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Colitides Other Than Ulcerative Colitis And Crohn's Disease

W. Donald Buie, MD
Clinical Associate Professor of Surgery and Oncology
Department of Surgery, University of Calgary

The non-IBD colitides are a diverse group of acute and chronic diseases that range from an acute self-limiting diarrheal illness, to a fulminant toxic disease requiring urgent resuscitation and immediate surgical intervention. The following is a brief outline including a diagnostic approach followed by a discussion of the more common colitides categorized into infectious and noninfectious etiologies.

I. DIAGNOSTIC APPROACH

a. History. A complete history is essential as it narrows the differential diagnosis and helps to focus primary and secondary investigations. The typical symptom complex of colitis includes abdominal cramps, diarrhea with/without blood and mucous, occasional fever and dehydration. Each of these symptoms may be absent, mild or prominent depending on the etiology.

A diarrhea history including onset, progression, volume, frequency, consistency and presence of blood is essential. Profuse watery diarrhea is suggestive of an infectious cause. The presence of blood suggests an enteroinvasive organism or inflammatory cause. The history must also include information on travel, recent antibiotic use, exposure to animals, the patients’ water supply and the health of other family members. Most diarrheal illnesses are self-limiting however a complete medical workup should occur with one or more of the following:

  • profuse watery diarrhea,
  • passage of many small volume stools containing blood and mucus,
  • temperature > 38.5 C,
  • passage of > 6 unformed stools/24 hours or a duration of illness > 48 hrs
  • severe abdominal pain in a patient over the age of 50
  • diarrhea in the elderly ( >70 years of age) or the immunocompromised.

The patient’s past medical history is important and must include information on coexistent cardiac or peripheral vascular disease often associated with ischemic colitis, previous pelvic radiation and recent or concurrent medications including new drugs, antibiotics, cardiac medications and immunosuppressants. The family history should be obtained as it pertains to gastrointestinal disease along with information on the patients’ social history and sexual practices.

b. Physical examination. Physical examination is essential to assess disease acuity and the need for resuscitation and urgent intervention. It must include an assessment of vital signs including postural drop to assess dehydration. Fever usually suggests enteroinvasive bacteria (Salmonella, Shigella or Campylobacter), enteric viruses or a cytotoxic organism such as C. difficile or Entamoeba histolytica. Abdominal examination must determine whether there is focal or generalized tenderness or the presence of peritoneal signs indicating transmural involvement and possibly imminent perforation. Perianal and genital examination may demonstrate condyloma or herpetic lesions that may give a clue to a sexually transmitted disease. Finally, a digital rectal exam for masses and proctoscopic examination of the mucosa for edema, inflammation and ulcerations completes the physical.

c. Investigations

i. Endoscopy. Both flexible sigmoidoscopy and colonoscopy are useful in distinguishing IBD from infectious diarrhea, diagnosing C. difficile (pseudomembranes), diagnosing an opportunistic infection in an immunocompromised patient and in cases of ischemic colitis. In addition to assessing the extent of involvement, it confirms suspected mucosal breakdown and permits a biopsy of suspicious lesions.

ii. Radiography. Plain films are useful to rule out free air. There may be enough air in the colon to provide contrast and establish mucosal edema (thumbprinting), and assess colonic diameter. As a general rule contrast studies do not add much additional information and are often contraindicated in severely ill patients at risk of perforation. A CT may be useful to examine the colon for edema and rule out other pathology.

iii. Laboratory Studies
Stool analysis
.
Entero-invasive organisms such as Shigella, Campylobacter and some strains of E. coli are characterized by the presence of fecal leukocytes. This suggests an inflammatory colitis with mucosal breakdown. On the other hand colitides caused by enterotoxins secreted by parasites and other strains of E. coli show an absence of fecal leukocytes as the diarrhea is secretory. Although non-specific, stool analysis is inexpensive and may lead to earlier institution of therapy while waiting for definitive results. In addition gram stain can identify Campylobacter, ova and parasites.
Stool cultures. Generally stool cultures have a low sensitivity and specificity. They are most helpful in immunocompromised patients and in patients with underlying inflammatory bowel disease in whom the distinction between a flare and superimposed infection is critical. Routine stool culture identifies Salmonella, Campylobacter and Shigella. The lab must be notified in advance to identify Aeromonas or Yersinia species. Other organisms that can be cultured include enterohemorrhagic E. coli, viruses and vibrios. Stool for ova and parasites is indicated for persistent diarrhea which is usually associated with Giardia, Cryptosporidium, Entamoeba and Cyclospora. It is especially useful following a history of travel to mountainous regions, diarrhea in men who have sex with men or a patient with AIDS ( Giardia, Entamoeba histolytica), a community waterborne outbreak ( Giardia or Cryptosporidium) or bloody diarrhea with few or no fecal leukocytes. Excretion is often intermittent depending on the life cycle thus several specimens may need to be sent over several days.
Serology. Serologic tests are available to identify antibodies to a number of organisms including syphilis, Chlamydia, CMV. Generally these tests are expensive and take several days for results. They are useful when there is difficulty establishing a diagnosis.
Histopathology. Colonic biopsy can identify specific infectious colitidies. Unfortunately acute colitis from most causes may look very similar on H and E as they are all characterized by edema, inflammation with neutrophils in the lamina propria and cryptitis with crypt abscesses.

II. INFECTIOUS COLITIDES

a. Bacterial

  1. Escheriscia coli
  2. This gram negative rod is a prominent component of normal intestinal flora. Most strains are harmless however several are a common cause of infectious diarrhea. They are most dangerous in the very young, the old and the debilitated. The diarrhea ranges from watery to bloody.
    Findings : Endoscopy demonstrates erythema, edema, ulceration and occasional pseudomembranes. Fecal leukocytes are present. Following plating on sorbitol medium, strain identification is through serotyping and bioassays using DNA probes for toxins. At least 5 different intestinal pathogens have been recognized. Although 0157 is the best-known serotype, others are becoming more important.
    Enterotoxigenic E. coli (ETEC) - watery diarrhea, may be mild or purging, lasting for 24h to 4-5 days. It is easily picked up from contaminated food and water supplies and produces heat labile and heat stable toxins that stimulate chloride secretion causing secretion of water into the lumen.
    Enteropathogenic E. coli (EPEC) - severe persistent watery diarrhea, vomiting and dehydration with resultant malnutrition, most common in neonates. The organism attaches itself to the enterocyte and alters water and electrolyte secretion.
    Enterohemorrhagic E. coli ( EHEC) - colitis with bloody diarrhea and hemolytic uremic syndrome (HUS; microangiopathic edema, renal failure and thrombocytopenia). Acquired from undercooked ground meat (hamburgers at fast food chains), lettuce, sprouts, and unpasteurized apple cider. Only a small innoculum is required (100-200 organisms). The most common serotype is 0157:H7. Two types of cytotoxins are produced; Shiga toxins, causing secretory diarrhea, and an enterohemolysin causing enterocyte invasion.
    Enteroinvasive E. coli ( EIEC) – watery diarrhea which may or may not progress to bloody diarrhea similar to shigella. Acquired from contaminated food and water supplies. Organisms can invade and multiply within the intestinal cell like shigella.
    Enteroaggregative E. Coli (EAEC) – persistent diarrhea in children and patients with HIV. Acquired from contaminated food and water supply. The physiologic mechanism is not entirely known however organisms have the ability to adhere, destroy mucosal cells and be cytotoxic.
    Treatment - Oral rehydration utilizing glucose linked sodium absorption of water and electrolytes. Diarrhea is self limited and antibiotics are not needed. Ciprofloxacin decreases the duration of diarrhea in EAEC. Antibiotic therapy appears to increase the risk of developing HUS in EHEC and is contraindicated.

  3. Shigella
  4. Shigellosis is a common cause of dysenteric or colonic diarrhea and is the second most common food borne disease in the United States. Ingestion of 10 organisms can cause disease. There are four subgroups the most common in the United States being S. sonnei. The organism produces Shiga toxin which allows it to invade into the intestinal cells where it multiplies. The average incubation period is 3 days. Clinically the disease is characterized by high fever, abdominal cramps and bloody mucoid diarrhea. Stool frequency on average is 8-10 but may be up to 100 times per day and is associated with tenesmus. It is small volume without large fluid shifts. The spectrum of disease depends on the infecting organism: S. sonnei causes mild watery diarrhea while S. dysenteriae and S. flexneri cause bloody diarrhea. Intestinal complications include proctitis, rectal prolapse, toxic megacolon, intestinal obstruction, and perforation. Patients may also suffer from bacteremia, neurologic symptoms, Reiter’s syndrome and HUS.
    Findings: Endoscopy demonstrates friable erythematous mucosa involving the rectum and sigmoid. About half of the patients have involvement to the splenic flexure. Diagnosis is by culture. On histology, an intense local inflammatory response is present in the lamina propria with crypt abscesses. The primary differential diagnosis is ulcerative colitis.
    Treatment: General supportive measures including rehydration, avoidance of narcotics and antidiarrheals are required. The course of disease in a healthy individual is 7 days without treatment. Ampicillin is used in many patients (not amoxicillin) for 5 days. Resistant strains are becoming common and TMP/SMX or quinolone antibiotics may be necessary. Recurrent diarrhea may also be due to the development of C. difficile as development of a carrier state following Shigella infection is rare.

  5. Salmonella
  6. Salmonellosis is the second leading cause of food borne disease in the United States. It is associated with ingestion of poultry, eggs and milk products and is seasonal (commonly in the summer and fall). Spread is through the 5 F’s – flies, food, fingers, feces and fomites. It is a gram negative facultative anaerobe. S. typhimurium and S. enteritidis are the most frequently isolated serotypes. Susceptibility is increased to infection with impaired cellular immunity (AIDS, steroid use, malignancy, chemoradiotherapy), alterations in intestinal flora, extremes of age, decreased gastric acidity and impaired phagocytic function. Salmonella attacks the ileum and to a lesser extent the colon causing bloody diarrhea. Toxic megacolon along with perforation may result. Depending on the strain, five clinical syndromes are seen; gastroenteritis (75%), bacteremia with or without GI involvement ( 5-10%), typhoidal or enteric fever (5-10%), localized infections in the bones, joints and meninges (5%) and an asymptomatic carrier state where the organism is harboured in the gallbladder (<1%). Although the disease may be mild or asymptomatic, the usual presentation includes nausea, vomiting, fever, diarrhea and cramping within 6-72 hours of ingesting contaminated food or water. With larger inoculums, there is an increase in the severity of the diarrhea, duration of the illness and weight loss.
    Findings: Stool examination shows leukocytes and diagnosis is through stool cultures. Proctoscopic findings include hyperemia, granularity, friability and ulcerations. Histopathology reveals mucosal ulcerations, hemorrhage and crypt abscesses.
    Treatment: General supportive care including, fluids and electrolytes are paramount as it is usually self limited. The fever resolves within 48-72 hours and diarrhea within 4-10 days. Antibiotics are considered for patients with very severe sepsis, lymphoproliferative disorders, organ transplants, AIDS, sickle cell disease, endovascular or osseous prothesis or children less than 1 year of age. Concerns have arisen about strains with a 5 drug resistance pattern. Treatment with quinolones or chloramphemicol are usually first line. Patients excrete bacteria for a median of 5 weeks post resolution of their clinical syndrome.

  7. Campylobacter
  8. This motile gram-negative rod or spiral is the most frequently identified pathogen associated with acute diarrhea in western countries. It is caused by ingestion of improperly cooked poultry products although water born and milk born outbreaks can occur. Ingestion does not always lead to disease however it is the most commonly identified antecedent to Guillain-Barre syndrome. After a 3 day incubation, infection is established in the jejunum, ileum and often in the colon and rectum followed by abdominal pain and diarrhea. In one third of the cases, there is a 1-3 day prodrome of fever, rigors, aches, dizziness or delirium prior to the onset of intestinal symptoms. Diarrhea is watery and profuse (10 bowel movements per day) and frank blood is commonly seen in the stools on the second or third day of diarrhea. Pain is usually severe mimicking appendicitis although patients do not have genuine rebound or guarding.
    Findings: Proctoscopy reveals diffuse inflammation, bloody exudates, 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 stool often shows the organism as a curved motile rod with corkscrew movements. Histopathology is nonspecific revealing edema with neutrophils in the lamina propria, ulceration and crypt abscesses.
    Treatment: Mild cases do not benefit from antibiotics as diarrhea typically lasts for 4-5 days. Patients with dysentery or high fever suggesting bacteremia, should be treated. Erythromycin is the drug of choice with a relapse rate of < 5 %. Resistance has been reported and fluoro-quinolones may become first line therapy. There is an increased incidence in AIDS patients with induction of a carrier state.

  9. Yersinia
  10. Yersinia enterocolitica is a nonlactose fermenting gram negative coccobacillus. It invades the epithelium and localizes to the lymphatic tissue of the intestine especially peyer’s patches and mesenteric lymph nodes where it causes disease through production of an endotoxin. It is spread through contaminated food and water. Three clinical syndromes can occur: acute gastroenteritis, pseudo-appendicular syndrome and mesenteric adenitis. Clinically patients experience diarrhea, abdominal pain, fever, occasional nausea and vomiting and associated pharyngitis. Bowel movements peak at 5-10 per day. About 4% of appendectomies will culture Y. enterocolitica.
    Findings: there are no distinct clinical, radiologic, hematologic or biochemical findings. Stool culture is the standard. Findings at endoscopy range form normal to a pattern resembling Crohn’s disease with inflammation and ulceration. Granulomas may be present on microscopy.
    Treatment: There is no data to suggest that antimicrobial treatment of acute uncomplicated yersinosis is beneficial nor does it affect the incidence of chronic sequelae. For patients with septicemia or other complications, IV ceftriaxone combined with gentamycin is recommended for 3 days followed by oral ciprofloxacin. Bacteria are shed for 40 plus days. Complications include suppurative appendicitis, diffuse ulcerative ileitis and colitis, intestinal perforation, peritonitis, intussusception, toxic megacolon, necrotic small bowel, cholangitis and mesenteric vein thrombosis. Overall mortality is low. Chronic sequelae including erythema nodosum, reactive arthritis and Reiter’s syndrome may occur.

  11. Clostridium difficile Colitis
  12. Clostridium difficile has become one of the most common hospital acquired infections. The intestinal tract is colonized when the normal bacterial flora are disrupted usually through antibiotic use. This can occur in as little as a few days or up to 10 weeks following even a single prophylactic dose. The most common associated antibiotics include the penicillins, clindamycin and cephalosporins however virtually any antibiotic excluding vancomycin can be causative. The aminoglycosides are rarely involved. Metronidazole is not protective. The clinical presentation ranges from an asymptomatic carrier state to antibiotic colitis to pseudomembranous colitis to acute fulminant colitis and toxic megacolon.
    Carrier state - Approximately 2/3 of infected hospitalized patients are asymptomatic carriers continuously passing organisms in the stool and acting as a reservoir for repeated contamination of the hospital ward.
    Antibiotic colitis - Patients present with mild diarrhea and a normal physical examination. Fever and leukocytosis are absent and sigmoidoscopy is normal. C. difficile toxins are present in the stool. Most antibiotic colitis is not associated with C. difficile but is a form of osmotic diarrhea due to disruption of the colonic microflora and accumulation of complex carbohydrates normally broken down into short chain fatty acids. Colitis is usually self-limited and cured by discontinuing the offending antibiotic.
    Pseudomembranous colitis - Patients present with a systemic illness including malaise, abdominal pain, nausea, anorexia and profuse watery diarrhea (10-15 times per day). On physical examination the patients have left or right lower quadrant pain and cramps. They have a low-grade fever with a leukocytosis. Sigmoidoscopic examination may or may not reveal raised yellow or off-white plaques (pseudomembranes) covering the mucosa. Occasionally they are located in the right colon. On CT scan the colonic wall is diffusely thickened.
    Fulminant colitis - This occurs in approximately 2- 3 % of patients. The presentation includes diffuse abdominal pain, high fever, chills, marked leukocytosis and diarrhea. Diarrhea may cease or may be absent as the colon becomes atonic and dilated. A dangerous complication of fulminant colitis is toxic megacolon where the patient becomes extremely toxic with a massively dilated colon and distended abdomen. In addition to a dilated colon on plain abdominal x-ray, there may be thumbprinting and air fluid levels in the small bowel. An acute abdomen with rebound and guarding should alert the surgeon to the possibility of perforation.
    Rare presentations - Pseudomembranous colitis can also occur after cancer chemotherapy or a bowel preparation. It can also affect the small bowel (enteritis) following proctocolectomy. Infection with C. difficile may complicate ulcerative or Crohn’s colitis. Diagnosis is difficult as the symptoms overlap and pseudomembranes are not present. Identification of C. difficile infection is important prior to treatment with corticosteroids or other immunosuppressive therapy.
    Findings: Cytotoxic assay is the gold standard (sensitivity 94-100%, specificity 99%), however test results take 2-3 days. The most common test is an enzyme linked immune-absorbent assay (ELISA) test for toxin A (sensitivity 70-90%, specificity - 99%) which are available in several hours however there is a 5-10% miss rate as some strains produce primarily toxin B or a mutant strain of toxin A. Endoscopy is useful when there is doubt about the diagnosis or to guide treatment prior to the results of the toxin assays. The presence of pseudomembranes in the rectosigmoid is pathognomonic. However, pseudomembranes may not be present or may be present only in the right colon.
    Treatment: In general the offending antibiotic must be stopped, the patient resuscitated and started on oral metronidazole. If an ileus is present metronidazole may be given intravenously however there is no treatment advantage. In severe cases oral vancomycin may be added. Intravenous vancomycin is of no benefit. In situations of increasing leukocytosis, bandemia, clinical deterioration or systemic compromise, surgery must be considered. The procedure of choice is a subtotal colectomy with an end ileostomy. Lesser procedures have a high mortality rate. Relapsing infection occurs in 15-20% of patients. The carrier state may be eliminated by administering Vancomycin however most carriers become culture positive after therapy is discontinued. Pulse therapy or recolonization of the bacterial flora may be considered.

  13. Spirochetosis
  14. Treponema pallidum and other spirochete species are sexually transmitted commonly found in homosexual men and acquired through ano-receptive intercourse. The bacteria attaches perpendicularly to the apical surface of the epithelial cells of the colon, rectum and appendix. The infection is most commonly asymptomatic. If the mucosa is penetrated, inflammation occurs with symptoms of small volume diarrhea, rectal bleeding, mucous and tenesmus.
    Findings: diffuse ulcerations and mucopurulent discharge are seen on endoscopy. The presence of a thick blue band on Hand E or silver staining on histology makes the diagnosis.
    Treatment: High dose benzathine penicillin is curative. In allergic patients, doxycycline, tetracycline or erythromycin is recommended.

  15. Colonic tuberculosis (TB)

Mycobacterium tuberculosis can involve any region of the GI tract although the most common area is the cecum and terminal ileum (85-90%). The organism is ingested and penetrates the intestinal mucosa. The most common symptom is abdominal pain (90%) often with diarrhea and blood and a palpable mass (60%). Patients may also become constipated. The primary differential diagnosis is Crohn’s disease. Complications include hemorrhage, perforation, obstruction, fistula formation and malabsorption. Less than 50% of patients have pulmonary TB.
Findings: Endoscopy reveals three patterns: ulcerative (60%), hypertrophic (10%) with scarring and fibrosis that may look like carcinoma and ulcero-hypertrophic (30%) with features of both. Histologically non-caseating granuloma are seen with acid-fast bacilli on Ziehl-Neelsen stain or on tissue culture. Stool cultures are positive in 1/3 of patients. Skin testing is non-specific for GI involvement.
Treatment: usually a three drug regimen (isoniazid, pyrasinamide, rifampin) for 12 months. Surgery is required for complications of obstruction, perforation or to rule out carcinoma. Fistulas usually respond to medical treatment.

b. Viruses

  1. Cytomegalovirus

CMV is a double stranded DNA virus from the Herpes family. It causes disease primarily in immunosuppressed patients (AIDS, transplant recipients) due to hematogenous spread of CMV secondary to decreased CD4 activity. Ileocolitis is the most common GI manifestation. Symptoms include intractable diarrhea associated with abdominal pain, hematochezia and tenesmus. The virus causes tissue destruction leading to hemorrhage. In severe cases, perforation can occur requiring surgical intervention with resection and stoma formation. CMV enterocolitis is the single most common reason for emergency abdominal surgery in AIDS patients.
Findings: It is important to rule out other causes that may be associated with colitis in these patients. This includes a series of stool specimens including bacterial culture, ova and parasites and assay for C. difficile toxin. Colonoscopy is the preferred method of visualization due to frequent proximal involvement with nonspecific ulcerations. Biopsy demonstrates mucosal inflammation with tissue necrosis, vascular endothelial involvement and cytomegalic cells (large cells with eosinophillic intranuclear and basophilic intracytoplasmic inclusions). The diagnosis may be confirmed by seroconversion or a four-fold increase in antibody titer.
Treatment: Treatment is with gancyclovir or foscarnet. Surgery is required for complications. The mortality rate is high due to the underlying disease state and other comorbidities.

c. Parasites

  1. Amebiasis
  2. Amebiasis is caused by the protozoan Entamoeba histolytica. Most infections (90%) are asymptomatic. The organism exists in two forms; a cyst stage, which is infective, and a trophozoite stage which causes invasive disease. The primary mode of transmission occurs through contaminated food or water with ingestion of cysts. Venereal transmission occurs through fecal oral route in homosexuals. Symptoms range from mild diarrhea to severe dysentery with abdominal pain and severe bloody diarrhea. Weight loss and fever are also present. Fulminant colitis with bowel necrosis and perforation occurs in 0.5% of cases. There is occasional liver involvement. A dense fibrous granulomatous mass (ameboma) can form in the colon leading to obstruction and intussusception.
    Findings: At endoscopy, characteristic ulcers covered with small yellow hemispheric exudates are present. They may grow to more than one inch, have a flask like shape and are located primarily in the cecum and ascending colon. Diagnosis is through the demonstration of cysts or trophozoites in the stool on saline wet mount. The presence of cysts represents the carrier state while trophozoites with intracytoplasmic red blood cells are pathognomonic for active infection. Serology helps to exclude disease but does not differentiate a previous infection from an acute one. Amebiasis must be differentiated from IBD as corticosteroids can be fatal.
    Treatment: All patients are treated even if asymptomatic to prevent invasive disease and spread to other family members. Metronidazole 750 mg tid for 7-10 days cures 90% of patients. Resistance has not been reported. Although a 10 day course is effective against cysts as well as trophozoites, treatment with a second agent, such as paromomycin/ iodoquinol or diloxanide foruoate is recommended. Follow-up stool examination is recommended in all patients to ensure clearance. In the case of toxic colitis or perforation, a subtotal colectomy with an ileostomy is the treatment of choice. Amebomas should be treated with antibiotics first as primary resection has a high morbidity and mortality rate.

  3. Cryptosporidia
  4. Cryptosporidiosis presents as a severe dehydrating but self-limiting diarrheal illness. It is a protozoal illness caused by ingestion of oocytes from contact with farm animals. Trophozoites attach to the intestinal epithelium throughout the large and small intestine. Symptoms also include low-grade fever, cramps and occasional rectal bleeding.
    Findings: On sigmoidoscopy the mucosa is erythematous and nonfriable without ulcers. Diagnosis is made by biopsy, which demonstrates the characteristic dark stained, rounded organism embedded just below the enterocyte membrane. Cryptosporidial oocysts can also be detected on special preparation of fresh stool specimens.
    Treatment: Supportive treatment including rehydration is all that is necessary in immunocompetent patients. When required, parmomycin is the treatment of choice.

  5. Lymphogranuloma venerum (LGV)

LGV is caused by Chlamidia trachomitis an obligatory intracellular parasite that is transmitted primarily through sexual contact. The disease progresses in three recognized clinical stages. First there is the development of shallow ulcers 1-2 weeks after exposure that completely disappear. This is followed by inguinal adenopathy with fevers, abscesses and fistulas. The late stage is characterized by fibrosis leading to rectosigmoid strictures. Infection is usually limited to the rectum but may extend into the sigmoid.
Findings: Endoscopy reveals cobblestone ulceration of the mucosa. Biopsy demonstrates diffuse inflammation, crypt abscesses, granulomas and giant cells. There may be a stricture in the rectum. Diagnosis is made by culture and serology (complement-fixation and immunofluorescence).
Treatment: Acute infection is treated with doxycycline or tetracycline for 7 days. If a rectal stricture is present, periodic dilatation may be used however resection with or without sphincter preservation may be required.

d. Fungi

  1. Histoplasmosis

Histoplasmosis is endemic in some areas of the Midwest. It produces a subclinical infection in healthy patients however in immunocompromised patients (HIV) disseminated disease can occur. The entire GI tract may be involved particularly the terminal ileum and right colon. Symptoms include diarrhea, hematochezia. Complications include obstruction secondary to strictures and perforation.
Findings: Ulcers, pseudopolyps, plaques and skip areas of inflammation may be seen in the right colon on colonoscopy. Diagnosis is made with biopsy revealing intracellular oval budding yeasts within the mucosa and fungal cultures. A serologic complement fixation test can confirm the diagnosis.
Treatment: Ketoconazole, fluconazole or amphotericin B is effective medical therapy. Surgery is indicated for complications or an inability to rule out carcinoma and includes resection or diversion. Clearance may require prolonged medical therapy.

III. NON INFECTIOUS COLITIDES

  1. Ischemic colitis
  2. Ischemic colitis is a spectrum of disease caused by a decrease or interruption in blood flow to the colon. The etiology is varied and can be classified into major vascular occlusion, venous thrombosis, small vessel disease, shock, mechanical obstruction, blood dyscrasias, surgical, drugs and miscellaneous. The most common areas of ischemia are the watershed areas. Approximately 70% of the cases occur in the left colon. The clinical presentation depends on the extent, completeness and the ischemic time. Acute colonic ischemia is characterized by rapid onset of mild to moderate abdominal pain and tenderness typically associated with bloody diarrhea. An acute precipitating event is rare and 90% of the patients are over age 60. Three clinical stages have been described:
    Hyperactive phase characterized by severe pain, frequent passage of bloody stools. Mostof these patients have mucosal and submucosal injury that is transient and resolves with conservative measures without complications.
    Paralytic phase characterized by diminished pain which becomes continuous and diffuse. The abdomen is tender without bowel sounds.
    Shock phase characterized by massive fluid shifts and electrolyte imbalance caused by gangrene of the bowel wall with progression to shock and metabolic acidosis. This severe form occurs in 10-20% of patients and requires urgent surgical intervention with resection.
    Findings: On endoscopy, changes range from pale mucosa with petechial bleeding and bluish hemorrhagic nodules to discreet ulcers with surrounding edema to necrosis with mucosal friability. The changes are often abrupt and segmental. Rectal sparing is common with rapid resolution on repeat endoscopy. Endoscopy is contraindicated in patients with an acute abdomen. Differential diagnosis includes infectious colitis, IBD, diverticulitis, radiation enteritis, solitary rectal ulcer syndrome and malignancy. Stool samples for culture and ova and parasites should be sent. Lab investigations are non-specific. Plain abdominal x-rays are usually non-specific; thumbprinting and pneumatosis suggests edema and necrosis respectively. CT scan demonstrates thickening of the involved colon however initially it may be normal.
    Treatment: Depends on the severity of the disease and the clinical circumstances. Vascular reconstruction is rarely used as large vessel disease is not the primary problem. Suspected colonic gangrene or perforation requires immediate resuscitation and laparotomy with resection. Supportive care in the absence of colonic gangrene or perforation includes IV fluids, bowel rest and broad-spectrum antibiotics. The prognosis depends on the stage of the disease and associated comorbidities. Mild cases resolve spontaneously. Improvement usually occurs in one to two days with complete resolution in one to two weeks. More severe disease can develop into a chronic segment of colitis or stricture.

  3. Radiation colitis
  4. Radiation injury to the rectosigmoid can be classified as acute and chronic. Acute injury occurs within 6 weeks and is characterized by symptoms of diarrhea, tenesmus, and urgency with occasional bleeding. Symptoms are due to acute inflammation and edema in the bowel and usually resolve within 2 to 6 months without specific treatment. Chronic radiation injury usually occurs 9 to 14 months following treatment but may occur up to 30 years later. It usually develops after radiation doses from 4500 to 5500 cGy. Predisposing conditions include age, combined chemotherapy and poor radiation technique and postoperative radiation. Radiation causes the production of free radicals, oxidative damage and progressive fibrosis of the end arterioles (obliterative end arteritis) with chronic mucosal ischemia, ulceration and fibrosis. This may result in a chronic ischemic segment that strictures and is prone to bleeding. Symptoms include, diarrhea, tenesmus and urgency. Incontinence may be prominent if the sphincter was involved with radiation.
    Findings: On endoscopy the mucosa has a pale, friable appearance with multiple telangiectasias. Biopsies are not pathognomonic but are used to rule out other causes of proctitis.
    Treatment: No specific treatment is required in patients with mild symptoms and minimal rectal bleeding. Unfortunately there is no treatment that is completely reliable. Sulfasalazine and aminosalicylates have had varied success. Topical sucralfate (enema) appear to be more effective than oral sulfasalazine. Rectal pain or tenesmus may respond to sucralfate or steroid enemas. If topical therapy fails then endoscopic methods including bipolar cautery, heater probe or the argon plasma coagulator can be used. Intrarectal formalin instillation is also reported although this is not as popular. Patients with strictures may be improved symptomatically with stool softeners. Balloon dilatation is effective for short narrow strictures although there is a risk of perforation. The final option is resection with or without a defunctioning colostomy.

  5. Collagenous and lymphocytic colitis (microscopic colitis)
  6. Microscopic colitis is characterized by chronic secretory diarrhea without bleeding. There are three types of microscopic colitis:
    Lymphocytic - characterized by a sub epithelial lymphocytic infiltrate in the colonic mucosa
    Collagenous - characterized by a thickened sub epithelial collagenous band in the colonic mucosa without lymphocytic infiltration
    Mixed form – characterized by both a thickened collagen plate with an increased number of lymphocytes.
    Theories regarding the pathophysiology of the disease include abnormal collagen metabolism, mucosal injury secondary to bacterial toxins and NSAID use. Other drugs including simvastatin, lansoprazole, timclopidine are implicated in collagenous colitis while flutamide, gold salts and lansoprazole have been associated with lymphocytic colitis. Patients present with up to 2 liters per day of nonbloody chronic watery (secretory) diarrhea. The course is usually intermittent but may be continuous.
    Findings: Macroscopically the mucosa is normal on colonoscopy. Diagnosis is made by biopsy which reveals colitis without mucosal ulceration.
    Treatment: Therapy is nonspecific and includes stopping NSAIDs treating diarrhea with loperamide. Aminosalicylates, sulfasalazine or a short trial with cholestyramine (4 mg qid) may be useful. Systemic steroids or budesonide can be used in refractory cases. Resolution or significant improvement is more likely in lymphocytic colitis. Long-term remission occurs in up to 70% of patients while 25-30% relapse. Occasionally a stoma is required.

  7. Eosinophilic colitis
  8. Eosinophilic gastroenteritis may involve any part of the gastrointestinal tract, however colonic involvement is usually confined to the right colon. It presents as acute colicky 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: The gross endoscopic appearance is identical to Crohn’s disease. On histology there is an inflammatory infiltrate composed of eosinophils in the mucosal and submucosal layers.
    Treatment: Most patients can be treated with dietary manipulation and avoidance of specific foods. In more severe cases, corticosteroids, immunosuppressive agents and sodium chromoglycate may be beneficial. Surgery is neither curative nor advisable and the prognosis is good.

  9. Diversion colitis
  10. Diversion colitis is a nonspecific inflammation of the colorectum following diversion of the fecal stream with an ostomy. It is due to a lack of short chain fatty acids (SCFA), normally produced from the breakdown of complex carbohydrates by resident bacteria. SCFA are the preferred energy substrate for colonocytes and are necessary for normal metabolism. Most patients are asymptomatic. The most common symptoms are rectal bleeding, tenesmus and mucous discharge. In a prospective study colitis occurred in 91% of adults following diversion and was mild in 52%, moderate in 44% and severe in 4%. Occasionally patients require a blood transfusion or proctectomy for ongoing sepsis. Symptoms may occur within a few months or after a long delay. The differential diagnosis includes self-limited colitis, antibiotic induced colitis and persistent IBD. Pathologically differentiating diversion from persistent IBD may be difficult.
    Treatment: Restoration of fecal continuity is the treatment of choice and is curative. Early operation is preferred as prolonged diversion causes involution and atrophy of the segment with a poorer functional result. If this is not an option, a trial of SCFA enemas (60cc instilled twice daily for 6 weeks) is warranted. The results are variable but are best in patients without pre-existing colitis. 5-ASA enemas may be beneficial.

  11. Neutropenic enterocolitis (typhlitis)
  12. Necrotizing enterocolitis or typhlitis is a life threatening infectious colitis that occurs in neutropenic immunosuppressed patients. It is caused by a number of factors including mucosal injury secondary to cytotoxic drugs, profound neutropenia ( < 500 WBC/mm3) and impaired host defense to invasion of microorganisms. The infection leads to necrosis of the intestinal wall primarily in the cecum but it may extend into the ascending colon and terminal ileum. Polymicrobial infection is common including gram negative rods, gram positive cocci, anaerobes and candida. Bacteremia is common. Clinical manifestations include fever and abdominal pain usually in the right lower quadrant in a patient receiving cytotoxic chemotherapy. The symptoms often occur 10-14 days post chemotherapy and include abdominal distension, nausea, and vomiting and watery or bloody diarrhea. Peritoneal signs and shock suggests intestinal perforation. CT is the preferred method of diagnosis and demonstrates a distended fluid filled edematous cecum. Free air, intramural air, or soft tissue mass or abscess are ominous signs. The differential diagnosis includes appendicitis, pseudomembranous colitis, ischemic colitis and Ogilvie's syndrome. Stool should be sent for C. difficile toxin. Barium enema and colonoscopy are contraindicated due to the risk of cecal perforation.
    Treatment: Barring evidence of perforation, patients require close observation with supportive care including bowel rest, nasogastric suction, intravenous fluids, nutritional support and broad spectrum antibiotics. If the patient remains febrile more than 72 hours while on antibiotics, fungal coverage should be added. Anticholinergics, antidiarrheals and narcotic agents should be avoided. Granulocyte colony stimulating factor (G-CSF) should be considered to accelerate leukocyte production. Patients require close observation with repeated physical examination and CT scan as necessary. Most patients will recover fully once the white count returns to normal. Surgery is required for complications including free perforation, peritonitis, persistent gastrointestinal bleeding despite correcting coagulopathies or clinical deterioration despite maximum medical therapy. A right hemicolectomy with ileostomy and mucous fistula is the procedure of choice. Care should be taken during resection as the serosal appearance underestimates true colonic involvement.

  13. Chemical / drug induced
  14. Many different chemicals and drugs have been implicated in inflammation of the colon. Soap colitis occurs within hours following administration of a soapsuds enema. Other agents include hydrogen peroxide, herbal medications, vinegar, potassium permanganate, Hypaque and Fleet phosphosoda. Medications include NSAIDs, 5-ASA and purine analogs (5FU, tomudex, irinotecan). The clinical picture depends primarily on the agent, the concentration or dose and contact time with the mucosa. It is also modulated by the presence of underlying colonic disease.
    Findings: At endoscopy the colitis is usually limited to the area of contact (rectosigmoid) and reveals hyperemia and mucous. As these are nonspecific findings it is important to ensure that other common causes are ruled out (i.e. C. difficile can occur following chemotherapy).
    Treatment: Treatment is supportive. Cessation and avoidance allow most patients to recover completely after 4 to 6 weeks. Broad spectrum antibiotics are indicated in severe cases.

  15. Rare causes include: connective tissue disease, vasculitis, amyloidosis, Behcet’s syndrome, chronic lymphocytic leukemia, lymphoma, lipid proctocolitis

REFERENCES

General:

  1. Bruce CJ. Colitides other than ulcerative colitis and Crohn’s disease. Core Subject 2000, pg13-27
  2. Dupont HL. Guidelines on acute infectious diarrhea in adults. The Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol 1997;92:1962.
  3. Gastrointestinal and Liver Disease, 7thed. Mark Feldman, Lawrence Friesman, Marvin Sleisenger, editors. W.B. Saunders, New York, 2002. Chapters 10,55,56,57,58,62,75,76.
  4. Colon, rectum and anus. Welton M, Varma MG, Amerhauser A, in Surgery Basic Science and Clinical Evidence. Norton JA, Bollinger RR, Chang AE, Lowry SF, Mulvihill SJ, Pass HI, Thompson RW. Editors. Springer-Verlag New York 2001, Chapter 33, pg667.
  5. Sexually transmitted disease Smith L, in Principles and Practice of Surgery for the Colon Rectum and Anus.2nd ed. Phillip H. Gordon MD, Santhat Nivatvongs MD, editors. Quality Medical Publishing, Inc, St.Louis, 1999, pg341.

Specific:

  1. Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. N Engl J Med 1994;330:257.
    McFarland LV, Mulligan ME, Kwok RY, Stamm WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989;320:204.
  2. Kyne L, Warny M, Quamar A, et al. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med 2000;342:390.
  3. Johnson S, Homann SR, Bettin KM et al. Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, placebo controlled trial. Ann Intern Med 1992;117:297.
  4. Hunter GC, Guernsey, JM, Mesenteric Ischemia Med Clin North Am 1988;72:1091
  5. Babb RR, Radiation proctitis: a review. Am J Gastroenterol 1996;91:1309.
  6. Denton A, Forbes A, Andreyev J, Maher EJ. Non-surgical interventions for late radiation proctitis in patients who have received radical radiotherapy to the pelvis. Cochrane Database Syst Rev 2002; :CD003455.
  7. Kochar RM, Patel F, Dhar A et al. Radiation-induced proctosigmoiditis. Prospective randomized, double-blind controlled trial of oral sulfasalazine plus rectal steroids versus rectal sucralfate. Dig Dis Sci 1991;36:103.
  8. Glotzer DJ, Glick ME, Goldman H. Procitis and colitis following diversion of the fecal stream. Gastroentterology 1981;80:438.
  9. Whelan RL, Abrahamson D, Kim DS, Hashimi HF. Diversion colitis,. Surg Endosc 1994;8:19.
  10. Asplund S, Gramlich T, Fazio V, Petras R. Histologic changes in defunctioned rectums in patients with inflammatory bowel disease: a clinicopatholigc study of 82 patients with long-term follow-up. Dis Colon Rectum 2002;45:1206.
  11. Roe AM, Warren BF, Brodribb AJ, Brown C. Diversion colitis and involution of the defunctined anorectum. Gut 1993;34:382.