Colitis

What is Colitis?

Colitis is a general term given to an inflammatory disease of the colon, and is often used to describe an inflammation of the large intestine. Colitis describes a spectrum of diseases rather than a single disease, and several different forms have been identified, which are normally classified by their underlying etiology.

The autoimmune form of colitis is known as inflammatory bowel disease (IBD). The major types of inflammatory bowel disease are ulcerative colitis and Crohn’s disease. Ulcerative colitis is characterized by diffuse mucosal inflammation limited to the colon, while Crohn's disease is characterized by patchy, transmural inflammation, which may affect any part of the gastrointestinal tract, but is most common in the terminal ileum or the perianal region. Both are chronic forms of colitis.

Microscopic colitis, also known as lymphocytic colitis or collagenous colitis, is a relatively common cause of chronic diarrhea in older adults. Initially described in 1976, microscopic colitis currently accounts for 4–13% of patients investigated for chronic diarrhea.

Some forms of colitis can result from side effects of medical treatment (iatrogenic). These include complications derived from an ileostomy or colostomy (diversion colitis) and inflammations resulting from the introduction of a harsh chemical to the colon (chemical colitis).

Finally, the term "ischemic colitis" is used to designate inflammations or injuries to the colon resulting from inadequate blood supply. Ischemic colitis occurs with greater frequency in the elderly, and is the most common form of bowel ischemia.

What Causes Colitis?

The two major types of inflammatory bowel disease (ulcerative colitis and Crohn’s disease) are caused by a combination of environmental influences, genetic variations, alterations in the microflora of the gut and disturbances in the innate and adaptive immune responses. A diet high in fat and protein, but low in fruits and vegetables is thought to be a contributing factor as well.

The etiology of microscopic colitis is unknown, but possible causes include autoimmunity, an inflammatory response to luminal factors and myofibroblast dysfunction. Patients with microscopic colitis appear to have impaired electrolyte absorption or increased secretion. Increased mucosal and luminal concentrations of prostaglandins might also promote diarrhea in these patients.

Ischemic colitis may develop as a consequence of low blood pressure or constriction of the vessels feeding the colon (non-occlusive ischemia), or it may result from a blood clot that has cut off blood flow to the colon. Thromboembolisms are a common trigger of colitis caused by occlusive ischemia. Iatrogenic colitis is the direct result of a surgical procedure or the introduction of a harsh chemical in the colon. Colitis may also result from infection with the pathogens Clostridium difficile and Escherichia coli, among others.

Symptoms of Colitis

The symptoms of colitis may vary according to the specific etiology of the condition, but a general list includes the following:

• Diarrhea
• Bloody / Mucous Discharge
• Incontinence / Uncontrollable Bowel Movements
• Abdominal Pain / Abdominal Cramps
• Weight Loss
• Anaemia / Decrease in Red Blood Cells
• Fever

Diagnosis of Colitis

For ulcerative colitis, the confirmation of the diagnosis following the appearance of symptoms is attained by appropriate macroscopic findings on sigmoidoscopy or colonoscopy, typical histological signs present in a biopsy sample and negative stool examinations for infectious agents. The presence of focal, asymmetric and often granulomatous inflammation in any part of the gastrointestinal tract is strongly indicative of Crohn's disease. Imaging technologies such as ultrasound, MRI or CT scans are often used by clinicians for the diagnosis of inflammatory bowel disease and to assess its extent.

A diagnosis of microscopic colitis is obtained by examination of the patient’s medical history combined with endoscopic evaluation of the colon. The hallmark histological feature of microscopic colitis is intraepithelial lymphocytosis, with the mucosal architecture remaining more or less intact. In collagenous colitis, the subepithelial collagen band is abnormally thickened. Flexible sigmoidoscopy can be used to confirm the diagnosis, but its effectiveness is controversial.

Assessing oxygen delivery to the colon is key for the diagnosis of ischemic colitis. This can be done by using visible light spectroscopy to measure oxygen levels in the capillaries. Stool examinations are required to confirm the presence of C. Difficile or other pathogens in the diagnosis of pseudomembranous colitis.

Treatment of Colitis

Optimal treatment depends on the specific form of colitis suffered by the patient, and therefore an accurate diagnosis is essential to select the appropriate treatment. Aminosalicylates such as 5-aminosalicylic acid ("mesalazine") have traditionally been used to alleviate the symptoms of ulcerative colitis, but it is less effective in cases of Crohn's disease. This form of colitis responds well to corticosteroids, but their use has to be closely monitored due to a number of side effects. Autoimmune forms of colitis can be treated with immunosuppressive agents such as azathioprine and 6-mercaptopurine in order to inhibit the proliferation and activation of lymphocytes and therefore attain remission of the symptoms. If the disease does not respond to intensive medical therapy, a surgical intervention may be necessary. Surgery for severe forms of autoimmune colitis is a demanding procedure and carrys certain risk for the patient, such as developing pouchitis.

Nonspecific antidiarrheal therapy such as loperamide or diphenoxylate/atropine can be effective in the treatment of microscopic colitis and are often used as first-line therapy. This should be combined with the discontinuation of any drug or product that might exacerbate diarrhea. Aminosalicylates can also be used in this case. For patients with more severe symptoms, treatment with corticosteroids may be considered as a first line therapy, with budesonide being the best studied therapeutic agent.

Infectious colitis is usually treated with antimicrobial agents. Antibiotics have also been used to treat ischemic colitis, although supportive care is considered the treatment of choice for this form except in the most severe cases.

Prognosis of Colitis

Inflammatory bowel disease can become chronic and limit quality of life because of pain, vomiting, diarrhea and other symptoms. It is rarely fatal, except in severe cases of ulcerative colitis. There is no real cure for autoimmune colitis, and even patients with long periods of quiescent disease can experience a sudden recurrence ("flare") or a complication that requires surgery. Patients also have an increased risk of developing colorectal cancer and are strongly encouraged to undergo regular screening colonoscopies accompanied of biopsies to check for dysplasia.

Microscopic colitis is generally considered a benign illness, with most patients recovering from their diarrhea and exhibiting remission of their histological abnormalities. Ischemic colitis is also self-limited in the majority of cases, and a full recovery can be achieved with bowel rest and antibiotic treatment. However, a minority of patients can develop gangrene as a consequence, with a mortality rate close to 100% unless they are provided surgical treatment. Chronic ischemic colitis and colonic stricture are other complications that may result from this form of the disease.

Infectious colitis responds to antibiotic treatment but recurs in 20% of patients following the first treatment. This percentage can be as high as 60% in subsequent treatments.

Preventing Colitis

There are no clear guidelines on how to prevent an episode of Crohn's disease or ulcerative colitis, since their effective causes remain poorly understood. The chances of developing Crohn's disease increase with tobacco smoking, but the same cannot be said regarding ulcerative colitis. The situation is similar for microscopic colitis, with a lack of prevention guidelines due to the mostly unknown etiology of the disease.

On the other hand, infectious and ischemic colitis are considered preventable. C. difficile infection surveillance is an important preventive measure for infectious colitis, as this pathogen is the major cause of this specific form of colitis. This should be combined with appropriate use of contact or barrier precautions, careful environmental cleaning and disinfection using sporicidal agents. Regarding ischemic colitis, appropriate treatment of medical conditions that predispose to its development (heart disease and hypertension, among others) can be considered an effective preventive measure. Avoidance of tobacco, monitoring of sugar levels in the blood and consumption of low dose aspirin on a regular basis to prevent blood clots can also reduce the risk of ischemic colitis.

Living with Colitis

Both of the main forms of autoimmune colitis, Crohn's disease and ulcerative colitis, are characteristically chronic, require prolonged medical and surgical interventions and significantly impair the quality of life of the patient. Results from surveys showed that fatigue, loss of energy, fear of losing control and of producing unpleasant odors and a negative body image are very common in autoimmune colitis. Recommendations for coping during daily life include keeping a symptoms diary to understand which factors are more likely to trigger an acute episode, doing regular exercise, managing stress and avoiding situations conducive to social anxiety, eating a balanced diet, seeking psychological counseling and being open about the condition and its associated symptoms with family members, friends and work colleagues.

The quality of life is also significantly diminished in patients suffering from microscopic colitis. Incontinence is common with increasing diarrhea and is a significant factor in the decrease in social functioning and quality of life shown by these patients, in addition to abdominal pain and urgency. The mostly benign prognosis associated with this form of the disease means that patients respond to treatment and the quality of life improves in a few weeks.

Both infectious and ischemic colitis have clearly defined underlying causes and the symptoms disappear shortly after the patients receive appropriate treatment. There is no need for long-term adaptation to these particular forms of the disease.

Current Research of Colitis

Therapy for autoimmune colitis is a rapidly evolving field, with many new biological agents under investigation that are likely to change therapeutic strategies radically in the next decade. Antisense and short interfering RNAs technology capable of blocking the inflammatory response is being successfully transferred from molecular biology labs to a clinical setting. Stem cell-based therapies using mesenchymal stem cells or MSCs could potentially reduce the effects of inflammatory disease by down-regulating immune responses and promoting epithelial cell repair in the gastrointestinal tract.

Confocal endomicroscopy (CEM) is a recent advancement in imaging technology that incorporates a confocal laser microscope into the tip of a flexible endoscope, offering up to a 1000-fold magnification of the gastrointestinal tract mucosa. CEM is particularly useful for the diagnosis of microscopic colitis, a condition in which macroscopic lesions are usually absent.

New pathogens are continually being reported to cause infectious colitis, and there have been important advances in the identification of genetic host factors determining susceptibility to the disease. This holds the promise of a better identification of subpopulations at risk that could benefit from early intervention and prophylactic measures.