Colitides
Associate Professor of Surgery
Section of
The colitides excluding inflammatory Bowel Disease (IBD) are a diverse group of acute and chronic diseases that range from an acute self-limiting diarrheal illness to a fulminant colitis requiring immediate surgical intervention. They can be categorized into infectious and non-infectious etiologies. Many of these colitides occur in immunocompromised patients, but others may occur in patients without any known risk factors. The following discussion is a brief outline of a diagnostic approach and treatment outline of such colitides.
I. Evaluation & Diagnostic Approach
A. History
A complete and detailed history is vital to narrowing the differential diagnosis and directing the diagnostic studies. The classic symptoms of colitis include cramping abdominal pain and bloody or non-bloody diarrhea, which may be associated with mucous. The onset, progression, frequency and the volume of the diarrhea should be sought and may be an indicator of the etiology of the condition and the patient’s volume status. In addition, the patient should be queried about constitutional symptoms such as fever, malaise or weight loss. Information regarding similar symptoms in family members, recent travels, exposure to antibiotics and animals is essential.
The patient’s past medical history is important, as a history of a prior malignancy and its treatment such as chemotherapy or radiation therapy may be the etiology of the colitis. A history of atherosclerotic cardiovascular disease may be associated with ischemic colitis. A careful review of the patient’s medications including non-steroidal anti-inflammatory drugs (NSAIDS), new antibiotics, or immunosuppressants should be carried out. Information regarding the patient’s sexual practices, including ano-receptive intercourse and HIV status is also essential, since opportunistic infections attack immunosuppressed patients.
B. Physical Examination
Physical examination is essential in assessing the acuity of the disease and need for resuscitation and urgent intervention. Evaluation of the vital signs for tachycardia and hypotension as well as assessment of orthostatic hypotension in determination of hypovolemia is important. Fever usually suggests an infection with enteroinvasive bacteria (Escherichia, Salmonella, Shigella, or Campylobacter) or a cytotoxic organism (C.difficile, or E.histolytica). Abdominal examination should determine the presence of localized or generalized tenderness or peritoneal signs and distention. Inspection and examination of the perineum and genitals may reveal sexually transmitted diseases such as condylomata, syphilitic, herpetic lesions, fissures, or fistulae. A digital rectal exam should be performed to evaluate any masses, tenderness, fluctuance, strictures and sphincter tone. A bimanual examination should be performed in women and the rectovaginal septum should be evaluated. Anoscopy should be performed to evaluate fistulous openings or anal canal ulcers.
C. Investigations
1. Endoscopy
Flexible sigmoidoscopy is valuable in differentiating IBD from infectious (C.difficile, enteroinvasive bacteria) and non-infectious (ischemia) colitides. Mucosal abnormalities such as erythema and ulcers may be assessed and biopsied and abnormalities such as fluid, purulence or exudates may be aspirated and collected. Bowel preparation and enemas should be avoided as it may interfere with collection of infectious agents. Endoscopic examination should be performed carefully with minimal insufflation and terminated upon visualization of moderate to severe colitis due to the risk of perforation of the inflamed segment. Certain colitides (amebiasis, collagenous colitis) have a predilection for the proximal colon and if sigmoidoscopy has not confirmed the diagnosis, a complete colonoscopic evaluation is indicated. Patients with persistent diarrheal states and normal lower GI tract evaluation may benefit from an esophagogastroduodenoscopy (EGD) to exclude malabsorption and sprue as the etiology of the diarrhea.
2. Radiography
Though plain films may be used to exclude free air, contrast studies of the colon add little additional information and are usually contraindicated in patients at risk of perforation. An abdominal CT scan may be useful in assessing colonic dilation, wall edema and in excluding other intra-abdominal pathologies.
3. Laboratory Evaluation
a. Stool analysis
Though generally non-specific, stool analysis is inexpensive and may allow earlier institution of therapy. Gram stains of stool samples can detect ova, parasites and Campylobacter. Fecal leucocytes are present in stool specimens of patients with inflammatory colitis with mucosal disruption and may be helpful in establishing a diagnosis. Patients with secretory diarrhea will lack fecal leucocytes.
b. Stool cultures
Stool cultures generally have a low sensitivity and specificity. They are most helpful in immunocompromised patients and when a super-infection must be excluded in IBD patients who present with an exacerbation of colitis. Routine stool cultures for enteric organisms will detect Salmonella, Shigella, Campylobacter, and Aeromonas. Some laboratories will perform Yersinia cultures only if requested in advance. Viruses, Vibrios and Enterohemorrhagic E.coli may also be cultured. Collection of stool for ova and parasites is indicated for persistent diarrhea. 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), a community waterborne outbreak (Giardia, Cryptosporidium) or bloody diarrhea with few or no fecal leucocytes. Excretion is often intermittent depending on the life cycle thus several specimens may need to be collected over several days.
c. Serology
Serologic tests may be used to detect antibodies to several organisms including Treponemapallidum, Chlamydiatrachomatis, Cytomegalovirus, and Herpes Simplex Virus. These tests are usually expensive and take several days for results. They are used when there is difficulty in establishing a diagnosis.
d. Histopathology
Although most acute colitides appear similar on H & E stain with mucosal edema, PMN’s in the lamina propria and cryptitis, colonic biopsies may identify specific causes of infectious colitides.
II. Infectious Colitides
A. Bacterial Colitides
1. Clostridiumdifficile Colitis
Clostridium difficile colitis is one of the most important and common causes of colitis in hospitalized patients. The main risk factors for development of Clostridium difficile colitis are age greater than 60, recent or current antibiotic use and nursing home or institutionalized individuals.In the past few years, an increasing number of community-acquired cases have been reported; many of the patients who acquire this infection in the community have not received antibiotics in the past 90 days. Proton pump inhibitor use is associated with C.difficile colitis. The intestinal tract becomes colonized with this anaerobic, Gram-positive bacillus, once the native bacterial flora have been modified by antibiotics. This can occur in as little as a few days or up to 10 weeks following even a single prophylactic dose. Virtually all antibiotics with the exception of oral vancomycin have been implicated with the most common antibiotics being the penicillins, cephalosporins and clindamycin.
Clinical Presentation & Physical Findings:The clinical presentation depends on the severity of the disease and ranges from an asymptomatic carrier state to a mild self-limiting diarrheal illness to pseudomembranous colitis to fulminant colitis with toxic megacolon. Approximately 1-3% of healthy adult population are asymptomatic carriers of this organism who excrete the spores but rarely secrete the cytotoxin responsible for the clinical manifestations. Patients with pseudomembranous colitis present with a systemic illness characterized by crampy abdominal pain, profuse watery diarrhea (10-15 times per day), malaise, nausea and anorexia. Physical examination reveals localized abdominal tenderness. Fever and leucocytosis may be present. Sigmoidoscopic examination reveals raised yellow or whitish round plaques (pseudomembranes) covering the mucosa in some patients. These mucosal findings may only be present in the right colon. Fulminant colitis occurs in only 2-3% of patients and is characterized by diffuse abdominal pain, distention, high fever, chills, prominent leucocytosis and diarrhea. Diarrhea may be absent or cease as the colon becomes dilated and atonic. Toxic megacolon with severe abdominal distention and clinical deterioration may ensue. Guarding and rebound tenderness should alert the surgeon to the possibility of colon perforation. Pseudomembranous colitis may also occur following bowel preparation or chemotherapy for cancer. It may also affect the small intestine (pseudomembranous enteritis) following proctocolectomy.
Diagnosis:The gold standard for diagnosis is the stool cytotoxin assay, which is a tissue culture assay in which cytotoxin B produces a rounding of fibroblast cell bodies which is easily visualized under light microscopy. This assay carries a sensitivity of 94-100% and specificity of 99%, but requires 2-3 days for completion. The Enzyme-Linked Immunosorbent Assay (ELISA) for enterotoxin A (sensitivity 70-90%, specificity 99%) is now the most common test for diagnosis and theresults are available within a few hours. Endoscopy is helpful for confirmation of the diagnosis or as a guide to initiation of therapy prior to the availability of the test results. Visualization of pseudomembranes in the rectosigmoid is pathognomonic, however, these may only be present in the right colon and the rectum may be devoid of pseudomembranes in up to one-third of patients.
Treatment: In general, the offending antibiotic should be immediately discontinued, if possible. In out-patients with mild disease, no other specific therapy is indicated, however, the patient must remain well-resuscitated. This approach is not recommended for in-patients as the diarrhea contributes to the contagionPatients with moderate to severe disease should be resuscitated and started on oral metronidazole. Intravenous metronidazole may be given in patients who are systemically ill and have an ileus. For severe cases, oral vancomycin may be added but intravenous vancomycin is ineffective. Most clinicians agree that anti-motility agents are contraindicated. Surgical therapy must be considered in patients who deteriorate physiologically or in those who fail to improve with appropriate medical therapy. The surgical procedure of choice is a subtotal colectomy with end ileostomy. Lesser procedures such as segmental colectomy or defunctioning stomas carry a high mortality rate. Symptomatic relapses are seen in up to 25% of patients and a second, longer course of antibiotic therapy is recommended. Antibiotic pulse therapy or recolonization of the colonic flora may be considered.
2. Esherichia coli
This Gram-negative bacillus is a prominent component of the normal intestinal flora. Most strains of E. coli are harmless however several strains are a common cause of infectious diarrhea. Individuals at the extremes of age and the debilitated are at high risk of such infections. The diarrhea can range from watery to bloody.
Findings:Erythema, edema, friable mucosa and ulcerations are seen during endoscopy and fecal leucocytes are noted on stool examination. The best-known serotype is O157:H7, however, other strains are becoming an increasingly important etiology of Escherichial infections.
Enteroinvasive E. coli (EIEC) – This form of E. coli infection is characterized by a watery diarrhea, which may progress to bloody diarrhea. This organism is contracted from contaminated food and water supplies and can invade and multiply within the colonocyte.
Enterotoxigenic E. coli (ETEC) – Presents with watery diarrhea, which may be relatively mild or explosive and may last from 24-48 hours to several days. This organism is acquired from contaminated food and water supplies and its toxins stimulate chloride secretion into the bowel lumen producing a secretory diarrheal illness.
Enterohemorrhagic E. coli (EHEC) – is characterized by colitis with associated bloody diarrhea and Hemolytic Uremic Syndrome (HUS: microangiopathis edema, renal failure and thrombocytopenia). It may be contracted from unwashed produce as well as undercooked meat. A very small inoculum (100-200 organisms) is required for a symptomatic infection. The most common serotype is O157:H7. Two types of cytotoxins are produced: Shiga toxin, which causes a secretory diarrhea and an enterohemolysin,which causes enterocyte invasion.
Enteropathogenic E. coli (EPEC) – produces a severe persistent watery diarrhea, with vomiting and dehydration with malnutrition most common in neonates. This organism adheres to the enterocyte and alters water and electrolyte secretion.
Enteroaggregative E. coli (EAEC) – presents with diarrhea in children and patients with HIV. Acquired from contaminated food and water supplies.
Treatment: Oral rehydration with glucose-linked sodium absorption of water and electrolytes. Diarrhea is usually self-limited and antibiotic therapy not required. Ciprofloxacin decreases the duration of diarrhea in EAEC. Antibiotic treatment appears to increase the risk of HUS in EHEC and is contraindicated.
3. Shigella
Shigella are a group of virulent Gram-negative bacilli that invade enterocytes and colonocytes to a cause a characteristic diarrheal illness termed bacillary dysentery. These organisms are acquired via ingestion of contaminated food and water through person-to-person contact and ingestion of as little as 10 organisms can cause disease with an incubation period ranging from 1-3 days. The incidence is highest in children and infection is endemic in day-care centers and other institutions. Shigella invade the enterocytes via production of Shiga toxin and cause a crampy abdominal pain, high fever, and voluminous watery diarrhea. Colonic involvement is associated with crampy lower abdominal pain, and the onset of bloody, mucoid diarrhea, with urgency and tenesmus. The spectrum of disease is associated with the infecting organism: S.sonnei causes a mild watery diarrhea, whereas, S.dysenteriae and S. flexneri cause bloody, mucoid diarrhea. Paralytic ileus, toxic megacolon, perforation, neurologic symptoms, Reiter’s syndrome and HUS may occur in some patients.
Diagnosis: is readily made by culture of a fresh stool specimen as most laboratories routinely culture stool specimens for Shigella. Endoscopy demonstrates friable, erythematous, and sometimes ulcerated mucosa involving the rectum and sigmoid colon. Approximately 50% of patients have colonic involvement up to the splenic flexure.
Treatment:General supportive measures including fluid resuscitation, avoidance of narcotics and anti-diarrheals are required. In healthy individuals, the illness is self-limited lasting an average of one week. Patients may excrete viable organisms for up to one month following resolution of symptoms and antibiotics may be used to shorten the clinical illness and limit the active shedding of the organisms. Ampicillin is used in most patients for 7 days. Shigella species develop antibiotic resistance rapidly, and ciprofloxacin and trimethoprim/sulfamethoxazole (TMP/SMX) should be used to treat such resistant strains. An asymptomatic carrier state for Shigella is rare, however, such patients should be treated until culture negative.
4. Salmonella
Salmonella are facultative anaerobic Gram-negative rods that invade the small bowel and colonic mucosa and induce an enterocolitis with bloody diarrhea and are responsible for the second leading cause of food borne illness in the United States. They are acquired through the ingestion of poultry, eggs and milk products and are spread through flies, fingers, food, fomites, and feces. Salmonellosis is seasonal and occurs most commonly in the summer and fall. Though infection may occur at any age, children younger than 5 years of age have the highest incidence of infection. Susceptibility to infection is increased with impaired cellular immunity, such as AIDS, organ transplantation, malignancy and chemoradiotherapy. Alterations in intestinal flora, decreased gastric acidity and impaired phagocytic function also increase the risk of infection with Salmonella. Infection becomes apparent within 48 hours of ingestion in most patients. Symptoms include diarrhea, which may be bloody, nausea, vomiting, fever, chills, and abdominal pain. Toxic megacolon with perforation may result. Larger inocula of the organism result in more severe diarrhea, longer duration of disease and weight loss.
Diagnosis: is through stool cultures and endoscopy reveals hyperemia, friability, granularity and ulcerations.
Treatment: As the illness is usually self-limited, antibiotics are not necessary; however, fluid and electrolyte replacement is imperative. Antibiotics are considered in immunosuppressed patients, those with lymphoproliferative disorders, organ transplantation, or children less than 1 year of age. Quinolones, chloramphenicol, and trimethoprim/sulfamethoxazole (TMP/SMX) are usual first line therapies. Less than 3% of individuals become chronic asymptomatic carriers.
5. Campylobacter
This invasive, curved motile Gram-negative bacillus is the most frequently identified pathogen associated with acute diarrhea in western countries. Ingestion of undercooked poultry is thought to be responsible for the majority of sporadic cases in the United States. Following a 48-72 hour incubation period, infection is established in jejunum, ileum, and often in colon and rectum followed by abdominal pain and diarrhea which ranges widely in severity. Fever, rigors, aches may precede the onset of diarrhea in up to 30% of patients. Abdominal pain may be localized to any part of the abdomen and when in the right lower quadrant, may be mistaken for appendicitis, though rebound tenderness is absent. Complications such as toxic megacolon may ensue in a small percentage of patients and extraintestinal manifestations such as arthralgias and tender hepatosplenomegaly may occur.
Findings: Endoscopy demonstrates a non-specific colitis with edema, bloody exudates and ulcerations and stool examination reveals leucocytes and red blood cells. Dark field microscopic examination of stool specimens demonstrates rapidly moving, curved, rod-shaped organisms. The most definitive means of establishing a diagnosis is via stool culture on selective isolation medium. Most laboratories do not routinely culture for Campylobacter, therefore specific requests are necessary in suspected cases. Histpathologic examination reveals a non-specific acute inflammatory response with edema, neutrophils in the lamina propria and cryptitis.
Treatment: is directed to correction of fluid and electrolyte imbalances as the diarrhea is self-limiting and lasts for 3-5 days. Patients with signs of systemic illness and sepsis such as fever and leucocytosis should be treated with antibiotics. Erythromycin is the antibiotic of choice with a relapse rate of <5%. Fluoroquinolones become first line therapy for resistant strains. Relapses occur in 5-10% of cases.
6. Yersinia
Yersiniaenterocolitica is a Gram-negative coccobacillus, which invades enterocytes and causes an enterocolitis that may mimic acute appendicitis, as the terminal ileum is the most commonly affected site. It is spread through contaminated food and water. Clinical manifestations are usually seen within 7 days of ingestion with the most common symptoms being diarrhea, abdominal pain, fever, nausea, and vomiting. Occasional instances of pharyngitis, polyarthritis and erythema nodosum have also been reported. Yersinia may also cause a pseudo-appendicular syndrome or mesenteric adenitis by infecting the lymphatics in the Peyer’s patches in the terminal ileum. Toxic megacolon, intestinal perforation with peritonitis have been reported. Y.enterocolitica can be cultured in 4% of appendectomies.
Findings: Stool cultures are the most reliable means of establishing diagnosis but cultures for this organism must be specifically requested. Endoscopic findings are non-specific and may resemble Crohn’s disease with inflammation and ulceration and granulomata may be present on biopsy.
Treatment: As with all diarrheal illnesses, adequate hydration must be provided. Antibiotic therapy with IV ceftriaxone and gentamicin followed by oral ciprofloxacin is reserved for those with severe septicemia.
7. Spirochetosis
Infections with Treponemapallidum and other spirochetes are sexually transmitted and generally asymptomatic. They are most commonly found in men who have sex with men and are transmitted during ano-receptive intercourse. The organism adheres to and invades the epithelium and induces an inflammatory response manifested by small volume diarrhea, tenesmus, rectal bleeding and mucous discharge.
Findings: Endoscopy demonstrates mucopurulent discharge and ulcerations. The Venereal Disease Research Laboratory (VDRL) assay is reactive (positive) in 75% of patients with primary syphilis and in all patients with secondary syphilis. The Fluorescent Treponemal Antibody – Absorption test (FTA-ABS) becomes positive 4-6 weeks after infection and remains positive for life. The presence of a thick blue band on H&E staining or silver staining on histology makes the diagnosis.
Treatment: High-dose benzathine penicillin is curative. Erythromycin, tetracycline, or doxycycline may be used in penicillin-allergic patients.
8. Colonic Tuberculosis
Mycobacteriumtuberculosis may affect any region of the GI tract, though the most common areas are the terminal ileum and cecum (85-90%). The organism is ingested and penetrates the intestinal mucosa. Abdominal pain is the most common symptom (90%) and is often associated with diarrhea and rectal bleeding. A palpable mass is found in 60% of patients. Colonic TB may mimic Crohn’s disease and complications include hemorrhage, perforation, obstruction, and fistula formation. Pulmonary TB is seen in less than 50% of patients.
Findings: Three patterns of disease may be seen during endoscopic examination: ulcerative (60%), hypertrophic (10%) with scarring that may mimic a carcinoma, and ulcero-hypertrphic (30%), with features of both. Stool cultures are positive in only 30% of patients. The diagnosis is confirmed histologically by visualization of non-caseating granulomas on an acid-fast bacilli stain. Skin testing in unhelpful in determination of GI involvement.
Treatment: Triple drug therapy with isoniazid, rifampin, and pyrazinamide is recommended for 12 months. Surgical therapy is reserved for complications such as obstruction, bleeding, perforation, or the inability to exclude carcinoma. Fistulous tuberculosis generally responds to medical treatment.
B. Viral Colitides
1. Cytomegalovirus (CMV)
CMV is a double stranded DNA virus belonging to the Herpes virus family. Some healthy individuals infected with CMV may develop infectious mononucleosis, a syndrome with fever, aches, lymphadenopathy and mild hepatitis, but most are asymptomatic carriers. Nearly all healthy homosexual men are seropositive for CMV. Clinical disease occurs primarily in immunosuppressed patients (HIV/AIDS, organ transplantation) due to hematogenous spread of CMV secondary to reduced CD4 activity. Ileocolitis is the most common intestinal infection, occurring in at least 10% of AIDS patients. Symptoms include intractable diarrhea, which is often bloody associated with abdominal pain and tenesmus. In severe cases, perforation can occur requiring surgical intervention with total abdominal colectomy and end ileostomy. CMV enterocolitis is the most common reason for emergency abdominal colectomy in AIDS patients.
Findings:Non-specific ulcerations with patchy submucosal erythema and edema are noted on endoscopy and violaceous submucosal lesions may mimic Kaposi’s sarcoma. Colonoscopy is preferred to sigmoidoscopy due to right-sided involvement in most patients. Mucosal CMV infection causes inflammation and tissue necrosis with vascular endothelial involvement and ischemic necrosis leading to hemorrhage. Other causes of colitis in such patients must be ruled out by obtaining fresh stool specimens for ova and parasites, bacterial culture and assay for C.difficile toxin. Biopsy may show the characteristic basophilic intranuclear inclusion bodies with acute and chronic inflammatory cells. Diagnosis is confirmed by viral tissue culture.
Treatment: is with IV foscarnet or IV or PO gancyclovir. Foscarnet has been associated with irreversible renal failure and abnormalities in calcium metabolism. Gancyclovir can cause bone marrow suppression, which may be exacerbated in patients taking zidovidune (AZT). Lifelong maintenance therapy may be required in some patients as these drugs are only virustatic. Surgery is required for complications and carries a very high mortality rate.
C. Parasitic Colitides
1. Amebiasis
Amebiasis is caused by the anaerobic intestinal protozoan parasite Entamoebahistolytica. Most infections (90%) are asymptomatic. E.histolytica exists in two forms: a cyst, which is infective, and a trophozoite, which is invasive. The active trophozoites are fragile and exist only in the host and fresh, loose stool and parish quickly outside of the host, while the cysts can survive for months outside the host in water, soils, and food under moist conditions. The cysts can be killed heat and by freezing temperatures. Ingestion of cysts through contaminated food or water is the primary mode of transmission, but venereal transmission via the fecal-oral route can also occur. The disease is limited to a mild dysentery in most symptomatic patients. Some patients may develop severe bloody diarrhea with fever and weight loss. Fulminant colitis with bowel necrosis and perforation is rare. Amebic liver abscess may occur in a subset of patients. Anorectal abscesses and fistulae may occur rarely. Amebomas are dense, fibrous, granulomatous masses containing inflammatory cells, trophozoites and necrotic debris and are most commonly found in the cecum and the sigmoid colon and may be difficult to differentiate from a carcinoma.
Findings: Examination of fresh stool for amoeba (cysts or trophozoites) is the most commonly used test for diagnosis of amebic colitis. The presence of cysts represents a carrier state while motile trophozoites with intracytoplasmic red blood cells (hemocytophagia) is associated with active disease. At least three stool specimens should be examined before excluding this diagnosis. Early in the course of infection endoscopy may be normal or demonstrate non-specific diffuse erythema. Yellow exudate covered ulcers with a small mucosal opening and wider base in the submucosal or muscularis propria (flask-shaped ulcers) are characteristic of amebic infection. Serologic tests help exclude the disease but do not differentiate active infection from a carrier state.
Treatment: All infected patients should be treated to eradicate disease and prevent spread to family members. Metronidazole 750 mg PO TID for 10 days is the regimen of choice to treat cysts and trophozoites as it provides amebicidal concentration of drug systemically and intraluminally. Following this regimen, a course of iodoquinol 650 mg PO TID for 3 weeks is recommended to clear the colon of amebic cysts, and follow up stool cultures are recommended to ensure eradication of the cysts form the colon.In patients with toxic megacolon or perforation subtotal colectomy with end ileostomy, is the treatment of choice but carries a high morbidity and mortality. Amebomas should be treated initially with amebicidal agents and surgery reserved for treatment failures.
2. Cryptosporidia
Cryptosporidium is a small protozoan, which does not utilize an insect vector and is capable of completing its life cycle within a single host. Cryptosporidiosis is typically an acute, self-limited diarrheal infection but can become severe and fatal in AIDS patients and children. The oocytes are transmitted via the fecal-oral route and contaminated water. The diarrhea is usually watery or bloody and profuse with losses of up to 10 liters of fluid per day and associated with low-grade fever and abdominal cramps.
Findings: Endoscopic findings are non-specific with edematous, friable mucosa. Diagnosis is established by histopathologic examination of endoscopic biopsy specimens, which demonstrate the oocysts. Cryptosporidial oocysts can also be demonstrated on special preparation of fresh stool specimens.
Treatment: Immunocompetent patients only require supportive measures with hydration. Parmomycin is the antibiotic of choice in immunocompromised patients.
3. Lympogranuloma venereum (LGV)
LGV is caused by the L1, L2, or L3 serotypes of Chlamydia trachomatis. This organism is an obligate intracellular parasite and is transmitted primarily through sexual contact via breaks in the skin or mucous membranes. LGV may begin as a self-limited painless ulcer at the site of infection. This is followed by inguinal lymphadenopathy with fevers, abscess and fistulae. The late stage is characterized by fibrosis and strictures. LGV is usually limited to the rectum but may extend into the sigmoid colon.
Findings: Endoscopy reveals granular proctitis with friable, erythematous, and ulcerated mucosa. Cultures are unhelpful as the organism is an obligate intracellular parasite. Diagnosis is established by culture and serology with complement-fixation and immunofluorescence.
Treatment: Acute infections are treated with doxycycline, tetracycline or erythromycin for 7 days. Chronic, rectal strictures may be treated with dilations; however, restorative or non-restorative proctectomy may be required.
D. Fungi
1. Histoplasmosis
Histoplasmosis is caused by Histoplasmacapsulatum and is endemic in Ohio River valley and lower Mississippi River. H.capsulatum grows in soil and areas contaminated by bird or bat feces. Histoplasmosis is acquired by inhalation of the spores from disturbed soil. Most individuals have a clinically silent infection and show no ill effects. The disease primarily affects the lungs, but other organs including the GI tract may be affected in disseminated histoplasmosis, which occurs in immunocompromised patients (AIDS) and is fatal unless treated. Although the entire GI tract may be involved, the most common sites of involvement are the terminal ileum and right colon due to abundant lymphoid tissue in this area (Peyer’s patches). Symptoms include abdominal pain, fever, diarrhea, and weight loss. Hepatosplenomegaly may be present in some patients. Bowel obstruction secondary to large inflammatory masses or stricutres that mimic malignancy may occur. Intestinal perforation with peritonitis has also been reported.
Findings: Ulcers, pseudopolyps, plaques and skip areas of inflammation resembling Crohn’s disease are seen on colonoscopy. Diagnosis made with biopsy revealing intracellular oval, budding yeasts within the mucosa and with fungal cultures. Serologic complement fixation test also confirms the diagnosis. Histoplasma skin tests indicate exposure not active disease.
Treatment: Antifungal medications such as amphotericin B, fluconazole, and ketoconazole are effective therapy. Surgical therapy with resection or diversion is indicated for complications or inability to exclude carcinoma. Clearance may require prolonged medical therapy.
III. Non-infectious Colitides
1. Ischemic Colitis
Ischemic colitis is a spectrum of disease caused by an interruption or reduction of blood flow to the colon. Ischemic colitis has numerous causes, which can be classified as either occlusive or non-occlusive. Occlusive disease may be due to thrombosis, atherosclerosis, embolism or trauma. Non-occlusive disease may be due to small vessel disease, vasospasm, mechanical obstruction, systemic vasculitides and hematologic disorders and may be exacerbated by hypovolemia, shock, or medications. The most commonly affected areas are the watershed areas, which have the weakest blood supply. Approximately 70% of cases occur in the left colon and the clinical presentation depends on the etiology and the severity of the ischemia as well as the ischemic time.Acute colonic ischemia is characterized by rapid onset of mild to moderate left-sided abdominal pain and tenderness usually associated with bloody diarrhea and “red currant jelly” stools. Although majority of patients are older than 60, younger patients may be affected. Clinically, ischemic colitis may be divided into non-gangrenous (80-85%) type, which is subdivided into a transient, reversible and chronic form, and gangrenous type (15-20%). The transient reversible type involves only the mucosa and the submucosal and is generally followed by complete recovery within 2 weeks without any further sequelae. The non-gangrenous chronic form is characterized by ischemic injury to the muscularis propria and healing by fibrosis generally results in varying degrees of stricture. Gangrenous ischemic colitis involves transmural colonic injury, metabolic acidosis, and progression to shock and requires surgical intervention with bowel resection.
Findings: Endoscopic findings range from pale mucosa with petechial hemorrhage to discrete ulcers with mucosal edema to necrotic mucosa in severe cases. Endoscopy is contraindicated in patients with an acute abdomen. The rectum is usually spared due to its generous vascular supply form multiple sources. Infectious colitides, IBD, radiation enteritis, diverticulitis, solitary rectal ulcer syndrome and malignancy should be excluded. Laboratory tests may be normal or reveal varying degrees of leucocytosis and acidosis. Plain abdominal x-rays are usually non-specific but may demonstrate thumbprinting (mucosal edema) and pneumatosis (mural necrosis). CT scan may be normal or demonstrate colonic wall thickening.
Treatment: is directed by the severity of the disease and the clinical circumstances. Gangrenous ischemic colitis with perforation and peritonitis mandates volume resuscitation, celiotomy with bowel resection. In the absence of gangrene and peritonitis, supportive care with bowel rest, IV fluids, broad-spectrum antibiotics are initiated. Prognosis depends on severity of disease and patient’s comorbidities. Mild cases improve in one to two days with complete resolution in one to two weeks. More severe disease resolves more slowly and develops into a chronic segment of colitis or stricture.
2. Radiation-induced colitis
Radiation proctocolitis can be classified as acute and chronic. Acute injury occurs during radiation therapy and may last up to 6 months. It is directly related to fraction size, frequency of treatment and total volume of irradiated tissue. Higher doses over shorter intervals generally induce greater toxicity. Symptoms include diarrhea, tenesmus and mucous discharge (75%). Cessation of therapy allows regeneration of crypts and resolution of symptoms. Histologic recovery may take up to 6 months. Chronic radiation injury occurs 6 – 12 months following treatment but may occur up to 30 years later. Chronic radiation injury is characterized by progressive fibrosis of the supportive microvasculature resulting in “obliterative end-arteritis.” Predisposing factors include mesenteric vascular disease, prior abdomino-pelvic surgery, chemotherapeutic agents (5-FU, methotrexate, actinomycin), pre-existing inflammatory conditions (IBD, diverticulitis), improper radiation technique, and post-operative radiation. Diarrhea, tenesmus, urgency and hematochezia are common symptoms. Incontinence may be prominent if the sphincter complex was involved with radiation.
Findings: Endoscopically, the mucosa appears pale and friable with mucosal telangiectasias, which can be a source of hematochezia. Biopsies are not diagnostic in this case, but are used to exclude other etiologies of proctitis.
Treatment: Proctocolitis during radiation treatment is treated non-operatively with a low-residue diet, antispasmodics, stool softeners and steroid or 5-ASA enemas. Most symptoms will resolve over one to two weeks. When these measures fail to control the symptoms, the radiation dose may be reduced. Rarely, treatment may need to be discontinued for acute toxicity. Chronic radiation-induced proctocolitis may be treated similarly with a combination of steroids, sucralfate, or 5-ASA enemas, but success is variable. Coagulating the mucosa, or direct application of 4% formalin solution using a cotton-tipped applicator may be effective in treating recalcitrant or recurrent bleeding. Patients with strictures may improve symptomatically with stool softeners. Balloon dilation is effective for short segment strictures but may not be durable and risks perforation. Proximal diversion, resection with or without diversion, and intestinal bypass should be considered depending on the clinical circumstances, though bypass does not address intestinal bleeding.
3. Collagenous and Lymphocytic Colitis (Microscopic Colitis)
Microscopic colitis is characterized by a chronic watery, secretory diarrhea without bleeding and account for 5% of secretory diarrheas. Patients are predominantly females in the sixth decade of life who present with chronic watery diarrhea of 500 – 2000 cc per day. Microscopic colitis may be associated with rheumatoid arthritis, scleroderma, atrophic gastritis, hepatitis, primary biliary cirrhosis, thyroid disorders and Hodgkin’s disease. Three types of microscopic colitis have been described:
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 – characterized by both a thickened collage layer and lymphocytic infiltrate.
The natural history of microscopic colitis is highly variable; symptoms may persist for years or resolve spontaneously only to return months or years later. There appears to be no malignant potential. It is thought that the presence of the collagen layer prevents proper water and electrolyte absorption leading to the watery diarrhea. Other proposed etiologies include mucosal injury secondary to bacterial toxins, and medications such as NSAIDS, simvastatin, lansoprazole, and flutamide.
Findings: On endoscopy, the mucosa appears normal. There appears to be a predilection for the right side of the colon, therefore colonoscopy is preferred. Diagnosis is made by biopsy,which reveals colitis without ulceration.
Treatment: is non-specific and includes stopping NSAIDs, and treating the diarrhea with loperamide. Aminosalicylates, sulfasalazine, topical or systemic steroids, or bismuth subsalicylate may be used but have variable success.
4. Eosinophilic Colitis
Eosinophilic gastroenteritis is rare and may involve any portion of the GI tract diffusely or in a segmental fashion and colonic involvement is usually right-sided. Symptoms include colicky abdominal pain, diarrhea, hematochezia, and weight loss. Most patients have a history of food allergy or intolerance. Peripheral eosinophilia may be seen but is not diagnostic.
Findings:Endoscopic findings are identical to Crohn’s disease. Diagnosis is by colonoscopic biopsy and histologic examination, which reveals an eosinophilic infiltrate in the mucosa and submucosa.
Treatment: is with dietary modification and avoidance of specific foods in most patients. In more severe cases, steroids, immunosuppressive agents, and sodium cromoglycate may be beneficial.
5. Diversion Colitis
Diversion colitis, bypass colitis, exclusion colitis, and disuse colitis are terms for the colitis that occurs following fecal diversion from a colonic segment. It is due to a lack of short-chain fatty acids (SCFA, butyrate, acetate and propionate), normally produced from the breakdown of unabsorbed complex carbohydrates by the resident fecal bacteria. Symptoms include rectal bleeding, tenesmus, and mucous discharge, however most patients are asymptomatic. Symptoms may occur within a few months or after a long delay. Differentiation of diversion colitis from persistent IBD may be difficult.
Findings: Endoscopy reveals typical findings of colitis including erythema, friability, ulceration, exudate and distorted vascular pattern. Histologic findings are non-specific and include mucosal edema, granulocyte infiltration and fibrosis.
Treatment: Restoration of intestinal continuity is the treatment of choice and is curative. Early operation is preferred as prolonged diversion causes involution and atrophy of the segment with worse functional results. If stomal closure is not an option, then a trial of SCFA enemas (60 cc instilled twice daily) is warranted. The results are variable but best in patients without pre-existing colitis. Sulfasalazine enemas may also be beneficial.
6. Neutropenic Enterocolitis (Typhlitis)
Neutropenic enterocolitis or typhlitis is a life-threatening infectious colitis that occurs in Neutropenic immunosuppressed patients. Pathogenesis is poorly understood but is thought to include mucosal injury by cytotoxic drugs, neutropenia (<500 WBC/mm3, and impaired host defense to intestinal organisms. Cytotoxic injury to the mucosa allows bacterial invasion of the bowel wall, which is facilitated by the neutropenia. The cecum is almost always affected, but the disease may also involve the small intestine and the right and left colon. Polymicrobial infection is common including Gram-negative rods, Gram-positive cocci, anaerobes and candida. Bacteremia and fungemia are frequently seen. Symptoms including right lower abdominal pain, distension, nausea, and watery or bloody diarrhea usually occur 10-14 days post chemotherapy. Peritonitis accompanies intestinal perforation. CT scan is the preferred method of diagnosis and demonstrates a distended, fluid filled, edematous cecum and bowel wall thickening. Free air, pneumatosis, and soft tissue air are ominous signs. Contrast studies and colonoscopy are contraindicated due to the risk of perforation. The differential diagnosis includes C. difficile colitis, appendicitis, Ogilvie’s syndrome, and ischemic colitis.
Treatment: In patients without peritonitis, perforation, or massive hemorrhage, non-surgical management with bowel rest, fluid resuscitation, broad-spectrum IV antibiotics, and nutritional support should be the initial approach. Antifungal coverage should be initiated in patients who remain febrile after 72 hours. Granulocyte-Colony Stimulating Factor (G-CSF) should be strongly considered to accelerate leucocyte production. Patients should be monitored closely with repeated examinations and CT scan as required. Most patients will fully recover once the neutropenia is corrected. Surgical treatment is recommended for patients with perforation, bleeding despite correction of coagulopathies, and clinical deterioration on maximal medical therapy. Resection without anastomosis and proximal diversion is the procedure of choice. Care should be taken during resection as serosal involvement underestimates true colonic involvement.
7. Chemical/Drug-induced Colitis
A number of medications and chemicals have been implicated in proctitis and colitis. Soap colitis may occur within hours of administration of soapsuds enemas. Other agents include herbal medications, vinegar, potassium permanganate, Hypaque, and Fleets phosphosoda. Mucosal inflammation of the colon is a rare adverse effect of some commonly used medications such as NSAIDs or oral contraceptives. Other medications include methyldopa, penicillamine, potassium supplements, 5-FU, oral gold and isotretinoin.
Findings: Endoscopy reveals colitis that is limited to the area of contact and is non-specific with hyperemia, friability, and edema. It is imperative that other important causes of colitis (C.difficile colitis) are excluded.
Treatment: is supportive with cessation of the offending agent and complete recovery is observed in 4-6 weeks. Antibiotics may be considered in sever cases.
8. Miscellaneous causes of colitis include vasculitides, connective tissue disorders, amyloidosis, Behcet’s syndrome, chronic lymphocytic leukemia, and lymphoma.
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