Version May 2024
INTRODUCTION — Diverticular disease of the colon is an important cause of hospital admissions and a significant contributor to health care costs in Western and industrialized societies [1,2].
This topic will review the epidemiology, risk factors, and the pathogenesis of diverticulosis and diverticular disease. The clinical manifestations, diagnosis, and treatment of diverticulitis, diverticular bleeding, and segmental colitis associated with diverticula (diverticular colitis) are discussed in detail, separately. (See "Clinical manifestations and diagnosis of acute colonic diverticulitis in adults" and "Acute colonic diverticulitis: Medical management" and "Colonic diverticular bleeding" and "Segmental colitis associated with diverticulosis".)
TERMINOLOGY
●Diverticulosis is defined by the presence of diverticula, which are sac-like protrusions of the colonic mucosa through weak points in the muscular wall (figure 1). Diverticulosis may be asymptomatic or symptomatic.
●Diverticular disease is defined as clinically significant and symptomatic diverticulosis due to diverticulitis or its complications, diverticular bleeding, segmental colitis associated with diverticula, or symptomatic uncomplicated diverticular disease.
DIVERTICULOSIS
Epidemiology
Prevalence — The prevalence of diverticulosis is age-dependent, and the prevalence and distribution within the colon varies by geography and race [3]. In the United States, the prevalence of diverticulosis increases from fewer than 20 percent at age 40 to 60 percent by age 60 (image 1) [4]. The number and size of diverticula also increase with age, suggesting that diverticulosis is a progressive process [4]. The prevalence of diverticulosis appears to be higher in the left colon in countries in the West. In a study of 624 individuals undergoing first-time screening colonoscopy of whom 260 (42 percent) had diverticulosis, 72 percent had diverticula in the sigmoid colon, 10 percent in the descending, 6 percent in the transverse, 11 percent in the ascending, and 1 percent in the cecum. Black Americans were more likely to have diverticula in the proximal colon than White Americans. Data from more than 270,000 colonoscopy procedures indicate that females are less likely to have diverticulosis than males, particularly in younger age groups [5]. Non-Hispanic White Americans were more likely to have diverticulosis than non-Hispanic Black Americans and Asian/Pacific Islanders. Non-Hispanic Black Americans were at increased odds of having any proximal diverticulosis and Asian/Pacific Islanders were at increased odds of having only proximal diverticulosis, which are often congenital in nature.
Contemporary studies of the prevalence of diverticulosis in other countries are limited. In one series that included 302 patients, the prevalence of diverticulosis in Nigeria was 9.4 percent [6]. Prevalence rates in studies performed in Southeast Asia range from 12 percent in Korea, to 25 percent in Japan, and 29 percent in Thailand [6,7]. In Asia, diverticulosis is predominantly right-sided [8].
Time trends — The prevalence of diverticulosis has increased both in the Western hemisphere and in countries that have adopted a more Western lifestyle. As an example, Japan has experienced an increase in the prevalence of right-sided diverticulosis similar to the increase in left-sided diverticula in westernized countries [9,10].
Risk factors — In well-characterized, cross-sectional cohorts of patients undergoing screening colonoscopy, older age, male sex, smoking, and elevated body mass index have been identified as risk factors for diverticulosis [4,11]. White race was also a risk factor for diverticulosis [5]. Contrary to popular belief, low dietary fiber intake and constipation were not associated with increased risk of diverticulosis found on colonoscopy [3,11]. Dietary red meat and fat, alcohol consumption, and physical inactivity also do not appear to contribute to the risk of diverticulosis.
Pathogenesis — The pathogenesis of diverticulosis and its complications have not been clearly elucidated. Several theories exist that are supported largely by indirect evidence. These theories are evolving over time and build on advancements in genetics and the gut microbiome. Diverticula develop at well-defined points of weakness, which correspond to where the vasa recta penetrate the circular muscle layer of the colon (figure 1) [12]. In the West, most colonic diverticula are acquired and are "false" or pulsion diverticulum, in which mucosa and submucosa herniate through the muscle layer, covered only by serosa. In Asia, congenital diverticula are common, tend to be in the right colon, and include all layers of the colon wall.
Abnormal colonic motility is hypothesized to be an important predisposing factor in the development of diverticula [13,14]. Patients with diverticulosis have exaggerated segmentation contractions in which segmental muscular contractions separate the lumen into chambers (image 2). This may result in an increase in intraluminal pressure that predisposes to herniation of mucosa and submucosa. However, studies have also shown that constipation and a low fiber diet are not associated with asymptomatic diverticulosis. The neural basis for the abnormal motility observed in patients with diverticulosis remains unclear, although one report found that a central event appeared to be upregulation of smooth muscle M3 receptors [13].
There are also structural changes in collagen that are similar to, but greater in magnitude than, those that occur because of aging [15]. Structural changes in the wall may also be responsible for the appearance of diverticula at an early age in connective tissue disorders such as Ehlers-Danlos and Marfan's syndromes and in autosomal dominant polycystic kidney disease [16]. Genome-wide association studies have identified susceptibility loci in areas with genes associated with intestinal motility and enriched for expression in connective tissue cell types [17]. (See "Clinical manifestations and diagnosis of Ehlers-Danlos syndromes" and "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders" and "Autosomal dominant polycystic kidney disease (ADPKD): Extrarenal manifestations".)
DIVERTICULITIS — Diverticulitis is defined as inflammation of one or several adjacent diverticula. Diverticulitis may be uncomplicated or complicated by a diverticular abscess, fistula, bowel obstruction, or free perforation. Smoldering diverticulitis is an uncommon presentation of diverticulitis defined as diverticulitis that persists or relapses shortly after treatment. (See "Clinical manifestations and diagnosis of acute colonic diverticulitis in adults".)
Incidence — Approximately 4 percent of patients with diverticulosis develop diverticulitis [18]. The incidence of diverticulitis increases with age. The mean age at admission for acute diverticulitis is 63 years [19]. While the incidence of acute diverticulitis is lower in younger individuals, approximately 16 percent of admissions for acute diverticulitis are in patients under 45 years of age [20]. Diverticulitis is predominantly left-sided in western countries, with right-sided diverticulitis being present in only 1.5 percent of cases [21]. In the United States, diverticulitis is more common in non-Hispanic Whites than in non-Hispanic Blacks, and is lowest in Asians [22].
The incidence of diverticulitis is increasing. A nationwide inpatient study of hospitalizations in the United States showed an increase in admissions for acute diverticulitis of 26 percent from 1998 to 2005 [19], although in another nationwide study, prevalence appeared to plateau after 2008 [22]. The largest increase was in patients aged 18 to 44 years (82 percent). Elective operations for diverticulitis also increased by 29 percent with the largest increase in patients aged 18 to 44 years (73 percent). Under age 50 years, diverticulitis is more common in men; there is a slight female preponderance between the ages of 50 and 70, and a marked female preponderance over age 70 [22-26].
Risk factors
Lifestyle factors — Several lifestyle factors have been associated with risk of diverticulitis including diet, lack of physical activity, body mass index, and smoking. A prospective cohort study evaluated the association between lifestyle factors and the risk of incident diverticulitis in over 51,000 males aged 40 to 75 years at study baseline [27]. The risk of diverticulitis decreased incrementally with the number of low-risk lifestyle factors (fewer than four servings of red meat/week, at least 23 g/day of dietary fiber, BMI 18.5 to 25, at least two hours/week of vigorous physical activity, and never-smoker). Males who adhered to all five low-risk factors were 73 percent less likely to develop diverticulitis, and 50 percent of the population attributable risk of diverticulitis was due to these lifestyle factors.
Diet — Dietary factors that increase the risk of diverticulitis include high intake of red meat alone and a Western dietary pattern (high in red meat, fat, and refined grains). In a large, prospective study of men, those in the highest quintile of Western dietary pattern score were 55 percent more likely to develop incident diverticulitis than those in the lowest quintile after adjustment for multiple confounders [28]. Similarly, males who consumed the most red meat had a 58 percent higher risk of diverticulitis. The risk plateaued after six servings per week and substitution of poultry or fish for red meat decreased risk [29]. In contrast, high intake of dietary fiber, and a prudent dietary pattern (high in fruits, vegetables, and whole grains) and a vegetarian diet have been associated with decreased risk of incident diverticulitis [28,30-32]. The inflammatory potential of diet and circulating levels of inflammatory markers have also been associated with an increase in risk of subsequent diverticulitis, and changes in the gut microbiome are seen in individuals who have had diverticulitis [33-35]. Together these findings suggest that diet acts through the gut microbiome and chronic inflammation to contribute to diverticulitis risk.
Nut, corn, and popcorn consumption are not associated with an increase in risk of diverticulitis. In a large prospective cohort study that included 47,228 males, there was an inverse association between nut and popcorn consumption and risk of incident diverticulitis in highest to lowest consumption comparisons (hazard ratio [HR] nuts 0.8, 95% CI 0.63-1.01; HR popcorn 0.72, 95% CI 0.56-0.92) [36]. No association was found between consumption of corn and diverticulitis or between nut, popcorn, or corn consumption and diverticular bleeding or uncomplicated diverticulosis. (See "Acute colonic diverticulitis: Medical management", section on 'Recurrent diverticulitis'.)
Physical activity — Physical activity, particularly vigorous activity, decreases the risk of diverticulitis [37-39]. In a prospective study of males, those in the highest category of physical activity had an adjusted HR of 0.75 for diverticulitis when compared with those in the lowest category; for vigorous activity the HR was 0.66 and jogging/running specifically was associated with a decreased risk [37].
Obesity — Obesity is a strong and consistent risk factor for diverticulitis. Large, prospective cohorts studies as well as case-control studies have found that body mass index (BMI) is positively associated with risk of diverticulitis [38,40,41], with a relative risk ranging from 1.3 to 4.4 for a BMI in the highest category (eg, >30 kg/m2) compared with the lowest. Central obesity and weight gain have also been shown to be risk factors for diverticulitis [40,41].
Smoking and alcohol — Smoking increases the risk of diverticulitis, particularly for perforated diverticulitis [42-44]. Heavy alcohol use is also associated with diverticulitis [45]. However, it is uncertain whether smaller amounts of alcohol use increase the risk of diverticulitis.
Medications
Immunosuppression — Corticosteroids increase the risk of diverticulitis and particularly of complicated diverticulitis. In a large case-control study, corticosteroids were associated with a threefold increased risk of diverticular perforation (odds ratio [OR] 2.74, 95% CI 1.63-4.61) [46]. Patients who are immunocompromised for other reasons, such as after organ transplant or while receiving chemotherapy, are also at risk of complications, but the risks are less well-defined due to small sample sizes and the heterogeneity in immunosuppressive agents in available studies [47,48].
Other — Nonsteroidal anti-inflammatory drugs, menopausal hormone therapy, and opiates are associated with an increased risk of diverticulitis [46,49-51]. In a large case-control study, higher levels of vitamin D were associated with a reduced risk of hospitalization for diverticulitis [52]. The risk of hospitalization for diverticulitis decreased with increasing vitamin D levels (adjusted relative risk [RR] highest versus lowest quintile of 25 hydroxy vitamin D levels 0.49, 95% CI 0.38-0.62). Another study found that ultraviolet (UV) light exposure was negatively associated with risk of diverticulitis presumed to be related to vitamin D levels given that UV exposure is the major contributor to vitamin D status [53]. Studies evaluating the risk of diverticular perforation and use of statins have been conflicting [46,54].
Family history/genetics — Genetic susceptibility may also contribute to the risk of diverticulitis. Two population-based twin studies in Scandinavia found the risk of diverticulitis in a twin whose co-twin had diverticulitis was higher in monozygotic twins (14.5, 95% CI 8.9-23) than dizygotic twins (5.5, 95% CI, 3.3-8.6). Non-twin siblings of an individual with diverticulitis were three times more likely to have diverticulitis than the general population (2.92, 95% CI 2.50-3.39 [55,56]). These studies estimated that about 50 percent of the tendency to develop diverticulitis was due to inherited factors. Genome-wide association studies have identified loci that associate with diverticular disease. Genes in these loci are related to immunity, the extracellular matrix, cell adhesion, membrane transport, and intestinal motility [17].
Pathogenesis — The underlying cause of diverticulitis is unknown. It was previously believed that obstruction of diverticula (eg, by fecaliths) increased diverticular pressure and caused perforation. However, such obstruction is now thought to be rare (picture 1) [57]. One theory posits that erosion of the diverticular wall by increased intraluminal pressure or inspissated food particles leads to inflammation, focal necrosis, and micro or macro perforation. This process is similar to what occurs in appendicitis. However, a study of nut, corn, and popcorn consumption, once felt to be the particles responsible for diverticular injury, found no increased risk of diverticulitis in individuals who consume the highest amount of these foods as compared with those who consumed them infrequently [36]. (See "Clinical manifestations and diagnosis of acute colonic diverticulitis in adults" and "Acute colonic diverticulitis: Medical management".)
Newer theories suggest that changes in the microbiome and chronic inflammation are important factors in the development of diverticulitis and there is growing evidence to support them. Diseases known to be associated with chronic systemic inflammation, including diabetes and cardiovascular disease, share many risk factors with diverticulitis. Circulating inflammatory markers including C reactive protein (CRP) and interleukin (IL)-6 are elevated in patients who go on to develop diverticulitis when compared with those who do not [33]. In addition, the composition and function of the gut microbiome in patients with diverticulitis is different than those who have not had diverticulitis [34,58,59].
DIVERTICULAR BLEEDING — Diverticular bleeding is characterized by painless hematochezia due to luminal rupture of the vasa recta associated with a diverticulum. (See "Colonic diverticular bleeding".)
Incidence — The incidence of diverticular bleeding increases dramatically with age and is highest among non-Hispanic Blacks [22]. Among patients with diverticulosis, bleeding occurs in approximately 0.5 per 1000 person-years [60]. In a study of 1514 asymptomatic patients with diverticulosis in Japan, the cumulative incidence of bleeding was 0.2 percent at 12 months, 2.2 percent at 60 months, and 9.5 percent at 120 months [60]. These estimates may be higher than in Western countries where similar estimates are not available. In both Asian and Western populations, the right colon is the source of colonic diverticular bleeding in the majority of patients. In a multicenter study of 10,342 patients in Japan, of patients with definitive diverticular bleeding on computed tomography (CT) angiography, 63 percent were located proximal to the splenic flexure [61]. A prospective study of 83 United States patients with definitive diverticular bleeding identified on colonoscopy also found that 63 percent were located proximal to the splenic flexure [62]. A possible explanation for this is that right-sided diverticula have wider necks and domes, exposing a greater length of vasa recta to injury. Another contributing factor may be the thinner wall of the right colon [63].
Risk factors — Nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, and antiplatelet medications have been consistently identified as risk factors for diverticular bleeding [49,60,64]. In a meta-analysis of six studies, the relative risk for diverticular bleeding in NSAID users was 2.24 (95% CI 1. 63-3.09) and for aspirin users was 1.73 (95% CI 1.31-2.30) [65]. The combination of aspirin or antiplatelet drugs with anticoagulants increases the risk of lower gastrointestinal bleeding compared to the use of single agents alone. Given that diverticular bleeding is the most common cause of lower gastrointestinal bleeding, this drug combination likely also increases the risk of diverticular bleeding. However, it is less clear if anticoagulant medications alone increase the risk of diverticular bleeding [66,67].
Several studies have found that individuals with diverticulosis in the left and right colon are at an increased risk of bleeding [60,66,68]. Hypertension has also been associated with diverticular bleeding in a number of studies from Japan [68-70]. Less is known about diet and lifestyle risk factors for diverticular bleeding than for diverticulitis. In a large prospective cohort study, males with a BMI ≥30 had a threefold higher risk of bleeding as compared with males with a BMI <21 (RR 3.19, 95% CI 1.45-7.0) [40]. In the same cohort, vigorous physical activity was associated with a decreased risk of diverticular bleeding (RR 0.66, 95% CI 0.51-0.86 [37]). In small case control studies, smoking and alcohol have not been associated with diverticular bleeding [68,70,71]. Nut, corn, and popcorn consumption are not associated with an increase of diverticular bleeding [36].
Pathogenesis — As a diverticulum herniates, the penetrating vessel responsible for the wall weakness at that point becomes draped over the dome of the diverticulum, separated from the bowel lumen only by mucosa (picture 2) [12]. It is hypothesized that over time, the vasa recta is exposed to injury along its luminal aspect, leading to eccentric intimal thickening and thinning of the media. Hypertension is a risk factor for diverticular bleeding and may also contribute to the vascular injury [69]. These changes may result in segmental weakness of the artery, predisposing to rupture into the lumen. Diverticular bleeding typically occurs in the absence of diverticulitis [12]. (See "Colonic diverticular bleeding", section on 'Clinical manifestations'.)
OTHER DIVERTICULAR DISEASES — Symptomatic uncomplicated diverticular disease and segmental colitis associated with diverticulosis are less well-defined manifestations of diverticular disease.
Symptomatic uncomplicated diverticular disease — Symptomatic uncomplicated diverticular disease (SUDD) is characterized by persistent abdominal pain attributed to diverticula in the absence of macroscopically overt colitis or diverticulitis. The prevalence of SUDD is unknown.
Altered colonic motility may be one of the underlying causes of abdominal pain and constipation in patients with SUDD. In one study, patients with SUDD displayed an increase in duration of rhythmic, low-frequency contractile activity particularly in segments of the colon with diverticula [72]. In another study, patients with diverticulosis were demonstrated to have a significantly reduced density of interstitial cells of Cajal as compared with controls, suggesting that abnormal colonic motility may be the underlying cause of symptoms [73]. SUDD is difficult to differentiate from smoldering diverticulitis and irritable bowel syndrome. Usually, CT scan in patients with smoldering disease reveals ongoing inflammation. Although the data are sparse, in the authors' practice, fecal calprotectin is often elevated in patients with smoldering diverticulitis. Irritable bowel syndrome is common following an episode of diverticulitis perhaps due to visceral hypersensitivity. However, it is controversial whether SUDD is a separate entity from irritable bowel syndrome, particularly in those without prior diverticulitis [74].
It has been hypothesized that visceral hypersensitivity plays an important role in the development of symptoms in patients with diverticulosis who do not have overt diverticulitis. A study compared colonic visceral pain perception in response to luminal distention in patients with SUDD, asymptomatic diverticulosis, and healthy controls. In this study, patients with SUDD but not asymptomatic diverticulosis and healthy controls demonstrated a heightened pain perception both in the sigmoid colon with diverticula and in the unaffected rectum. The mechanism of hypersensitivity in patients with SUDD may relate to increased neuropeptides and alterations in enteric innervation following an episode of diverticulitis [75].
Segmental colitis associated with diverticulosis — Segmental colitis associated with diverticulosis (SCAD) or diverticular colitis is characterized by chronic inflammation involving regions of the left colon that contain diverticulosis. It spares the rectum, which is not susceptible to diverticulosis. Histologically, inflammation involves the interdiverticular mucosa but not the diverticular orifices. It is a rare manifestation of diverticulosis that overlaps significantly with inflammatory bowel disease. The epidemiology, clinical manifestations, diagnosis, and treatment of SCAD are discussed in detail separately. (See "Segmental colitis associated with diverticulosis".)
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: Colonic diverticular disease".)
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: Diverticulitis (The Basics)")
●Beyond the Basics topics (see "Patient education: Diverticular disease (Beyond the Basics)")
SUMMARY
●Terminology – A diverticulum is a sac-like protrusion of the colonic wall. Diverticulosis merely describes the presence of diverticula. These may not be symptomatic or complicated. Diverticular disease is defined as clinically significant and symptomatic diverticulosis. Diverticular symptoms may be due to diverticulitis or diverticular bleeding. Symptomatic uncomplicated diverticular disease, and segmental colitis associated with diverticulosis are less well-defined manifestations of diverticular disease. (See 'Terminology' above.)
●Epidemiology – The prevalence of diverticulosis increases with age from less than 20 percent at age 40 to 60 percent by age 60. In the Western hemisphere, diverticulosis is predominantly left-sided. In contrast, in Asia, the prevalence of diverticulosis is lower and diverticulosis is predominantly right-sided. Among patients with diverticulosis, bleeding occurs in approximately 0.5 per 1000 person-years of follow-up, with the right colon being the predominant location of bleeding. Approximately 4 percent of patients with diverticulosis develop diverticulitis.
●Risk factors
•Risk factors for diverticulosis include male sex, White race, smoking, and obesity. Importantly, constipation and low dietary fiber intake do not appear to be associated with an increased risk of diverticulosis.
•Diet and lifestyle factors are associated with an increased risk of diverticulitis including a dietary pattern that is high in red meat and low in fiber, physical inactivity, and obesity. Avoiding these risk factors as well as smoking may reduce the risk of diverticulitis by as much as 75 percent. Use of certain medications also increases the risk for diverticulitis including aspirin, nonsteroidal anti-inflammatory drugs, opiate analgesics, and immunosuppressive agents. There is no association between nut, corn, and popcorn consumption and the risk of diverticulosis. Constipation is also not a risk factor. (See 'Risk factors' above.)
•Diverticular bleeding is more common in patients who use aspirin and nonsteroidal anti-inflammatory drugs, are obese and physically inactive, and/or have diverticulosis in both the right and left colon.
●Pathogenesis – The pathogenesis of diverticulosis and its complications have not been clearly elucidated. Several theories exist that are supported largely by indirect evidence. These theories are evolving over time and currently build on advancements in genetics and the gut microbiome.
•Diverticula occur at points of weakness in the bowel wall where blood vessels penetrate (figure 1). The development of diverticula is probably multifactorial, involving both abnormalities in motility and connective tissues of the bowel wall. (See 'Diverticulosis' above.)
•Segmental weakness of the artery in the diverticular wall predisposes to rupture into the lumen, resulting in a diverticular bleed (picture 2). In contrast, the underlying cause of diverticulitis is micro- or macroscopic perforation of the diverticulum itself. The inflammation is frequently mild, and a small perforation is walled off by pericolic fat and mesentery. This may lead to a localized abscess or, if adjacent organs are involved, a fistula or obstruction. Poor containment of the inflamed diverticulum or abscess results in free perforation and peritonitis. (See 'Pathogenesis' above.)
•Alterations in the gut microbiome and chronic inflammation have been implicated in the pathogenesis of diverticulitis. Visceral hypersensitivity may contribute to abdominal symptoms in individuals following resolution of acute diverticulitis. (See 'Pathogenesis' above.)
•Altered colonic motility and visceral hypersensitivity may be responsible for the symptoms of symptomatic uncomplicated diverticular disease. (See 'Symptomatic uncomplicated diverticular disease' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Tonia Young-Fadok, MD, who contributed to an earlier version of this topic review.
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