Colitides Other Than Ulcerative Colitis And Crohn's Disease
Christopher J. Bruce, M.D.
Clinical Assistant Professor of Surgery
New York Medical College
White Plains, New York
Introduction
Patients with acute colitis present with a wide spectrum of illness ranging from a very mild self-limited episode to an acute fulminant toxic colitis requiring aggressive resuscitation and operative management. It is important to identify the etiology of the colitis in order to allow for prompt and accurate treatment. Establishing the diagnosis is dependent upon obtaining a careful history and a complete physical examination; often endoscopy and directed laboratory studies are required to confirm the diagnosis.
This chapter focuses on the distinguishing features and treatment of a variety of colitides excluding ulcerative colitis and Crohn's disease.
Evaluation
History
A complete history is essential since it can often lead to the specific diagnosis or at least focus the work-up. The signs and symptoms of patients with acute colitis are variable and may include abdominal cramping, diarrhea with or without blood, mucorrhea, and dehydration. The clinical course usually varies from mild to moderate but on occasion, patients may present with severe colitis with perforation requiring urgent operative intervention.
Inquiring about the timing and onset of symptoms as it relates to possible recent foreign travel history, antibiotic use, addition of new pets to the household, and similar symptoms in others in close contact may all provide clues to the etiologic factor. The character of the diarrhea is also important as voluminous, watery diarrhea generally implies an infectious agent, whereas significant hematochezia is often associated with more severe, inflammatory reactions in the colon. Obtaining the patient's past medical history is also paramount. Coexistent cardiac or peripheral vascular disease is often related to ischemic colitis and patients that have undergone radiation therapy to the abdomen and pelvis may develop colitis several years later. Current medications such as new drugs, antibiotics, cardiac medications, and immunosuppressive agents may all provide insight into the etiology of the colitis. A family history of gastrointestinal disorders should be obtained as well as the patient's social history as it relates to their sexual practices, since both homosexual males and heterosexual females are at risk for sexually transmitted diseases as a result of anoreceptive intercourse.
Physical Examination
A complete physical examination is essential with particular focus on the oral cavity, abdomen, anus and rectum. Vitals signs including the patient's temperature, pulse and blood pressure gives insight into the severity of the illness. Careful palpation of the abdomen may elicit peritoneal signs that signify severe colitis with transmural involvement and possible perforation. Auscultation of the abdomen may reveal hyperactive bowel sounds with active colitis, but often they are normal or even hypoactive. Identification of perianal or genital lesions such as condyloma or herpetic lesions gives a clue to an increased risk for sexually transmitted diseases. Rectal examination, consisting of a digital exam and proctoscopic evaluation is mandatory. Examination of the stool will reveal its consistency and the presence of occult or gross blood. Inspection of the mucosa may identify edema, ulcerations, and inflammation as well as specific findings that are pathognomonic for certain disease processes. The pattern and level of the mucosal involvement are also important and should be noted.
Investigations
Further investigations are necessary to establish or confirm the diagnosis and in some cases, to evaluate the severity of the disease. Adjunctive testing may involve endoscopy, radiographic imaging, stool testing, bloodwork, and histolopathologic evaluation of tissue biopsies. The type and timing of any testing is dictated by the severity of the illness and the patient's clinical status.
Endoscopy
Evaluation of the colonic mucosa utilizing flexible sigmoidoscopy and/or colonoscopy can be very useful in establishing the diagnosis and determining the extent of the disease. Endoscopic evaluation is contraindicated in acutely ill patients with severe colitis for fear of perforation. Flexible sigmoidoscopy can be performed in the office setting with or without bowel preparation. Colonoscopy may add additional information especially in situations where the inflammatory changes are proximal to the sigmoid colon plus it also allows for inspection of the terminal ileum. Biopsies of inflamed and normal mucosa should be obtained for histopathologic evaluation.
Radiography
Plain abdominal radiographs, including upright and supine views, are useful when trying to rule out the presence of free air. On occasion the xrays may also reveal thickening of the colonic wall and thumbprinting suggesting ischemia. Contrast radiography often does not provide any useful information in the acute setting but if performed, consideration should be given to using water-soluble contrast material to prevent barium peritonitis if perforation occurs.
Laboratory Studies
Stool Analysis and Cultures
The presence of a large number of leukocytes in the stool indicates an inflammatory process characteristic of certain invasive organisms such as Shigella, Campylobacter, and certain strains of E. coli (EIEC, EHEC). The absence of fecal leukocytes is typical of colitides caused by enterotoxins secreted by viruses (V. cholerae, rotavirus, Giardia lamblia), parasites (Entamoeba histolytica), certain strains of E. coli (ETEC, APEC, EAEC), and food poisoning bacteria (Staph aureus, Clostridium perfringens, Bacillus cereus). Several organisms produce variable findings on microscopic stool examination including Salmonella, Yersinia, and Clostridium difficile. Although fecal microscopic examination is neither infallible nor even helpful in all cases, it is inexpensive and yields immediate information that can often guide therapy. In addition, a gram stain should be performed to identify Neisseria gonorrhea, Campylobacter, and ova and parasites (O&P). At least 3 specimens may be required for O&P analysis because of the intermittent shedding of ova cysts.
Because of the relatively low yield of stool cultures, testing should be performed when there are signs of systemic illness, fever, bloody diarrhea, dehydration or a prolonged course of the diarrhea. Routine blood agar cultures are sufficient for the identification of most causes of acute colitis. If Neisseria gonorrhea is suspected, immediate plating on Thayer-Martin medium should be performed. Cultures to isolate Chlamydial infections require the use of a plastic or metal cotton swab because wood interferes with the assay. Viral cultures should be considered in immunosuppressed patients and may require several weeks to complete. With all cultures, multiple specimens may be necessary to increase the yield of a positive result.
Serology
In particular cases serologic testing can be useful in identifying serum antibodies to organisms such as syphilis, Chlamydia, CMV and others. However, these tests are expensive and although rising serum titers may imply a systemic infection, they are not specific for gastrointestinal involvement. Genetic probes, polymerase chain reaction technology, and DNA hybridization techniques are becoming available to identify several pathogens in the stool but their expense prohibits their widespread use at this time.
Histopathology
Histopathologic examination of colonic mucosa obtained by endoscopic biopsy can be helpful if obtained within 4 days of the onset of symptoms. Specimens should be examined under routine H&E staining and special stains where appropriate. In the acute setting, distinguishing between infectious colitis and idiopathic ulcerative colitis may be difficult since both will show edema, neutrophils in the lamina propria, and superficial cryptitis with preservation of the normal crypt pattern.
Specific Colitides
Infectious Etiologies
1. Escherichia coli
These organisms are major components of the normal intestinal microflora in humans and although most strains are relatively harmless in the bowel, others possess virulence factors that are related to diarrheal disease. At least 5 types of E. coli intestinal pathogens have been recognized and their virulence is determined by either toxin production (enterohemorrhagic E. coli = EHEC, enterotoxigenic E. coli = ETEC) or adherence to the colonocytes with or without invasion (enteropathogenic E. coli = EPEC, enteroinvasive E. coli = EIEC, enteradherent E. coli = EAEC).
Hemorrhagic E.coli (EHEC) serotype 0157:H7 produces bloody diarrhea and has been associated with outbreaks following the ingestion of contaminated hamburger meat. Most cases are self-limited but in severe cases, it is associated with the hemolytic-uremic syndrome and thrombotic thrombocytopenia.
Findings: Endoscopy reveals focal erythema, edema, ulcerations, and occasional pseudomembranes. Fecal leukocytes are usually present and several laboratory methods are used to diagnose EHEC including a toxin assay and plating the specimen on sorbitol-containing medium. The timing of stool collection is important as virtually all stool specimens are positive for EHEC within two days of symptoms but only one third are positive after seven days.
Treatment: Because most cases are self-limited, supportive treatment with hydration is sufficient and antibiotics should be use selectively. Although Trimethoprim-sulfamethoxazole (TMP-SMX) is effective, there are reports suggesting antibiotics may have a detrimental effect on the development of the hemolytic-uremic syndrome. Severe cases associated with acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia may require corticosteroids and hemodialysis.
2. Shigella
Shigellosis is a major diarrheal disease throughout the world. Shigellae are lactose nonfermenting, non-motile gram-negative rods that are comprised of four subgroups that are responsible for bacillary dysentery, the most common type in the United States being S. sonnei. The organism invades into the colonic epithelium causing loose bowel movements with an inflammatory exudate composed of polymorphonuclear leukocytes and blood. Humans are the only natural host and the organism primarily affects only the colon. The mode of transmission is fecal-oral and the organisms invade colonocytes but rarely invade the blood stream. There is often a biphasic illness with initial symptoms of fever, abdominal pain, and nonbloody watery diarrhea followed 3 to 5 days later by tenesmus and small volume bloody stools. There is an extensive list of extraintestinal manifestations.
Findings: Endoscopy reveals friable, hyperemic mucosa that involves that rectum and sigmoid colon in a confluent pattern very similar to ulcerative colitis. Approximately 50% of patients have involvement to the splenic flexure but it is rare to have ulcerations in the terminal ileum. Histopathologically there is an intense local inflammatory response in the lamina propria and crypt abscesses are a prominent feature. Distinguishing from idiopathic ulcerative colitis may be difficult but 2 major differences are a positive culture for Shigella and dramatic improvement on appropriate antimicrobial agents.
Treatment: Rehydration, general supportive measures, and the avoidance of narcotics and anti-diarrheal agents are important components in the treatment of shigellosis. Antibiotics are indicated for most patients and ampicillin, but not amoxicillin, has been the treatment of choice. Antibiotics are usually given for 5 days but plasmid-mediated resistant strains of Shigella are now common and TMP-SMX or quinolone antibiotics may be necessary. One must also consider Clostridium difficile-associated diarrhea if symptoms recur after treatment since chronic carriers of Shigella are uncommon.
3. Salmonella
Salmonella organisms are motile, gram-negative bacilli that are found in a wide range of hosts and it is one of the great food-borne infections. The major route of passage is by 5 F's - flies, food, fingers, feces, and fomites. The disease can occur in large outbreaks and the most common serotype in the United States is S. typhimurium. Salmonella infections have been increasing in the United States and infants and the elderly are most susceptible. Over 50% of outbreaks are related to contaminated poultry, meats, eggs and dairy products. Salmonella are unique in attacking the ileum, and, to a lesser extent, the colon. In the colonic form, bloody diarrhea is usually present and toxic megacolon and perforation may result. Depending on the strain, five clinical syndromes are seen with Salmonella infections: gastroenteritis (75%), bacteremia with or without GI involvement (5-10%), typhoidal or enteric fever (5-10%), localized infections such as bones, joints, and meninges (5%), and a carrier state in asymptomatic people, where the organism is usually harbored in the gallbladder (<1%). Predisposing conditions include sickle cell anemia, neoplastic disease (leukemia, lymphoma, and metastatic cancer), AIDS, prior gastric resection, and the use of corticosteroids, chemotherapy, and radiation.
Findings: In patients with colonic involvement, proctoscopic findings include hyperemia, granularity, friability, and ulcerations. Histopathology reveals mucosal ulcerations, hemorrhage, and crypt abscesses.
Treatment: Antibiotics have failed to alter the rate of clinical recovery and may actually increase the incidence and duration of intestinal carriage of these organisms. Therefore, general supportive measures are usually all that is necessary. Antibiotics are indicated in certain clinical situations such as lymphoproliferative disorders, immunosuppression, prosthetic heart valves, vascular grafts, prosthetic orthopedic devices, extreme ages of life, and severe sepsis. Resistance to ampicillin and TMP-SMX is now common and treatment with quinolone antibiotics or chloramphenicol are usually first-line.
4. Campylobacter
The organism is a motile gram-negative rod or spiral and the most common Campylobacter species isolated in humans is C. jejuni. It accounts for approximately 10% of all cases of infectious diarrhea in the United States. Most human infections are related to the ingestion of improperly cooked or contaminated foods and in particular, chicken seems to be the major source. The most common symptoms include fever and diarrhea (90%), abdominal pain (70%), and bloody stools (50%). Prodromal symptoms such as coryza, headache, and generalized malaise are frequent.
Findings: Proctoscopy reveals diffuse inflammation, bloody exudate, edema, and ulcerations while colonoscopy typically reveals focal rather than diffuse colonic involvement. Stool examination reveals fecal leukocytes in addition to occult blood. The most reliable way to diagnose Campylobacter is by stool culture on selective isolation media; darkfield microscopy of fresh diarrhea stool often shows the organism as a curved, highly motile rod, with darting, corkscrew movements. Histopathology is nonspecific and reveals neutrophils in the lamina propria, ulceration, and crypt abscesses.
Treatment: Mild cases do not benefit from antibiotic therapy but treatment should be given to those with dysentery and to those with high fever suggesting bacteremia. Due to emerging resistant strains against erythromycin, quinolone antibiotics are usually first-line therapy.
5. Yersinia
Yersinia enterocolitica causes a spectrum of clinical illness ranging from simple gastroenteritis to invasive ileitis and colitis. It is a nonlactose-fermenting, gram-negative coccobacillus with the ability to invade epithelial cells, particularly in the terminal ileum, as well as produce an enterotoxin. Enterocolitis is the most common clinical condition usually affecting children less than 5 years old. It is believed that animals, either as pets or food sources, are involved in the transmission of this disease. In children older than 5 years of age, mesenteric adenitis may occur and the presentation mimics acute appendicitis. The diagnosis should be suspected in atypical cases of appendicitis or when a normal appendix is found at surgery.
Findings: Findings on endoscopy may be normal but when inflammation and ulcerations are present, it closely resembles Crohn's disease. Microscopic granulomas may also be present adding confusion to the diagnosis. Stool analysis may reveal leukocytes but stool culture is usually diagnostic. Serology tests are available for equivocal cases.
Treatment: The disease is usually self-limited and therefore does not require antibiotic therapy. In severe cases or in immunocompromised patients most antibiotics (quinolones, chloramphenicol, gentamicin, TMP-SMX, tetracycline) are effective although penicillins and cephalosporins are not.
6. Clostridium
C. difficile is a gram-positive, spore-forming, anaerobic bacillus that produces 2 enterotoxins that account for its pathogenicity. The clinical manifestation of C. difficile infection is pseudomembranous colitis (PMC). It is a nosocomial infection that is associated with virtually all antibiotics. Diarrhea and crampy abdominal pain usually occur from 1 to 3 weeks after antibiotic therapy. Tenesmus, nausea, vomiting, fevers, and dehydration may occur, and in severe cases toxic megacolon with perforation and shock can develop. PMC should be considered in all patients who develop diarrhea following a course of antibiotics. C. septicum found on blood culture is an indication for a colonic evaluation to rule out a carcinoma.
Findings: Proctosigmoidoscopy typically reveals the characteristic pseudomembranes but colonoscopy may be necessary if only right-sided disease is present. Fecal leukocytes are usually present but the organism is difficult to isolate on routine culture. Assay for the cytotoxin is the preferred method of diagnosis since it is noninvasive, readily available, and positive in over 90% of cases. Plain abdominal radiographs should be obtained in severe cases to rule out megacolon and/or perforation.
Treatment: Treatment consists of discontinuing the antibiotic if possible in addition to supportive measures. Stool precautions and strict handwashing are important as well as minimizing narcotics, and avoiding anticholinergics and antidiarrheal agents. Oral metronidazole and oral vancomycin are the antibiotics of choice for PMC but metronidazole is favored due to its lower cost. Recurrences are common (10-25%) and prolonged treatment may be necessary. Other options include bacitracin, cholestyramine, and colestipol. If oral therapy is not possible, intravenous metronidazole is indicated but not vancomycin. If surgery is required for perforation, a total colectomy with ileostomy is preferred in most cases.
7. Aeromonas
Aeromonas species are ubiquitous environmental organisms found principally in fresh or brackish water. Symptoms are due to an enterotoxin and occur after drinking untreated water. There is a wide spectrum of diarrheal illness ranging from a self-limited episode to chronic diarrhea, sometimes with blood (22%).
Findings: Endoscopic findings are nonspecific and the diagnosis is made by stool culture.
Treatment: Mild cases only require supportive treatment but for severe cases, antibiotics are indicated. These organisms are consistently resistant to ampicillin and cephalosporins. TMP-SMX, tetracycline, and chloramphenicol may shorten the duration of illness.
8. Spirochetosis
Anaerobic spirochetes such as Treponema pallidum and other species attach perpendicularly to the apical surface of epithelial cells lining the appendix, cecum, colon and rectum. Inflammation occurs if the mucosa is penetrated. The organisms are sexually transmitted and are commonly found in homosexual men but most are asymptomatic. When symptoms occur, they include small volume diarrhea, rectal bleeding, mucopus, and tenesmus.
Findings: Endoscopy in symptomatic patients reveals diffuse ulcerations and mucopurulent discharge. Spirochetes are visualized as a thick blue band along the luminal surface on H&E or silver-stained on histologic sections.
Treatment: Therapy consists of high dose benzathine penicillin. In allergic patients, doxycycline, tetracycline, or erythromycin is recommended.
9. Colonic Tuberculosis (TB)
Any region of the GI tract can be involved with tuberculosis and the major pathogen is Mycobacterium tuberculosis. The incidence seems to be increasing and TB should always be in the differential diagnosis of Crohn's disease. The organisms are ingested and penetrate the intestinal mucosa. The most common symptom is abdominal pain (90%) often with diarrhea and blood, but constipation is also seen. A palpable mass in the right lower quadrant occurs in 2/3 of patients. Complications include hemorrhage, perforation (rare), obstruction, fistula formation, and malabsorption. Less than 50% have pulmonary TB.
Findings: The most frequent site of involvement is the cecum and terminal ileum (85-90%). The disease process may make the ileocecal valve incompetent distinguishing TB from Crohn's disease. Endoscopy reveals 3 patterns of involvement: 1) ulcerative (60%), 2) hypertrophic (10%) with scarring and fibrosis that may mimic carcinoma, and 3) ulcerohypertrophic (30%) with features of both. Histologically, the distinguishing feature is a granuloma that is often noncaseating. The acid-fast bacilli may be seen on Ziehl-Neelsen stain or on culture of the tissue. Stool cultures are positive in 1/3 of patients but may represent swallowed organisms if pulmonary disease is present. Tuberculin skin testing is nonspecific for GI involvement.
Treatment: Standard antituberculosis treatment gives a high cure rate for intestinal TB. Usually a 3-drug regimen (isoniazid, pyrazinamide, rifampin) for 12 months is adequate. Surgery may be needed for obstruction if medical therapy fails or carcinoma can not be ruled out. Fistulas usually respond to medical treatment.
10. Mycobacterium Avium Intracellulare (MAI)
MAI is a frequent cause of acute diarrheal illness in sexually active homosexual males with AIDS. The symptoms include crampy abdominal pain, diarrhea often with blood, fever, and weight loss.
Findings: Sigmoidoscopy reveals friable, ulcerated mucosa with both linear and ovoid ulcerations. On histology the glandular architecture is preserved and there is a diffuse PAS-positive histiocytic interstitial infiltrate. Acid-fast bacilli are also demonstrated.
Treatment: Standard treatment for TB is used.
Viruses
1. Cytomegalovirus (CMV)
CMV is a double-stranded DNA virus from the herpes family. It is an opportunistic infection seen most commonly in AIDS patients with over 90% testing positive. CMV is a sexually transmitted disease that rarely produces GI symptoms although acute ulcerative proctocolitis has been reported. Virtually every organ system can be involved but ileocolitis is the most common GI manifestation. Symptoms include bloody diarrhea, fever, abdominal cramping, and weight loss and perforation may occur.
Findings: Colonoscopy is preferred over sigmoidoscopy due to the frequent proximal involvement and it usually reveals ulcerations that are indistinguishable from other colitides. Biopsy specimens will reveal an inflammatory infiltrate but may also demonstrate the characteristic cytomegalic intranuclear inclusion bodies. The diagnosis is confirmed by either seroconversion or a four-fold increase in antibody titer.
Treatment: When symptoms are present and infection is suspected treatment is with ganciclovir. CMV enterocolitis is the single most common reason for emergency abdominal surgery in patients with AIDS. The mortality rate is high due to the underlying disease and therefore early diagnosis and medical treatment is warranted.
Parasites
1. Amebiasis
Amebiasis is caused by the protozoan Entamoeba histolytica, and although multiple organs may be involved, the colon is the usual site of initial disease. Symptoms vary from asymptomatic carriers to fulminant sepsis with a high mortality. The disease is most prevalent in the tropics and in areas with poor sanitation. The mode of transmission is fecal-oral and E. histolytica exists in the colon in 2 forms: the motile trophozoite and the nonmotile cyst. The cyst form is ingested and divides into 8 trophozoites in the colon; trophozoites are the pathogens responsible for amebic colitis. Cysts present in the stool represent the asymptomatic carrier state while trophozoites with intracytoplasmic red blood cells are pathognomonic for active infection. Symptomatic patients develop abdominal pain and bloody diarrhea with progression to toxic colitis in 10% and occasional systemic dissemination with the liver being the most common extraintestinal site. A dense, fibrous, and granulomatous mass lesion, an ameboma, sometimes forms in the colon that may lead to obstruction or intussusception. It is important to distinguish amebic colitis from inflammatory bowel disease since the administration of corticosteroids can be fatal.
Findings: Endoscopy reveals characteristic ulcers that appear to be covered with a small yellow hemispheric exudate. The ulcers may grow to greater than 1 inch and typically have a flask-shape. The ulcers occur throughout the colon but most are located in the cecum and ascending colon with sparing of the terminal ileum. The intervening mucosa appears normal distinguishing it from bacillary dysentery and ulcerative colitis. On histology, the inflammation is indistinguishable from other forms of colitis although sometimes the amebae can be see at the leading edge of the ulcer (enemas should be avoided to avoid washing them off). Microscopic examination of repeated (3 to 6) fresh stool specimens will reveal trophozoites in over 90% of cases. Barium, mineral oil, and antibiotics all interfere with identification of the organism. Serologic testing, including the indirect hemagglutination test and ELISA may also be helpful in detecting invasive disease and distinguishing from IBD.
Treatment: Various agents are used depending upon the severity of the illness. For asymptomatic intestinal infection, iodoquinol, diloxanide furoate (Furamide), or paromomycin is given. For mild to moderate disease, metronidazole plus iodoquinol, or paromomycin alone is given but for severe intestinal disease, metronidazole, or paromomycin, or emetine each combined with iodoquinol is necessary. For unrelenting toxic colitis or perforation due to amebiasis, a subtotal colectomy is the operation of choice. Occasionally closure of the perforation with exteriorization of the diseased segment and drainage of the peritoneum will allow for recovery. Resection of an ameboma has a very high morbidity and mortality rate and every effort should be made to make the diagnosis preoperatively and treat with antiamebic therapy.
2. Cryptosporidia
Cryptosporidia are protozoa that have become recognized due to improved diagnostic capability. The oocytes are ingested after contact with farm animals or in day-care centers and the trophozoites attach to the intestinal epithelium throughout the large and small intestine. Symptoms include low-grade fever, abdominal cramps, and profuse watery diarrhea. Mild rectal bleeding may also occur and dehydration is common.
Findings: Sigmoidoscopy reveals an erythematous, nonfriable mucosa without ulcers. Histopathology usually demonstrates the characteristic darkly stained, rounded organisms embedded just below the enterocyte membrane. Cryptosporidial oocysts can also be detected on special preparation of fresh stool specimens.
Treatment: Rehydration and supportive treatment is usually all that is necessary in immunocompetent patients, but when treatment is necessary, paromomycin is the drug of choice.
3. Balantidiasis
Although human infection with B. coli is rare, it is important to recognize because it is curable and if left untreated, may lead to severe symptoms and sometimes death. It is a ciliated protozoan and the trophozoite is large enough to be seen with the naked eye. The mode of transmission is uncertain but may be from infected pigs. After ingesting the oocyst, the trophozoite passes to the colon where it penetrates the mucosa by producing hyaluronidase. Patients may be asymptomatic carriers, have mild symptoms of nonbloody diarrhea alternating with constipation, or present acutely ill with bloody diarrhea, abdominal pain, tenesmus and dehydration. This severe form may progress to shock and even death within a few days. Extraintestinal involvement is similar to amebiasis.
Findings: Endoscopy is similar to amebiasis and biopsies will usually demonstrate the organisms. The diagnosis is best made by scraping the base of the ulcer for trophozoites.
Treatment: All patients should be treated with either tetracycline, iodoquinol, or metronidazole.
4. Whipworm
Trichuris trichiura is a roundworm that is found in the tropics and in the Southeast United States. Humans are the principle hosts and after the egg is ingested, the digestive juices dissolve the shell releasing the larvae. The adult worms, 3-5 cm in length, attach themselves to the mucosa of the cecum and may survive here for several years. In heavy infestations, the entire colon and rectum may be involved. Most patients are asymptomatic but some develop right lower quadrant abdominal pain, blood-streaked stools, diarrhea, anemia and emaciation. Appendicitis and rectal prolapse have been described.
Findings: Patients will have a peripheral eosinophilia but the diagnosis is best made by finding the characteristic barrel-shaped ova in the feces. In severe infections, the writhing worms may be seen on endoscopy.
Treatment: As for most worm infestations, mebendazole is highly effective and well tolerated.
5. Lymphogranuloma venereum (LGV)
LGV is caused by Chlamydia trachomatis, an obligatory intracellular parasite that is transmitted primarily through sexual contact. Three stages are present: 1) development of shallow ulcers 1-2 weeks after exposure that disappear, 2) inguinal adenopathy with fevers, abscesses and fistulas, and 3) fibrotic changes leading to rectal strictures. Infection is often limited to the rectum but may extend into the sigmoid colon.
Findings: Endoscopy reveals cobblestoning of the mucosa with friability and ulcerations. Biopsy shows diffuse inflammation with crypt abscesses, granulomas, and giant cells. Barium enema may demonstrate a stricture, termed proctitis obliterans. Diagnosis is made by culture and serology (complement-fixation test and microimmunofluorescent test).
Treatment: Doxycycline or tetracycline is given for 7 days for patients with acute C. trachomatis infection. The treatment of rectal strictures is often problematic. Periodic rectal dilatations may be tried but are often unsuccessful due to scarring. Surgery, with or without preservation of the anal sphincter, may be necessary.
Fungi
1. Candidiasis or Moniliasis
Fungal infections of the GI tract are very rare in healthy individuals but may occur in immunosuppressed patients (chemotherapy, AIDS, steroids) and following the prolonged administration of broad-spectrum antibiotics. Symptoms include nonbloody diarrhea and abdominal pain.
Findings: Endoscopy reveals hyperemia of the mucosa but no ulcerations and biopsy may demonstrate the characteristic pseudohyphae. The diagnosis is established by identifying the yeast, spores, or pseudomycelia on microscopic examination.
Treatment: Nystatin, ketoconazole, fluconazole, or amphotericin B may be used.
2. Histoplasmosis
Histoplasmosis is endemic to areas of the Midwest and it usually produces a subclinical infection in healthy individuals but in immunocompromised patients (esp. AIDS), disseminated disease can occur. The lung is the most common organ affected but the entire GI tract may be involved, particularly the terminal ileum and right colon. Symptoms include diarrhea, hematochezia, obstruction from strictures, and perforation.
Findings: Colonoscopy is preferred due to the proximal colonic involvement and may demonstrate ulcers, pseudopolyps, plaques and skip areas of inflammation. Biopsy reveals the characteristic intracellular oval budding yeasts within the mucosa. High serologic complement-fixation titers confirm the diagnosis as well as fungal cultures of the biopsy specimen.
Treatment: Ketoconazole, fluconazole, or amphotericin B is effective medical therapy. Diversion or resection may be indicated for persistent obstruction or the inability to rule out carcinoma. Prolonged postoperative antifungal therapy is given to prevent recurrence.
Miscellaneous Etiologies
1. Ischemic colitis
This entity refers to a syndrome due to occlusive or to nonocclusive vascular disease as it affects the colon. The diagnosis should be considered in patients with cardiovascular disease, arrythmias, vasculitis, previous aortic surgery, and those in shock. It is classified into 3 categories: gangrenous, strictured, and transient or reversible. Symptoms range from painless hematochezia to those with abdominal pain with bloody stools, fever, and tenesmus. Tenderness on abdominal examination implies full-thickness ischemia and peritoneal signs may indicate a perforation. Patients with strictures, the long-term effect of ischemia, present with obstruction.
Findings: Endoscopy will almost always reveal rectal sparing due to the extensive blood supply to the rectum. Inflammatory changes begin at 15cm and the mucosa appears pale or even gangrenous. Biopsy is nonspecific and the inflammatory changes are localized to the mucosa and submucosa since these areas are most sensitive to a reduction in blood flow; hemosiderin-laden macrophages may be evident. A plain abdominal radiograph may reveal "thumbprinting" usually in the region of the splenic flexure and in more severe cases, pneumatosis or even free air may be present. Usually the history and endoscopic findings are sufficient to make the diagnosis but arteriography may be helpful in some cases.
Treatment: Medical management includes bowel rest, rehydration, and broad-spectrum antibiotics. Surgery is reserved for cases with perforation or stricture. When performing surgery in the acutely ill patient, intraoperative assessment of the degree of ischemia can be difficult but it is imperative that the anastomosis has a good blood supply; subtotal or total abdominal colectomy with ileostomy is often necessary. The mortality rate is high owing to the underlying medical problems of these patients.
2. Radiation colitis
This entity is becoming more common as the use of radiation is increasing. Radiation has both short-term and long-term effects with proctitis, colitis, and proctocolitis occurring months to years after treatment. Symptoms usually include small volume bloody stools, mucorrhea, tenesmus, and sometimes incontinence. Other chronic complications include stricture, obstruction, and fistula formation.
Findings: Endoscopy during acute radiation colitis reveals capillary dilatation, hemorrhage, and edema. Biopsy demonstrates an inflammatory cell infiltration of the mucosa and submucosa. Endoscopy during chronic radiation colitis reveals telangectasias and friability and histopathologic findings are similar to ischemic colitis. These chronic changes are caused by an obliterative endarteritis and fibrosis.
Treatment: Bleeding is rarely life threatening and dietary modification including bulking agents and stool softeners may ameliorate symptoms. A variety of treatments have been used including corticosteroid enemas, suppositories, foams, and topical 5-ASA products. Argon beam coagulation and Nd-YAG laser treatments have been effective in some series. Recent studies indicate that topical formaldehyde instillation on the rectal mucosa is successful in refractory cases.
3. Collagenous and lymphocytic colitis
The disease most commonly affects middle-aged females who report symptoms of nonbloody, watery diarrhea up to 2 liters per day. Most patients are in good health and dehydration is uncommon. The etiology is unknown and the hallmark of collagenous colitis is a subepithelial thickened acellular band of collagen greater than 15µm, and in lymphocytic colitis, there is increased numbers of intraepithelial lymphocytes.
Findings: Contrast radiography of the small and large intestine is usually normal. Endoscopy is also normal and thus requires a high degree of suspicion to obtain the proper biopsies to make the diagnosis. Biopsies should be taken from the right colon, or at least the descending or sigmoid colon since rectal biopsies are often unrevealing.
Treatment: Both collagenous and lymphocytic colitis can spontaneously resolve or wax and wane making evaluation and treatment difficult. Antidiarrheal agents and hydrophilic compounds may help symptoms and if symptoms are not improved, sulfasalazine or 5-ASA drugs should be tried. If still no clinical improvement, a short course of systemic corticosteroids may be helpful. The response in collagen and/or lymphocytes is variable and only clinical parameters need to be followed.
4. Eosinophilic colitis
Eosinophilic gastroenteritis is a rare disease characterized by the infiltration of eosinophils into different layers of the gut wall. Like Crohn's disease, it may involve any part of the GI tract although the stomach and small intestine are the most common sites. When the colon is involved it is typically confined to the right colon and symptoms include colicky abdominal pain, diarrhea, rectal bleeding, and weight loss. Most patients have a history of food intolerance or allergy. Peripheral eosinophilia is present in 80% of cases and parasitic disease must be ruled out.
Findings: Endoscopic findings of the right colon are indistinguishable from Crohn's disease but on histology there is an inflammatory cell infiltrate that is almost entirely composed of eosinophils. The eosinphilia is most pronounced in the mucosal and submucosal layers but the muscular wall and serosa may also be involved. Radiographic findings are nonspecific.
Treatment: Dietary manipulation is the mainstay of treatment but in refractory cases, corticosteroids, immunosuppressive agents, and/or sodium cromoglycate may be tried. Surgery is not curative and should only be reserved for perforation (rare) since obstruction almost always responds to medical management. Prognosis is good and there is no increased risk of GI cancer.
5. Diversion colitis
Patients who have undergone surgery with diversion of the fecal stream may develop inflammation in the distal segment that is often found incidentally on endoscopy and/or radiography. Patients may develop symptoms including crampy abdominal pain, tenesmus, and a purulent or bloody rectal discharge. There are several hypotheses regarding the pathogenesis of diversion colitis but it is most likely due to a deficiency in normal luminal nutrients, namely short-chain fatty acids.
Findings: Endoscopy reveals erythema, friability, edema, and granularity of the mucosa with occasional inflammatory polyps and aphthous ulcerations. There may also be a mucopurulent discharge and histopathology on biopsy specimens is indistinguishable from ulcerative colitis.
Treatment: Definitive treatment involves reconstitution of the GI tract. For symptomatic patients, enemas containing either corticosteroids, 5-ASA, or short-chain fatty acids have been effective.
6. Neutropenic typhlitis
Typhlitis is a necrotizing cecitis that occurs in neutropenic patients. It tends to occur in patients receiving immunosuppression and those with aplastic anemia and AIDS. Symptoms include right lower quadrant abdominal pain, watery and/or bloody diarrhea, and sepsis and shock in severe cases implying gangrene and possible perforation. A 50% mortality rate is attributable to bowel gangrene and perforation in immunocompromised patients. The etiology of typhlitis is unknown but neutropenia is a universal predisposing factor.
Findings: Plain abdominal radiographs may demonstrate dilatation of the small bowel and cecum with thumbprinting, pneumatosis, or free intraperitoneal air. CT scan may show pericecal inflammation and a mass if there is perforation, while ultrasonography may demonstrate a "target" or "halo" sign corresponding to thickening of the colonic wall. Contrast radiography should generally be avoided but if performed, a single-contrast, water-soluble material should be used. Endoscopy is relatively contraindicated unless decompression is needed or pseudomembranous colitis is to be excluded.
Treatment: A high-degree of suspicion and early recognition of this entity is crucial to reduce the high mortality rate. Treatment for patients without peritonitis or perforation includes aggressive rehydration, bowel rest, parenteral broad-spectrum antibiotics, and correction of the underlying neutropenia. Anticholinergic medications, antidiarrheal agents, and narcotics should all be avoided if possible. If perforation is present, urgent surgery is indicated with the resection of all diseased bowel. Care must be taken as the serosal surface often underestimates the extent of involvement. Generally a 2-stage right hemicolectomy should be performed and continuity reestablished only after a full recovery and chemotherapy has been completed since recurrences are high. It is unclear if an aggressive surgical approach is warranted in patients with a protracted illness without perforation but the trend is toward nonoperative management. Consideration for an elective right hemicolectomy can be given to patients who recover with a good long-term prognosis who are in need of further chemotherapy.
7. Chemical/Drugs
It is important to obtain a complete medical history since many different chemicals and drugs can cause an acute inflammatory reaction in the colon. Soap colitis usually develops within hours following the administration of a "cleansing" soapsuds enema. Other agents that may cause colitis include hydrogen peroxide, herbal medications, vinegar, potassium permanganate, Hypaque, and possibly Fleet's Phospho-Soda. The clinical spectrum is variable but the severity of the symptoms depend upon the type and concentration of the caustic agent, the contact time with the mucosa, and the presence or absence of underlying colonic disease.
Findings: Sigmoidoscopy usually reveals hyperemia and mucopus usually limited to the rectum and sigmoid colon but more severe reactions can occur.
Treatment: Treatment is generally supportive as corticosteroid enemas are generally not very effective. Broad-spectrum antibiotics are indicated in severe cases but most patients recover completely after 4 to 6 weeks.
8. Other rare causes
Hemolytic-uremic syndrome
Connective tissue disease
Vasculitis
Amyloidosis
Behcet's syndrome
Chronic lymphocytic leukemia
Lymphoma
Lipid proctocolitis
Allergic proctocolitis
Suggested Readings
- Colon and Rectal Surgery, 3rd ed. Marvin L. Corman, M.D., editor J.B. Lippincott Company, 1993 Chapters 16, 20
- Gastrointestinal Disease, 5th ed. Marvin H. Sleisenger, M.D., John S. Fordtran, M.D., editors W.B. Saunders Company, 1993 Chapters 10, 55, 56, 57, 58, 62, 75, 76
- Gastroenterology, 5th ed. Bockus, Haubrich, Schaftner, Berk. editors W.B. Saunders Company, 1995 Chapters 69, 89
- Gastroenterology, 2nd ed. Yamada, et al. editors J.P. Lippincott Company, 1995 Chapters 80, 84