Medical Aspects

A distinction needs to be made between gastroesophageal reflux (GER) and reflux leading to symptoms or disease (GERD). GER can be a physiologic phenomenon that occurs in asymptomatic individuals. In contrast, GERD is defined as a condition in which reflux leads to “troublesome symptoms and/or complications.”² Patients may experience mild symptoms with an esophagus that appears to be clinically normal, or they may have severe symptoms with surface abnormalities that can be detected with an endoscope. The process by which GER leads to GERD consists of a sequence of events spanning the esophagogastric junction, the esophageal body, and the central nervous system.

GERD is one of the most commonly occurring upper gastrointestinal tract conditions with up to 10% of the population experiencing symptoms daily. There is no gender difference in a condition that can have a significant effect on daily activities.

“Heartburn” is the cardinal symptom of GERD and is defined as a sensation of burning or heat that spreads upward from the epigastrium to the neck.³ Although symptoms of GERD are variable, they primarily arise in relation to mucosal injury, for example esophagitis, esophageal ulceration, stricture, and dysplasia. Other symptoms include chest pain, which due to its similarity to that arising from an acute cardiovascular event may prompt the patient to seek medical advice and dysphagia.

Airway problems such as laryngitis, chronic cough, hoarseness, and asthma may arise as a result of microaspiration of refluxate into the airway.^4,5 This constellation of symptoms is known as laryngopharyngeal reflux (LPR) or extraesophageal reflux disease (EERD). However, these symptoms may also arise from disorders of the upper or lower respiratory tracts.

GORD complications include premalignant and malignant conditions of the esophagus. Barrett’s esophagus is a variant of GERD in which normal squamous epithelium is replaced by columnar epithelium.⁶ Patients with this phenomenon show an increased incidence of adenocarcinoma. This condition may increase the incidence of carcinoma by as much as 10%,⁷ although the majority of patients with Barrett’s esophagus die from unrelated causes.^8,9 The major reason to evaluate patients with chronic symptoms of GERD is to recognize Barrett’s esophagus. Endoscopic screening is recommended for patients with multiple risk factors for cancer in Barrett’s esophagus, including chronic GERD, hiatal hernia, advanced age, male sex, white race, cigarette smoking, and obesity with an intra‐abdominal body fat distribution. During the last decade, new techniques have been introduced for diagnosis of GERD and Barret’s esophagus.¹⁰

The relaxation of the lower esophageal sphincter for the purpose of relieving pressure in the stomach (from gas and the ingestion of food) is called the “burp” mechanism. This phenomenon is a physiologic process and only occurs when a person is in an erect posture; gastric contents are thereby prevented from flowing into the esophagus and possibly being aspirated. The gastroesophageal junction prevents regurgitation (retrograde or upward flow) of gastric contents and is composed of an internal lower esophageal sphincter. External pressure on the junction by the diaphragm also assists in this function. When this barrier fails, gastric contents may make their way into the esophagus and cause symptoms. The cause of lower esophageal sphincter incompetence, while not mechanical, remains unclear. However, surgery, scleroderma, and drugs, including anticholinergics, cardiac vasoconstrictors, nicotine, and estrogen‐progesterone combinations used in contraceptives, can cause an incompetent sphincter, as may also happen during pregnancy.

Symptoms occur when refluxate proceeds through the junction. The severity of the symptoms depends on the amount of acid in the refluxate, the speed with which the esophagus can clear the refluxate, and the presence of buffering agents, such as swallowed saliva. An insufficient amount of alkaline fluid prohibits the esophagus from properly buffering the acid that has moved up from the stomach. Patients who smoke tobacco, take certain drugs, have had high‐dose head and neck radiotherapy, or suffer from diseases such as Sjögren’s syndrome may not produce sufficient saliva to protect the esophagus from the acid in the refluxate. Increased abdominal pressure as a result of obesity, pregnancy, or a large meal may predispose patients to gastric content reflux. Moving into or out of various positions, for instance lying down too soon, especially after eating, will also promote reflux.

Medical Management

Lifestyle modification is often effective, with weight loss having a dose‐dependent association with symptom reduction: a 3.5 kg/m² reduction in the body mass index can achieve nearly a 40% reduction in the risk of having frequent symptoms. Other lifestyle modifications include elevation of the head of the bed and avoidance of meals 2–3 hours before bedtime, if there are nocturnal symptoms. Patients should also avoid foods that specifically trigger their symptoms. Tobacco and alcohol cessation, while often recommended, has not been shown to improve symptoms overall. Drugs with anticholinergic or smooth muscle–relaxing properties may exacerbate reflux symptoms, as may those causing a chemical esophagitis, such as oral bisphosphonates.

If symptoms persist, the addition of acid suppression therapy, in the form of H₂ receptor antagonists, may improve or eliminate the symptoms of “heartburn” and regurgitation and heal mild to moderate esophagitis. However, proton pump inhibitors (PPIs) such as omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole (available by prescription), which block the final common pathway of acid secretion by irreversibly binding to and inactivating the proton pump (H+/K+‐ATPase exchange) are commonly used. These are more effective in reducing symptoms and in healing erosive esophagitis than H₂ receptor antagonists (84% ± 11% vs. 52% ± 17%).¹¹ Daily PPI treatment provides the best long‐term reduction of symptoms for patients with moderate to severe esophagitis.

Surgical intervention is generally reserved for those patients unresponsive to maximal medical therapy or unable to tolerate treatment. Laparoscopic fundoplication is the most common procedure and is highly effective in well‐selected patients. Fundoplication involves construction of a cuff of gastric (fundus) tissue around the lower esophageal sphincter junction.¹² This improves function via a variety of mechanical factors and also modifies the reflexes involved in the pathophysiology. The strongest predictors of success include abnormal 24‐hour pH scores, classic symptoms of GERD, and a positive PPI trial.¹³ Gastric bypass surgery and laparoscopic gastric banding decrease GERD symptoms primarily through the resulting weight loss.¹⁴

Oral Health Considerations

Patients who experience GERD may complain of extraesophageal symptoms including laryngitis, asthma, cough, chest pain, dental erosion, dysgeusia (foul taste), halitosis, tongue sensitivity, burning sensations, dental sensitivity related to hot or cold stimuli, and/or pulpitis.¹⁵

Oral mucosal changes are minimal; however, erythema and mucosal atrophy may be present as a result of chronic exposure of tissues to acid. Noncarious tooth surface loss (NCTSL), comprising erosion, attrition, and abrasion, is multifactorial and it is rarely possible to identify a single etiology in a specific patient.¹⁶ Factors that determine whether an individual with GERD will or will not develop dental erosion have not been clearly identified and the strength and prevalence of the association are highly variable.¹⁷ However, a significantly lower oral pH was found in patients with GERD and bulimia nervosa as compared to healthy individuals.¹⁸ The chemical dissolution of enamel (erosion) may lead to exposed dentin and resultant thermal sensitivity or, if severe, irreversible pulpal (nerve) damage necessitating root canal therapy. The rate of progression and severity of erosion may be exacerbated by associated attrition and abrasion, inadequate oral hygiene, poor or reduced salivary flow, consumption of acidic beverages or foods, occupation, alcoholism, and eating disorders. OHCPs should therefore closely examine their patients for evidence of NCTSL and instigate appropriate prevention and treatment. In particular, patients with erosion on the palatal and lingual surfaces should be questioned for a history of GERD, with a view to onward referral to their primary care physician if appropriate. Dental management should be tailored to the extent and rate of progression of the condition and any associated symptoms, and include early dietary and preventive advice, and topical fluoride applications to ensure optimal dental mineralization and reduction of thermal sensitivity. The restoration of lost tooth structure will provide symptomatic relief as well as enhancing function and esthetics and help to minimize further hard tissue damage.

The medical management of GERD may impact on dental care. Many of the listed potential drug interactions, for example cimetidine and H₂ receptor antagonists with local anesthetic agents, are either theoretical and may not have been seen in dental practice, or are relevant to much higher doses used for different indications. Reports of serious drug interactions associated with currently recommended doses of local anesthetics and vasoconstrictors in the dental setting are exceedingly rare.¹⁹ Similarly, while H₂ receptor antagonists and PPIs may be associated with a degree of xerostomia, this is not usually clinically significant. Likewise, although H₂ receptor antagonists may cause central nervous system effects, from fatigue and lethargy to confusion, delirium, and seizures, these effects are dose dependent and are rarely problematic. As cimetidine inhibits the absorption and therefore the blood concentration of azole antifungal drugs such as ketaconazole (via inhibition of the cytochrome P‐450 3A4 [CYP3A4] enzyme system), topical antifungal therapy should be considered in the first instance. Finally, soft tissue changes such as esophageal stricture and fibrosis may complicate intubation if the patient requires general anesthesia for dental treatment.

Medical Aspects

The esophagus passes through the diaphragmatic hiatus and into the stomach just inferior to the diaphragm. The hiatus causes an anatomic narrowing of the opening into the stomach, which helps prevent reflux of stomach contents into the esophagus. Some patients have a weakened or enlarged hiatus, possibly due to hereditary factors. It may also be caused by increased intra‐abdominal pressure, for instance from obesity, or chronic straining when passing stools. When a weakened or enlarged hiatus occurs, a portion of the stomach herniates into the chest cavity through this enlarged hole, resulting in a hiatal hernia.²⁰ Hiatal hernias are quite common; occurrence rates are between 20% and 60%.²⁰ The incidence of hiatal hernia increases with age, although the condition is also seen in infants and children. As the diaphragm separates the thorax from the abdomen, symptoms of hiatal hernia often include chest pain, which may mimic those of myocardial infarction. If the hiatal hernia is small, there may be no symptoms, while if the area of the hiatus is very weak, there may be entry of acidic digestive juices into the esophagus.²⁰

Hiatal hernias are classified into one of four types (I, II, III, and IV) based on the location of the gastroesophageal junction in relation to the pillars of the crura.²⁰ A type I hernia is the classic “sliding” form and the most common. In this type, the herniated portion of the stomach slides back and forth through the diaphragm into the chest. These hernias are normally small and often present with minimal (if any) symptoms. The remaining three types are true paraesophageal hernias and account for only 5%–15% of all hiatal hernias.²⁰ The common feature of these is herniation of the stomach into the thoracic cavity, due to laxity of the gastrosplenic and gastrocolic ligaments in addition to crural deformation.²⁰ Complications associated with these hernias include obstruction, volvulus, and ischemia.

Infants with hiatal hernia usually regurgitate bloodstained food and may also have difficulty in breathing and swallowing. Adult patients with hiatal hernia may experience chronic acid reflux into the esophagus, with its associated symptoms. Chronic gastroesophageal reflux can erode the esophageal lining, causing bleeding, which may lead to anemia or cause inflammation and scarring, leading to esophageal narrowing. This narrowing may impair the passage of food into the stomach, resulting in dysphagia and an uncomfortable feeling of fullness or “bloating.” In contrast to abdominal hernias, hiatal hernias have no outward physical signs and are usually discovered on endoscopy, manometry, or other radiographic studies investigating GERD or other upper gastrointestinal complaints.²⁰

Medical Management

Defects present at birth may sometimes correct themselves. Until this occurs, however, the infant should sleep in a crib with the head raised and be given an altered diet consisting of food that has a thicker than normal consistency. In adults the management is similar to that of GERD, for example weight loss, antacids, elevation of the head of the bed, and avoidance of meals 2–3 hours before bedtime (if there are nocturnal symptoms), as well as avoidance of foods that trigger symptoms and H₂ receptor antagonists.

Lifestyle modification and drug therapy usually allow patients to minimize the symptoms of hiatal hernia without significant inconvenience and form the preferred management.²¹ When conservative measures fail to control the condition, laparoscopic²² or open surgical correction, which may be complex, can be considered.

Oral Health Considerations

If a hiatal hernia is associated with reflux into the oral cavity, those oral manifestations seen in GERD may be present. While medical intervention may include xerostomic medication, it is rarely clinically significant.

Medical Aspects

The incidence of gastric ulcers is one‐tenth to one‐fourth that of duodenal ulcers. Gastric ulcers are more common in lower socioeconomic groups and in those over 50 years of age, and are seen at a male to female ratio of 3:1. Gastric ulcers are of more concern, as approximately 3%–8% represent malignant ulceration of the gastric mucosa.²⁹ Similarly, gastric ulcers with H. pylori infection have an increased risk of mucosa‐associated lymphoid tissue (MALT) lymphomas, which in the early stages may go into remission after antibiotic eradication of the bacteria.³⁰

Accurate diagnosis, in both cases, involves endoscopy to obtain multiple biopsies and brush specimens for cytologic examination. In gastric ulcers, gastric acidity levels are additionally taken to establish the presence or absence of histamine‐fast achlorhydria, as it is associated with a very high chance of malignancy.

Patients with gastric ulcers often present with epigastric pain radiating to the back which, unlike the pain of duodenal ulcers, is aggravated by food. The management of gastric ulcers involves antacid compounds, antibiotics to eradicate H. pylori, H₂‐blocking agents, and other protective drugs. Follow‐up studies to confirm healing are essential. Additional information about PUD and its implications for oral healthcare is presented in the following section on duodenal ulcers.

Medical Aspects

A duodenal ulcer represents a break through the mucosa into the submucosa or deeper, the base of which is necrotic tissue consisting of pus and fibrin. Continued erosion may lead to hemorrhage from associated vessels, involvement of adjacent organs, or perforation into the peritoneal cavity. When conditions are favorable, the ulcer heals, with granulation tissue and new epithelium. However, chronic ulceration is associated with scar tissue formation and possible deformity.

The incidence of duodenal ulcer is thought to be declining, but it is still a common disorder, developing in about 10% of the US population. Of all peptic ulcers, 80%–85% are duodenal, and duodenal ulcers occur at a male to female ratio of 4:1. The most common primary cause is H. pylori infection, but NSAID use can also be an associated etiologic factor. Less commonly, factors such as stress, exogenous glucocorticosteroids, parathyroid disease, malignant carcinoid, cirrhosis, gastrinoma of the pancreas (Zollinger–Ellison disease), polycythemia vera, and chronic lung disease have been associated with duodenal ulcers.²⁷ The ulceration, which is often recurrent, is usually located in the first part of the duodenum, because the acidic chyme ordinarily becomes alkaline after pancreatic secretions enter the intestines in the second part of the duodenum.

The most common symptom of an uncomplicated ulcer is epigastric pain, frequently perceived as a burning or gnawing sensation, sometimes associated with nausea and vomiting. This usually occurs when the stomach is empty or when not enough of a meal remains in the stomach to adequately buffer the acid stimulated by the meal. The pain is characteristically relieved within a few minutes by buffering or diluting the gastric acid with ingestion of an antacid, milk, or food. When an ulcer perforates and hemorrhages, the patient often vomits gross blood, which on interacting with acid can appear as coffee grounds. Bleeds can also be associated with black or tar‐like stools, or these may sometimes contain gross blood. Repeated blood loss can lead to iron‐deficiency anemia, while acute, severe blood loss may cause the patient to feel weak, lightheaded, or short of breath.

The early diagnostic cues for duodenal ulcers lie in the history of a periodic pain pattern: duodenal ulcers usually feel better postprandially, while the pain of gastric ulcers is frequently exacerbated by meals. Physical examination is often unremarkable and the mainstay of the diagnosis is an upper gastrointestinal radiologic examination (barium swallow), which will demonstrate the presence of an ulcer in up to 85% of patients, or endoscopy. Endoscopy has a greater sensitivity and offers the opportunity for a biopsy if malignancy or the presence of H. pylori is suspected.³¹

Zollinger–Ellison syndrome can cause multiple ulcers and debilitating diarrhea. It is caused by a pancreatic gastrinoma that secretes gastrin, a potent acid producer, and the diagnosis is made on the basis of extremely high levels of gastric acid and elevated levels of serum gastrin.³² The usual investigations include a full blood count to detect anemia and leukocytosis, an examination of the stool for occult blood, and a serum calcium test to investigate the possibility of an associated hyperparathyroidism or endocrine tumors.

Medical Management

In the absence of complications such as massive bleeding, obstruction due to scarring, or perforation, medical rather than surgical treatment is preferred. Conservative measures include antacids and avoidance of foods that cause discomfort and of substances and drugs that have potent acidogenic properties, including alcohol, tobacco, aspirin, and NSAIDs. If NSAIDs cannot be avoided, the patient should also be treated with misoprostol. Attempts to eradicate H. pylori are necessary in all patients with a peptic ulcer in which the organism can be demonstrated. Bismuth, metronidazole, amoxicillin, and tetracycline have been shown to be effective.³¹ In addition to elimination of H. pylori, medical treatment may include the following six other classes of drugs: (1) sedatives to reduce mental stress if anxiety is thought to be etiologic; (2) antacids to neutralize acid; (3) drugs that act by covering and protecting the ulcer; (4) anticholinergic drugs to decrease the production of acid by the gastric mucosa; (5) histamine H₂ receptor antagonists (cimetidine, famotidine, nizatidine, or ranitidine), which block the action of histamine on the gastric parietal cells, thus reducing food‐stimulated acid secretion up to 75%; and (6) omeprazole, which also suppresses gastric acid secretion but has a different mechanism of action from that of anticholinergics or H₂ receptor antagonists. Anticholinergics are sometimes prescribed, particularly for reducing acid production at night. However, limited effectiveness and side effects such as oral dryness make anticholinergics less attractive than histamine H₂ receptor antagonists. In most patients, the pain is controlled within 1 week, and most ulcers heal by the sixth week. Intractable symptoms or complicated duodenal ulcers may require surgery.³²

Oral Health Considerations

If a patient presents with symptoms of epigastric pain, as described previously, the OHCP should refer them to the primary care physician. Oral manifestations of PUD are rare, but may occur in relation to severe anemia from repeated gastrointestinal bleeding. In this case there may be new or worsening recurrent oral ulceration, depapillation, and soreness of the dorsum of the tongue due to loss of the filiform papillae. Such patients should be referred to an appropriate clinician to establish their hematologic parameters and correct any deficiency that may delay wound healing or otherwise complicate surgical procedures or anesthesia. Anemia also predisposes to oral candidosis, which may cause mucosal or tongue soreness, particularly in denture wearers. Exceptionally, dental erosion of the palatal aspect of the maxillary teeth due to persistent regurgitation of gastric acid as a result of pyloric stenosis has been reported. Vascular malformations of the lip have also been reported and range from a very small macule to a large venous pool.^33,34

H. pylori has been isolated from dental plaque³⁵ and its eradication has been reported to reduce the frequency and severity of recurrent aphthous stomatitis (RAS) in patients who tested positive.³⁶

OHCPs should avoid administering drugs that exacerbate ulceration and cause gastrointestinal distress, such as aspirin and other NSAIDs where possible. Similarly, exogenous corticosteroid administration may promote or exacerbate PUD via its action on the mucus layer. Corticosteroid therapy should therefore be minimized and appropriate prophylaxis provided to minimize the risk. Similarly, as many antacids contain calcium, magnesium, and aluminum salts that bind antibiotics, for instance erythromycin and tetracycline, patients should be advised to take their antibiotics 1 hour before or 2 hours after their antacids to avoid a significant (75%–85%) reduction in antibiotic absorption.

Hyposalivation and dry mouth (xerostomia) may occur in patients taking anticholinergic drugs. This is most likely to present in those patients who wear either complete or partial acrylic dentures. While denture adhesives and artificial saliva may aid in the retention of their dental prostheses, the reduced salivary flow predisposes them to an increased risk of oral candidosis. Dentate patients are at increased risk of dental caries, particularly affecting cervical margins and exposed root surfaces, if the hyposalivation is prolonged or if they place sugar‐containing foods into the mouth in an effort to stimulate saliva flow. In these cases, appropriate preventive measures should be instituted. If the patient specifically complains of dry mouth, it may be possible to alter the specific drug type or dosage in consultation with the patient’s physician. Commonly used sialagogues, such as pilocarpine or cevimeline, may be contraindicated due to their parasympathomimetic action.

Cimetidine and ranitidine, which are commonly prescribed for duodenal ulcer patients, have occasionally been associated with thrombocytopenia and may compete with antibiotics or antifungal medications.¹⁹

Medical Aspects

The inflammation in UC most commonly affects the rectum, but can spread to affect more proximal parts of the colon.⁵⁶ Macroscopically, the mucosa may have a granular appearance if the disease is mild, while stripping of the mucosa, with areas of sloughing, ulceration, and bleeding, may be seen when more severe. As the superficial mucosal lesions enlarge, they may be perpetuated by secondary bacterial invasion.^23–32

Patients usually complain of cramping abdominal pain that is worse prior to a bowel movement, which is associated with rectal bleeding and bloody diarrhea. The frequency and volume of blood present give an indication of the activity of the condition. Typically patients will pass 5–8 movements in a 24‐hour period, including at night.^23–32 Extraintestinal manifestations present and include erythema nodosum, characterized by red swollen nodules that are usually on the thighs and legs; ocular changes such as episcleritis, uveitis, corneal ulcers, and retinitis; and joint symptoms usually affecting the ankles, knees, and wrists.^23–32 Severe oral ulceration may be seen secondary to ulcerative colitis (Figure 15.1). A microcytic, hypochromic anemia may result from blood loss, while leukocytosis occurs in active disease, as may electrolyte imbalances, hypoalbuminemia, and low serum magnesium and potassium levels with severe diarrhea.^23–32

Medical Management

The diagnosis of UC is based on a careful history, physical examination, gastrointestinal radiography, and direct visualization via sigmoidoscopy and endoscopy revealing multiple tiny mucosal ulcers covered by blood and pus.

The aim of therapy is to reduce the inflammation and correct the effects of the disease. Sulfasalazine in the form of its active component 5‐aminosalicylic acid (5‐ASA) is the standard therapy for mild to moderately active UC⁵⁷ and most patients respond to 2–3 g 5‐ASA, with higher doses used in those with more severe symptoms or those not responding initially. Oral corticosteroids are superior to 5‐ASA,⁵⁸ but have significant side effects and are reserved for patients with failure of response or who are intolerant to oral and/or rectal 5‐ASA. The current recommended dose is 40 mg once daily⁵⁹ and approximately 50% of patients experience short‐term adverse events such as acne, edema, sleep and mood disturbance, glucose intolerance, and dyspepsia.⁵⁹ The dose should be tapered over 6–8 weeks.

Patients with chronic active UC failing 5‐ASA therapy may benefit from ciclosporin⁶⁰ or thiopurine therapy in the form of azathioprine or its active metabolites, 6‐mercaptopurine or thioguanine.⁶¹ However, as the range of alternatives grows and costs of biologics fall, there is strong justification for moving directly to other immunosuppressive drugs with less toxicity that may be easier to manage.⁶¹ Thiopurines still have a role as combination therapy and to reduce immunogenicity, but the therapeutic pyramid is changing rapidly.⁶⁰ Infliximab and other anti‐TNF drugs are often effective, but it is also important to consider surgery in patients failing a therapeutic agent, particularly as there is generally a reduction in response to each successive immunosuppressive or biologic drug.⁵⁶ Proctocolectomy combined with ileostomy is a curative procedure for UC.

Medical Aspects

CD is an inflammatory disease that can affect any part of the small or large intestine, from the mouth to the anus. Discontinuous segments of disease (“skip lesions”), ileal involvement, and granulomatous inflammation are suggestive of CD, as is a tendency for inflammation to be worse in the proximal colon.⁶² Gross examination may reveal mucosal ulceration (aphthous ulcers within the mucosa that appear normal, deep ulcers within areas of swollen mucosa, or long linear serpiginous ulcers). Microscopic examination reveals inflammatory infiltrate in all layers of affected bowel, with plasma cells and lymphocytes predominating in the lamina propria.^23–32

Epidemiologic evidence suggests that there are two forms of CD: a nonperforating form that tends to recur slowly, and a perforating or aggressive form that evolves more rapidly. Patients with the aggressive perforating type are more prone to develop fistulae and abscesses, whereas the more indolent nonperforating type tends to lead to stenotic obstruction.^23–33 Intestinal fistulas occur in about 20%–40% of patients with CD^63,64 and can link to any adjacent structure, including to the bowel, bladder, skin, or vagina. Strictures can present throughout the gastrointestinal tract and present with obstructive features, including abdominal pain, nausea, and vomiting. Up to one‐third of patients with CD have perianal involvement, most commonly presenting as fistulas, fissures, abscesses, or skin tags.⁶⁵

The severity of CD and its location determine the associated symptoms and signs, resulting in a broad spectrum of presentations. The clinical presentation usually involves a young person with colicky abdominal pain, frequently associated with, and relieved after, bowel movements, together with watery diarrhea and weight loss. Involvement of the terminal ileum is common and may result in pain being localized to the right lower quadrant. The pain tends to come and go, reflecting disease activity, but if acute and severe may resemble appendicitis.

Inflammation of the small intestine may impair the absorption of vital nutrients, leading to deficiency states. Duodenal involvement affects calcium, iron, and folate, while disease in the terminal ileum affects bile salts and vitamin B₁₂. Widespread involvement of the small or large intestines may affect fat, fat‐soluble vitamins, salt, water, protein, and iron.

Medical Management

The signs and symptoms of CD are often subtle and may delay the diagnosis, which is usually made on the basis of a careful history, physical examination, and diagnostic testing. Ileocolonoscopy with biopsy is the first‐line investigation for suspected Crohn’s disease.⁶⁶ CD is likely where there is (1) involvement of the small intestine or the upper part of the alimentary canal; (2) segmental disease of the colon, with “skip” areas of normal rectum; (3) the appearance of fissures or sinus tracts; and (4) the presence of well‐formed noncaseating granulomas.^23–32 Luminal barium fluoroscopic techniques have largely been replaced by cross‐sectional imaging techniques.⁶⁶