Inflammatory bowel disease (IBD), which includes Crohn disease Crohn Disease Crohn disease is a chronic transmural inflammatory bowel disease that usually affects the distal ileum and colon but may occur in any part of the gastrointestinal tract. Symptoms include diarrhea... read more and ulcerative colitis Ulcerative Colitis Ulcerative colitis is a chronic inflammatory and ulcerative disease arising in the colonic mucosa, characterized most often by bloody diarrhea. Extraintestinal symptoms, particularly arthritis... read more , is a relapsing and remitting condition characterized by chronic inflammation at various sites in the gastrointestinal tract, which results in diarrhea and abdominal pain.
Inflammation results from a cell-mediated immune response in the gastrointestinal mucosa. The precise etiology of inflammatory bowel disease unknown, but evidence suggests that the normal intestinal flora inappropriately trigger an immune reaction in patients with a multifactorial genetic predisposition (perhaps involving abnormal epithelial barriers and mucosal immune defenses). No specific environmental, dietary, or infectious causes have been identified. The immune reaction involves the release of inflammatory mediators, including cytokines, interleukins, and tumor necrosis factor.
Although Crohn disease and ulcerative colitis are similar, they can be distinguished in most cases ( see Table: Differentiating Crohn Disease and Ulcerative Colitis Differentiating Crohn Disease and Ulcerative Colitis ). About 10% of colitis cases are not initially distinguishable and are termed unclassified; if a surgical pathologic specimen cannot be classified, it is termed indeterminate colitis. The term colitis applies only to inflammatory disease of the colon (eg, ulcerative, granulomatous, ischemic, radiation-induced, infectious). Spastic (mucous) colitis is a misnomer sometimes applied to a functional disorder, irritable bowel syndrome Irritable Bowel Syndrome (IBS) Irritable bowel syndrome is characterized by recurrent abdominal discomfort or pain with at least two of the following characteristics: relation to defecation, association with a change in frequency... read more .
Differentiating Crohn Disease and Ulcerative Colitis
Small bowel is involved in 80% of cases.
Disease is confined to the colon.
Rectum is often spared; colonic involvement is usually right-sided.
Rectum is invariably involved; colonic involvement is usually left-sided.
Gross rectal bleeding is rare, except in 75‒85% of cases of Crohn colitis.
Gross rectal bleeding is always present.
Fistula, mass, and abscess development is common.
Fistulas do not occur.
Perianal lesions are significant in 25‒35% of cases.
Significant perianal lesions never occur.
On x-ray, bowel wall is affected asymmetrically and segmentally, with skip areas between diseased segments.
Bowel wall is affected symmetrically and uninterruptedly from rectum proximally.
Endoscopic appearance is patchy, with discrete ulcerations separated by segments of normal-appearing mucosa.
Inflammation is uniform and diffuse.
Microscopic inflammation and fissuring extend transmurally; lesions are often highly focal in distribution.
Inflammation is confined to mucosa except in severe cases.
Epithelioid (sarcoid-like) granulomas are detected in bowel wall or lymph nodes in 25‒50% of cases (pathognomonic).
Typical epithelioid granulomas do not occur.
Inflammatory bowel disease (IBD) affects people of all ages but usually begins before age 30, with peak incidence from 14 to 24. IBD may have a second smaller peak between ages 50 and 70; however, this later peak may include some cases of ischemic colitis.
IBD is most common among people of Northern European and Anglo-Saxon origin and is 2 to 4 times more common among Ashkenazi Jews than non-Jewish White people from the same geographic location. The incidence is lower in central and southern Europe and lower still in South America, Asia, and Africa. However, the incidence is increasing among Black and Latin American people living in North America. Both sexes are equally affected. First-degree relatives of patients with IBD have a 4- to 20-fold increased risk; their absolute risk may be as high as 7%. Familial tendency is much higher in Crohn disease than in ulcerative colitis. Several gene mutations conferring a higher risk of Crohn disease (and some possibly related to ulcerative colitis) have been identified.
Cigarette smoking seems to contribute to development or exacerbation of Crohn disease but decreases risk of ulcerative colitis. Appendectomy done to treat appendicitis also appears to lower the risk of ulcerative colitis. Nonsteroidal anti-inflammatory drugs (NSAIDs) may exacerbate IBD. Oral contraceptives may increase the risk of Crohn disease. Some data suggest that perinatal illness and the use of antibiotics in childhood may be associated with an increased risk of IBD.
For unclear reasons, people who have a higher socioeconomic status may have an increased risk of Crohn disease.
Pearls & Pitfalls
Crohn disease and ulcerative colitis both affect organs other than the intestines. Most extraintestinal manifestations are more common in ulcerative colitis and Crohn colitis than in Crohn disease limited to the small bowel. Extraintestinal manifestations of inflammatory bowel disease are categorized in 3 ways:
1. Disorders that usually parallel (ie, wax and wane with) IBD flare-ups: These disorders include peripheral arthritis, episcleritis Episcleritis Episcleritis is self-limiting, recurring, usually idiopathic inflammation of the episcleral tissue that does not threaten vision. Symptoms are a localized area of hyperemia of the globe, irritation... read more , aphthous stomatitis Recurrent Aphthous Stomatitis Recurrent aphthous stomatitis (RAS) is a common condition in which round or ovoid painful ulcers recur on the oral mucosa. Etiology is unclear. Diagnosis is clinical. Treatment is symptomatic... read more , and erythema nodosum Erythema Nodosum Erythema nodosum is a specific form of panniculitis characterized by tender, red or violet, palpable, subcutaneous nodules on the shins and occasionally other locations. It often occurs with... read more . Arthritis tends to involve large joints and be migratory and transient. One or more of these parallel disorders develops in more than one third of patients hospitalized with IBD.
2. Disorders that are clearly associated with IBD but appear independently of IBD activity: These disorders include ankylosing spondylitis, Ankylosing Spondylitis Ankylosing spondylitis is the prototypical spondyloarthropathy and a systemic disorder characterized by inflammation of the axial skeleton, large peripheral joints, and digits; nocturnal back... read more sacroiliitis, uveitis Overview of Uveitis Uveitis is defined as inflammation of the uveal tract—the iris, ciliary body, and choroid. However, the retina and fluid within the anterior chamber and vitreous are often involved as well.... read more , pyoderma gangrenosum Pyoderma Gangrenosum Pyoderma gangrenosum is a chronic, neutrophilic, progressive skin necrosis of unknown etiology often associated with systemic illness and sometimes skin injury. Diagnosis is clinical. Treatment... read more , and primary sclerosing cholangitis Primary Sclerosing Cholangitis (PSC) Primary sclerosing cholangitis (PSC) is patchy inflammation, fibrosis, and strictures of the bile ducts that has no known cause. However, 80% of patients also have inflammatory bowel disease... read more . Ankylosing spondylitis occurs more commonly in IBD patients with human leukocyte antigen B27 (HLA-B27). Most patients with spinal or sacroiliac involvement have evidence of uveitis and vice versa. Primary sclerosing cholangitis, which is a risk factor for cancer of the biliary tract, is strongly associated with ulcerative colitis and Crohn colitis. Cholangitis may appear before or concurrently with the bowel disease or even 20 years after colectomy. Liver disease (eg, fatty liver, autoimmune hepatitis, pericholangitis, cirrhosis) occurs in 3 to 5% of patients, although minor abnormalities in liver tests are more common. Some of these conditions (eg, primary sclerosing cholangitis) may precede IBD by many years and, when diagnosed, should prompt an evaluation for IBD.
3. Disorders that are consequences of disrupted bowel physiology: These disorders occur mainly in severe Crohn disease of the small bowel. Malabsorption Overview of Malabsorption Malabsorption is inadequate assimilation of dietary substances due to defects in digestion, absorption, or transport. Malabsorption can affect macronutrients (eg, proteins, carbohydrates, fats)... read more may result from extensive ileal resection and cause deficiencies of fat-soluble vitamins, vitamin B12, or minerals, resulting in anemia, hypocalcemia, hypomagnesemia, clotting disorders, and bone demineralization. In children, malabsorption retards growth and development. Other disorders include kidney stones resulting from excessive dietary oxalate absorption, hydroureter and hydronephrosis resulting from ureteral compression by the intestinal inflammatory process, gallstones resulting from impaired ileal reabsorption of bile salts, and amyloidosis secondary to long-standing inflammatory and suppurative disease.
Thromboembolic disease may occur as a result of multiple factors in all 3 categories.
Treatment of Inflammatory Bowel Disease
Small-molecule agents Small-molecule agents Several classes of drugs are helpful for inflammatory bowel disease (IBD). Details of their selection and use are discussed under each disorder (see Crohn disease treatment and ulcerative colitis... read more (eg, Janus kinase inhibitor, sphingosine 1-phosphate [S1P] receptor modulator)
Sometimes antibiotics Antibiotics Several classes of drugs are helpful for inflammatory bowel disease (IBD). Details of their selection and use are discussed under each disorder (see Crohn disease treatment and ulcerative colitis... read more (eg, metronidazole, ciprofloxacin) and probiotics Probiotics Several classes of drugs are helpful for inflammatory bowel disease (IBD). Details of their selection and use are discussed under each disorder (see Crohn disease treatment and ulcerative colitis... read more
Several classes of drugs are helpful for IBD. Details of their selection and use are discussed under each disorder and in Drugs for Inflammatory Bowel Disease Drugs for Inflammatory Bowel Disease Several classes of drugs are helpful for inflammatory bowel disease (IBD). Details of their selection and use are discussed under each disorder (see Crohn disease treatment and ulcerative colitis... read more .
Most patients and their families are interested in diet and stress management. Although there are anecdotal reports of clinical improvement on certain diets, including one with rigid carbohydrate restrictions, controlled trials have shown no consistent benefit. Stress management may be helpful.
Patients with IBD should receive the yearly influenza vaccination Influenza Vaccine Based on recommendations by the World Health Organization and the Centers for Disease Control and Prevention (CDC), vaccines for influenza are modified annually to include the most prevalent... read more and the pneumococcal vaccination Pneumococcal Vaccine Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more . Those ≥ 50 years of age should receive the recombinant herpes zoster vaccine Herpes Zoster Vaccine Chickenpox (varicella) and shingles ( herpes zoster) are caused by the varicella-zoster virus; chickenpox is the acute invasive phase of the virus, and shingles represents reactivation of the... read more . Those < 50 years of age who have IBD may receive the vaccine, and clinicians should engage in a shared decision-making discussion with patients to determine whether they should be vaccinated (see the Canadian Association of Gastroenterology's 2021 Clinical practice guideline for immunizations in patients with inflammatory bowel disease—Part 2: Inactivated vaccines). This vaccine should be given before starting immunosuppressive therapy when possible.
Routine vaccinations such as tetanus-diphtheria Tetanus-Diphtheria Vaccine A vaccine for tetanus alone is available, but the tetanus vaccine is typically combined with those for diphtheria and/or pertussis. The vaccine for diphtheria is available only in combination... read more , hepatitis A Hepatitis A (HepA) Vaccine Both hepatitis A vaccines provide long-term protection against hepatitis A. For more information, see Hepatitis A Advisory Committee on Immunization Practices Vaccine Recommendations and Centers... read more , hepatitis B Hepatitis B (HepB) Vaccine The hepatitis B vaccine is 80 to 100% effective in preventing infection or clinical hepatitis B in people who complete the vaccine series. For more information, see Hepatitis B Advisory Committee... read more , and human papillomavirus Human Papillomavirus (HPV) Vaccine Human papillomavirus (HPV) infection is the most common sexually transmitted disease. HPV can cause skin warts, genital warts, or certain cancers, depending on the type of HPV. Vaccines are... read more should be given as per the Advisory Committee on Immunization Practices (ACIP) guidelines.
The Centers for Disease Control and Prevention (CDC) and the Canadian Association of Gastroenterology recommend patients with IBD, including those on immunosuppressive therapy, receive an mRNA COVID-19 vaccine COVID-19 Vaccine COVID-19 vaccines provide protection against COVID-19. COVID-19 is the disease caused by infection with the SARS-CoV-2 virus. There are multiple COVID-19 vaccines currently in use worldwide... read more .
Female patients who are not receiving immunosuppressive therapy should be screened for cervical cancer with a Papanicolaou (Pap) test Diagnosis Cervical cancer is usually a squamous cell carcinoma caused by human papillomavirus infection; less often, it is an adenocarcinoma. Cervical neoplasia is asymptomatic; the first symptom of early... read more every 3 years. Patients who are receiving immunosuppressive therapy should have a Pap test yearly.
All patients who are taking or plan to take immunomodulating drugs or biologic agents should be evaluated for skin cancer Overview of Skin Cancer Skin cancer is the most common type of cancer and commonly develops in sun-exposed areas of skin. The incidence is highest among outdoor workers, sportsmen, and sunbathers and is inversely related... read more annually.
Patients at risk of osteoporosis Risk Factors Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. Skeletal weakness leads to fractures... read more should have a dual-energy x-ray absorptiometry (DXA) scan Dual-energy x-ray absorptiometry (DXA) Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. Skeletal weakness leads to fractures... read more .
The following are English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
Advisory Committee on Immunization Practices (ACIP): Information about routine vaccination recommendations and guidelines and vaccine-specific updates
Canadian Association of Gastroenterology: Clinical practice guideline for immunizations in patients with inflammatory bowel disease—Part 2: Inactivated vaccines (2021)