine neoplasia type 2A (MEN 2A) or 2B (MEN 2B)

Visceral myopathies include the following:

  • Mitochondrial neurogastrointestinal encephalopathy (MNGIE) - Only type III involves marked dilatation of the colon

  • Oculogastrointestinal neuropathy (OGIN)

  • Idiopathic

In the newborn period, an unrecognized imperforate anus may be the cause of megacolon.

Epidemiology

United States data

No large-scale studies have been conducted to determine prevalence/incidence of acquired megacolon.

International data

The most common cause of megacolon worldwide is infection with Trypanosoma cruzi (Chagas disease).

Race-, sex-, and age-related demographics

Race has not been documented to play a role in megacolon.

The frequency of acquired megacolon is equally distributed between the sexes. The congenital megacolon, Hirschsprung disease, predominantly occurs in males.

Although clinically chronic megacolon can occur in any age group, inherited types usually present in young patients, and acquired types usually present in older patients.

Prognosis

Prognosis is related to the severity of the megacolon and the severity of the patient's comorbid diseases.

Although some patients cannot be managed on any type of bowel program and quickly require surgery, other patients may be maintained on a strict bowel program. No detailed longitudinal studies, however, have been performed to assess strict prognostic associations or indicators.

Mortality/morbidity

No large-scale studies have been conducted to determine prevalence/incidence of acquired megacolon. However, once present, the approximate risk of a spontaneous perforation from nontoxic megacolon is 3%.

Complications

The most dangerous complication is perforation, which rarely occurs. Perforation is generally due to overdistention of the bowel or to stercoral ulcer. If the etiology is overdistention, perforation typically occurs in the cecum. Stercoral ulcers typically occur in the sigmoid/rectosigmoid region.

Patient Education

Education of the patient with regard to the strict bowel program is essential to management. Maintaining effective management requires extensive effort and discipline from both the health care provider and the patient. To this end, educating the patient about the entire process is crucial.

 

Presentation

History and Physical Examination

Historically, chronic megacolon has been categorized into two groups, according to when symptoms begin. The congenital group experiences onset of constipation before the age of 1 year. The acquired group develops symptoms after age 10 years until adulthood.

Physical examination generally reveals a distended abdomen, which may or may not be tense. Tympany is invariably present.

Digital rectal examination may demonstrate a hard mass of stool just above the anorectal ring. Digital rectal examination in a patient with Hirschsprung disease may bring about a large gush of retained fecal material.

Megarectum with a rectum distended with stool, if chronic, tends to cause the anus to gape open secondary to the dysfunction of the internal sphincter mechanism. These patients may present with factitious diarrhea secondary to overflow incontinence.

 

DDx

Diagnostic Considerations

Intestinal/colonic obstruction (eg, malignancy, imperforate anus, fecal impaction, rectal prolapse) should also be considered in the differential diagnosis of chronic megacolon.

Differential Diagnoses

 

Workup

Laboratory Studies

Laboratory studies are important to exclude other etiologies, including electrolyte abnormalities (eg, calcium, magnesium, phosphorus).

Thyroid function tests should also be performed.

Imaging Studies

Abdominal plain films are useful for initial screening and assessment of severity.

After plain films reveal the megacolon, water-soluble contrast enema may be helpful for a number of reasons, as follows[12] :

  • Accurately assesses the size of the colon

  • Helps to differentiate the presence of megacolon, megarectum, or both

  • Helps to define the anatomy

  • Can be used therapeutically to evacuate the colon

Distinguishing a colonic inertia etiology from that of a functional outlet obstruction is probably best accomplished by colonic marker transit studies. Numerous ways to perform this test are available. Note the following:

  • One method is to instruct the patient to consume 30 g of dietary fiber daily and to stop using laxatives, enemas, and all other nonessential medications for at least 2 days prior to (as well as during) the test.

  • The patient swallows the markers, and abdominal plain films are obtained on days 1, 3, and 5.

  • Patients with colonic inertia tend to have markers distributed throughout the large bowel from cecum to rectum, while patients with outlet obstruction exhibit markers proceeding normally through the colon but accumulating in the rectum.

Other Tests

Anorectal manometry may help to distinguish congenital from acquired megacolon. The presence of a rectoanal inhibitory response means that there are intact ganglia, and the patient does not have Hirschsprung disease. If the inhibitory response is absent, a rectal biopsy is still needed to confirm the diagnosis of Hirschsprung disease.

Pudendal nerve latency testing may elucidate problems related to peristaltic movement, anatomical and/or mechanical problems with evacuation, and nerve-associated problems with defecation.

Colonoscopy should be used to rule out an obstructive/mechanical cause of colonic dilatation.

Histologic Findings

Histology is helpful for determining the etiology of the condition. Although full-thickness biopsy is the criterion standard to establish a diagnosis of Hirschsprung disease, mucosal suction biopsy is adequate in most instances. The absence of ganglion cells is characteristic of Hirschsprung disease, and specific stains for acetylcholinesterase are used to highlight abnormal morphology. Other than Hirschsprung disease, however, the presence of ganglion cells does not specify one cause over another. For most cases, there is no indication for histology because Hirschsprung disease is not considered or excluded by normal manometric findings.

Ohkubo et al reported that histopathologic abnormalities may precede the clinical manifestations of idiopathic megacolon.[13] They compared histopathologic features of dilated and nondilated loops in 53 full-thickness samples from 31 patients with idiopathic megacolon with 16 samples from 8 controls and defined hypoganglionosis as fewer than 60 ganglion cells/cm. The investigators noted the presence of neuropathy in 61.3% of patients (n=19), myopathy in 35.5% (n=11), and mesenchymopathy in 32.2% (n=10), with some overlap of subtypes. In most cases, there were similar histopathologic abnormalities between the dilated and nondilated loop samples.[13]

 

Treatment

Medical Care

Managing patients with chronic megacolon requires a multidisciplinary approach, including the primary care provider, a gastroenterologist, a nutritionist/dietitian, and possibly a surgeon.

In the absence of perforation, the initial management is conservative. Some experts believe a role exists for as-needed fecal disimpaction and for evacuation by enemas and suppositories.

Pay close attention to the exclusion of any underlying cause. If identified, correct electrolyte/metabolite abnormalities, and remove medications that may influence colonic motility (eg, narcotics, anticholinergic agents, calcium channel antagonists).

The use of biofeedback for a colonic inertia etiology for chronic megacolon is probably not effective, although successful treatment of functional outlet obstruction with biofeedback has been reported.

In patients requiring hospitalization, decompression using nasogastric tubes and rectal tubes may assist in treatment. When such tubes are used, anecdotal experience has demonstrated that frequent position changes for the patient may help to improve decompression.

If the dilatation persists or worsens, colonoscopic decompression can be attempted, with consideration of placement of a decompression tube, per rectum, in the right side of the colon. Unfortunately, following decompression, the dilatation usually recurs; therefore, decompression with colonoscopy must be carefully considered, as it is not without risk in an unprepared, dilated colon. Many gastroenterologists no longer consider placement of a drainage tube at the time of colonoscopy, as it nearly always becomes clogged with stool and rapidly ceases to function.

Maintenance of a strict bowel habit retraining program is important. Therefore, beyond the above options for the treatment of acute megacolon, the recommended regimen for chronic megacolon in a stable patient is as follows:

  • Empty the bowel (eg, osmotic laxatives, enemas, suppositories, cathartics, digital disimpaction).

  • Practice a bowel habit retraining program (eg, scheduled times for defecation, increased physical activity if possible).

  • Consume bulking agents/bowel agents.

  • Slowly alter/individualize the regimen.

Surgical Care

Surgical care is generally recommended if the dilatation is persisting or worsening after the above medical measures have been exhausted.

Megacolon operative options include total abdominal colectomy with ileorectal anastomosis, total proctocolectomy with ileostomy, and total proctocolectomy with ileoanal anastomosis, depending on the site of the colon affected.

Total abdominal colectomy with ileorectal anastomosis is the operation of choice of megacolon with normal-sized rectum.

Diet

Patients with acquired, nonacute megacolon should follow a high-fiber, high-fluid intake diet, which usually helps to decrease constipation. Some patients with severe constipation state that a high-fiber diet produces greater difficulty with bloating and constipation.

 

Medication

Medication Summary

A high water intake is an essential measure. A minimum of 6-8 8-oz glasses a day is recommended.

Bulking agents, through the increase of fiber, are also important. Many agents are on the market for this purpose and typically contain psyllium husk or cellulose; each patient may respond differently to each agent. No single agent is superior to another.

Laxatives may be considered and continued if found to be helpful. The best laxatives for this purpose are osmotic agents, such as magnesium salts, sorbitol, or lactulose (the latter two may increase flatulence). Patients need encouragement to take sufficient amounts to produce a result. Stimulant laxatives are best left as a last resort because they may possibly induce deterioration in the ability of the colon to evacuate. Typical stimulant laxatives are senna and bisacodyl-containing medications. Many patients take natural herbal laxatives; these typically contain cascara.

For more information, see the FDA MedWatch Product Safety Alert.

Laxatives

Class Summary

Increase peristalsis of the intestine, reducing the time toxic substances remain in the lower GI tract.

Psyllium (Metamucil, Fiberall)

Promotes bowel evacuation by forming viscous liquid and perhaps by inducing peristalsis.

Magnesium hydroxide (Philips' Milk of Magnesia)

Causes osmotic retention of fluid, which distends the colon and probably increases peristaltic activity; promotes emptying of bowel.

Sorbitol

Hyperosmotic laxative that has cathartic actions in the GI tract.

Lactulose (Cephulac, Cholac, Constilac)

Produces osmotic effect in colon that results in distention and promotes peristalsis.

Senna (Senexon, Ex-Lax, Senokot, Senna-Gen, Black-Draught, Agoral)

Anthraquinone stimulant hydrolyzed by colonic bacteria into active compound. More potent than cascara sagrada and produces considerably more abdominal pain. Usually produces action 8-12 h after administration.

Bisacodyl (Bisac-Evac, Bisco-Lax, Dulcolax, Dacodyl)

Stimulates peristalsis, possibly by stimulating colonic intramural plexus. Alters water and electrolyte secretion, producing net intestinal fluid accumulation and laxation.

Cascara sagrada

Irritates intestinal mucosa, increasing the rate of colonic motility and changes the fluid and electrolyte secretion.

Polyethylene glycol (PEG) solution

For the treatment of occasional constipation. In theory, there is less risk of dehydration or electrolyte imbalance with isotonic polyethylene glycol compared with hypertonic sugar solutions. The laxative effect is generated because polyethylene glycol is not absorbed and continues to hold water by osmotic action through the small bowel and the colon, resulting in mechanical cleansing. Supplied with measuring cap marked to contain 17 g of laxative powder when filled to the indicated line. May require 2-4 d (48-96 h) to produce bowel movement.