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Definitions, epidemiology, and risk factors for inflammatory bowel disease

Definitions, epidemiology, and risk factors for inflammatory bowel disease
Authors:
Mark A Peppercorn, MD
Adam S Cheifetz, MD
Section Editor:
Sunanda V Kane, MD, MSPH
Deputy Editor:
Kristen M Robson, MD, MBA, FACG
Literature review current through: Dec 2022. | This topic last updated: Aug 10, 2021.

INTRODUCTION — Inflammatory bowel disease (IBD) is comprised of two major disorders: ulcerative colitis and Crohn disease. Ulcerative colitis affects the colon, whereas Crohn disease can involve any component of the gastrointestinal tract from the mouth to the perianal area. These disorders have somewhat different pathologic and clinical characteristics, but with substantial overlap; their pathogenesis remains poorly understood. (See "Immune and microbial mechanisms in the pathogenesis of inflammatory bowel disease".)

The definition, epidemiology, and risk factors for IBD will be reviewed here. The clinical manifestations, diagnosis, and treatment of ulcerative colitis are discussed separately:

(See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults".)

(See "Medical management of low-risk adult patients with mild to moderate ulcerative colitis".)

(See "Management of the hospitalized adult patient with severe ulcerative colitis".)

(See "Management of moderate to severe ulcerative colitis in adults".)

The clinical manifestations, diagnosis, and treatment of Crohn disease are discussed separately:

(See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults".)

(See "Overview of the medical management of mild (low risk) Crohn disease in adults".)

(See "Overview of medical management of high-risk, adult patients with moderate to severe Crohn disease".)

The epidemiology of IBD in children is presented in more detail separately. (See "Clinical presentation and diagnosis of inflammatory bowel disease in children", section on 'Epidemiology'.)

DEFINITIONS

Ulcerative colitis — Ulcerative colitis is a chronic inflammatory condition characterized by relapsing and remitting episodes of inflammation limited to the mucosal layer of the colon. It almost invariably involves the rectum, and the extent often involves more proximal portions of the colon in a continuous fashion. Different terms have been used to describe the degree of involvement [1,2]:

Ulcerative proctitis refers to disease limited to the rectum (within 18 cm of the anal verge, distal to the rectosigmoid junction)

Ulcerative proctosigmoiditis refers to disease limited to the rectum and sigmoid colon and not involving the descending colon

Left-sided colitis is defined as disease that extends beyond the rectum, from the sigmoid colon and as far proximally as the splenic flexure

Extensive colitis refers to disease extending proximal to the splenic flexure

The severity of ulcerative colitis is generally classified as mild, moderate, or severe disease; however, the definitions of disease activity may vary depending on the specific index or score being used [1,3-5]. In addition to clinical parameters, practice guidelines stratify patients into either a low- or high-risk category by assessing inflammatory status to estimate the risk of long-term sequelae (eg, colectomy). The assessment of disease activity, severity, and risk is discussed in more detail separately. (See "Medical management of low-risk adult patients with mild to moderate ulcerative colitis", section on 'Disease activity, severity, and risk'.)

Crohn disease — Crohn disease is characterized by transmural inflammation and by skip areas of involvement (ie, segments of normal-appearing bowel interrupted by areas of disease). The transmural inflammatory nature of Crohn disease may lead to fibrosis and strictures and to obstructive clinical presentations that are not typically seen in patients with ulcerative colitis. Transmural inflammation may also result in sinus tracts, giving rise to microperforations and fistula formation.

Crohn disease most commonly involves the ileum and proximal colon; however, any part of the gastrointestinal tract may be affected. (See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults".)

The assessment of disease activity, severity, and risk for patients with Crohn disease is discussed in more detail separately. (See "Overview of the medical management of mild (low risk) Crohn disease in adults", section on 'Assessing disease activity, severity, and risk'.)

GENETIC FACTORS — There are two issues related to genetic factors in IBD: factors that increase the susceptibility to IBD and genetic syndromes that are associated with an increased risk of IBD. These issues are discussed separately. (See "Genetic factors in inflammatory bowel disease".)

EPIDEMIOLOGY

Geographic and time trends — The prevalence of IBD has been increasing globally with variations by geographic region [6,7]. The number of individuals affected by IBD across the globe increased from 3.7 million in 1990 to 6.8 million in 2017 [7]. At a regional level, the highest age-standardized prevalence rates of IBD were observed in North America (422.0 cases per 100,000 population), while the lowest age-standardized prevalence rates were observed in the Caribbean (6.7 cases per 100,000 population).

The incidence and prevalence of Crohn disease and ulcerative colitis appear to be lower in Asia and the Middle East; however, in some newly industrialized countries in Africa, Asia, and South America, the incidence of IBD has been rising [8-10]. In a large systematic review of population-based studies on the incidence of Crohn disease and ulcerative colitis, the following temporal trends were noted: in Brazil, the annual percentage change (APC) increased for Crohn disease by 11.1 percent (95% CI 4.8-17.8) and for ulcerative colitis by 14.9 percent (95% CI 10.4-19.6), and in Taiwan, the APC increased for Crohn disease by 4 percent (95% CI 1.0-7.1) and for ulcerative colitis by 4.8 percent (95% CI 1.8-8.0) [10].

There seems to be a north-to-south gradient with higher incidence rates of both Crohn disease and ulcerative colitis in northern locations compared with southern latitudes [11,12]. This trend may be related to less sunlight and vitamin D exposure as risk factors for IBD [13-16]. (See 'Dietary factors' below.)

Demographics — Demographic factors including age, sex, and race/ethnicity have been described in population-based studies [13,17,18]:

Age – The age of onset for many patients with ulcerative colitis and Crohn disease is between 15 and 30 years, although IBD can present at any age. Some studies suggest a bimodal age distribution for both disorders with a possible second peak between 50 and 80 years of age [18,19]. It is not clear whether this second peak relates to greater susceptibility to disease with older age, the late expression of an earlier environmental exposure, or higher rates of health care utilization in older persons.

There also appear to be differences in incidence of Crohn disease by age. In a study using data from the Rochester Epidemiology Project, younger age was associated with higher incidence of Crohn disease [6]. Young adults (ie, the 20- to 29-year-old age group) had the highest incidence of Crohn disease (16.6 cases per 100,000 person-years).

Sex – Small differences in IBD incidence by sex have been reported. There is a slight female predominance in adult-onset Crohn disease, which suggests that hormonal factors may play a role in disease expression. In contrast, there may be a slight male predominance in ulcerative colitis [6,20]. In a study using data from the Rochester Epidemiology Project, male sex was associated with a higher incidence rate of ulcerative colitis compared with female sex (12.8 versus 8.8 cases per 100,000 person-years) [6].

Race and ethnicity – Both ulcerative colitis and Crohn disease are more common in Jewish compared with non-Jewish populations [21,22]. The incidence of IBD is lower in Hispanic populations and Black populations compared with White populations [14,23,24].

However, ethnic and racial differences may be related to environmental and lifestyle factors as well as due to underlying genetic differences [12,25-27]. As an example, in a large population-based study in Denmark, the risk of IBD was lower in first-generation immigrants compared with individuals from Denmark (incidence rate ratio [IRR] 0.76, 95% CI 0.74-0.79); however, the risk of IBD was not significantly different for second-generation immigrants [27]. The potential associations of IBD with specific genes or major histocompatibility complex loci are discussed separately. (See "Genetic factors in inflammatory bowel disease".)

CLINICAL RISK FACTORS

Lifestyle factors

Smoking — Smoking is a risk factor for Crohn disease but not for ulcerative colitis [28,29]. While the basis for this dichotomy has yet to be resolved, nicotine and/or smoking byproducts may directly affect mucosal immune responses, smooth muscle tone, gut permeability, and microvasculature [30].

Crohn disease – Smoking is associated with an increased risk of Crohn disease. In a cohort study including over 200,000 women, both current and former smokers were more likely to develop Crohn disease compared with those who had never smoked (hazard ratio [HR] 1.9, 95% CI 1.4-2.5 and HR 1.4, 95% CI 1.05-1.73, respectively) [29].

Smoking also increases the risk complications from Crohn disease (eg, strictures, fistula) and the need for surgery [28,31,32].

Ulcerative colitis – Data suggest that current smoking is not a risk factor for and may lower the risk of developing ulcerative colitis [28,33]. In a cohort study including over 200,000 women, the risk of ulcerative colitis was not significantly different for current smokers compared with those who had never smoked, while former smokers had an increased risk of ulcerative colitis as compared with lifetime nonsmokers (HR 1.6, 95% CI 1.3-1.9) [29]. The increase in risk associated with smoking cessation may be explained by loss of the protective effect of smoking, which then precipitates the onset of or unmasks the symptoms of ulcerative colitis.

Cigarette smoking may also influence the course of ulcerative colitis [34]. Smoking cessation in patients with ulcerative colitis is associated with an increase in disease activity and risk of hospitalization.

Physical activity — Physical activity has been associated with a decrease in risk of Crohn disease, but not ulcerative colitis [35,36]. In two large prospective cohort studies including 194,711 women who provided data on physical activity, the risk of Crohn disease but not ulcerative colitis was inversely associated with physical activity (hazard ratio [HR] Crohn disease highest fifth of physical activity as compared with lowest fifth 0.64, 95% CI 0.44-0.94) [35]. The absolute risk of Crohn disease and ulcerative colitis among women in the highest fifth of physical activity was 6 and 8 events per 100,000 person-years as compared with 16 and 11 events per 100,000 person-years among women in the lowest fifth of physical activity, respectively. Limited data also suggest that physical activity is associated with a reduction in disease activity in patients with an established diagnosis of Crohn disease [37].

Dietary factors — Data from epidemiologic studies suggest that dietary factors may play a role in the risk of developing IBD:

Fiber – High intake of dietary fiber, particularly from fruit and cruciferous vegetables, has been associated with a decrease in risk of Crohn disease but not ulcerative colitis [38-40].

Fats – Increased dietary intake of total fat, animal fat, and polyunsaturated fatty acids has been correlated with an increased incidence of ulcerative colitis and Crohn disease [39,41,42] and relapse in patients with ulcerative colitis [43]. In addition, a higher intake of omega-3 fatty acids and a lower intake of omega-6 fatty acids has been associated with a lower risk of developing Crohn disease [44].

Vitamin D – Data suggest that vitamin D intake is inversely associated with risk of Crohn disease and that vitamin D deficiency is common among patients with IBD [15,45].

Dietary interventions to improve nutrition and eliminate food triggers for patients with IBD are discussed separately. (See "Nutrition and dietary management for adults with inflammatory bowel disease".)

Food antigens are thought to trigger an immunologic response resulting in the development of IBD; however, specific pathogenic antigens have not been identified [46].

Sleep duration — Sleep deprivation has been associated with an increased risk of incident ulcerative colitis and of disease flares in patients with IBD [47,48]. A prospective cohort study evaluated sleep duration in 151,871 women and the incidence of IBD [47]. During a follow-up of 2,292,849 person-years, there were 191 incident cases of Crohn disease and 230 cases of ulcerative colitis (incidence 8 per 100,000 and 10 per 100,000 person-years, respectively). Women with reported sleep duration of <6 or >9 hours per day had a higher risk of ulcerative colitis compared with women with reported sleep durations of seven to eight hours per day (odds ratio [OR] 1.5, 95% CI 1.1-2.1, and OR 2.1, 95% CI 1.4-2.9, respectively). In contrast, sleep duration did not modify the risk of Crohn disease. Further studies are needed to explore the mechanisms by which sleep may influence intestinal inflammation and if modification of sleep duration can decrease the risk of IBD.

Infection and the immune response — Infection and the immune response have been implicated in the pathogenesis of IBD. Studies have identified roles for both host and microbial factors in the pathogenesis of IBD, ultimately leading to inappropriate immune responses to intestinal microbes, and this is discussed in more detail separately [49]. (See "Immune and microbial mechanisms in the pathogenesis of inflammatory bowel disease".)

While no specific pathogen has been consistently implicated in the development of IBD, the following clinical studies evaluated the role of infection:

Gastroenteritis – Several observational studies have suggested an association between acute gastroenteritis and the development of IBD [50-53]. As an example, a case control study included over 3000 patients with incident IBD and over 11,000 controls [50]. After excluding patients who had acute gastroenteritis within six months of IBD diagnosis and adjusting for potential confounders, the risk of IBD was higher in patients with a prior episode of acute gastroenteritis compared with controls (OR 1.4; 95% CI 1.2-1.7).

An increased risk of developing IBD was also found in a population-based cohort study of 13,148 patients with documented Salmonella or Campylobacter gastroenteritis when compared with a matched control group (1.2 versus 0.5 percent, HR 2.9, 95% CI 2.2-3.9) [51]. While the increased risk was highest during the first year after infection, it remained elevated during 15 years of follow-up.

Other infectious pathogens – A number of studies have evaluated the possible role of several infectious agents (eg, mycobacteria, viruses, fungi) in the pathogenesis of IBD; however, no specific pathogen has been identified as a causal factor [54-58].

Medications

Antibiotics — While antibiotic use has been associated with IBD, it is unclear if this is a causal association [59-62]. In a meta-analysis of 11 observational studies that included 7208 patients diagnosed with IBD, antibiotic exposure was associated with an increased risk of Crohn disease (OR 1.74, 95% CI 1.35-2.23) but not ulcerative colitis [60]. In a case-control study including nearly 24,000 patients with IBD, antibiotic use was associated with higher risk for diagnosis of IBD compared with no antibiotic use after adjusting for other risk factors (adjusted OR 1.88, 95% CI 1.79-1.98) [62]. The role of antibiotics in the treatment of IBD is discussed separately. (See "Overview of the medical management of mild (low risk) Crohn disease in adults", section on 'Antibiotics' and "Management of Crohn disease after surgical resection", section on 'Antibiotics' and "Management of acute and chronic pouchitis".)

NSAIDs — Nonsteroidal antiinflammatory drugs (NSAIDs) may increase risk for developing IBD, but the magnitude of the risk appears small [63-65]. For example, in a cohort study including over 70,000 women, NSAID use for at least 15 days per month increased the risk of ulcerative colitis (HR 1.87, 95% CI 1.16-2.99) and for Crohn disease (HR 1.59, 95% CI 0.99-2.56) compared with no NSAID use [63]. However, the absolute increase in risk was small (absolute difference 7 cases per 100,000 person-years for ulcerative colitis and 6 cases per 100,000 person-years for Crohn disease).

While NSAIDs are associated with intestinal mucosal injury, some patients with IBD can tolerate NSAIDs, particularly when they are given in low doses (eg, ibuprofen ≤200 mg daily, naproxen <220 mg daily) [66,67]. NSAID-induced mucosal injury and the use of NSAIDs for patients with arthritis associated with IBD are discussed separately. (See "NSAIDs: Adverse effects on the distal small bowel and colon" and "Treatment of arthritis associated with inflammatory bowel disease".)

Experience with the cyclooxygenase-2 (COX-2) selective inhibitors in patients with IBD is limited. Although small case series suggested an increased risk of exacerbation of IBD [68,69], randomized controlled trials have demonstrated no significant increase in disease activity or relapse in patients treated with short-term COX-2 selective inhibitors [70,71].

The association of NSAIDs with IBD may be due to several mechanisms. Cyclooxygenase-mediated disruption of the intestinal epithelial barrier associated with NSAID use can affect the interaction between the gut microbiome and immune cells in the intestine lining. In addition, NSAIDs alter platelet aggregation, the release of inflammatory mediators, and microvascular response to stress, which are key events in the pathogenesis of IBD. (See "Immune and microbial mechanisms in the pathogenesis of inflammatory bowel disease".)

Oral contraceptives and hormone replacement — Oral contraceptives and hormone replacement therapy may increase the risk for developing IBD; however, the risk appears to be small [72-74]:

In a meta-analysis of 14 studies including 75,815 premenopausal women, oral contraceptive use was associated with a higher risk of ulcerative colitis (relative risk [RR] 1.3, 95% CI 1.1-1.5) and Crohn disease (RR 1.5, 95% CI 1.3-1.7) compared with no oral contraceptive use [72].

In a prospective study of 108,844 postmenopausal women, hormone replacement therapy was associated with an increased risk of ulcerative colitis but not Crohn disease [73]. The risk of ulcerative colitis was increased among both current and past users compared with women who had never used postmenopausal hormone therapy (HR current users 1.7, 95% CI, 1.1-2.7; HR past users 1.7, 95% CI, 1.0-2.7). The risk of ulcerative colitis increased with longer duration of hormone use and decreased with time since discontinuation.

The risks associated with oral contraceptives and hormone replacement therapy are discussed separately. (See "Menopausal hormone therapy: Benefits and risks" and "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Gastrointestinal disorders'.)

The mechanism by which oral contraceptives or hormone replacement therapy increase the risk of IBD is unclear, but it may involve thrombotic effects on the microvasculature or the effect of estrogen in enhancing the inflammatory response [75].

Isotretinoin — An association between isotretinoin, used in the treatment of acne vulgaris, and IBD has been suggested by case reports [76,77]. While an association may be biologically plausible based on the pleiotropic effects of isotretinoin on the innate and adaptive intestinal immunoregulatory capacity, observational studies evaluating this association have yielded variable results [78-85].

Potentially confounding the association of isotretinoin use and the development of IBD is the fact that many patients with acne who are treated with isotretinoin have also been treated with oral tetracycline class antibiotics, which some data suggest may be associated with the development of IBD [61,83]. (See 'Antibiotics' above and "Oral isotretinoin therapy for acne vulgaris".)

Other factors

Appendectomy — The relationship between appendectomy and IBD depends on whether the diagnosis is Crohn disease or ulcerative colitis:

Crohn disease – Some studies have suggested that the risk of Crohn disease is increased after appendectomy [86]. However, a meta-analysis suggested that the apparent increased risk may be due to a misdiagnosis in patients with incipient Crohn disease [87].

Ulcerative colitis – Data suggest that appendectomy may lower the risk of developing ulcerative colitis, while the mechanism of the protective effect is unknown [53,88-90]. In a case-control study including 212,963 patients who underwent appendectomy, the risk of developing ulcerative colitis was lower for patients with appendicitis or mesenteric lymphadenitis compared with controls (adjusted HR 0.58, 95% CI 0.38-0.87) [89]. However, the risk of ulcerative colitis was not lower for patients with nonspecific abdominal pain who underwent appendectomy compared with controls.

Psychological factors – Studies examining the association between psychological factors and the risk of developing IBD have yielded inconsistent results [91-95]. However, stress may have a role in the exacerbation of symptoms in patients with established IBD, possibly via activation of the enteric nervous system and the production of proinflammatory cytokines [96,97]. (See "Medical management of low-risk adult patients with mild to moderate ulcerative colitis", section on 'Anxiety/depression screening'.)

Obesity – It is unclear if obesity is associated with an increased risk of developing IBD [98,99]. However, accumulation of intra-abdominal fat may contribute to mucosal inflammation, thereby affecting the clinical course in patients with established IBD [100]. In a study of patients with Crohn disease, anoperineal complications occurred earlier in patients with obesity. In addition, patients with obesity were more likely to develop active disease (OR 1.5, 95% CI 1.1-2.1) and to require hospitalization (OR 2.4, 95% CI 1.6-3.5) [101].

EARLY LIFE EXPOSURES — The relationship of breastfeeding or early life exposure to antibiotics with inflammatory bowel disease is discussed separately. (See "Infant benefits of breastfeeding", section on 'Long-term benefits' and "Immune and microbial mechanisms in the pathogenesis of inflammatory bowel disease", section on 'Role of microbes'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ulcerative colitis in adults" and "Society guideline links: Crohn disease in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Crohn disease in adults (The Basics)" and "Patient education: Ulcerative colitis in adults (The Basics)")

Beyond the Basics topics (see "Patient education: Crohn disease (Beyond the Basics)" and "Patient education: Ulcerative colitis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn disease (see 'Definitions' above):

Ulcerative colitis is a chronic inflammatory condition characterized by relapsing and remitting episodes of inflammation limited to the mucosal layer of the colon. It almost invariably involves the rectum, and the extent often involves more proximal portions of the colon in a continuous fashion.

Crohn disease is characterized by transmural inflammation that may lead to fibrosis and strictures and may result in sinus tracts, giving rise to microperforations and fistula formation. Crohn disease most commonly involves the ileum and proximal colon; however, any part of the gastrointestinal tract may be affected.

There are two issues related to genetic factors in IBD: factors that increase the susceptibility to IBD and genetic syndromes that are associated with an increased risk of IBD. These issues are discussed separately. (See "Genetic factors in inflammatory bowel disease".)

The number of individuals affected by IBD across the world increased from 3.7 million in 1990 to 6.8 million in 2017. In North America, the age-standardized prevalence rate of IBD was 422 cases per 100,000 population. (See 'Geographic and time trends' above.)

The age of onset for many patients with ulcerative colitis and Crohn disease is between 15 and 30 years, although IBD can present at any age. Some studies suggest a bimodal age distribution for both disorders with a possible second peak between 50 and 80 years. (See 'Demographics' above.)

Cigarette smoking increases the risk for Crohn disease but may lower the risk of developing ulcerative colitis. (See 'Smoking' above.)

Nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk for developing IBD, but the magnitude of the risk appears small. (See 'NSAIDs' above.)

NSAID-induced mucosal injury and the use of NSAIDs for patients with IBD-associated arthritis are discussed separately. (See "NSAIDs: Adverse effects on the distal small bowel and colon" and "Treatment of arthritis associated with inflammatory bowel disease".)

ACKNOWLEDGMENT — We are saddened by the death of Paul Rutgeerts, MD, who passed away in September 2020. UpToDate gratefully acknowledges Dr. Rutgeerts' work as our Section Editor for Gastroenterology.

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Topic 4066 Version 41.0

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