Inflammatory Bowel Disease

What is Inflammatory Bowel Disease?

Inflammatory bowel disease is an autoimmune disorder characterized by inflammation of the gastrointestinal tract (GIT). It is an idiopathic (of unknown cause) disease thought to be caused by a dysregulated mucosal immune response to gut microbiota. It includes Crohn’s disease (CD) and Ulcerative Colitis (UC). CD is the intermittent inflammation of three layers of any part of GIT while UC is the continuous inflammation of the mucosa of the colon and rectum. IBD occurs in genetically predisposed people but environmental factors are equally important. The most important environmental factor is diet. IBD is not life-threatening but it greatly affects the quality of life. Remission can be achieved through proper treatment but relapsing is common even in patients who have undergone surgery. IBD can retard growth in children. There is no cure for IBD, and the purpose of treatment is to restore normal life activities and growth in children.



Epidemiology

The incidence of IBD is greater in developed countries and according to some studies, it is increasing. Incidence varies a lot depending on region, ethnicity, and socioeconomic status. White and Jewish people are at greater risk of IBD. The prevalence of IBD is high due to its young-onset and chronic nature. Historically this disease has been more prevalent in North America and Europe and these places still lead in the number of patients but recently the incidence of IBD has been reported to increase in Asia owing to some improvement in the socioeconomic situation there. In general, it affects males and females equally. The chances of onset of IBD are greatest in the fourth decade of life. Pediatric patients account for as much as one-third of all patients. People with first-degree family members suffering from IBD are at five times greater risk of IBD and they tend to have an early onset of symptoms. Besides genetics, environment and diet are major risk factors of IBD and prevention mainly revolves around bringing dietary changes. Environmental factors include smoking, drugs, water pollution, geography, sleep, and stress.


Symptoms

Some common symptoms of CD and UC include diarrhea, abdominal pain, rectal bleeding, and weight loss. Symptoms of UC are limited to the colon and rectum but the symptoms of CD are diverse depending upon the exact site of inflammation. Abdominal pain, watery diarrhea, and weight loss are the characteristic symptoms of CD. Abdominal pain is sometimes so severe that patients might suspect they have appendicitis. Diarrhea is usually watery but rectal bleeding can occur in CD. Bloody diarrhea is more common in UC. Malnutrition can occur when the small intestine fails to absorb food properly, which causes weight loss and growth retardation in children. The characteristic symptoms of UC are blood in the stool with mucus, abdominal pain, frequent diarrhea, fever, loss of appetite, and tenesmus (a feeling that you need to pass stool even though your bowel is empty). Sometimes constipation can also occur accompanied by blood and mucus. Symptoms of IBD are not restricted to GIT. Endoscopy with multiple biopsies is the gold standard of diagnosis. Imaging and biomarkers are used for further evaluation. Ileocolonoscopy and chromoendoscopy are most often utilized. At least two biopsies should be taken from normal-appearing tissues of five sites including the ileum and rectum. Magnetic resonance elastography (MRE) is used to evaluate disease activity. IBD does not have a specific biomarker. Two biomarkers, C-reactive protein (CRP) and fecal calprotectin (FC) can give valuable information about disease activity but they cannot be used in diagnosis. Our gut harbors a vast population of microbes mostly bacteria which have a role in our overall health.


Treatment

Any change in the composition of this microbiota has far-reaching effects on our health. Pathogenesis of IBD involves disruption of gut microbiota in genetically predisposed individuals. Immune response to this disruption goes out of control in the presence of genetic mutations and begins damaging the healthy cells in the intestine. Treatment of IBD with biologics mostly targets the autoimmune aspect of pathogenesis. These include Immunomodulators, anti-TNF agents, aminosalicylates, corticosteroids, antibiotics, and anti-integrin agents. Originally used for the treatment of rheumatoid arthritis, oral 5-aminosalicylic acid (5-ASA) is effective in maintaining remission in IBD. Corticosteroids are commonly prescribed in IBD. Antibiotics can be used to restore balance in the microbiota population. mercaptopurine, azathioprine (AZA), and methotrexate (MTX) are commonly used immunomodulators in IBD. Anti-TNF agents work by blocking cytokines. Infliximab, adalimumab, certolizumab, and golimumab are the anti-TNF agents approved by the FDA for the treatment of IBD. If the patient does not show a response to anti-TNF therapy, then anti-integrin agents are used. Natalizumab and vedolizumab are anti-integrin agents approved by the FDA. Specific diets have been designed to achieve remission by helping the intestine heal faster. Exclusive enteral nutrition (EEN) is a commonly used nutritional approach to treat active CD. In a specific carbohydrate diet, the patient is given those carbohydrates which are easy to digest. CD exclusion diet (CDED) helps maintain healthy microbiota. Fecal microbiota transplantation (FMT) is the direct transplant of feces from a healthy person to an IBD patient to change the recipient's gut microbiota and stabilize its composition. This method of treatment is still in the developmental stages. Surgery is the last resort treatment in IBD. Despite the advent of advanced therapeutics, the rates of surgery have not declined. Surgery in IBD has evolved over the years. In the past, surgery was the only therapeutic option but biologic agents have helped delay surgery. There are several types of surgeries depending upon which specific part of the intestine is damaged. Inflammation can come back in CD after the surgery so postoperative care is important. There is a need for disease-modifying drugs for IBD. Novel therapeutic approaches are currently under investigation. New therapeutic strategies in inflammatory bowel disease (IBD) have shifted from symptom control towards treat-to-target algorithms in order to optimize treatment results.



Written By: Numair Arshad & Lawrence D. Jones, Ph.D.