Crohn’s disease (CD) is a chronic, relapsing inflammatory bowel disease (IBD). Crohn’s disease (CD) is a chronic inflammatory bowel disease, first described as a regional ileitis by Crohn, Ginzburg and Oppenheimer in a case series presented at the annual meeting of the American Medical Association in 1932. It is characterized by a transmural granulomatous inflammation that may affect any part of the gastrointestinal tract, most often the ileum, colon or both. Malnutrition is very common in Crohn’s disease as the small intestine is responsible for nutrient uptake, and Chron’s disease damages the small intestine. While biological treatment is associated with health-related quality of life improvements, patients still report a significant barrier to lifestyle and daily activities during outbreaks and remissions.
Pathogenesis results from interactions between environmental factors, the immune system, susceptibility genes and host microbiome changes, causing disruption of the intestinal mucosa. The role of inflammatory cells in sustaining an active disease is well known and most treatments aim to stop the cascade of inflammatory and pro-inflammatory cytokines. Mortality among patients with Crohn’s disease is consistently higher than in the general population, with a meta-analysis showing a pooled estimate of the standardized mortality ratio of 1.52.
PREVELANCE
Its prevalence has steadily increased over the last 50 years, with Northern Europe, the United Kingdom and North America registering the highest rates. A high prevalence was also observed among Jewish populations, although the variable prevalence in different geographical locations suggests the influence of environmental factors too.
CLINICAL FEATURES
Crohn’s disease is a clinical diagnosis formed by correlating clinical signs and symptoms, objective imaging data, including endoscopy with histological information as well as laboratory studies. Chronic diarrhea, defined as reduced fecal consistency for more than 4 weeks, is the most common symptom. Abdominal pain (70%), weight loss (60%) and blood, mucus or both in stool (40–50%) are also common symptoms of Crohn’s disease. Extraintestinal manifestations affect about one-third of patients with IBD. The most commonly observed extraintestinal manifestation is primary peripheral arthritis (33%); aphthous stomatitis, uveitis, erythema nodosum and ankylosing spondylitis can be seen whereas pyoderma gangrenosum, psoriasis and primary sclerosing cholangitis are comparatively infrequent.
Fistulas, a complication of Chron’s disease, occur in up to 35% of Chron’s disease sufferers, with perianal fistula occurring in 20%. These clinical characteristics associated with disease activity were found to contribute 37% of the health-related quality of life (HRQL) in a systematic review analyzing the determinants of health-related quality of life (HRQL) in the Chron’s disease. According to a qualitative analysis reported by the patient, there is an impact on lifestyle with regard to taking regular medication, restricting diet and avoiding certain trigger foods, as well as impact on daily activities, when patients report being absent from their employment or school during acute episodes of pain and fatigue.
RISK FACTORS
The prevalence of Crohn’s disease is between 30 and 39 years old, and the influence of gender varies among demographic groups. In a Canadian and New Zealand population, women are 10-30% more likely to contract the disease than men, while men with communicable disease are up to three times more likely in Japan and Korea. Although the exact etiology remains unknown, this is a complex interaction between genetic predisposition, environmental risk factors and immune dysregulation at the intestinal microbiota.
Smoking was confirmed to affect the phenotype of Chron’s disease and a meta-analysis indicated that smoking increased the risk of Chron’s disease more than twice. Previous history of symptomatic mumps and a high dietary intake of fats, polyunsaturated fatty acids, Omega-6 fatty acids and meats were both associated with an increased risk of CD, whereas a diet rich in fibre and fruit was considered protective. Oral birth control pills have also been associated with the growth of Crohn’s disease and a meta-analysis evaluating the quantitative risk of oral contraceptive pill (OCP) in the etiology of Chron’s disease found a common relative risk.
INVESTIGATIONS
A normal finding about ileocolonoscopic is not enough to exclude the diagnosis of Chron’s disease, as 27% of patients have a disease located in the terminal ileum, which can be difficult to diagnose. Capsule endoscopy is a relatively new, simple, non-invasive imaging technique that is increasingly known for small bowel exploration. The investigation involves consumption of a disposable, small, wireless camera within a capsule which passes through the gastrointestinal tract allowing direct visualization of the mucosa. A meta-analysis comparing the diagnostic performance of capsule endoscopy with other imaging modalities found a 15% increase in diagnostic rate compared to colonoscopy with ileoscopy.
MANAGEMENT
Usually, medications such as corticosteroids, budesonides or mesalazine are prescribed initially for the induction of remission. Immunosuppressant tumour necrosis factor (TNF) treatments are also used in patient’s refractory to conventional treatment. The medical management of Chron’s disease depends on compliance and patient education is crucial, with patient age and follow-up by a gastroenterologist being independently associated with non-adherence. 5-aminosalicylates have also long been used in IBDs, initially as sulfasalazine, a compound consisting of 5-aminosalicylic acid and sulphapyridine. Methotrexate, another antagonistic antimetabolite against folic acid, was superior to placebo in maintaining remission at 40 weeks: 65% of patients receiving intramuscular methotrexate remained in remission compared with 39% in the placebo group.
Most recently, vedolizumab, a monoclonal antibody targeting α4β7, demonstrated its efficacy in a randomized controlled trial for inducing remission of Chron’s disease compared to placebo (14.5% and 6.8%) as well as maintenance of remission. Ustekinumab, a monoclonal antibody against interleukin-12, has also shown a role in maintaining remission from Chron’s disease and these biological agents has the potential to alter the approach to physician management in the near future.
(Author is a post graduate medical student: Email: [email protected])
