Approximately 15% of patients have a first-degree relative with inflammatory bowel disease.
Affects approximately 3 million people in the U.S.
The onset of IBD is traditionally during young adulthood, but all the patients represent a growing fraction of all patients accounting for up to 15% of patients with new diagnoses and a greater percentage of patients who are hospitalized for the condition.
The initial clinical manifestations depends on the extent and activity of disease and may include: abdominal pain, diarrhea, passage of blood and mucus, fever, signs of bowel obstruction, anemia, and increased markers of inflammation.
Process felt to be a result of inappropriate inflammatory response to intestinal microbes in a genetically susceptible host.
In most patients manifests in adolescence or adulthood.
Proportion of older patients with IBD is increasing.
IBD has possible involvement of virtually the entire body and requires lifelong care to prevent or delay progression.
Highest incidence and prevalence of IBD is in northern Europe and North America, and the lowest in Asia.
Western environment and lifestyle is associated with IBD as is smoking, high fat and sugar diets, medication use, stress and higher socioeconomic status.
IBD has been associated with appendectomy.
Patients have higher rates of postoperative complications than patients without IBD.
In IBD the combination of a chronic inflammatory state, poor nutrition, immunosuppressive medications leaves such patients at higher risk for venous thromboembolism, wound infections, deep organ space infection, intestinal fistula, and anastomotic leak.
The disease may present in infancy and may be inherited as an autosomal recessive trait.
Primary differences between Crohnâ€™s disease and ulcerative colitis are the location and nature of the inflammatory response.
Crohn’s disease most commonly affects the terminal ileum, whereas ulcerative colitis is restricted to the colon and or rectum.
Crohnâ€™s disease characterized by granulomas and transmural inflammation, while ulcerative colitis inflammatory changes are restricted to the mucosa and submucosa.
Patients with ulcerative colitis and Crohn’s disease have depleted and reduced diversity of mucosal associated Firmicutes and Bacteroidetes compared to controlled subjects.
The intestinal epithelium plays a significant role in shaping the mucosal immune response as it is the interface between intestinal bacteria and lymphoid tissue of the gastrointestinal tract.
Intercellular junctions maintain an intact epithelial mucosal barrier by sealing the space between adjacent epithelial cells.
When the regulation of tight junctions is impaired and the para-cellular space has increased permeability inflammatory bowel disease may result.
Goblet cells and Paneth cells are specialized epithelial cells that defend against bacterial invasion in the intestine.
Goblet cells regulate mucus production and contributes to epithelial repair and regulation of inflammation.
Paneth cells secrete antimicrobial peptides.
Intestinal mucus overlies epithelial cells and limits contact between the cells and bacteria.
Epithelial regeneration and repair controls and inflammatory responses to injury.
Inflammatory responses in inflammatory bowel disease may result in ongoing epithelial injury, resulting in erosions, ulcerations, and a decrease in the production of defensin, and this increases exposure to intestinal bacteria and amplifies it the inflammatory response.
Patients with IBD have alterations in gut microbiota such as lower diversity of micro organisms and increased numbers of pro inflammatory and enteroadherentb bacteria species.
Intestinal dysfunction causes the loss of intestinal epithelial barrier function, contributing to increased severity of IBD mainly within the colon, and as a result to the development of colorectal cancer.
Defective intracellular junctions may be due to a defect in the area function or may be a result of inflammation.
In the presence of inflammatory bowel disease, inflammatory responses promote epithelial injury, which results in erosion formation, ulcerations and decreased production of defensin.
The essential finding in inflammatory bowel disease a profound infiltration of immune cells, including neutrophils, macrophages, and dendritic cells, and natural killer T cells and adaptive immune cells of both B and T cell type.
Increased immune cells which are activated in the intestinal mucosal increase levels of tumor necrosis factor-alpha, interleukin-1 beta, interferon-gamma, and cytokines of interleukin-23-Th17 pathway.
The intestinal layer of epithelial cells express innate immune receptors that mediate the defense against luminal bacteria and also conditioned epithelial and antigen-presenting cells for inducing tolerance mechanisms to maintain immune homeostasis in the intestine.p
The risk of developing IBD among first-degree relatives of IBD patients is 30 to 100 times greater than in the general population.
Peak onset occurs in persons 15 to 30 years of age.
Most people with IBD are diagnosed before the age of 30.
Crohn’s disease can be associated with granulomas, strictures and fistulas of the intestine, but these are not typically seen in ulcerative colitis.
Risk of colorectal cancer for individuals with irritable bowel disease increases by 0.5% to 1% per year, after 8-10 years following the diagnosis.
Inflammatory bowel disease is associated with cancers of the gastrointestinal tract and some lymphoproliferative cancers.
The cumulative five-year risk of malignancy in IBD ranges from 33-54%, and the risk of developing colorectal cancer increases four fold in IBD patients.
Increased prevalence during the past century, may reflect changes in diet, antibiotic use, and intestinal colonization.
Associated with osteoporosis 2-30% of time.
Associated arthritis in up to 25% of cases .
Spinal involvement seen in 3-6% of cases.
Increased risk of venous thromboembolism in patients with IBD and the nephrotic syndrome.
Patients with IBD have a higher risk of venous thromboembolism with the relative risk, higher by a factor of 3 to 4 compared to matched controls, and an absolute risk of 2.6 per 1000 person-years.
Risk of thromboembolism increases with disease flare.
Smokers are at increased risk for Crohn’s disease and tend to have more severe illness, whereas former smokers and non-smokers are at greater risk for ulcerative colitis.
Patients undergoing appendectomy for appendicitis early in life is associated with a decreased incidence of ulcerative colitis, whereas the opposite is true for Crohn’s disease.
Extraintestinal manifestations such as rheumatologic, dermatologic, ophthalmologic, hematologic, and hepatic manifestations affect one third of all patients with inflammatory bowel disease at any one time.
Patients with IBD have a higher risk for sclerosing cholangitis, ankylosing spondylitis and cirrhosis.
Crohnâ€™s disease is characterized by involvement of the gastrointestinal tract from mouth to anus in a discontinuous fashion, with the development of strictures, abscesses, or fistulas that can penetrate into neighboring organs or the peri anal skin.
Familial clustering and twin studies suggest a genetic relationship, which is more prominent in Crohn’s disease then in ulcerative colitis.
Studies suggest that both diseases can occur within a family, indicating that some genes may be common to both disorders.
A meta-analysis confirmed the presence of 47 loci with ulcerative colitis, of which 19 are specific, and 28 are shared with Crohn’s disease (Anderson, CA al).
Laboratory parameters helpful in determining disease activity in both ulceraticpve colitis and Crohnâ€™s disease include C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, and fecal lactoferrin.
Treatments have focused almost exclusively on suppressing the aberrant immune response.
The IBD armamentarium includes untargeted therapies, such as aminosalicylates, glucocorticoids, and immunomodulators, as well as targeted biologic therapies.
Medications act through one of the following mechanisms:
neutralization of cytokines that promote inflammation, drive the differentiation and function of specialized immune subsets, block signal transduction cascades downstream of these pathways, or modulation of lymphocyte trafficking.
Biologic agents have improved clinical outcomes, but concerns related to risk of infection, malignancy, and is a cause of anxiety for patients who must be treated with medications long-term.
Most patients with Crohn’s disease and ulcerative colitis initially respond to corticosteroids.
At 1 year, 32% of patients with Crohn’s disease and 48% with ulcerative colitis are corticosteroids free without operation.
Corticosteroids are often the intervention of choice for the initial management of moderately to severely active Crohn’s disease and ulcerative colitis.
5-Aminosalicylic acid agents are the mainstay of therapy for the induction of remission and mild to moderate active ulcerative colitis and for the maintenance of remission in ulcerative colitis and possible Crohn’s disease.
Oral and/or topical aminosalicylates are the first line therapy for mild inflammatory bowel disease.
Oral mesaline treatment in mild to moderate ulcerative colitis is associated with clinical response and clinical remission rates of only 60% and 29%, respectively.
For Crohnâ€™s disease sulfasalazine was only modestly effective for induction of remission and mesalamine was not significantly more effective then placebo for induction for maintenance of remission.
Multiple biologic agents with immunosuppressive effects, including anti-tumor necrosis factor alpha, anti-integrins, and anti-IL 12/IL 23 agents have been used in moderate to severe ulcerative colitis and Crohnâ€™s disease.
Crohn’s disease with fistulas or extra intestinal manifestations may warrant biologic therapy.
13-to 1/2 have patients do not have significant clinical response and among responders a large proportion lose response over time with less than 50% maintaining clinical remission at 6-12 months.
Outcomes worse among elderly treated with certain immunosuppressant agents, such as anti-tumor necrosis factor compared with a younger population.
Presence of large numbers of inflammatory cells in areas of affected disease which normally does not have many of such cells.
Cell surface integrins important in recruitment and activation of cells in inflammatory bowel disease.
Morbidity of IBD surgery increased among malnourished patients, individuals 60-80 years of age, patients undergoing emergency surgery, patients with fistulae, and patients treated at low volume surgical centers.
Laparoscopic surgery for IBD associated with shorter postoperative periods and fewer complications.
Surgical complications, infections and wound healing problems increased in patients on long-term immunosuppressive agents.
Because of the presence of chronic debilitating disease patients with IBD have a 2-5 higher cardiac complication rate with surgery.
For ulcerative colitis most common elective surgical procedure is a total proctocolectomy with ileoanal anastomosis.