Saqib S. Ansari, Sulleman Moreea, Christopher A. Rodrigues
The Small Bowel
Diseases of the small bowel can be divided into two categories for clinical purposes: (1) diffuse processes, such as celiac disease, that result in the malabsorption syndromes, and (2) discrete diseases, such as small bowel tumors, that produce focal manifestations. Some conditions, such as Crohn disease and radiation enteritis, can cause a combination of malabsorption and focal features. Malabsorption in older adults is not due to aging alone, as the absorption of most nutrients is unaffected with a few exceptions. Lactose malabsorption is common in otherwise healthy older individuals1,2 and can coexist with other diffuse small bowel diseases. Calcium absorption declines with age because of a higher prevalence of vitamin D deficiency.3 Lastly, atrophic gastritis is more common in older adults and can adversely affect the absorption of vitamin B12 and folic acid. Food-cobalamin malabsorption, the impaired release of the vitamin B12 from food, is a result of reduced or absent gastric acid secretion or of the use of acid-suppressing drugs. This is the most common cause of B12 deficiency in older people,4 pernicious anemia and terminal ileal disease/resection being much rarer. Folic acid absorption in the proximal jejunum is also pH dependent and declines with achlorhydria. However, jejunal bacterial overgrowth, another consequence of achlorhydria, can compensate for reduced absorption of the vitamin because of bacterial folate synthesis.5 Three conditions account for most cases of malabsorption in older individuals: bacterial overgrowth syndrome, celiac disease, and chronic pancreatitis (the latter is actually maldigestion resulting in malabsorption).
Steatorrhea, the typical symptom of fat malabsorption, is much less likely to occur in older adult patients, who may even be constipated despite an increased stool volume. Carbohydrate malabsorption can cause watery diarrhea, abdominal distention, borborygmi, and flatulence. These symptoms are due to the action of bacteria on carbohydrate residues in the colon. The clinical presentation of malabsorption in older adults is nonspecific. It consists of a variable combination of the following: fatigue, poor mobility, anorexia, nausea, diarrhea, anemia, weight loss, depression, and confusion.6,7 Peripheral edema can result from hypoproteinemia. Vague generalized body ache and muscle weakness can be early clinical indicators of osteomalacia. Vitamin K deficiency may cause bruising, petechiae, and bleeding manifestations. Abdominal discomfort and distention are common, but abdominal pain is relatively rare. Recurrent abdominal pain occurs with chronic pancreatitis, inflammation as in Crohn disease, subacute obstruction as a result of strictures, or chronic mesenteric ischemia.
The diagnosis of malabsorption should therefore be considered in older adult patients with clinical and anthropometric evidence of undernutrition, even in the absence of gastrointestinal (GI) symptoms. A dietary assessment is important in determining whether the malnutrition can reasonably be attributed to inadequate nutrient intake. The details of previous surgical procedures should be ascertained: gastric surgery or intestinal bypass procedures can result in the bacterial overgrowth syndrome, and extensive small bowel resection can cause malabsorption because of a critical reduction in the mucosal absorptive surface area.
Investigation of Small Bowel Disorder
Screening Tests
Routine blood tests are often helpful in the diagnosis of small bowel disease. The full blood count and blood film may show anemia with macrocytosis, an iron-deficient picture, or a dimorphic film. Macrocytosis, leukopenia, and thrombocytopenia suggest megaloblastic anemia. Ferritin, vitamin B12, and red cell folate levels should be measured in patients with suspected malabsorption, even with a normal blood film, as typical changes may not be present in early deficiency. B12 deficiency should be further investigated with serologic tests for pernicious anemia (gastric parietal cell and intrinsic factor antibodies), celiac disease (discussed later, a rare cause of isolated B12 deficiency), and, if necessary, radiologic or endoscopic evaluation of the terminal ileum. A low B12 level with a normal or increased red cell folate level raises the possibility of small bowel bacterial overgrowth. Howell-Jolly bodies in the blood film indicate splenic atrophy, which occurs in association with celiac disease. Osteomalacia results in a raised alkaline phosphatase level with low calcium and phosphate levels and is confirmed by a low serum 25-hydroxycholecaliferol. Vitamin K deficiency prolongs the international normalized ratio (INR). Hypoalbuminemia is a common although nonspecific finding, as it also occurs with poor dietary intake, injury, sepsis, and malignancy. Malabsorption is unlikely if these screening tests are completely normal.
Tests of Absorption
Tests of nutrient absorption such as fecal fat estimation and xylose absorption are no longer used in clinical practice because they are cumbersome to perform, relatively insensitive, and unpopular with patients and professionals. Lactose absorption is the only nutrient absorption test that is widely used.8 In the standard lactose tolerance test, blood glucose levels are measured before, and 30 and 60 minutes after, the ingestion of 50 g of lactose. A rise of less than 1.1 mmol/L indicates lactose malabsorption, and accompanying (transient) symptoms of abdominal bloating, discomfort, diarrhea, and wind are indicative of intolerance. Alternatively, a lactose hydrogen breath test can be used: after an oral dose of 25 to 50 g lactose, end-expiratory breath samples are collected every 30 minutes for 3 hours. Malabsorption of lactose results in fermentation of the sugar by colonic flora, producing a rise in breath hydrogen. This rise can also occur in patients with small bowel bacterial overgrowth, although usually much earlier than in patients with lactose malabsorption. Approximately 25% of patients will have a false negative test, and hence a trial of a lactose-free diet is reasonable if the diagnosis is suspected clinically.
Radiology and Endoscopy
Double-contrast barium follow-through examination and enteroclysis (small bowel enema) have been used for many years to investigate the small bowel. Enteroclysis is probably more accurate but is more invasive. The role of abdominal ultrasound and computed tomography (CT) scanning is described in the relevant sections.
Advances in magnetic resonance (MR) imaging of the small bowel (MR enterography) now allow excellent visualization of the small bowel noninvasively and without exposure to radiation. MRI is now the investigation of choice for patients with suspected inflammatory bowel disease and small bowel tumors. Older adult patients can find the test difficult to tolerate as they have to lie supine and still for at least 30 minutes. Noise levels can be high because of vibration of the magnetic coils and earplugs or headphones need to be worn. Claustrophobia as a result of the tight cylindrical scanner can lead to a significant number of patients being unable to complete the test. Sedation can be used to improve compliance to the test. Open coil magnets are increasingly being used for claustrophobic patients and for patients who are too large for the cylindrical scanner. MR contrast agents, such as gadolinium, are safer than the iodinated contrast agents used for CT scanning and rarely cause contrast reactions. However, they can cause contrast nephropathy and, in rare cases, nephrogenic systemic fibrosis in patients with moderate to severe chronic kidney disease. Contraindications include implanted devices such as cardiac pacemakers, implantable cardioverter-defibrillators (ICDs), nerve stimulators, cochlear implants, and embedded metallic foreign bodies such as intraorbital metallic fragments that could have been present from the working days of the now retired patients. Transdermal patches need to be removed before MRI is performed. The following are not contraindications and are considered MR safe: joint prostheses, coronary/peripheral vascular stents, prosthetic heart valves, sternal wires, inferior vena caval filters, and embolization coil.9 The composition of intracranial aneurismal clips needs to be ascertained because most may not be MR safe.
Esophagogastroduodenoscopy (EGD) is the usual method for collecting fluid for culture and for obtaining biopsies from the distal duodenum. The detection of villous atrophy at endoscopy can be improved by viewing the duodenal mucosal surface at high magnification after spraying with indigo carmine.10
Wireless capsule endoscopy or video capsule endoscopy is a noninvasive technology that was introduced in 2000.11 It has made possible the direct visualization of the entire small bowel12 with a magnification higher than conventional endoscopes, allowing detailed views to the level of individual villi. It consists of a capsule, which is swallowed and propelled by peristalsis, transmitting between two and six images per second via a belt to a data recorder worn by a patient. Approximately 75,000 images are recorded over a 12-hour period, by which time the capsule has usually reached the caecum in most patients. The latest capsule generation has vastly improved image quality and tissue coverage. The data recorder has a built-in real-time viewer that enables live viewing of the capsule progress as it progresses through the small bowel. The images are then downloaded onto a computer workstation and are viewed as a video. The software on which the video is viewed has a built-in Atlas, which has more than 600 small bowel pathology images to aid diagnosis for those who are new to this technology. Capsule endoscopy is currently used for the investigation of obscure GI bleeding (discussed later), of small bowel Crohn disease, in suspected or refractory malabsorption syndromes (e.g., celiac disease), and in suspected small bowel tumors, including screening in familial polyposis syndromes.13 The major drawbacks of capsule endoscopy are the inability to take biopsies, incomplete visualization of the mucosal surface, and capsule retention requiring surgical or endoscopic removal (1% to 7%). A biodegradable patency capsule without recording facilities is available to ascertain small bowel patency in cases where symptoms suggest possible structuring disease not shown on small bowel barium studies of MR enterography.
Double-balloon enteroscopy (DBE), a technique that can traverse the whole of the small bowel using an enteroscope with an overtube, was first described in 2001. The enteroscope is inserted by either the oral or anal route, so that therapeutic procedures can be carried out.12,14 General anesthesia is often required for this complex and prolonged technique. The overall diagnostic yield is between 43% and 83%, with a subsequent change in management for 57% to 84% of patients. Complications include postprocedural abdominal pain, pancreatitis, bleeding, and small bowel perforation. Push enteroscopy is currently the most widely available technique for endoscopic examination of the small bowel. The instrument can be inserted 30 to 160 cm beyond the ligament of Treitz and has a channel for biopsies and therapeutic procedures including thermocoagulation of bleeding lesions, polypectomy, and placement of feeding jejunostomy tubes. Lastly, intraoperative enteroscopy, in which the small bowel is “pleated” over an endoscope at laparotomy or laparoscopy, is the most accurate technique but has a significant complication rate.
Small Bowel Diseases
Celiac Disease
Celiac disease is an immune-mediated small intestinal enteropathy that is triggered by exposure to dietary gluten in genetically predisposed individuals.15 Dietary gluten in cereals like wheat, barley, and rye leads to characteristic histologic changes, including intraepithelial lymphocytosis, crypt hyperplasia, and, ultimately, villous atrophy. The disease mainly affects the proximal small bowel and decreases in severity distally and may spare the distal jejunum and ileum. A large-scale screening study in subjects from Finland, Italy, the United Kingdom, and Germany found a prevalence of celiac disease of approximately 1%,16–18 with a recent U.S. study showing a prevalence of 0.71%.19
Sixty percent of newly diagnosed patients are adults20 with a peak incidence in the third decade and a second, smaller peak in the fifth and sixth decades.21 In a multicenter Italian study, only 60 (4.4%) of 1353 patients with celiac disease were older than 65 years at diagnosis.22 However, the seroprevalence of celiac disease in an English population of 7257 people aged 45 to 76 years was 1.2% with no significant difference between those younger and older than 65 years of age.18 In a Finnish population-based study of 2815 individuals, the prevalence of celiac disease in those aged 52 to 74 years was 2.13%, double that in younger adults.23 The female-to-male ratio in adults is approximately 2 : 1, and this is no different in older adult patients.18,22 Only 30% to 40% of patients are symptomatic; the rest have clinically silent disease. This variable clinical picture is probably related to the extent of affected bowel. Traditionally patients with celiac disease presented with malabsorption dominated by diarrhea, steatorrhea, weight loss, or failure to thrive,15 but over time the proportion of newly diagnosed patients with malabsorptive symptoms has decreased.24 Patients can present with a wide range of symptoms and signs, including anemia, vague abdominal symptoms, neuropathy, ataxia, depression, short stature, osteomalacia, osteoporosis, and lymphoma. Asymptomatic patients are typically diagnosed through screening, which may be initiated because the individual has a related disorder or has symptoms and is a first-degree relative to a patient with celiac disease.
Celiac disease is associated with a number of autoimmune conditions, the most important being insulin-dependent diabetes mellitus, autoimmune thyroid disease, Sjögren syndrome, autoimmune hepatitis, primary biliary cirrhosis, and Addison disease.21,25–27 Dermatitis herpetiformis can be regarded as an extraintestinal manifestation of celiac disease, as virtually all patients have an enteropathy with characteristic histologic changes. Neurologic disorders such as epilepsy, cerebellar syndrome, dementia, peripheral neuropathy, myopathy, and hyporeflexia have been reported in patients with celiac disease.28
Immunoglobulin A (IgA) deficiency affects 2% to 3% of patients with celiac disease and can result in false negative serologic tests. From 90% to 95% of celiac patients have the human leukocyte antigen (HLA) class 2 molecule DQ2, and most of the remainder have DQ8. At least 1 in 10 first-degree relatives are affected.26
Diagnosis
Serologic markers are now used routinely for screening patients and high-risk groups with associated disorders or a positive family history. IgA endomysial antibody (EMA) has a specificity of over 98%, but antibody to IgA tissue transglutaminase (tTG) is also very accurate and is a simpler and less expensive test.25,29
Patients with an absent tTG or those in whom there is a strong clinical suspicion of celiac disease should have an IgA level test to exclude deficiency—this is routinely carried out by some laboratories. If IgA deficiency is present, tests for IgG tTG or EMA should be carried out. Antibody titers can decrease or disappear with treatment, but this is not a reliable marker of histologic remission.30,31 Patients with positive serology should have an endoscopy for duodenal biopsies.32 The diagnosis of celiac disease is readily established in those who, while consuming a gluten-containing diet, have positive serology and a duodenal biopsy with obvious celiac histology (increased intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy). These changes, accompanied by a clinical response to a gluten-free diet, are adequate to establish the diagnosis.27,33 Biopsy remains essential for the diagnosis of adult celiac disease and cannot be replaced by serology. To state a definite diagnosis of celiac disease, villous atrophy is required. However, lesser degrees of damage (≥25 intraepithelial lymphocytes but no villous atrophy) combined with positive serology (IgA-EMA or tTG) may also represent celiac disease (“probable celiac disease”), and in these circumstances a trial with a gluten-free diet may be considered to further support the diagnosis of celiac disease.34
Follow-up biopsies should be undertaken in patients with celiac disease whose condition does not respond to a gluten-free diet.34 However, follow-up biopsies are not mandatory in asymptomatic patients on a gluten-free diet with no other worrying features. Rebiopsy after a gluten challenge is rarely carried out now but may be required in cases where there is diagnostic difficulty, such as when the original biopsy was taken while the patient was on a gluten-free diet. The absence of HLA DQ2 and DQ8 virtually excludes the diagnosis and is useful when the patient does not wish to undergo a gluten challenge. Lastly, 5% to 10% of patients have serology-negative disease, and thus histologic confirmation should be undertaken if the likelihood of celiac disease is high (e.g., in symptomatic patients with a positive family history).
Management
The mainstay of management for celiac disease is a lifelong gluten-free diet. Specialist input is central in achieving this, so all patients are referred to a dietitian. It is now generally accepted that patients can take a moderate amount of oats, providing there is no contamination with wheat gluten. Patients are encouraged to join a patient support organization. Patients should have regular clinical follow-up25,26 for assessment of symptoms and checking for dietary adherence. Annual blood tests should be performed, including full blood count, hematinics, liver function tests, calcium, thyroid function tests, glucose level, and also a vitamin D level at diagnosis.34 Lactose intolerance can cause apparently resistant disease in some patients. However, milk and milk products are an important source of calcium and should be restricted only if they exacerbate symptoms—ideally after confirming the diagnosis with an objective test. Adult patients with celiac disease should have a calcium intake of at least 1000 mg/day. Patients should receive supplements to correct nutrient deficiencies, as complete recovery of mucosal function can take months. Older adult patients with celiac disease should be given multivitamins and a calcium supplement initially. Bone mineral densitometry should be carried out at diagnosis in all older adult patients with celiac disease. Bone mass improves, but does not normalize, in adult and older adult patients on a gluten-free diet, and other therapeutic measures are often required.35 Hyposplenism36 associated with celiac disease may result in impaired immunity to encapsulated bacteria, which increases the risk of infections.37–39 Vaccination against Pneumococcus is therefore recommended.40 Approximately 5% of patients fail to respond to gluten withdrawal or relapse after an initial remission.25 Some patients with refractory disease respond to corticosteroids or immunosuppressive agents. Others (a proportion of whom have small intestinal ulcers and strictures [ulcerative enteritis]) have a cryptic T cell lymphoma of the intraepithelial lymphocytes41 with 5-year survival rates of less than 50%.25 Patients with ulcerative enteritis often require surgery for complications such as perforation or obstruction.
Neoplasms
The twofold increase in mortality in the first year after diagnosis is largely due to the development of malignant complications.42 The overall risk of malignancy is less than previously reported43 and is approximately 30% greater than that of the general population.42 T cell lymphoma of the small intestine is the most common tumor,44–46 but there is an increased risk of developing squamous cell carcinomas of the esophagus, mouth, pharynx; adenocarcinoma of the small bowel; and colorectal carcinoma. The incidence of breast42,45 and lung cancer42 is decreased. Lymphoma may be the first manifestation of celiac disease, but the diagnosis should also be considered in established patients whose condition is either resistant to, or relapses on, a strict gluten-free diet. Weight loss is the most common symptom, and patients also experience profound lethargy, muscle weakness, abdominal pain, and diarrhea. The prognosis is poor: less than a fifth of patients survive for 30 months.47 A gluten-free diet has a protective effect against the development of malignancy in celiac disease.43,45,46
Bacterial Overgrowth Syndrome
Intestinal bacterial counts normally increase abnormally, and bacterial populations vary in different sections of the GI tract: the jejunum is colonized by gram-positive aerobes and facultative anaerobes, ileal flora contain some strict anaerobes as well, and the colon is heavily populated by predominantly anaerobic bacteria.48 Malabsorption can occur when the small bowel population increases and becomes more anaerobic. This is partly the result of direct injury to the intestinal mucosa, but uptake or binding of major nutrients and vitamin B12 by the proliferating bacteria also play a part.49 In addition, fat absorption is affected by deconjugation of bile salts by anaerobic bacteria, resulting in impaired micelle formation. Folic acid and vitamin K are synthesized by bacteria, and folate levels are often normal or raised when bacterial overgrowth is present. Two factors are largely responsible for regulating bacterial growth: gastric acid and intestinal motility.48,49 Gastric acid destroys microorganisms ingested with food and saliva. The interdigestive migrating motor complex, a cyclic fasting motility pattern, regularly propels luminal contents toward the colon, thus preventing stagnation and bacterial overgrowth.50
Pathogenesis
The classic disorders associated with bacterial overgrowth are those in which disordered intestinal motility, abnormal reservoirs, or abnormal communications between the proximal and distal intestine result in proliferation of bacteria. Examples of the former are diabetic autonomic neuropathy, late radiation enteropathy, collagen diseases such as scleroderma, and the numerous causes of chronic intestinal pseudo-obstruction. Partial small bowel obstruction due to strictures or adhesions has a similar effect. Abnormal reservoirs that permit stagnation of luminal contents may arise de novo (e.g., small bowel diverticula) or as a result of surgery (e.g., the afferent limb of a Billroth II gastrectomy). Abnormal communications between the proximal and distal intestine result in contamination of the former by denser, more anaerobic bacterial populations. Examples of this group include gastrocolic and jejunocolic fistulas, right hemicolectomy with resection of the ileocecal valve, and surgical bypass of obstructed or diseased intestinal segments. Small bowel bacterial overgrowth in older adults also occurs under conditions that impair gastric acid secretion, such as atrophic gastritis,49,51 treatment with acid-reducing drugs,52–54 or after surgery for peptic ulcer disease. Gut immune defenses may be impaired in older adults and thus contribute to their susceptibility to overgrowth.55
Clinical Picture
Older adult patients who have bacterial overgrowth with malabsorption typically have presenting symptoms of diarrhea, weight loss, and abdominal bloating associated with hypoalbuminemia and low B12 levels. Some anatomic abnormalities associated with bacterial overgrowth (e.g., small bowel diverticula) are more common with increasing age. Most patients who had surgery for peptic ulcer disease before the widespread use of proton pump inhibitors are now elderly. Bacterial overgrowth is thus more common in older adults and is found in 52.5% to 70.8% of patients with symptoms of malabsorption.6,54,56 It also affects 14.5% to 25.6% of older adults with no GI symptoms.53,57–59 Some of these individuals are on acid-suppressing medication53; others have factors that are associated with slower small bowel transit, such as reduced intake of dietary fiber53 and physical disability.59 Subclinical malabsorption is probably present in a proportion who have low albumin and B12 levels, and this may also adversely affect bone mineral density.60
Diagnosis
The literature on bacterial overgrowth is plagued by the absence of a reliable diagnostic test. Historically, culture of proximal small bowel aspirate (currently usually obtained during EGD) was the gold standard for establishing the diagnosis: proximal jejunal counts greater than 105 colony-forming units (CFU)/mL were accepted as abnormal.48 Although this is probably true for postsurgical patients with blind loops, jejunal bacterial counts in healthy individuals are much lower, in the range of 0 to 103 CFU/mL, and a systematic review found no evidence to support culture as a gold standard test.61 Furthermore, this technique only samples a limited region of the small bowel and may miss overgrowth in the more distal segments. Breath tests were developed as an alternative to the invasive procedure and cumbersome culture techniques were involved.61,62 However, these tests were largely validated against culture, which raises serious doubts about their reliability.
In the [14C]-glycocholate breath test, 5 to 10 µCi of glycocholic acid, a conjugated bile acid radiolabeled with 14C, is administered with a test meal. Bacterial deconjugation results in separation of [14C]-glycine from cholic acid, and 14CO2 produced from the former is measured in breath samples collected over the next 4 to 8 hours. Terminal ileal disease or resection also results in a positive test because the bile acid is not reabsorbed and is then metabolized by colonic flora. The test has largely been abandoned because of its poor sensitivity with a false negative rate of 30% to 40%.
Breath hydrogen measurement after ingestion of 50 to 80 g of glucose or 10 to 12 g of lactulose is an alternative technique that avoids the use of a radioisotope. Metabolism of either carbohydrate by the abnormal bacterial population produces hydrogen, which can be detected by breath testing. The timing of the hydrogen rise is crucial for the lactulose test, as this sugar is not absorbed in the small bowel and produces a second, higher “colonic” hydrogen peak. It is not possible to reliably distinguish the peak produced by small bowel bacterial overgrowth from that due to normal colonic flora without using an oral contrast medium as well. Glucose is thus a better substrate as it is absorbed completely in the proximal small bowel. Furthermore, a small study in healthy volunteers has shown that even a 10-g quantity of lactulose accelerates small bowel transit,63 and hence the glucose-hydrogen breath test is probably more reliable. Approximately 15% of individuals are colonized by colonic flora, which produce methane, not hydrogen, and false negative tests will occur unless breath methane and hydrogen are both measured.62 In the [14C]-xylose breath test, elevated 14CO2 levels appear in breath samples within 60 minutes of taking 10 µCi of [14C]-xylose with 1 g of unlabeled xylose by mouth. Although the sensitivities and specificities of breath tests are variable, even when compared against culture, they are simple to perform and are probably useful if positive. Until a better test for bacterial overgrowth becomes available, the most practical strategy would be to test, treat, and then retest, in addition to evaluating the clinical response.61 Patients with confirmed overgrowth should have a small bowel x-ray series to look for abnormal communications or reservoirs.
Management
The conditions underlying bacterial overgrowth (with the exception of strictures and some enteroenteric fistulas) are rarely amenable to surgical correction, and hence antibiotics are the mainstay of treatment.49 Tetracycline was traditionally used to reduce bacterial flora, but approximately two thirds of patients do not benefit from this drug. Chloromycetin and clindamycin are rarely used now because of their toxicity. Co-amoxiclav and norfloxacin are effective in standard doses given for 7 to 10 days, as is metronidazole in combination with one of the cephalosporins.64,65 Rifaximin is also effective, and systemic toxicity does not occur because the drug is not absorbed.66 In some patients, a single antibiotic course produces a satisfactory response lasting for months, but many patients need cyclic courses given at monthly intervals for 4 to 6 months. Octreotide, a long-acting analogue of somatostatin, has been tested in small numbers of patients with connective tissue diseases and chronic intestinal pseudo-obstruction. It improves motility and appears to be highly effective on its own67 or in combination with erythromycin.68
Prokinetic agents (including erythromycin) may play a role in the management of bacterial overgrowth, particularly in older adult patients with prolonged small bowel transit. Probiotics may also be helpful, but further work is required to define their role. Clinicians should avoid using acid-suppressing agents in older adults without a clear indication: apart from their possible role in promoting clinically significant bacterial overgrowth, these drugs can cause food-cobalamin malabsorption and are implicated in an increased susceptibility to Clostridium difficile infection.
Crohn Disease
Crohn disease is an idiopathic chronic relapsing disorder, characterized by transmural inflammation and ulceration, occurring in a segmental distribution. Intestinal ulceration ranges from aphthoid erosions to deep fissures, and the course is often complicated by the formation of strictures, abscesses, and fistulas. The disease has a predilection for the terminal ileum, but any region of the GI tract can be affected.
The Montreal classification groups patients according to clinical phenotype, including age at diagnosis, location, and disease behavior.69 This classification considers three age groups, with those older than 40 years comprising the most advanced group, and the majority of patients have inflammatory disease (70%), followed by stricturing disease (17%) and penetrating disease (13%).70,71 Penetrating disease includes fistulas, abscesses, or both.
At diagnosis, approximately 28% of patients have terminal ileal involvement only, 50% have ileocolic disease, and 25% colonic disease alone.72 Small bowel disease is less common in older people.73 In a study in northern France, 34% of patients older than 60 years had small bowel involvement compared to 64% of younger patients.70 The prevalence of inflammatory bowel disease is increasing worldwide, and with an aging population, this makes Crohn disease in older adults a growing problem. Although Crohn disease predominantly affects teenagers and young adults, there is also a second smaller peak from the sixth to the eighth decades,74 although not all studies describe this bimodal pattern consistently.75,76 Nevertheless, a substantial minority of patients with Crohn disease first develop it in later life. In the French study, 24% of patients were diagnosed with Crohn disease at or above the age of 60 years.70 In another population-based study from Belgium, 23 of 137 patients (17%) were older than 60 years at diagnosis, with an annual incidence of 3.5 per 100,000 (4.8 per 100,000 in patients younger than 60 years).77 Smoking, a family history of inflammatory bowel disease, and (in most studies) previous appendicectomy are risk factors for Crohn disease.76
Clinical Picture and Investigations
Crohn disease in older adults generally follows clinical pattern similar to that in young people.78 Main symptoms of Crohn disease include abdominal pain, diarrhea, weight loss, nausea, vomiting, fatigue, fever, abdominal mass, and perianal symptoms. However, it is noted that older adult patients are more likely to have colonic rather than small bowel involvement and thus presenting symptoms of diarrhea and bleeding rather than abdominal pain and vomiting.79 Diagnostic delay is more common in older than in younger patients with Crohn disease (up to 6 years compared with 2 years).80–82 This delay may be because of the higher prevalence of conditions that may mimic Crohn disease in older adults, conditions such as diverticulosis, acute ischemic or infectious colitis, or drug-related colitis. Complications of Crohn disease, including stricture formation and penetrating disease, are less common in older adults compared to children.83
There is no single definitive test for Crohn disease.84 The diagnosis is established (and disease activity assessed) by clinical features, inflammatory markers, endoscopic, or radiologic imaging and histology. Standard activity indices incorporating some of these features (Crohn disease activity index [CDAI], Harvey-Bradshaw Index) are used in trials but can also be helpful in clinical practice (e.g., in assessing patients for therapy with anti–tumor necrosis factor [TNF] agents).85 For example, a CDAI of less than 150 is used to define remission, and severe disease is characterized by a score of higher than 450.85,86
A discussion of investigative techniques used in small bowel Crohn disease inevitably overlaps with the investigation of colonic disease. In practice, ileocolonoscopy will probably be the initial investigation of choice. Only a short segment of terminal ileum is examined at colonoscopy, and hence either a double-contrast barium follow-through or enteroclysis is traditionally used to define the extent and severity of small bowel disease. Advances in MRI (including MR enteroclysis) have resulted in improved small bowel visualization,72,87,88 including the ability to distinguish between inflammatory and fibrotic strictures. MRI has the advantage of not using ionizing radiation and is likely to replace barium studies. CT and ultrasound imaging have been used for many years in patients with Crohn disease to outline phlegmons (inflammatory masses) and abscess cavities and to drain the latter percutaneously. Technical advances have extended the range of both modalities. Ultrasound is now also employed to image the bowel wall and detect strictures. Contrast-enhanced examinations with multislice helical CT scanners have high sensitivity (71% to 83%) and specificity (90% to 98%) in the evaluation of small bowel inflammation.88 Wireless capsule endoscopy can provide endoscopic images of the entire small bowel.12,72,88 The diagnostic accuracy of wireless capsule endoscopy is now considered to be superior to that of CT or MR enterography, making it the new gold standard for suspected Crohn disease.89 As stated previously, wireless capsule endoscopy carries a risk of capsule retention, and a patency capsule may be used to reduce this risk. Push enteroscopy is rarely used in Crohn disease, as the terminal ileum is not visualized with this technique. DBE can be used to take biopsies and do therapeutic procedures such as dilation of strictures.14,72,88
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