Definition and Epidemiology

Ulcerative colitis (UC) and Crohn disease (CD) are chronic inflammatory bowel diseases (IBDs) that are on the rise. Both are thought to be heterogeneous groups of intestinal inflammatory disorders.¹ A third category known as IBD–unclassified can account for up to 10% of all patients with IBD. The unclassified disease involves the colon but the distinction between UC and CD cannot be made. A diagnosis may be later determined as UC or CD as symptoms and features manifest. The diagnosis of indeterminate colitis should be used only after colectomy and histopathology of the colon could not distinguish between UC and CD. IBD typically has periods of remission and exacerbation. There is no known drug cure, and often there is significant morbidity over years. Although UC and CD have many similarities, there are significant differences.^1,2

UC is a chronic inflammation of the lining of the colonic mucosa and to some extent, the submucosal layer. Beginning in the rectum, the inflammation is diffuse and continuous and may involve the entire colon (pancolitis) or only part of the colon. The worst of the disease is seen in the rectum and may be indicative of the disease above, but it is not usually found worse higher in the colon compared with the rectal involvement. The disease can involve only the rectum (proctitis) or the rectosigmoid colon, accounting for approximately 40% to 50% of the cases of UC. An additional 30% to 40% of patients have disease extending proximally to the splenic flexure (left-sided UC). Many patients experience a major impact on their quality of life, and approximately 50% do not experience a stable period of remission for any significant amount of time.^2–5

CD also involves chronic inflammation, but all layers of the intestinal tract wall (transmural inflammation) and any portion of the intestinal tract from the mouth to the anus can be affected. CD is heterogeneous, with a variable presentation and a variable response to treatment. The presentation is affected by site involvement and whether the disease is only inflammatory or also complicated with fibrostenosis or penetration of the bowel wall creating fistulous tracts. Approximately 40% to 50% of patients with CD have disease only in the small intestine (ileitis or regional enteritis), 30% to 40% in the small and large intestines (ileocolitis), and 10% to 30% only in the colon (Crohn colitis, not to be confused with UC). CD occurs in the mouth, stomach, and duodenum in a very small percentage of patients.⁶

The transmural involvement in CD is responsible for many of the complications that occur. Research has shown that many patients with CD will have a worsening course over time. A study of Olmsted County, Minnesota found 18.6% of patients developed either a stricture or a penetrating complication within the first 90 days of diagnosis and that 50% had developed complications by 20 years after diagnosis.⁷ Although the inflammation can be patchy (unlike UC, which is nearly always continuous), the involvement of all layers of the bowel wall creates many problems. Fibrostenosis occurs from the inflammation and can partially or completely obstruct the lumen of the intestinal wall (stricturing). Weakening of the intestinal wall from inflammation results in sinus tracks or fistulas (penetrating disease), abscesses, and perforation. Fistulas can develop from bowel to bowel (enteroenteric), bowel to skin (enterocutaneous), bowel to bladder (enterovesical), or bowel to vagina (enterovaginal). The fistulas frequently occur perianally, and other complications include abscesses, large tender skin tags, and the need for surgically placed drains and repair.³ For a comparison of UC and CD, see Table 138-1.

There are approximately 1.5 million persons with IBD in the United States. The annual incidences of UC and CD are similar in both age at onset and worldwide distribution. The highest incidence of IBD is in colder climates and industrial-urbanized societies with a Westernized lifestyle, which includes North America, Europe, and Australia, but the incidence is rising in developing countries and in Asia, and IBD is seen as an emerging global disease. The annual incidence per 100,000 persons in the United States is 7 to 8 each for UC and CD, but in Canada the rate is 19 to 20 for each.² The prevalence in North America is estimated to be 249 cases per 100,000 persons for UC and 319 per 100,000 population for CD.² IBD affects men and women equally, but there may be some regional differences. The peak age at onset is the second and third decade, but 25% of IBD patients are younger than age 20 years at presentation. The incidence in the pediatric population is increasing, especially for CD.¹ However, IBD can appear at any age from infancy to older adulthood, and new onset of CD has been seen in the eighth decade. The rates in the elderly are increasing as well, and 4% to 12% are diagnosed after 60 years of age.⁸

The cause of IBD is unknown, although there have been many advances in the understanding of the pathogenesis. The most recent research has focused on the microbiome. There appears to be an abnormal immune response to intestinal microbial flora, shifting the composition of the flora in the affected individual. Altered interactions between the intestinal flora and the immune system in the mucosa of the intestines may be contributing to the inflammatory response. Although genetics plays a role, twin monozygotic studies show a low concordance with IBD. Multiple environmental factors also play a role. These include long-term dietary patterns and age, both of which affect the gut microbiota.⁹

Genetics are also proposed to be significant in the cause of IBD and may be a link with the microbiome as well. Several genes have been identified to increase the susceptibility of the individual to IBD, with different genetic patterns for UC and CD. Mutations of these genes have an impact on the microbiome, which increases the inflammatory response.⁹ In these individuals, the immune system is dysregulated, triggered by an environmental factor. These factors may include luminal bacteria, infection, or tobacco. For some persons with IBD, there seems to be a familial tendency in that these individuals have a first-degree relative with IBD. This is more commonly found in children with IBD than in adults.¹ In these families, most have the same form of IBD, although both UC and CD can occur in the same family. Persons of Jewish ethnicity originating in Europe (Ashkenazi Jews) have been shown to have a higher risk (up to fivefold to eightfold) for development of IBD.²

Cigarette smoking has been shown to be one of the strongest environmental factors affecting IBD. Many studies have documented a higher risk of UC in former smokers. Smoking may also affect the course of UC, demonstrating a protective role. The opposite relationship is evident with CD. Current smoking is a strong, independent risk factor for early development of structuring and fistulizing CD, postoperative recurrence of ileal CD, and disease requiring maintenance therapy, especially biologics. A higher level of tobacco pack-years will increase the risk. Researchers have documented that smokers are twice as likely to develop CD. Continued smoking after surgery increases the risk of needing further surgery. Smokers are also more likely to need immunosuppressives and have a poorer quality of life. Smoking cessation can improve the disease course, and individuals who quit can do better than those who continue to smoke.¹⁰

Pathophysiology

It is thought that several factors are responsible for IBD. A proposed mechanism of inflammation is an infection or other toxin that releases cell wall products that upregulate macrophages and granulocytes. Macrophages and granulocytes activate circulating cells that migrate into the mucosa, releasing a variety of inflammatory factors, such as cytokines, proteases, and oxygen-derived free radicals. These factors all promote inflammation, and the patient has no means of downregulating the system to inhibit the inflammation. Either the tissue responds by resolving with scarring or other secondary immune reactions continue to create irreversible damage.¹¹

Advances in pathophysiology over the past decade have included the role of the microbiome, and the impact from genetic profiles and environmental factors link together to help explain the development of IBD. It is known that NOD2 (CD susceptibility gene) mutations are associated with an altered gut microbiota structure.⁹ Anti–Saccharomyces cerevisiae antibodies (ASCAs) are associated with CD, and antineutrophil cytoplasmic antibodies (ANCAs) are associated with UC. More than 70 genes have been identified that are associated with IBD—UC, CD, or both.¹² Further studies have examined associations among genotype, phenotype, disease course, and response to treatment. This knowledge is contributing to the further understanding of the clinical manifestations of IBD, such as disease location, behavior, natural history, and response to and side effects of medications.¹³

Clinical Presentation

UC and CD can have similar presentations and can be difficult to distinguish. Approximately 10% of people will have IBD–unclassified, colitis that cannot be distinguished as UC or CD.¹ People may complain of symptoms for varying lengths of time, and it is not unusual to have someone report abdominal pain or diarrhea intermittently for years before other symptoms develop. Abdominal pain may be the only presenting complaint. The symptoms of abdominal pain and diarrhea are present in most persons with both diseases. The abdominal pain may be diffuse (generalized lower pain) or localized to the right or left lower quadrants. The pain is usually a cramping sensation and can be intermittent or constant.¹⁴

Tenesmus, spasms in the rectum, urgency, and fecal incontinence may be reported with active rectal inflammation. Stools are often loose or watery and may have blood if the colon is involved. Rectal bleeding is usually present with colitis, either UC or Crohn colitis (if the lower colon is involved). Patients may report blood seen only on the toilet paper after wiping, blood in the stool, clots, or large amounts of blood.¹⁵ With proctitis, rectal bleeding may be the only complaint, or constipation may be reported rather than diarrhea.

Other complaints may include fatigue, weight loss, anorexia, fever, chills, nausea, vomiting, joint pains, and mouth sores. CD may manifest with only vague complaints of fatigue and abdominal cramping, but it can also cause intestinal obstruction and symptoms of vomiting, bloating, and no stool as well as perianal disease of anal fissures, perirectal abscess, or fistula. Some patients, especially in late adolescence and early adulthood, have obstruction, abscesses, or fistula and are diagnosed at surgery.¹⁶

Pertinent history includes recent antibiotic use or travel, the health of other household members, family history of IBD, previous history of abdominal pain or diarrhea, and a thorough medication review.

Physical Examination

The presentation can vary from minimal or no distress to severe illness. Fever and accompanying tachycardia can be present but often are not. All weight ranges are seen, from underweight to obese. People, especially the young and the elderly, can demonstrate significant weight loss and failure to thrive. Conjunctival inflammation or oral aphthous ulcers may be present. Abdominal examination usually reveals a tender lower abdomen, which may be more prominent on one side or the other, although the abdomen can be diffusely tender. Hyperactive bowel sounds and palpation of loops of bowel may be noted as “fullness” in the lower abdomen. A mass, especially in the lower right quadrant, can signify ileocecal inflammation. Rectal examination for occult blood may be positive, with frank blood and tenderness. Perianal lesions, such as skin tags, anal fissure, and perianal fistula, are more suggestive of CD but can be seen in UC. Anal stenosis, abscess, or purulent drainage from a fistulous tract may be seen on rectal examination. Perianal disease is suggestive of IBD but can also be seen in healthy people. Joints do not usually appear red or edematous. Skin lesions (e.g., erythema nodosum, pyoderma gangrenosum, papulonecrotic skin lesions or rashes) may also be noted.

Anemia is the most frequently seen extraintestinal complication in IBD; iron deficiency is the most common cause. Indices that should be monitored include iron saturation, ferritin, and reticulocyte count. Depending on small bowel involvement of IBD and adverse gastrointestinal effects of oral iron supplements, patients may need iron supplementation parenterally. A hematology consultation would be appropriate for iron deficiency refractory to oral supplementation. There are also some data to suggest that oral iron may cause disease exacerbation.¹⁶

Genetic testing has continued to advance and may be helpful in identifying IBD, distinguishing CD from UC, and demonstrating the likelihood of more aggressive CD (prognostic test). The serogenetic markers include ANCAs and perinuclear antineutrophil cytoplasmic antibodies (pANCAs); ASCA immunoglobulin A (IgA) and IgG; outer membrane protein C (anti-OmpC) IgA; and flagellin (anti-Fla2, anti-FlaX, and anti-CBir1).¹⁷ Other markers can be tested in an IBD panel. NOD2/CARD15 genetic testing is prognostic for CD and can provide the likelihood of more aggressive disease over time.

A recent study reported sensitivity and specificity of biomarker testing in patients younger than 18 years of age (sensitivity for IBD 86%, CD 91%, UC 82%; specificity for IBD 86%, CD 76%, UC 91%).¹⁸ A positive test result can be helpful for diagnosis, but it does not obviate the need for other diagnostic testing. False-negative test results can happen with approximately one third of patients and clinical judgement would override the test results. For this reason testing may be useful on a limited basis. The additional markers that are continually being refined may help to distinguish subtypes of disease.¹⁹

Radiography

Enterography by computed tomography (CT) or magnetic resonance imaging (MRI) is a diagnostic and monitoring tool that has become important in the management of CD. It is a more accurate test for small bowel disease. CT scans can detect bowel wall inflammation, perforation, and abscess and are used selectively when appropriate. There is growing concern about exposure to excessive radiation that occurs especially with CT scans. Responsible practitioners need to carefully weigh the benefits of the scan versus the increasing radiation risk. This is especially important in IBD as a chronic, lifelong illness that potentially will require multiple radiologic tests. MR enterography is safer because there is no radiation and is an alternative to view the small bowel.

Small bowel series are used infrequently to determine small bowel involvement and can demonstrate an abnormal terminal ileum and fistulas, but they are not as sensitive as other testing. The barium enema is of limited use in diagnosis of IBD and is most useful in detecting colonic distention, obstruction, fistulas, strictures, or tumors. There are moderate false-positive and false-negative rates with barium studies, which needs to be considered. A barium enema should not be used in patients with moderate to severe colitis because there is perforation risk when the colon is weakened from inflammation. MRI may be helpful in detecting fistulas and abscesses in patients with perianal CD. A laxative should be taken by the patients after barium studies because they can become extremely constipated and the barium can remain for weeks in the intestines.

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

Hypotension Corns and Calluses Seborrheic Dermatitis Dry Skin Surgical Office Procedures Psoriasis