DISPATCHES FROM THE GUILD CONFERENCE, SERIES #43

Evaluation, Management, and Prevention of Diverticular Disease

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Diverticular disorders are frequently encountered in the primary care setting. Diverticular bleeding is the most common cause of lower gastrointestinal bleeding. Low risk patients with uncomplicated diverticulitis can be managed in the outpatient setting, in some cases without the need for antibiotics. In patients with diverticulosis and persistent abdominal pain, chronic smoldering diverticulitis, segmental colitis associated with diverticulosis (SCAD), symptomatic uncomplicated diverticular disease (SUDD), and visceral hypersensitivity should all be considered. To avoid these complications, patients should be encouraged to lead an active lifestyle, consume a healthy diet, and avoid tobacco, alcohol, and certain medications. Contrary to conventional teaching, seeds and nuts do not need to be avoided.

INTRODUCTION

Colonic diverticulosis is a common syndrome involving protrusion of mucosa and submucosa through weak points in the muscular layer of the wall of the colon, resulting in sac-like pockets called diverticula. Diverticulosis can develop anywhere in the colon, but is more commonly encountered in Western populations in the left colon (distal to the splenic flexure), where sigmoid involvement occurs in >90% of patients with diverticulosis.1 In comparison, while diverticulosis is overall less common in Asian populations, right-sided (proximal to the splenic flexure) diverticulosis predominates.2–4 The likelihood of diverticulosis increases with age and has been estimated to be over 50-60% in patients >60 years.5,6 Rates are increasing worldwide, and are significant contributors to healthcare costs.7–9 Most patients are incidentally found to have diverticulosis on imaging or colonoscopy and remain asymptomatic. However, a small proportion develop complications including bleeding, inflammation, and chronic pain. In this article, we will review the common clinical syndromes seen in patients with diverticulosis (Table 1), and provide a practical approach to the evaluation, management, and prevention of these diseases for the primary care clinician.

Diverticular Bleeding

Diverticular bleeding is the most common cause of overt lower gastrointestinal (GI) bleeding in the United States,10–12 and is seen in up to 15% of patients with diverticulosis with an incidence of ~0.5 per 1,000 person-years.13–15 Bleeding occurs when the vasa recta, blood vessels which penetrate the colonic wall at the site of diverticulum formation, hemorrhage into the gastrointestinal lumen. Diverticular bleeding most commonly arises from the right colon, where the colonic wall is thinner and diverticula tend to have larger openings.10,15–17

Presentation

Patients with diverticular bleeding most commonly present with painless hematochezia.18 Some patients report cramping or bloating (likely related to the cathartic effect of blood in the GI tract), however predominant pain should prompt investigation into alternative etiologies such as ischemic colitis or inflammatory bowel disease (IBD). For most patients, bleeding is relatively minor and selflimited.16,19 However, in some cases, bleeding can be brisk, and patients may present with signs of hemodynamic compromise including hypotension and tachycardia. The abdominal exam is typically benign, and rectal examination usually reveals bright red or maroon stool.

Diagnosis

The diagnosis of diverticular bleeding is generally suspected based on typical clinical signs and symptoms. Additional testing to support the diagnosis should include laboratory evaluation with a complete blood count and basic metabolic panel, with endoscopy or radiographic studies utilized for both diagnostic and therapeutic purposes.

Management

Patients with suspected diverticular bleeding should be managed in the inpatient setting, with initial care focusing on adequate intravenous (IV) access, telemetric monitoring, and fluid and blood product resuscitation when indicated. Patients with hemodynamically significant diverticular bleeding despite initial resuscitation should be cared for in an intensive care setting. In these patients, upper endoscopy (EGD) is generally performed first to exclude a brisk upper GI bleed, which is the underlying etiology in 10-15% of patients with brisk hemotochezia.20 Once upper GI bleeding has been excluded, colonoscopy can be pursued after appropriate colonic preparation. While rare to identify a culprit bleeding diverticulum at the time of colonoscopy, a presumptive diagnosis of diverticular bleeding can be given in patients with diverticula who are found to have colonic blood with no alternative explanation.14,21 If active bleeding is found endoscopically, various tools can be utilized by the endoscopist to achieve hemostasis including epinephrine injection, cautery, and hemostatic clips.14,22 If colonoscopy fails to reveal a source, or if the patient cannot undergo colonoscopy, radiographic evaluation with computed tomography (CT) angiography or nuclear scintigraphy can be used to localize bleeding and guide angiographic intervention.

Acute Diverticulitis

Approximately 4-5% of patients with diverticulosis will develop diverticulitis, with an annual incidence in the United States of approximately 188/100,000 persons per year.23,24 Historically, diverticulitis was felt to develop from diverticular obstruction by fecaliths, seeds, or other solid material, leading to inflammation or perforation of the diverticulum.25 However, this obstructive etiology is now felt to be uncommon. More likely, a combination of altered motility, gut microbiome changes, and underlying genetic and lifestyle factors over time cause breakdown of the colonic mucosal barrier and altered immunity, ultimately leading to a localized inflammatory response.26

Subtypes

Diverticulitis can be divided into uncomplicated and complicated disease. Most cases of diverticulitis are uncomplicated, with inflammation isolated to the diverticulum and surrounding colonic mucosa. However, 12-15% of cases are complicated by phlegmon or abscess (70% of complications), perforation, obstruction, stricture, or fistula.26–28 In most cases patients recover fully after an episode of acute diverticulitis, but in 5-10% symptoms and ongoing inflammation persist, resulting in chronic or “smoldering” diverticulitis.29,30

Presentation

Patients with acute diverticulitis typically present with cramping lower abdominal pain, most commonly in the left lower quadrant. Patients may also report low grade fevers, nausea, poor oral intake, or a change in bowel habits. Rectal bleeding is not commonly seen in acute diverticulitis. Abdominal guarding, rigidity, palpable mass, or the presence of hemodynamic instability should raise suspicion for complicated diverticulitis. Both inflammatory markers and white blood cell count are typically elevated. Given the nonspecific symptoms and laboratory findings in acute diverticulitis, a clinical diagnosis of diverticulitis is only accurate in 40-65% of patients.31,32 Therefore, in most cases CT of the abdomen with IV contrast should be obtained to confirm the diagnosis given its high sensitivity and specificity for the disease (94% and 99%, respectively).33

Management

The key initial decision in patients presenting with acute diverticulitis is to determine the need for inpatient care. Otherwise young, healthy patients with mild uncomplicated diverticulitis can generally be managed as an outpatient, whereas patients with complicated diverticulitis generally require hospitalization.34–36 Additional populations requiring inpatient care include the elderly, immunosuppressed, patients with extensive medical comorbidities, and those with signs of sepsis, high fever, significant leukocytosis, severe pain, inability to tolerate oral intake, or who have failed outpatient management.34,37,38

Role of Antibiotics

Antibiotics have historically been the cornerstone of medical therapy for acute diverticulitis, although recent data suggest that in certain populations antibiotic therapy may not be necessary.30,39–41 A meta-analysis including over 2,500 patients with mild uncomplicated diverticulitis showed no difference in relevant clinical outcomes between those treated with antibiotics and those who were not.42 Therefore, most major societies now endorse selective rather than routine use of antibiotics in immunocompetent patients with mild uncomplicated acute diverticulitis.27,36,38,43 In patients with complicated disease, hospitalized patients, and those with uncomplicated disease at high risk for complications, a 7-10 day course of antibiotics with enteric coverage is recommended.28 Surgical intervention is generally not necessary in most cases of acute diverticulitis.44 However, in patients with overt perforation, fistula, obstruction, non-resolving or recurrent abscess, or those with uncomplicated disease who fail to improve despite medical management, surgical consultation should be obtained.38

Role of Surgery

Surgery is no longer recommended routinely for patients with recurrent episodes of uncomplicated diverticulitis. While quality of life overall seems to be improved after resection, recent literature suggest that partial colectomy reduces (but does not eliminate) the risk for recurrent diverticulitis, and that a significant portion of patients have ongoing abdominal pain despite surgical resection.45–48 Therefore, the decision to perform segmental colectomy in patients with recurrent diverticulitis should be an individualized one. Prior to pursuing surgical intervention, patients and clinicians should consider the severity and frequency of diverticulitis episodes, presence of complications, medical comorbidities, effect on quality of life, and the patient’s ability to tolerate surgical intervention.38

Role of Colonoscopy

Anecdotal evidence and conventional wisdom suggest colonoscopy should not be obtained during an acute episode of diverticulitis due to increased procedural difficulty, patient discomfort, and the theoretical potential for perforation.28 However, data reveal an increased risk of colorectal cancer (CRC) in patients with diverticulitis, particularly in those with complicated diverticulitis (6-8%).49,50 Therefore, follow-up colonoscopy is recommended 6-8 weeks after presentation in patients with complicated diverticulitis and those with a first episode of uncomplicated diverticulitis to exclude concomitant CRC.28,51 This can be deferred in patients in whom a high-quality colonoscopy has been performed within the last 12 months. Patients with recurrent episodes of uncomplicated diverticulitis do not require a colonoscopy following every episode; rather, they should follow conventional screening or surveillance intervals.28,51

Other Diverticular Disorders Segmental Colitis Associated with Diverticulosis (SCAD)

In approximately 1% of patients with diverticulosis, inflammation of the mucosa between diverticula can develop, termed segmental colitis associated with diverticulosis (SCAD, also known as diverticularassociated colitis).52,53 Unlike in diverticulitis, the inflammation in SCAD typically spares the diverticula themselves. The exact pathogenesis of SCAD is not fully understood, but likely results at least in part from localized ischemia, mucosal prolapse, and stasis of fecal matter leading to chronic inflammatory changes.54 Rather than distinct, acute episodes as in diverticulitis, patients with SCAD typically present with chronic symptoms of diarrhea, abdominal pain, and sometimes mild hematochezia. These symptoms may mimic other diseases such as irritable bowel syndrome (IBS) or IBD; in fact, it is likely that SCAD lies on the spectrum of IBD, with debate surrounding whether SCAD is a distinct entity or merely represents the coexistence of IBD and diverticulosis.55 CT imaging and colonoscopic evaluation reveals mucosal inflammation in an area of diverticulosis, typically sparing the rectum.55–57 Data for management are limited, but first line therapy typically involves a course of antibiotics and high fiber diet, similar to diverticulitis. With refractory symptoms, therapies traditionally used in IBD including mesalamine, oral steroids, and anti-tumor necrosis factor-alpha (TNF-a) agents can be considered.57,58

Symptomatic Uncomplicated Diverticular Disease (SUDD)

SUDD should be suspected in patients with diverticulosis and persistent unexplained abdominal pain, in the absence of radiologic or endoscopic evidence of active inflammation that would suggest an alternative etiology such as diverticulitis or SCAD. SUDD has been reported in 15-25% of patients with diverticulosis,59 however, there is controversy surrounding this diagnosis, and there is likely a significant overlap with disorders of gutbrain interaction (DGBIs, previously referred to as functional gastrointestinal disorders) such as IBS.

Proposed underlying mechanisms are similar to those for IBS, including visceral hypersensitivity, microbial dysbiosis, altered GI motility, and lowlevel inflammation.60–64 Given the similarities to DGBIs, neuromodulators such as tricyclic antidepressants may be beneficial to patients with SUDD.65 Numerous other treatments including fiber, probiotics, antibiotics, and aminosalicylates have been investigated with inconclusive results, and cannot be recommended at this time.66–72 Prevention of Diverticular Disease

Given diverticular disease’s prevalence and effect on quality of life, many patients inquire as to what can be done to prevent future or recurrent episodes. Importantly, the development of diverticular disease can be attributed both to genetic influences as well as lifestyle factors. Various genetic loci have been implicated, with estimates of up to 50% of the risk for diverticulitis attributable to genetic effect.73–77 While of primarily academic interest at this time, these genetic associations may allow for targeted therapies in the future.

There are numerous lifestyle interventions patients can follow to decrease risk of diverticulitis and other diverticular disorders. For years, patients with diverticulosis were counseled to avoid ingestion of seeds, nuts, popcorn, and related foods, due to the concern for obstructing diverticula and precipitating diverticulitis. As mentioned previously, this is now felt to be a rare inciting factor for diverticulitis. In fact, a largescale observational study of nearly 50,000 patients showed an inverse correlation between ingestion of these foods and development of diverticular disease.78 Rather, studies have associated diets that are low in fiber and high in red meat and refined sugars as leading to increased risk for the development of diverticular disease.79 Additional risk factors include obesity, sedentary lifestyle, as well as tobacco, opioid, alcohol, and nonsteroidal anti-inflammatory drug (NSAID) use.80– 86 Therefore, patients with diverticulosis should be encouraged to follow a high fiber diet which is low in red meat and refined sugars, and counseled to maintain an active lifestyle with the goal of achieving a normal body mass index. Additionally, depending on each patient’s individual habits, they should be advised to quit smoking, and minimize use of opioids, alcohol, and NSAIDs whenever possible.

CONCLUSION

Diverticular disorders are commonly encountered conditions whose evaluation, management, and prevention can prove challenging for patients and clinicians alike. Patients with suspected diverticular bleeding should be carefully monitored in the inpatient setting, and usually require colonoscopy for diagnosis and potentially therapeutic intervention. When diverticulitis is suspected clinically, CT should generally be obtained to confirm the diagnosis. Healthy patients with uncomplicated diverticulitis can be treated in the outpatient setting, some without antibiotic therapy. Surgical resection is generally only pursued in certain patients with complicated diverticulitis, but can be considered in those with recurrent uncomplicated diverticulitis after weighing risks and benefits. Colonoscopy should follow first episodes of complicated diverticulitis in those without recent high-quality colonoscopy. In patients with diverticulosis and chronic abdominal symptoms, SCAD and SUDD should be considered. While genetics are a significant factor in the development of diverticular disorders, patients should be counseled that lifestyle modifications including physical activity, healthy diet, and smoking cessation play important roles in decreasing risk for diverticular disease.

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