Incidence

Ten percent of patients diagnosed with IBD are older than 60 years of age with an equal distribution between CD and UC. Of these about half are diagnosed between 60 and 69 years of age. The true incidence in the elderly is difficult to determine because of differences in populations studied, case definitions of IBD, and potential confusion with other diagnoses such as ischemic colitis or nonsteroidal anti-inflammatory drug (NSAID)-induced colitis. Incidence in Olmsted County, Minnesota increased from 1950 to the 1970s but has stabilized thereafter with rates of 7.9 and 8.8 per 100,000 for CD and UC, respectively. The highest incidence was in the 20- to 39-year age group. Rates for UC were consistently higher in men after 1960 compared with women whereas for CD there was no gender difference. Incidence remained stable after age 39, suggesting that there was no bimodal distribution for either disorder. Higher IBD incidence rates were reported in Manitoba, Canada probably because of differences in case ascertainment but rates again were highest in the 20- to 29-year age group for CD and the 20- to 39-year age group for UC. Rates declined progressively with age thereafter in CD and also in UC, but only for women.

Similar trends in incidence were found from population-based studies from Northern France, Germany, and Sweden, where again a bimodal distribution could not be demonstrated. However, in a nationwide French study incidence was increased in the 75- to 79-year age group for CD only but the magnitude was small. This newer data contradict older studies that have reported a significant bimodal distribution for age at onset for both UC and CD. These earlier studies had less strict criteria for making the diagnosis of IBD that included radiographic findings and gross appearance at endoscopy or surgery. In 81 patients who developed symptoms after age 50 who were labeled as having colitis, three quarters had ischemic colitis, suggesting that misclassification resulted in an artificial secondary peak in the incidence of IBD. Newer studies are enhanced by better case ascertainment because of more improved methods to diagnose IBD.

Although there are differences among populations studied, there are consistent findings in the incidence of IBD across the age spectrum. Among patients older than 40 years, CD incidence seems to decline dramatically from younger populations but remains similar among all later age groups. UC incidence also declines but at a lower rate in older age groups. Although the notion of a bimodal distribution of incidence in IBD remains controversial, it has not been adequately supported by recent studies.

Mortality

Overall mortality among patients with UC seems not to be higher than the general population. Furthermore, older age of diagnosis was not associated with higher mortality compared with younger ages even among those diagnosed after age 65. The effect of CD on overall mortality is controversial. Whereas some studies suggest a decreased overall survival, others have shown no effect on mortality. Survival differences may become apparent only after longer follow-up. In Olmsted County and Copenhagen, Denmark, increased mortality was seen only after follow-up was extended to 21 and 54 years, respectively. The effect of age at diagnosis on mortality is also controversial, with some suggesting an increased mortality risk with increasing age, particularly after age 40 years especially early after diagnosis, whereas others have not confirmed this association.

Overall, there does seem to be an increased mortality among patients with CD especially among those diagnosed at an older age or with very long-standing disease. The magnitude of the risk is relatively small and differences in studies may be due to different populations, calendar times, and lengths of follow-up. Higher mortality in CD compared with UC may be due in part to smoking habits, with CD patients more likely to be active smokers and have a higher overall mortality. As the population ages, further information should become available to definitively answer the question as to the impact of aging on the onset and severity of IBD.

Crohn Disease

CD is a heterogeneous disease that is classified based on age at diagnosis, disease location, and behavior. The Montreal classification (modified from the Vienna classification ) considers patient’s age at diagnosis as before 16, between 17 and 40, and after age 40 years. Disease presentation among individuals diagnosed after the age of 40 (mean 52.2 years) was similar to those diagnosed before age 40 (mean 24 years). Early reports suggested a higher proportion of isolated colonic disease with a propensity for the rectum and sigmoid in those older than 55 to 60 years of age. Prognosis was variable, which may have been because of small numbers of patients, differences in presentation and treatment, and misclassification of other disorders such as ischemic colitis or diverticular colitis as CD ( Table 1 ).

Subsequent studies from referral centers have found that the proportion of patients with colonic involvement increases with increasing age at diagnosis. Of those diagnosed after age 40, 48% had isolated colonic involvement compared with 28% and 20% for those diagnosed between age 20 and 40 and before age 20, respectively. In a population-based study from Brittany from 2004, 66% of patients diagnosed at 60 years of age or older had isolated colonic involvement. Furthermore, the proportion of patients with inflammatory (nonstricturing, nonpenetrating) behavior also increased among those diagnosed after age 40. Although overall probabilities for surgery were similar between patients older and younger than 60 years, azathioprine use and the likelihood for hospitalization from a second flare were lower in those diagnosed after age 60. These 3 studies suggest that isolated colon disease is more common in community than referral populations and is less severe among elderly patients.

Ulcerative Colitis

Although rectal bleeding and diarrhea remain the most common presentation of UC at any age, older patients (more than 50 years old) with ulcerative colitis may rarely present with atypical symptoms such as constipation. Younger patients tended to have more severe symptoms of diarrhea, fever, and weight loss but differences between older and younger patients were minimal. Older patients tended to have proctocolitis and younger patients extensive colitis. The first attack of colitis tended to be more severe in those older than age 50, with longer duration of symptoms and greater likelihood of needing oral corticosteroids. Overall, advanced patient age was not associated with overall poorer quality of life. Better quality of life was associated with lack of clinical symptoms and longer duration of disease, suggesting that patients may adjust to their illness ( Table 1 ).

Crohn Disease

CD is a heterogeneous disease that is classified based on age at diagnosis, disease location, and behavior. The Montreal classification (modified from the Vienna classification ) considers patient’s age at diagnosis as before 16, between 17 and 40, and after age 40 years. Disease presentation among individuals diagnosed after the age of 40 (mean 52.2 years) was similar to those diagnosed before age 40 (mean 24 years). Early reports suggested a higher proportion of isolated colonic disease with a propensity for the rectum and sigmoid in those older than 55 to 60 years of age. Prognosis was variable, which may have been because of small numbers of patients, differences in presentation and treatment, and misclassification of other disorders such as ischemic colitis or diverticular colitis as CD ( Table 1 ).

Subsequent studies from referral centers have found that the proportion of patients with colonic involvement increases with increasing age at diagnosis. Of those diagnosed after age 40, 48% had isolated colonic involvement compared with 28% and 20% for those diagnosed between age 20 and 40 and before age 20, respectively. In a population-based study from Brittany from 2004, 66% of patients diagnosed at 60 years of age or older had isolated colonic involvement. Furthermore, the proportion of patients with inflammatory (nonstricturing, nonpenetrating) behavior also increased among those diagnosed after age 40. Although overall probabilities for surgery were similar between patients older and younger than 60 years, azathioprine use and the likelihood for hospitalization from a second flare were lower in those diagnosed after age 60. These 3 studies suggest that isolated colon disease is more common in community than referral populations and is less severe among elderly patients.

Ulcerative Colitis

Although rectal bleeding and diarrhea remain the most common presentation of UC at any age, older patients (more than 50 years old) with ulcerative colitis may rarely present with atypical symptoms such as constipation. Younger patients tended to have more severe symptoms of diarrhea, fever, and weight loss but differences between older and younger patients were minimal. Older patients tended to have proctocolitis and younger patients extensive colitis. The first attack of colitis tended to be more severe in those older than age 50, with longer duration of symptoms and greater likelihood of needing oral corticosteroids. Overall, advanced patient age was not associated with overall poorer quality of life. Better quality of life was associated with lack of clinical symptoms and longer duration of disease, suggesting that patients may adjust to their illness ( Table 1 ).

Medical Therapy

Unfortunately, there are few data that directly compare treatment in older and younger patients but it is seems that outcomes are similar. The treatment of CD and UC is discussed in detail elsewhere based on clinical disease severity, location and for Crohn disease, and disease behavior. This review focuses on IBD treatment issues in the elderly.

Mesalamine is the mainstay of therapy for mild to moderate UC. All forms are equally effective but osalazine may cause diarrhea in some patients. Mesalamine suppositories, and enemas alone or in combination with oral mesalamine are effective among UC patients with proctitis (suppositories), proctosigmoiditis, or left-sided colitis. Older patients may have difficulty retaining suppositories or enemas because of difficulties with continence due to a compromised anal sphincter. Fecal incontinence is common in the general geriatric population with rates as high as 10% to 25% in hospitalized and 4% in outpatient geriatric patients. Continence may be further compromised by rectal inflammation with difficulties becoming apparent only after starting therapy. If enema retention is a problem, the volume of the enema can be decreased and patients still benefit. Other options for topical therapy include hydrocortisone enemas for proctosigmoiditis or left-sided colitis, and hydrocortisone foam for proctitis. Foam preparations are better retained, resulting in less incontinence.

Mesalamine therapy is generally not effective in CD although it may have a role in mild to moderately active Crohn colitis. Antibiotics, though not useful in UC, are beneficial in some cases of CD. Metronidazole is effective among some patients with colonic CD, as postoperative treatment to prevent recurrence following ileocolic resection and in the management of fistula. Unfortunately, side effects often lead to discontinuation of this medication. The most concerning is sensory peripheral neuropathy, which is most commonly associated with chronic use but can also occur when high doses are given for short periods. This requires a careful discussion with the patient and vigilant monitoring. Before starting therapy, a careful history should be taken to exclude preexisting neuropathy because, though generally infrequent, it is more common in the elderly at rates of about 4% after age 55. Preexisting neuropathy is typically seen in association with diabetes but can have multiple causes. In patients with preexisting neuropathy, metronidazole should be avoided. Ciprofloxacin is tolerated better but definitive data on its use are lacking. An extremely rare complication of ciprofloxacin is Achilles tendon rupture, with risk increasing with age and corticosteroid use.

For UC patients who fail mesalamine or have moderate to severe disease, and for those with active CD, parenteral or oral corticosteroids are effective. However, among hospitalized CD patients corticosteroid therapy was associated with a longer length of stay in those older than 50 years, and this persisted after adjustment for disease severity. These medications lead to more adverse effects in elderly populations including osteoporosis, bone fractures, changes in mental status, diabetes, and hypertension. Osteoporosis risk is increased in the elderly especially among those with chronic inflammatory disorders like UC and CD and those taking corticosteroids. For IBD overall, prevalence has been estimated at 15%. The Crohn’s and Colitis Foundation of America has recommended testing for osteoporosis by dual-energy x-ray absorptiometry at diagnosis of IBD and repeated 12 to 18 months later. Further assessments should be made based on the patient’s clinical course and continued need for corticosteroids.

Enteric release budesonide has replaced mesalamine as a first-line medication for the induction remission of mild to moderate CD involving the terminal ileum or ascending colon. Budesonide works topically and has a high first-pass metabolism in the liver, minimizing but not eliminating steroid-related side effects. There is no information available on differences in efficacy and toxicity among older and younger patients.

Among patients receiving corticosteroids, immunomodulator therapy is typically started to facilitate corticosteroid weaning and maintain disease remission. For UC and CD, azathioprine or 6-mercaptopurine is effective for this purpose. These agents require 3 to 4 months of therapy to be effective and there is no evidence of a difference in efficacy, metabolism, or toxicity in older compared with younger patients. However, hematological monitoring is essential in all patients with the potential for significant drug interactions, the most important of which in the elderly is with allopurinol. Allopurinol is more commonly used in the elderly for gout and may result in significant bone marrow toxicity when combined with azathioprine or 6-mercaptopurine. The toxicity is due to inhibition of xanthine oxidase by allopurinol, which is important in the breakdown of these immunomodulators. Despite recommended dosage reductions of azathioprine or 6-mercaptopurine, hematological toxicity has still been reported, underscoring the need for vigilant monitoring. Parenteral methotrexate is also useful as a primary treatment or to facilitate corticosteroid weaning in CD, and there is no evidence for differing efficacy among older and younger age groups. Liver toxicity with this agent may be more important in the elderly due to the greater potential for preexisting liver disease compared with younger patients.

Over the last 10 years biologic therapies that inhibit tumor necrosis factor α (infliximab, adalumimab, and certiluzimab) have revolutionized the management of IBD. These drugs are very effective in the induction and maintenance of remission and are attractive alternatives to oral or parenteral corticosteroids in nonstricturing, nonpenetrating CD. Infliximab and adalumimab are also proven effective in penetrating (fistulizing) CD and infliximab in UC. There is no evidence currently that the efficacy of these agents is altered by subject’s age or age at diagnosis. Infliximab is also used in rheumatoid arthritis and in one report there was a trend toward more severe infections requiring discontinuation among patients older than 70 years. However, this was not demonstrated in a randomized trial.

Due to the complexities of management of IBD, patients are often taking combinations of medications including corticosteroids, immunomodulators, biologic agents, or narcotics. The determination of toxicities of individual agents is difficult because of small numbers of subjects. However, Lichtenstein and colleagues developed a registry of 6290 CD patients with 3179 having been administered infliximab to determine the risk of toxicity. In a multivariate analysis, age and duration of disease were associated with a slight increase in mortality rates. However, the strongest influence on mortality was prednisone use, which increased the odds of death two-fold. Furthermore, prednisone and narcotic use each resulted in a two-fold increase in severe infections. Infliximab did not increase mortality or the risk of severe opportunistic infections.

Surgical Therapy

Surgery for CD is not curative, and is indicated for failure of medical therapy or the development of complications. Complications include perforation with abscess or fistula formation and obstruction. Malignancy may occur, especially in long-standing colitis, and is treated by total colectomy with ileostomy formation. The risk of surgery for nonneoplastic bowel disease decreases with age. Age at diagnosis older than 40 years and colonic disease (a location common in the elderly) were independently associated with lower rates of surgery. Older patients with isolated ileocecal disease had similar rates of resection to younger patients.

Surgery for UC is curative, and is typically performed for colonic dysplasia or treatment of refractory disease. Complete colectomy with ileal pouch-anal anastomosis (IPAA) is the preferred surgery in most patients. IPAA is usually performed as a two-stage procedure with the first stage being total colectomy, pouch construction, and diverting ileostomy, and the second stage being takedown of the diverting ileostomy about 3 months later. A permanent end-ileostomy (without an ileoanal pouch) is more appropriate in some patients. The decision on which operation to perform depends on the indication for the procedure and patient-specific factors.

Some studies have shown a marginally higher morbidity as measured by symptom index, and higher rates of fecal incontinence and stool frequency in patients older than 45 or 50 years. However, the overwhelming majority of older patients were satisfied with their result. Pouch failure rates between younger and older patients were similar as were rates of pouchitis. These studies are representative of a body of literature that led The American Society of Colon and Rectal Surgeons to recommend that “chronologic age should not itself be an exclusion criterion” for IPAA. Optimal patient selection is important, restricting this operation to motivated patients, without significant cognitive problems or compromised anal sphincter function.

Infection

Gastrointestinal infections are an important cause of diarrhea in the elderly that result in significant morbidity and mortality. In a comparison of healthy individuals aged 21 to 34 years with those aged 67 to 88 years, the older patients had alterations in the concentrations of “probiotic bacteria” (bifidobacteria and lactobacilli) that could increase the risk of enteric infections. Common source outbreaks are more likely to occur in nursing homes or assisted living facilities. Among all patients presenting with diarrhea including those with known IBD, routine studies should be performed to exclude common infectious pathogens such as Salmonella , Shigella , Campylobacter , and Clostridium difficile . Other less common pathogens should be excluded based on clinical presentation. Yersinia enterocolitica , for example, may result in ileitis and mimic IBD. Clinical laboratories vary in what is tested for in routine stool samples so clinicians may need to make specific requests for pathogens when suspected. This is particularly true of Escherichia coli O157:H7, which is a common cause of bloody diarrhea that can result in significant morbidity and mortality.

Among enteric pathogens, geriatric patients are more susceptible to C difficile . The clinical presentation of C difficile -associated disease (CDAD) can vary from watery diarrhea to fulminant colitis. From 2000 to 2005 in the United States there was a 23% annual increase in CDAD hospitalizations. The case fatality rate doubled from 1.2% in 2000 to 2.3% in 2004 due to increased virulence of the organism. Rates were highest and increased most dramatically in those older than 65 years. Infection with a newer hypervirulent strain prolonged hospitalization by 11 days and had a 30-day mortality of 23% compared with 7% in a control group adjusted for age and comorbidity. Rates of asymptomatic carriage increase with age, and are up to 13% in the hospital setting.

IBD (CD or UC) increases the risk of CDAD. Incidence of CDAD among hospitalized IBD patients doubled for CD and tripled for UC from 1998 to 2004. The majority of infections were acquired before hospitalization. CDAD pursues a more aggressive course among IBD patients resulting in a higher rate of complications and 4 times the mortality compared with those admitted for IBD alone. These findings underscore the need for a high level of suspicion among all patients with IBD presenting with diarrhea, even in the absence of antibiotic exposure or hospitalization.

Microscopic Colitis

Microscopic colitis (MC) is a chronic inflammatory disease of the colon that is an important cause of chronic watery diarrhea in the elderly. MC is separated into lymphocytic (LC) and collagenous colitis (CC), based on histology with a grossly normal colonoscopy. CC is much more common in women. MC is the cause in 10% of all patients and up to 20% of those older than 70 years of age presenting with chronic diarrhea. Overall population incidence rates from both Europe and the United States vary from 1.8 to 7.1 per 100,000 for LC and 4.4 to 12.6 per 100,000 for CC. The higher rates are from more recent studies, probably because of a lower threshold for colonoscopy with biopsy due to a greater physician awareness of this condition. This improvement also may in part be explained by increasing overall rates of colonoscopy and sigmoidoscopy with time.

The incidence of MC increases with age most dramatically after age 50 years, and diagnosis is usually made in the sixth or seventh decade of life. Patients older than 65 years are two times as likely to be diagnosed with MC compared with those younger than 65, with incidence rates of more than 30 per 100,000. Whether this represents a true increase in incidence in older populations or a lower threshold for colonoscopy is not clear. Although 10% of patients with MC will have celiac disease, in the absence of findings of malabsorption routine testing for celiac disease is not recommended. MC has also been associated with hypothyroidism. Despite the chronic inflammation in MC there seems to be no increased risk of colon cancer based on a series of patients with CC followed for 7 years.

The clinical course of MC is variable with treatment aimed at controlling symptoms. In mild cases avoidance of offending foods alone or with antidiarrheal medications will control symptoms. As severity increases, medication therapies such as mesalamine, enteric released budesonide, or systemic corticosteroids may be needed. Rarely immunomodulators or a colectomy may be necessary. Older patients may have a more benign course with a greater likelihood of spontaneous remission and more easily controlled disease, as suggested by a lower use of mesalamine and corticosteroids.

Among patients requiring mesalamine or corticosteroids, 23% and 54%, respectively were taking NSAIDs compared with only 6% managed with no treatment or antidiarrheal therapy only. However, withdrawal of NSAIDs did not lead to improvement. This result is in contrast to reports of improvement with discontinuation of NSAIDs and recurrence of symptoms with rechallenge. In one case report, diarrhea ceased and histologic changes reversed when aspirin was discontinued. Others have found no association of NSAIDs with development of MC. All of these studies suffer from small sample size, limiting their conclusions. Overall the existing evidence does suggest a role for NSAIDs in the development and worsening course in MC. Given the higher proportion of elderly with MC and the higher rates of NSAID use compared with younger populations, these medications in the setting of MC should be avoided.

Diverticular Colitis

Diverticulosis affects more than half of individuals older than 60 years and is described elsewhere in this issue. Diverticular colitis is an important cause of rectal bleeding, abdominal pain, and change in bowel habit, but is relatively uncommon, with only 3% developing inflammation in the mucosa surrounding diverticuli. Segmental colitis presents in individuals older than 60 years and can mimic the endoscopic and histologic appearance of CD. The inflammation is confined to the segment containing the diverticula with the rectum and uninvolved bowel having normal endoscopic appearance and histology. A nonspecific chronic colitis that may contain granulomas is seen on histology, further adding to the confusion with CD. However, diverticular colitis represents a distinct clinical entity separate from CD as evident from natural history studies, and is independent of classic diverticulitis.

Unfortunately, there are no randomized treatment studies for diverticular colitis and recommendations are based on reports from relatively few patients. Among 19 patients, 14 responded to conservative therapy with high fiber diet or antibiotics, with failures responding to sulfasalazine (three patients) or sulfasalazine and steroid enemas (two patients). Most patients treated with mesalamine have excellent results. Response rates of 80% within 6 months were reported among 21 patients taking oral mesalamine. Five patients who initially responded but were not compliant with this therapy relapsed, with three responding to further mesalamine and two requiring prednisone. Response rates were 100% among 14 patients treated with 2.4 g/d of oral mesalamine and 2 g/d of mesalamine enema at 6 weeks. In these 14 patients therapy was stopped and only one patient had clinical and endoscopic relapse at 1 year. Whereas a conservative approach may be effective in some patients, oral and topical mesalamine therapy seems to provide the best long-term response rate among patients with diverticular colitis. For patients who do not respond to conservative therapy, antibiotics, or mesalamine, steroid enemas may provide benefit, with only the minority of patients requiring surgery.

Nonsteroidal Anti-Inflammatory Medications

Although many different medications can cause gastrointestinal inflammation, the most common and arguably the most important are NSAIDs. NSAIDs can cause a myriad of complications in the small and the large intestine from ulceration or bleeding to perforation or stricture. Mucosal findings may range from acute inflammation to chronic nonspecific inflammation with fibrosis. Perforation can also occur, especially among patients with diverticulosis.

The strongest association of NSAIDs among the IBDs is with UC and CD. UC patients who relapsed were twice as likely to be using chronic NSAIDs. Subsequent studies have supported these findings. Rate of relapse was increased to 20% for UC and CD when patients were treated with a nonselective cyclooxygenase inhibitor (COX) or conventional NSAID for 4 weeks. Most patients relapsed within 9 days of starting these medications. No patients treated with acetaminophen relapsed. Patients assigned to acetaminophen, nimesulide (a selective COX-2 inhibitor), or aspirin (a selective COX-1 inhibitor) had lower rates of relapse than those taking nonselective agents.

In a randomized study comparing celecoxib (selective COX-2 inhibitor) to placebo among patients with UC in remission, rates of relapse over 14 days were similar, at 3% and 4%, respectively. All patients were taking maintenance therapy with mesalamine or azathioprine/6-mercaptopurine. It was not clear if the dose of celecoxib in this study adequately treated the arthritis or arthropathy in this population, but it does represent a standard dose. Furthermore, rofecoxib has been associated with cardiovascular risk and has been withdrawn whereas celecoxib results regarding this toxicity have been conflicting, leading to caution in its use among clinicians.

Arthralgias and arthritis remain common complaints in the elderly and also among those with IBD. Peripheral arthritis from IBD usually responds to treatment of the underlying active inflammatory bowel disease. Axillary arthritis such as ankylosing spondylitis and sacroileitis typically does not. Whereas occasional use of an NSAID is probably safe, many patients require long-term pain control that may not respond to acetaminophen. In these patients, unfortunately, clinicians have few effective options, leading to the decision to use NSAIDs in these patients when the benefit to quality of life outweighs the risks. Although selective COX-2 inhibitors may provide a better option, the evidence is not clear and cardiovascular toxicity needs to be considered in prescribing these agents.

Ischemic Colitis

Ischemic colitis is a common condition in the elderly with an average age at presentation of 68 years and is discussed elsewhere in this issue. Ischemic colitis results from an interruption of blood supply to the colon causing a segmental colitis that can be confused with CD. Areas affected tend to be “watershed areas” that are more susceptible to sparing of the rectum due to its rich blood supply. There are multiple causes of this condition including cardiac failure, thromboembolic disease, hypercoagulable states, and medications.

Most patients present with the abrupt onset of pain and bloody diarrhea with typical findings of segmental colitis on computed tomography that can be confirmed by colonoscopy with biopsy. Care is largely supportive with the minority of patients requiring surgery. Biopsy, clinical presentation, and course are all useful in distinguishing this entity from other IBDs. Full colonoscopy should be strongly considered to exclude malignancy, a rare but important cause of this presentation especially in the elderly.