Crohn's Disease

     The feeling one just cannot shake. That sudden urge to go to the restroom. It is monstrous and undeniable. But, what if that urge is more often than the norm? And, it is followed with abdominal pain, diarrhea and a fever? It may be something to look in to. A disease known as Crohn’s disease.  Crohn’s disease is increasing among all ethnicities; but, it is not something that cannot be treated. With extensive research and years of testing, adalimumab (Humira) has provided a treatment for those who suffer from this irritable disease. Because Crohn’s disease is growing in incidence and prevalence, adalimumab has been created to assist those who are battling with this disease.

      Crohn’s disease is a relapsing systematic inflammatory disease effecting the gastrointestinal tract that is associated with immune disorders. The exact cause of Crohn’s disease is unclear (1). However, it can be linked to environmental factors, aberrant immune function and bacterial factors (1). Those who suffer from the disease experience an array of symptoms such as consistent abdominal pain, high fever, unintended weight loss and frequent diarrhea with passage of blood or mucus (1). Crohn’s disease and Ulcerative colitis are the two main components of inflammatory bowel disease.

     There are five known types of Crohn’s disease that affect different location of the gastrointestinal tract (2). The severity of each depends on the progression of the disease and the genetic and environmental build-up of a person. The five types of Crohn’s disease are gastroduodenal which affects the stomach and duodenum. Those who suffer from this form of Crohn’s disease experience symptoms such as loss of appetite, weight loss, nausea and vomiting. Crohn’s colitis is also a form of Crohn’s disease but only affects the colon. Those who suffer from Crohn's colitis experience diarrhea, rectal bleeding and complications around the anus. Another type is ileocolitis. It is the most common form of Crohn’s disease and affects the ileum and colon. Those who suffer from ileocolitis experience symptoms such as diarrhea, cramping or pain in the right lower part or middle of the abdomen, and weight loss. Jejunoileitis is also a form of Crohn’s disease. Jejunoileitis creates patchy areas of inflammation in the jejunum and ileum. Those who suffer from jejunoileitis experience abdominal pain, cramps following meals and diarrhea. The fifth form of Crohn's disease is ileitis. It affects only the ileum and its symptoms are similar to those of ileocolitis (2).

     Large concordance studies in twins in northern Europe were early indicators of a genetic component in Crohn’s disease. The study showed that thirty five percent of monozygotic pairs and only three percent of dizygotic pairs were concordant for the disorder. In seventy percent of discordant monozygotic pairs, the first-born had inflammatory bowel disease. Substantial   phenotypic (such as the location, behavior, and age at diagnosis) concordance exists, both at diagnosis and longitudinally, in monozygotic twins. As stated above there has been a prevalence in all ethnicities. For example, prevalence in Ashkenazi Jews is higher than any other ethnic group. Genome wide association studies and computerized (in silico) meta-analyses have identified and confirmed seventy-one susceptibility loci for Crohn’s disease on seventeen chromosomes (3).

Environmental factors also affect the rate of Crohn’s disease. Rates of the disease in the northern and southern are equal. Because of industrialization, most people focus on their career and higher education. This led to a change in life events like breast feeding and there are smaller families with larger less crowded living conditions. The improved domestic hygiene and sanitation, consumption of diet and less active lifestyle are all factors that contribute to the gain (3) of Crohn’s disease. One of the most prominent risk factors is the use of tobacco products. Also, use of tobacco significantly increases the risk of developing the disease. An estimated three million U.S. adults have been diagnosed with either Crohn’s disease or ulcerative colitis. This is a one million person increase since the year 1999.

     But, let’s get down to the nitty gritty. How is it treated… with adalimumab of course? Adalimumab was approved by the FDA December 2002. It was initially launched for the treatment of rheumatoid arthritis but was later found to assist in the treatment of irritable bowel diseases such as Crohn’s disease. In two clinical studies, adalimumab showed fifty-eight and fifty-two percentage approval compared to the thirty-four percent who consumed the placebo. Thirty-six and twenty-one percent also achieved remission in comparison to the twelve and seven percent who consumed the placebo (4). This is how it works. Adalimumab binds to TNF-alpha and blocks its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab also lyses surface TNF expressing cells in vitro in the presence of complement. This mechanism blocks cytokine effects, thereby reducing TNF-induced inflammation and halting tissue destruction (5).

     With extensive research and years of testing, Humira has provided a treatment for those who suffer from this irritable disease. Because Crohn’s disease is growing in incidence and prevalence, adalimumab has been created to assist those who are battling with this disease. A total of sixty genes have been studied and evaluated to determine whether genetic variants are associated with irritable bowel syndrome. Also, there are five main pathways effected by Crohn’s: serotonin, adrenergic, inflammation, intestinal barrier, and psychiatric that have been found. As technology improves hopefully there will be further research for a cure for irritable bowel syndrome/disease.

Work Cited

1. Baumgart, Daniel C, and William J Sandborn. “Crohn's Disease .” Lancet, vol. 2012, no. 380, ser. 1590-1605, 20 Aug. 2012, pp. 1–16. 1590-1605, doi:http://dx.doi.org/10.1016/ S0140-6736(12)60026-9.

2. “HUMIRA (Adalimumab) Clinical Data | Ulcerative Colitis.” HUMIRA (Adalimumab) | Official Healthcare Professional Site, www.humirapro.com/gastroenterology/ulcerative-colitis-clinical-data.

3. Saito, Yuri A. “The Role of Genetics in IBS.” Gastroenterology clinics of North America 40.1 (2011): 45–67. PMC. Web. 28 Nov. 2017

4. HUMIRA (Adalimumab), Abbott Laboratories - Package Insert, www.accessdata.fda.gov/drugsatfda_docs/label/2002/adalabb123102lb.htm

5. “Adalimumab.” DrugBank, www.drugbank.ca/drugs/DB00051.

By Lexus Cabiness, Post Baccalaureate Student, University of Kentucky