Colitis is inflammation of the mucosal lining of the colon which may be acute or chronic. Colitis is common and increasing in prevalence worldwide. Patients with colitis present with watery diarrhea, abdominal pain, tenesmus, urgency, fever, tiredness, and blood in the stool. However, colitis has different types and results from several mechanisms including infection, autoimmunity, ischemia, and drugs. Also, it may occur secondary to immune deficiency disorders or secondary to exposure to radiation. Because the clinical presentation can be the same across different types of colitis, there is a need for a review presenting an approach to assess patients presenting with colitis. Searching the literature reveals that this area is deficient, and nearly most publications are focused on one aspect of colitis or are disease-based articles. This review discusses the etiology, epidemiology, pathophysiology, clinical presentation, evaluation, differential diagnosis, complications, and management of patients with colitis.
Types
There are many types of colitis. They are usually classified by the cause.
Types of colitis include:
Autoimmune
- Inflammatory bowel disease (IBD) – a group of chronic colitis.
- Ulcerative colitis (UC) – is chronic colitis that affects the large intestine.
- Crohn’s disease (CD) – is another type of IBD that often leads to colitis.
Unknown
- Microscopic colitis – colitis diagnosed by microscopic examination of colonic tissue; macroscopically (“to the eye”) it appears normal.
- Lymphocytic colitis
- Collagenous colitis
Treatment-caused
- Diversion colitis
- Chemical colitis
- Chemotherapy-induced colitis
- Radiation colitis
- Checkpoint inhibitor-induced colitis
Vascular disease
- Ischemic colitis
Infectious
- Infectious colitis
- A subtype of infectious colitis is Clostridioides difficile colitis, which is informally abbreviated as “C-diff colitis”. It classically forms pseudomembranes and is often referred to as pseudomembranous colitis, which is its (nonspecific) histomorphologic description.
- Enterohemorrhagic colitis may be caused by Shiga toxin in Shigella dysenteriae or Shigatoxigenic group of Escherichia coli (STEC), which includes serotype O157:H7 and other enterohemorrhagic E. coli.
- Parasitic infections, like those caused by Entamoeba histolytica, can also cause colitis.
Unclassifiable colitides
- Indeterminate colitis is the classification for colitis that has features of both Crohn’s disease and ulcerative colitis. Indeterminate colitis behavior is usually closer to ulcerative colitis than Crohn’s disease.
- Atypical colitis is a phrase that is occasionally used by physicians for colitis that does not conform to the criteria for accepted types of colitis. It is not an accepted diagnosis per se and, as such, colitis that cannot be definitively classified.
Causes
In adults, colitis may be the result of infection, inflammatory bowel disease, microscopic colitis, ischemia, drugs, secondary to immune deficiency disorders, or radiation.
- Infection: Bacterial infections including Campylobacter jejuni, Escherichia coli, Salmonella, Shigella, Mycobacterium tuberculosis, and Clostridium difficile responsible for Pseudomembranous colitis. Parasites such as Entamoeba histolytica, and viruses such as cytomegalovirus.
- Inflammatory bowel disease: This refers to Crohn’s disease (CD) and Ulcerative colitis (UC).
- Microscopic colitis: This condition is a relatively common cause of chronic watery diarrhea, especially in the elderly. The disease has two main subtypes, collagenous colitis (CC) and lymphocytic colitis (LC), which are very similar clinically with the main distinction being the presence or absence of a thickened subepithelial collagen band. The disease is associated with autoimmune disorders such as celiac disease, type 1 diabetes, thyroid dysfunction, and psoriasis.
- Ischemic colitis: Occurs when there is hypoperfusion in the blood supply below that required for the metabolic needs of the colon resulting in colonic mucosal ulceration, inflammation, and hemorrhage.
- Drug-induced colitis: Drugs such as non-steroidal inflammatory drugs, aspirin, proton pump inhibitors, Hreceptor antagonists, beta-blockers, statins, immunosuppressive drugs, and vasopressors may cause colitis.
- Secondary to immune deficiency disorders
- Tuberculous colitis
- Radiation colitis: This can occur secondary to pelvic radiotherapy for gynecological, urological, and rectal cancers.
The pathologic basis includes:
- Infection with Campylobacter jejuni is a result of orally ingested contaminated food or water. Infection influences include several factors including the dose of bacteria ingested, the virulence of organisms, and the immunity of the host. The median incubation period is 2 to 4 days. C jejuni multiplies in the bile and then invades the epithelial layers and travels to the lamina propria producing a diffuse, bloody, edematous enteritis. Pseudomembranous colitis is caused by toxin-producing Clostridium difficile. The disease develops as a result of altered normal microflora (usually by antibiotic therapy such as cephalosporin and beta-lactam antibiotics) that enables overgrowth and colonization of the intestine by Clostridium difficile and production of its toxins.[rx]
- Inflammation in ulcerative colitis involves the rectum in 95% of patients and extends proximally in a continuous pattern. The disease may affect the entire colorectum (termed pancolitis) or only be limited to the rectum (termed proctitis). Some patients may develop limited terminal ileal involvement (backwash ileitis) that can be challenging to differentiate from Crohn’s disease.[rx][rx]
- The pathophysiology of microscopic colitis is not well understood. Several hypotheses have been placed to explain the disease’s’s underlying mechanisms and pathogenesis including genetic predisposition, autoimmunity, immune dysregulation to a reaction to a luminal antigen such as various infectious agents and medications, as well as bile acid malabsorption.[rx][rx][rx]
- In ischemic colitis, the duration and severity of hypoperfusion will determine the colonic injury. Reperfusion injury could also be a significant contributing factor. Patients with ischemic colitis usually have (1) comorbidities including heart failure, atherosclerosis, systemic inflammatory response syndrome (SIRS), atrial fibrillation (emboli), concurrent malignancy, and hematological disorders (thrombosis). (2) Iatrogenic causes include abdominal aortic aneurysm repair, bowel preparation media for a colonoscopy,, and colonoscopy. Two mechanisms may cause bowel ischemia, the first is diminished bowel perfusion due to low cardiac output (heart failure, shock), and the second is occlusive disease including atherosclerosis and embolism with inadequate collateral circulation.[rx]
- In drug-induced colitis, the pathophysiology and pathology vary and may mimic microscopic colitis and or ischemic colitis.
- In colitis secondary to immune deficiency disorders, several factors might be responsible for colitis and diarrhea including HIV infection, antiretroviral therapy, opportunistic infection (particularly cytomegalovirus), and cryptosporidiosis.
Symptoms
Ulcerative colitis symptoms can vary, depending on the severity of inflammation and where it occurs. Signs and symptoms may include:
- Diarrhea, often with blood or pus
- Abdominal pain and cramping
- Rectal pain
- Rectal bleeding — passing a small amount of blood with stool
- Urgency to defecate
- Inability to defecate despite urgency
- Weight loss
- Fatigue
- Fever
- In children, failure to grow
- Swelling of the colon tissue
- Erythema (redness) of the surface of the colon
- Ulcers on the colon (in ulcerative colitis) which may bleed
- Mucus and/or blood in stool and rectal bleeding
- Diarrhea, may occur, although some forms of colitis involve constipation so the stool and bowel movements may appear normal.
Later you may also have:
- Blood, mucous, or pus in bowel movements.
- Severe cramping.
- Fever.
- Skin rashes.
- Mouth sores.
- Joint pain.
- Red, painful eyes.
- Liver disease.
- Loss of fluids and nutrients.
Most people with ulcerative colitis have mild to moderate symptoms. The course of ulcerative colitis may vary, with some people having long periods of remission.
Diagnosis
While there is no specific approach for assessing histological changes associated with colitis, the histological pattern approach described by Jessurun seems to be practical and the current recommendation. The patterns include (1) acute colitis associated with colonic infections and drug-induced injuries, inflammation may be patchy or diffuse, and mixed inflammatory cells and abundant neutrophils are usually present (2) focal active colitis, mostly seen in drug-induced injuries, but maybe a manifestation of inflammatory bowel disease especially Crohn disease. (3) Pseudomembranous colitis pattern associated with C. difficile infection, although it can result from other infections such as Shigella, drugs, and radiation injury, (4) hemorrhagic colitis is associated with the entero-hemorrhagic strain of E. coli 0157: H7. The lamina propria appears hemorrhagic and edematous. Fibrin thrombi are present within capillaries, crypts show ischemic injury, and (5) ischemic colitis is associated with acute ischemic colitis. The extent of mucosal injury determines the clinical presentation; however, colonoscopy and biopsies are seldom necessary for patients presenting with acute abdomen due to embolic occlusion, or intestinal obstruction.[rx]
History and Physical
Patients with colitis present with abdominal pain, watery diarrhea, fever, urgency, and blood in the stool. Examining doctor should look for red flags such as patient’s age, hemodynamic changes, nocturnal diarrheas, tenesmus, urgency, weight loss, comorbidities, history of heart failure, arrhythmias, autoimmune disorders, detailed history of patient’s medication, signs suggestive of toxic megacolon, and anemia.
In ulcerative colitis, extraintestinal manifestations associated with colitis and disease activity include arthropathies, eye changes (episcleritis, scleritis, uveitis), and skin changes (erythema nodosum and pyoderma gangrenosum). Other extraintestinal manifestations reported in colitis include sacroiliitis, ankylosing spondylitis, hepatic dysfunction, and primary sclerosing cholangitis.[rx]
Diagnosis of colitis has its basis in clinical findings, laboratory tests, endoscopy, and biopsy. Endoscopy and biopsy should not be the primary investigations and may be arranged after a critical evaluation of the patient’s condition and the results from the initial examinations.
- Because the colonic infection is a common etiology of colitis and can produce clinical presentations indistinguishable from inflammatory bowel disease, microbiological studies and cultures for bacterial and parasitic infestations should be the primary investigations. Laboratory workup including complete blood count, ESR, CRP, arterial blood gases, activated partial thromboplastin time, serum albumin, total protein, blood urea, creatinine, electrolytes, and purified protein derivative, should be ordered.
- D-lactate levels in the blood could be a sensitive marker of colonic ischemia; however, it is an experimental laboratory test.
- Electrocardiogram, transthoracic,, and even Holter monitoring may be necessary for patients with ischemic colitis.
- Plain X-ray is of limited value; however, it may be useful in the diagnosis of toxic megacolon, bowel obstruction, and intestinal perforation (pneumoperitoneum). Thumbprinting is a classic finding for mucosal edema though not specific for ischemic colitis.
- Multidetector CT and thin sections, can accurately demonstrate inflammatory changes in the colonic wall and help assess the extent of the disease. Ulcerative colitis is distinguishable from granulomatous colitis (Crohn’s’s disease) in terms of location of involvement, extent, and appearance of colonic wall thickening, and type of complications.
- Colonoscopy or proctosigmoidoscopy is essential for the final diagnosis; it typically appears normal in microscopic colitis although edema or erythema may present. Ulceration suggests an alternative diagnosis, although these can be present in patients on non-steroidal anti-inflammatory drugs.
- Other colonoscopy changes, depending on the etiology, include loss of typical vascular pattern, granularity, friability, and ulceration.
- Several laboratory tests specific to certain colitis may be ordered including perinuclear antineutrophil cytoplasmic antibodies (P-ANCA), which may present in Crohn’s’s disease, anti-saccharomyces cerevisiae antibodies (ASCA), a feature in both ulcerative colitis and Crohn disease, and carcinoembryonic antigen (CEA), which is elevated in patients with active ulcerative colitis.[rx]
- Assess the extent, degree, and severity of the disease and any complications.
Treatment
Not all infectious colitis requires antibiotic therapy; patients with mild to moderate C. jejuni or Salmonella infections do not need antibiotic therapy because the infection is self-limited. Treatment with quinolinic acid antibiotics is reserved for patients with dysentery and high fever suggestive of bacteremia. Also, patients with AIDS, malignancy, transplantation, prosthetic implants, valvular heart disease, or extreme age will require antibiotic therapy. For mild to moderate cases of C. difficile infection metronidazole is the preferred treatment. In severe cases of C. difficile infection oral vancomycin is recommended. In complicated cases, oral vancomycin with intravenous metronidazole is recommended. Cytomegalovirus colitis is treated with valganciclovir; the duration of treatment should be individualized depending on the clinical picture and laboratory parameters.[rx]
5-aminosalicylic acid (5-ASA) drugs are the standard treatment in ulcerative colitis for induction and maintenance of remission of mild and moderate cases. The place of 5-ASA in the management of Crohn’s’s disease is controversial. Immunomodulators including azathioprine, 6-mercaptopurine, and methotrexate, are the mainstay of treatment in maintenance therapy for patients with mild to moderately severe Crohn’s’s disease and frequently relapsing ulcerative colitis where 5-ASA drugs failed. Biological therapies, tumor necrosis factor-oe, such as infliximab, adalimumab, and certolizumab are available for the management of Crohn’s’s disease, to get the disease under control and long-term maintenance. Corticosteroids are effective in reducing remission in inflammatory bowel disease and are cheap. However, they are not recommended for maintenance therapy and are associated with serious side effects. [rx][rx][rx]
In microscopic colitis, discontinuation of any offending medication and smoking cessation are vital. While anti-diarrheal medications, bismuth subsalicylate or cholestyramine may help, budesonide is effective in inducing remission and should be the first medication to start.[rx] For patients in whom budesonide therapy is not feasible, bismuth salicylate or mesalamine is an option.
For patients with ischemic colitis without peritoneal signs, medical management may be safely employed including intravenous fluid resuscitation, optimizing cardiac output, use of supplementation of oxygen, placing the bowel on rest, parenteral nutrition, the use of broad-spectrum antibiotics to cover both aerobic and anaerobic coliform bacteria and close monitoring. Failure of medical management and the development of peritoneal signs or intestinal perforation necessitates surgical intervention and bowel resection.[rx][rx]
Anti-tuberculous treatment comprising isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months is recommended in tuberculous colitis followed by isoniazid and rifampin for 7 months. The duration of treatment is nine months, and patients should be regularly followed up for assessing their response to the treatment.[rx]
For children, teenagers and adults, your provider may recommend:
- Aminosalicylates: For mild to moderate ulcerative colitis, your healthcare provider may prescribe sulfasalazine (Azulfidine®). Let your provider know if you’re allergic to sulfa. He or she can prescribe a sulfa-free aminosalicylate instead, such as mesalamine (Canasa®, Delzicol®, Asacol® HD, Pentasa®, Lialda®, Apriso®). The medications come in both pill form and enema or suppository form, which can better reach the inflammation low down in the colon or rectum.
- Corticosteroids: If you have a severe form of ulcerative colitis, you may need a corticosteroid such as prednisone (Deltasone®) or budesonide (Entocort® EC, Uceris®). Because corticosteroids have serious side effects, healthcare providers only recommend them for short-term use. Other medications will be used to help maintain the remission.
Immune system suppressors
These drugs also reduce inflammation, but they do so by suppressing the immune system response that starts the process of inflammation. For some people, a combination of these drugs works better than one drug alone.
Immunosuppressant drugs include:
- Azathioprine (Azasan, Imuran) and mercaptopurine (Purinethol, Purixan). These are the most widely used immunosuppressants for the treatment of inflammatory bowel disease. Taking them requires that you follow up closely with your doctor and have your blood checked regularly to look for side effects, including effects on the liver and pancreas.
- Cyclosporine (Gengraf, Neoral, Sandimmune). This drug is normally reserved for people who haven’t responded well to other medications. Cyclosporine has the potential for serious side effects and is not for long-term use.
- Tofacitinib (Xeljanz). This is called a “small molecule” and works by stopping the process of inflammation. Tofacitinib is effective when other therapies don’t work. Main side effects include the increased risk of shingles infection and blood clots.
The U.S. Food and Drug Administration (FDA) recently issued a warning about tofacitinib, stating that preliminary studies show an increased risk of serious heart-related problems and cancer from taking this drug. If you’re taking tofacitinib for ulcerative colitis, don’t stop taking the medication without first talking with your doctor.
Biologics
This class of therapies targets proteins made by the immune system. Types of biologics used to treat ulcerative colitis include:
- Infliximab (Remicade), adalimumab (Humira) and golimumab (Simponi). These drugs, called tumor necrosis factor (TNF) inhibitors, or biologics, work by neutralizing a protein produced by your immune system. They are for people with severe ulcerative colitis who don’t respond to or can’t tolerate other treatments.
- Vedolizumab (Entyvio). This medication is approved for treatment of ulcerative colitis for people who don’t respond to or can’t tolerate other treatments. It works by blocking inflammatory cells from getting to the site of inflammation.
- Ustekinumab (Stelara). This medication is approved for treatment of ulcerative colitis for people who don’t respond to or can’t tolerate other treatments. It works by blocking a different protein that causes inflammation.
Other medications
You may need additional medications to manage specific symptoms of ulcerative colitis. Always talk with your doctor before using over-the-counter medications. He or she may recommend one or more of the following.
- Anti-diarrheal medications. For severe diarrhea, loperamide (Imodium A-D) may be effective. Use anti-diarrheal medications with great caution and after talking with your doctor, because they may increase the risk of an enlarged colon (toxic megacolon).
- Pain relievers. For mild pain, your doctor may recommend acetaminophen (Tylenol, others) — but not ibuprofen (Advil, Motrin IB, others), naproxen sodium (Aleve) and diclofenac sodium, which can worsen symptoms and increase the severity of disease.
- Antispasmodics. Sometimes doctors will prescribe antispasmodic therapies to help with cramps.
- Iron supplements. If you have chronic intestinal bleeding, you may develop iron deficiency anemia and be given iron supplements.
Surgery
Surgery can eliminate ulcerative colitis and involves removing your entire colon and rectum (proctocolectomy).
In most cases, this involves a procedure called ileoanal anastomosis (J-pouch) surgery. This procedure eliminates the need to wear a bag to collect stool. Your surgeon constructs a pouch from the end of your small intestine. The pouch is then attached directly to your anus, allowing you to expel waste relatively normally.
In some cases a pouch is not possible. Instead, surgeons create a permanent opening in your abdomen (ileal stoma) through which stool is passed for collection in an attached bag.
Complications
Complications include:
- Intestinal perforation
- Bowel strictures, fistulas, abscesses, and intestinal obstruction
- Fecal incontinence
- Pelvic abscess
- enterocutaneous fistulas, particularly in Crohn’s’s disease
- Pouchitis
- Guillain-Barre syndrome (Campylobacter jejuni colitis, cytomegalovirus colitis, and reported in ulcerative colitis)
- Hemolytic uremic syndrome (enterohemorrhagic E Coli, Shigella)
- Encephalopathy, seizures (Shigella)
Toxic megacolon is an uncommon complication of colitis, characterized by total or segmental nonobstructive colonic dilatation, associated with systemic toxicity,, and has an overall mortality of 19%.[rx] Diseases such as ulcerative colitis and pseudomembranous colitis are well-known to be complicated and develop toxic megacolon in over 60% of cases.[rx] Other conditions associated with inflammation of the colon including Campylobacter and shigella colitis may develop toxic megacolon.
Prevention
Many people have found that one or more of the following foods have triggered their symptoms:
- Alcohol
- Caffeine
- Carbonated beverages
- Dairy products (if lactose intolerant)
- Dried beans, peas, legumes, dried fruits or berries
- Fruits with pulp or seeds
- Foods containing sulfur or sulfate
- Foods high in fiber (including whole-grained products)
- Hot sauces and spicy foods
- Meats
- Nuts and crunchy nut butters
- Popcorn
- Products containing sorbitol (sugar-free gum and candies)
- Raw vegetables
- Refined sugar
- Seeds
References
