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Acute Gastritis

June 13, 2024

Acute and chronic gastritis. The role of oral cavity diseases in the development of gastritis. Etiology. Pathogenesis. Clinical pattern. Stomatological manifestation. Diagnostics. Treatment. The role of a doctor-dentist in prophylaxis.

Peptic stomach and duodenal ulcers. Etiology, pathogenesis. Classification. Clinical pattern. Stomatological manifestation. Diagnostics, complications. Treatment. The role of a doctor-dentist in prophylaxis.

Enteritis and colitis. Etiology. Pathogenesis. Clinical pattern. Diagnostics. Treatment. The role of a doctor-dentist in prophylaxis.

History Abdominal pain is common to many gastrointestinal disorders, including DU and GU, but has a poor predictive value for the presence of either DU or GU. Up to 10% of patients with NSAID-induced mucosal disease can present with a complication (bleeding, perforation, and obstruction) without antecedent symptoms. Despite this poor correlation, a careful history and physical examination are essential components of the approach to a patient suspected of having peptic ulcers.

Epigastric pain described as a burning or gnawing discomfort can be present in both DU and GU. The discomfort is also described as an ill-defined, aching sensation or as hunger pain. The typical pain pattern in DU occurs 90 min to 3 h after a meal and is frequently relieved by antacids or food. Pain that awakes the patient from sleep (between midnight and 3 A.M.) is the most discriminating symptom, with two-thirds of DU patients describing this complaint. Unfortunately, this symptom is also present in one-third of patients with NUD. The pain pattern in GU patients may be different from that in DU patients, where discomfort may actually be precipitated by food. Nausea and weight loss occur more commonly in GU patients. In the United States, endoscopy detects ulcers in <30% of patients who have dyspepsia. Despite this, 40% of these individuals with typical ulcer symptoms had an ulcer crater, and 40% had gastroduodenitis on endoscopic examination.

The mechanism for development of abdominal pain in ulcer patients is unknown. Several possible explanations include acid-induced activation of chemical receptors in the duodenum, enhanced duodenal sensitivity to bile acids and pepsin, or altered gastroduodenal motility.

Variation in the intensity or distribution of the abdominal pain, as well as the onset of associated symptoms such as nausea and/or vomiting, may be indicative of an ulcer complication. Dyspepsia that becomes constant, is no longer relieved by food or antacids, or radiates to the back may indicate a penetrating ulcer (pancreas). Sudden onset of severe, generalized abdominal pain may indicate perforation. Pain worsening with meals, nausea, and vomiting of undigested food suggest gastric outlet obstruction. Tarry stools or coffee ground emesis indicate bleeding.

The term gastritis should be reserved for histologically documented inflammation of the gastric mucosa. Gastritis is not the mucosal erythema seen during endoscopy and is not interchangeable with “dyspepsia.” The etiologic factors leading to gastritis are broad and heterogeneous. Gastritis has been classified based on time course (acute vs. chronic), histologic features, and anatomic distribution or proposed pathogenic mechanism .

The correlation between the histologic findings of gastritis, the clinical picture of abdominal pain or dyspepsia, and endoscopic findings noted on gross inspection of the gastric mucosa is poor. Therefore, there is no typical clinical manifestation of gastritis.

Acute Gastritis

The most common causes of acute gastritis are infectious. Acute infection with H. pylori induces gastritis. However, H. pylori acute gastritis has not been extensively studied. Reported as presenting with sudden onset of epigastric pain, nausea, and vomiting, limited mucosal histologic studies demonstrate a marked infiltrate of neutrophils with edema and hyperemia. If not treated, this picture will evolve into one of chronic gastritis. Hypochlorhydria lasting for up to 1 year may follow acute H. pylori infection.

The highly acidic gastric environment may be one reason why infectious processes of the stomach are rare. Bacterial infection of the stomach or phlegmonous gastritis is a rare potentially life-threatening disorder, characterized by marked and diffuse acute inflammatory infiltrates of the entire gastric wall, at times accompanied by necrosis. Elderly individuals, alcoholics, and AIDS patients may be affected. Potential iatrogenic causes include polypectomy and mucosal injection with India ink. Organisms associated with this entity include streptococci, staphylococci, Escherichia coli, Proteus, and Haemophilus. Failure of supportive measures and antibiotics may result in gastrectomy.

Chronic Gastritis

Chronic gastritis is identified histologically by an inflammatory cell infiltrate consisting primarily of lymphocytes and plasma cells, with very scant neutrophil involvement. Distribution of the inflammation may be patchy, initially involving superficial and glandular portions of the gastric mucosa. This picture may progress to more severe glandular destruction, with atrophy and metaplasia. Chronic gastritis has been classified according to histologic characteristics. These include superficial atrophic changes and gastric atrophy.

The early phase of chronic gastritis is superficial gastritis. The inflammatory changes are limited to the lamina propria of the surface mucosa, with edema and cellular infiltrates separating intact gastric glands. Additional findings may include decreased mucus in the mucous cells and decreased mitotic figures in the glandular cells. The next stage is atrophic gastritis. The inflammatory infiltrate extends deeper into the mucosa, with progressive distortion and destruction of the glands. The final stage of chronic gastritis is gastric atrophy. Glandular structures are lost; there is a paucity of inflammatory infiltrates. Endoscopically the mucosa may be substantially thin, permitting clear visualization of the underlying blood vessels.

Video: chronic gastritis

Gastric glands may undergo morphologic transformation in chronic gastritis. Intestinal metaplasia denotes the conversion of gastric glands to a small intestinal phenotype with small-bowel mucosal glands containing goblet cells. The metaplastic changes may vary in distribution from patchy to fairly extensive gastric involvement. Intestinal metaplasia is an important predisposing factor for gastric cancer.

Chronic gastritis is also classified according to the predominant site of involvement. Type A refers to the body-predominant form (autoimmune) and type B is the central-predominant form (H. pylori-related). This classification is artificial in view of the difficulty in distinguishing these two entities. The term AB gastritis has been used to refer to a mixed antral/body picture.

Type A Gastritis. The less common of the two forms involves primarily the fundus and body, with antral sparing. Traditionally, this form of gastritis has been associated with pernicious anemia in the presence of circulating antibodies against parietal cells and intrinsic factor; thus it is also called autoimmune gastritis. H. pylori infection can lead to a similar distribution of gastritis. The characteristics of an autoimmune picture are not always present.

Type A (autoimmune gastritis)

Antibodies to parietal cells have been detected in >90% of patients with pernicious anemia and in up to 50% of patients with type A gastritis. Anti-parietal cell antibodies are cytotoxic for gastric mucous cells. The parietal cell antibody is directed against H+,K+-ATPase. T cells are also implicated in the injury pattern of this form of gastritis.

Parietal cell antibodies and atrophic gastritis are observed in family members of patients with pernicious anemia. These antibodies are observed in up to 20% of individuals over age 60 and in ~20% of patients with vitiligo and Addison’s disease. About half of patients with pernicious anemia have antibodies to thyroid antigens, and about 30% of patients with thyroid disease have circulating anti-parietal cell antibodies. Anti-intrinsic factor antibodies are more specific than parietal cell antibodies for type A gastritis, being present in ~40% of patients with pernicious anemia. Another parameter consistent with this form of gastritis being autoimmune in origin is the higher incidence of specific familial histocompatibility haplotypes such as HLA-B8 and -DR3.

The parietal cell-containing gastric gland is preferentially targeted in this form of gastritis, and achlorhydria results. Parietal cells are the source of intrinsic factor, lack of which will lead to vitamin B12 deficiency and its sequelae (megaloblastic anemia, neurologic dysfunction).

Gastric acid plays an important role in feedback inhibition of gastrin release from G cells. Achlorhydria, coupled with relative sparing of the antral mucosa (site of G cells), leads to hypergastrinemia. Gastrin levels can be markedly elevated (>500 pg/mL) in patients with pernicious anemia. ECL cell hyperplasia with frank development of gastric carcinoid tumors may result from gastrin trophic effects. The role of gastrin in carcinoid development is confirmed by the observation that antrectomy leads to regression of these lesions. Hypergastrinemia and achlorhydria may also be seen ion-pernicious anemia-associated type A gastritis.

Type B gastritis. Type B, or antral-predominant, gastritis is the more common form of chronic gastritis. H. pylori infection is the cause of this entity. Although described as “antral-predominant,” this is likely a misnomer in view of studies documenting the progression of the inflammatory process towards the body and fundus of infected individuals. The conversion to a pan-gastritis is time-dependent-estimated to require 15 to 20 years. This form of gastritis increases with age, being present in up to 100% of people over age 70. Histology improves after H. pylori eradication. The number of H. pylori organisms decreases dramatically with progression to gastric atrophy, and the degree of inflammation correlates with the level of these organisms. Early on, with antral-predominant findings, the quantity of H. pylori is highest and a dense chronic inflammatory infiltrate of the lamina propria is noted accompanied by epithelial cell infiltration with polymorphonuclear leukocytes.

Type B (Chronic antral gastritis)

Endoscopic examination in chronic gastritis: the devise, the principle of examination and the appearance of stomach mucosa in gastritis (hyperemia, erosions)

Multifocal atrophic gastritis, gastric atrophy with subsequent metaplasia, has been observed in chronic H. pylori-induced gastritis. This may ultimately lead to development of gastric adenocarcinoma. H. pylori infection is now considered an independent risk factor for gastric cancer. Worldwide epidemiologic studies have documented a higher incidence of H. pylori infection in patients with adenocarcinoma of the stomach as compared to control subjects. Seropositivity for H. pylori is associated with a three- to sixfold increased risk of gastric cancer. This risk may be as high as ninefold after adjusting for the inaccuracy of serologic testing in the elderly. The mechanism by which H. pylori infection leads to cancer is unknown. However, eradication of H. pylori as a general preventative measure for gastric cancer is not recommended.

Infection with H. pylori is also associated with development of a low grade B cell lymphoma, gastric MALT lymphoma. The chronic T cell stimulation caused by the infection leads to production of cytokines that promote the B cell tumor. Tumor growth remains dependent upon the presence of H. pylori in that its eradication is often associated with complete regression of the tumor. The tumor may take more than a year to regress after treating the infection. Such patients should be followed by EUS every 2 to 3 months. If the tumor is stable or decreasing in size, no other therapy is necessary. If the tumor grows, it may have become a high-grade B cell lymphoma. When the tumor becomes a high-grade aggressive lymphoma histologically, it loses responsiveness to H. pylori eradication.

H.pylori

X-ray examination is less informative in gastritis

History. Abdominal pain is common to many gastrointestinal disorders, including DU and GU, but has a poor predictive value for the presence of either DU or GU. Up to 10% of patients with NSAID-induced mucosal disease with a complication (bleeding, perforation, and obstruction) without antecedent symptoms. Despite this poor correlation, a careful history and physical examination are essential components of the approach to a patient suspected of having peptic ulcers

Physical Examination Epigastric tenderness is the most frequent finding in patients with GU or DU. Pain may be found to the right of the midline in 20% of patients. Unfortunately, the predictive value of this finding is rather low. Physical examination is critically important for discovering evidence of ulcer complication. Tachycardia and orthostasis suggest dehydration secondary to vomiting or active gastrointestinal blood loss. A severely tender, boardlike abdomen suggests a perforation. Presence of a succussion splash indicates retained fluid in the stomach, suggesting gastric outlet obstruction.

Diagnostic Evaluation. In view of the poor predictive value of abdominal pain for the presence of a gastroduodenal ulcer and the multiple disease processes that can mimic this disease, the clinician is often confronted with having to establish the presence of an ulcer. Documentation of an ulcer requires either a radiographic (barium study) or an endoscopic procedure.

Barium examination of the stomach and duodenum reveals an ulcer, 1 cm in diameter (arrow), in the duodenal bulb with radiating folds.

Barium studies of the proximal gastrointestinal tract are still commonly used as a first test for documenting an ulcer. The sensitivity of older single-contrast barium meals for detecting a DU is as high as 80%, with a double-contrast study providing detection rates as high as 90%. Sensitivity for detection is decreased in small ulcers (<0.5 cm), presence of previous scarring, or in postoperative patients. A DU appears as a well-demarcated crater, most often seen in the bulb. A GU may represent benign or malignant disease. Typically, a benign GU also appears as a discrete crater with radiating mucosal folds originating from the ulcer margin. Ulcers >3 cm in size or those associated with a mass are more often malignant. Unfortunately, up to 8% of GUs that appear to be benign by radiographic appearance are malignant by endoscopy or surgery. Radiographic studies that show a GU must be followed by endoscopy and biopsy.

Endoscopy provides the most sensitive and specific approach for examining the upper gastrointestinal tract. In addition to permitting direct visualization of the mucosa, endoscopy facilitates photographic documentation of a mucosal defect and tissue biopsy to rule out malignancy (GU) or H. pylori. Endoscopic examination is particularly helpful in identifying lesions too small to detect by radiographic examination, for evaluation of atypical radiographic abnormalities, or to determine if an ulcer is a source of blood loss.

Treatment in chronic gastritis is aimed at the sequelae and not the underlying inflammation. Patients with pernicious anemia will require parenteral vitamin B12 supplementation on a long-term basis. Eradication of H. pylori is not routinely recommended unless PUD or a low-grade MALT lymphoma is present.

Miscellaneous Forms of Gastritis. Lymphocytic gastritis is characterized histologically by intense infiltration of the surface epithelium with lymphocytes. The infiltrative process is primarily in the body of the stomach and consists of mature T cells and plasmacytes. The etiology of this form of chronic gastritis is unknown. It has been described in patients with celiac sprue, but whether there is a common factor associating these two entities is unknown. No specific symptoms suggest lymphocytic gastritis. A subgroup of patients has thickened folds noted on endoscopy. These folds are often capped by small nodules that contain a central depression or erosion; this form of the disease is called varioliform gastritis. H. pylori probably plays no significant role in lymphocytic gastritis. Therapy with glucocorticoids or sodium cromoglycate has obtained unclear results.

Marked eosinophilic infiltration involving any layer of the stomach (mucosa, muscularis propria, and serosa) is characteristic of eosinophilic gastritis. Affected individuals will often have circulating eosinophilia with clinical manifestation of systemic allergy. Involvement may range from isolated gastric disease to diffuse eosinophilic gastroenteritis. Antral involvement predominates, with prominent edematous folds being observed on endoscopy. These prominent antral folds can lead to outlet obstruction. Patients can present with epigastric discomfort, nausea, and vomiting. Treatment with glucocorticoids has been successful.

Several systemic disorders may be associated with granulomatous gastritis. Gastric involvement has been observed in Crohn’s disease. Involvement may range from granulomatous infiltrates noted only on gastric biopsies to frank ulceration and stricture formation. Gastric Crohn’s disease usually occurs in the presence of small-intestinal disease. Several rare infectious processes can lead to granulomatous gastritis, including histoplasmosis, candidiasis, syphilis, and tuberculosis. Other unusual causes of this form of gastritis include sarcoidosis, idiopathic granulomatous gastritis, and eosinophilic granulomas involving the stomach. Establishing the specific etiologic agent in this form of gastritis can be difficult, at times requiring repeat endoscopy with biopsy and cytology. Occasionally, a surgically obtained full-thickness biopsy of the stomach may be required to exclude malignancy.

Treatment of the ulcer diseases.

Before the discovery of H. pylori, the therapy of PUD disease was centered on the old dictum by Schwartz of “no acid, no ulcer.” Although acid secretion is still important in the pathogenesis of PUD, eradication of H. pylori and therapy/prevention of NSAID-induced disease is the mainstay.

Table 1. Drugs Used in the Treatment of Peptic Ulcer Disease
Drug Type/Mechanism	Examples	Dose
Acid-suppressing drugs
Antacids	Mylanta, Maalox, Tums, Gaviscon	100-140 meq/L 1 and 3 h after meals and hs
H₂ receptor antagonists	Cimetidine Ranitidine Famotidine Nizatidine	800 mg hs 300 mg hs 40 mg hs 300 mg hs
Proton pump inhibitors	Omeprazole Lansoprazole Rabeprazole Pantoprazole	20 mg/d 30 mg/d 20 mg/d 40 mg/d
Mucosal protective agents
Sucralfate	Sucralfate	1 g qid
Prostaglandin analogue	Misoprostol	200 g qid
Bismuth-containing compounds	Bismuth subsalicylate (BSS)	anti-H. Pylori regimens

Acid Neutralizing/Inhibitory Drugs

Antacids Before we understood the important role of histamine in stimulating parietal cell activity, neutralization of secreted acid with antacids constituted the main form of therapy for peptic ulcers. They are now rarely, if ever, used as the primary therapeutic agent but instead are often used by patients for symptomatic relief of dyspepsia. The most commonly used agents are mixtures of aluminum hydroxide and magnesium hydroxide. Aluminum hydroxide can produce constipation and phosphate depletion; magnesium hydroxide may cause loose stools. Many of the commonly used antacids (e.g., Maalox, Mylanta) have a combination of both aluminum and magnesium hydroxide in order to avoid these side effects. The magnesium-containing preparation should not be used in chronic renal failure patients because of possible hypermagnesemia, and aluminum may cause chronic neurotoxicity in these patients.

Calcium carbonate and sodium bicarbonate are potent antacids with varying levels of potential problems. The long-term use of calcium carbonate (converts to calcium chloride in the stomach) can lead to milk-alkali syndrome (hypercalcemia, hyperphosphatemia with possible renal calcinosis and progression to renal insufficiency). Sodium bicarbonate may induce systemic alkalosis.

H2 Receptor antagonists Four of these agents are presently available (cimetidine, ranitidine, famotidine, and nizatidine), and their structures share homology with histamine. Although each has different potency, all will significantly inhibit basal and stimulated acid secretion to comparable levels when used at therapeutic doses. Moreover, similar ulcer-healing rates are achieved with each drug when used at the correct dosage. Presently, this class of drug is often used for treatment of active ulcers (4 to 6 weeks) in combination with antibiotics directed at eradicating H. pylori.

Cimetidine was the first H2 receptor antagonist used for the treatment of acid peptic disorders. The initial recommended dosing profile for cimetidine was 300 mg four times per day. Subsequent studies have documented the efficacy of using 800 mg at bedtime for treatment of active ulcer, with healing rates approaching 80% at 4 weeks. Cimetidine may have weak antiandrogenic side effects resulting in reversible gynecomastia and impotence, primarily in patients receiving high doses for prolonged periods of time (months to years, as in ZES). In view of cimetidine’s ability to inhibit cytochrome P450, careful monitoring of drugs such as warfarin, phenytoin, and theophylline is indicated with long-term usage. Other rare reversible adverse effects reported with cimetidine include confusion and elevated levels of serum aminotransferases, creatinine, and serum prolactin. Ranitidine, famotidine, and nizatidine are more potent H2 receptor antagonists than cimetidine. Each can be used once a day at bedtime. Comparable nighttime dosing regimens are ranitidine, 300 mg, famotidine, 40 mg, and nizatidine, 300 mg.

Additional rare, reversible systemic toxicities reported with H2 receptor antagonists include pancytopenia, neutropenia, anemia, and thrombocytopenia, with a prevalence rate varying from 0.01 to 0.2%. Cimetidine and rantidine (to a lesser extent) can bind to hepatic cytochrome P450, whereas the newer agents, famotidine and nizatidine, do not.

Proton pump (H+,K+-ATPase) inhibitors Omeprazole, lansoprazole, and the newest additions, rabeprazole and pantoprazole, are substituted benzimidazole derivatives that covalently bind and irreversibly inhibit H+,K+-ATPase. These are the most potent acid inhibitory agents available. Omeprazole and lansoprazole are the proton pump inhibitors (PPIs) that have been used for the longest time. Both are acid labile and are administered as enteric-coated granules in a sustained-release capsule that dissolves within the small intestine at a pH of 6. These agents are lipophilic compounds; upon entering the parietal cell, they are protonated and trapped within the acid environment of the tubulovesicular and canalicular system. These agents potently inhibit all phases of gastric acid secretion. Onset of action is rapid, with a maximum acid inhibitory effect between 2 and 6 h after administration and duration of inhibition lasting up to 72 to 96 h. With repeated daily dosing, progressive acid inhibitory effects are observed, with basal and secretagogue-stimulated acid production being inhibited by >95% after 1 week of therapy. The half-life of PPIs is approximately 18 h, thus it can take between 2 and 5 days for gastric acid secretion to return to normal levels once these drugs have been discontinued. Because the pumps need to be activated for these agents to be effective, their efficacy is maximized if they are administered before a meal (e.g., in the morning before breakfast). Standard dosing for omeprazole and lansoprazole is 20 mg and 30 mg once per day, respectively. Mild to moderate hypergastrinemia has been observed in patients taking these drugs. Carcinoid tumors developed in some animals given the drugs preclinically; however, extensive experience has failed to demonstrate gastric carcinoid tumor development in humans. Serum gastrin levels return to normal levels within 1 to 2 weeks after drug cessation. As with any agent that leads to significant hypochlorhydria, PPIs may interfere with absorption of drugs such as ketoconazole, ampicillin, iron, and digoxin. Hepatic cytochrome P450 can be inhibited by these agents, but the overall clinical significance of this observation is not definitely established. Caution should be taken when using warfarin, diazepam, and phenytoin concomitantly with PPIs.

Cytoprotective Agents: Sucralfate Sucralfate is a complex sucrose salt in which the hydroxyl groups have been substituted by aluminum hydroxide and sulfate. This compound is insoluble in water and becomes a viscous paste within the stomach and duodenum, binding primarily to sites of active ulceration. Sucralfate may act by several mechanisms. In the gastric environment, aluminum hydroxide dissociates, leaving the polar sulfate anion, which can bind to positively charged tissue proteins found within the ulcer bed, and providing a physicochemical barrier impeding further tissue injury by acid and pepsin. Sucralfate may also induce a trophic effect by binding growth factors such as EGF, enhance prostaglandin synthesis, stimulate mucous and bicarbonate secretion, and enhance mucosal defense and repair. Toxicity from this drug is rare, with constipation being the most common one reported (2 to 3%). It should be avoided in patients with chronic renal insufficiency to prevent aluminum-induced neurotoxicity. Hypophosphatemia and gastric bezoar formation have also been rarely reported. Standard dosing of sucralfate is 1 g four times per day.

Bismuth-containing preparations Sir William Osler considered bismuth-containing compounds the drug of choice for treating PUD. The resurgence in the use of these agents is due to their effect against H. pylori. Colloidal bismuth subcitrate (CBS) and bismuth subsalicylate (BSS, Pepto-Bismol) are the most widely used preparations. The mechanism by which these agents induce ulcer healing is unclear. Potential mechanisms include ulcer coating; prevention of further pepsin/HCl-induced damage; binding of pepsin; and stimulation of prostaglandins, bicarbonate, and mucous secretion. Adverse effects with short-term usage are rare with bismuth compounds. Long-term usage with high doses, especially with the avidly absorbed CBS, may lead to neurotoxicity. These compounds are commonly used as one of the agents in an anti-H. pylori regimen.

Prostaglandin analogues In view of their central role in maintaining mucosal integrity and repair, stable prostaglandin analogues were developed for the treatment of PUD. The prostaglandin E1 derivative misoprostal is the only agent of this class approved by the U.S. Food and Drug Administration for clinical use in the prevention of NSAID-induced gastroduodenal mucosal injury. The mechanism by which this rapidly absorbed drug provides its therapeutic effect is through enhancement of mucosal defense and repair. Prostaglandin analogues enhance mucous bicarbonate secretion, stimulate mucosal blood flow, and decrease mucosal cell turnover. The most common toxicity noted with this drug is diarrhea (10 to 30% incidence). Other major toxicities include uterine bleeding and contractions; misoprostal is contraindicated in women who may be pregnant, and women of childbearing age must be made clearly aware of this potential drug toxicity. The standard therapeutic dose is 200 ug four times per day.

Miscellaneous drugs. A number of drugs aimed at treating acid peptic disorders have been developed over the years. In view of their limited utilization in the United States, if any, they will only be listed briefly. Anticholinergics, designed to inhibit activation of the muscarinic receptor in parietal cells, met with limited success due to their relatively weak acid-inhibiting effect and significant side effects (dry eyes, dry mouth, urinary retention). Tricyclic antidepressants have been suggested by some, but again the toxicity of these agents in comparison to the safe, effective drugs already described, precludes their utility. Finally, the licorice extract carbenoxolone has aldosterone-like side effects with fluid retention and hypokalemia, making it an undesirable therapeutic option.

Peptic ulcer

A peptic ulcer, also known as peptic ulcer disease (PUD), is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm. As many as 70–90% of such ulcers are associated with Helicobacter pylori, a spiral-shaped bacterium that lives in the acidic environment of the stomach; however, only 40% of those cases go to a doctor. Ulcers can also be caused or worsened by drugs such as aspirin, ibuprofen, and other NSAIDs.

Four times as many peptic ulcers arise in the duodenum—the first part of the small intestine, just after the stomach as in the stomach itself. About 4% of gastric ulcers are caused by a malignant tumor, so multiple biopsies are needed to exclude cancer. Duodenal ulcers are generally benign.

Clinical symptoms

Symptoms of a peptic ulcer can be:

abdominal pain, classically epigastric strongly correlated to mealtimes. In case of duodenal ulcers the pain appears about three hours after taking a meal;

bloating and abdominal fullness;

waterbrash (rush of saliva after an episode of regurgitation to dilute the acid in esophagus – although this is more associated with gastroesophageal reflux disease);

nausea, and copious vomiting;

loss of appetite and weight loss;

hematemesis (vomiting of blood); this can occur due to bleeding directly from a gastric ulcer, or from damage to the esophagus from severe/continuing vomiting.

melena (tarry, foul-smelling feces due to oxidized iron from hemoglobin);

rarely, an ulcer can lead to a gastric or duodenal perforation, which leads to acute peritonitis. This is extremely painful and requires immediate surgery.

picture of tongue

A history of heartburn, gastroesophageal reflux disease (GERD) and use of certain forms of medication can raise the suspicion for peptic ulcer. Medicines associated with peptic ulcer include NSAID (non-steroid anti-inflammatory drugs) that inhibit cyclooxygenase, and most glucocorticoids (e.g. dexamethasone and prednisolone).

In patients over 45 with more than two weeks of the above symptoms, the odds for peptic ulceration are high enough to warrant rapid investigation by esophagogastroduodenoscopy.

The timing of the symptoms in relation to the meal may differentiate between gastric and duodenal ulcers: A gastric ulcer would give epigastriс pain during the meal, as gastric acid production is increased as food enters the stomach. Symptoms of duodenal ulcers would initially be relieved by a meal, as the pyloric sphincter closes to concentrate the stomach contents, therefore acid is not reaching the duodenum. Duodenal ulcer pain would manifest mostly 2–3 hours after the meal, when the stomach begins to release digested food and acid into the duodenum.

Also, the symptoms of peptic ulcers may vary with the location of the ulcer and the patient’s age. Furthermore, typical ulcers tend to heal and recur and as a result the pain may occur for few days and weeks and then wane or disappear. Usually, children and the elderly do not develop any symptoms unless complications have arisen.

Burning or gnawing feeling in the stomach area lasting between 30 minutes and 3 hours commonly accompanies ulcers. This pain can be misinterpreted as hunger, indigestion or heartburn. Pain is usually caused by the ulcer but it may be aggravated by the stomach acid when it comes into contact with the ulcerated area. The pain caused by peptic ulcers can be felt anywhere from the navel up to the sternum, it may last from few minutes to several hours and it may be worse when the stomach is empty. Also, sometimes the pain may flare at night and it can commonly be temporarily relieved by eating foods that buffer stomach acid or by taking anti-acid medication. However, peptic ulcer disease symptoms may be different for every sufferer.

Adventitious methods of examination

Management

The diagnosis is mainly established based on the characteristic symptoms. Stomach pain is usually the first signal of a peptic ulcer. In some cases, doctors may treat ulcers without diagnosing them with specific tests and observe whether the symptoms resolve, thus indicating that their primary diagnosis was accurate.

Confirmation of the diagnosis is made with the help of tests such as endoscopies or barium contrast x-rays. The tests are typically ordered if the symptoms do not resolve after a few weeks of treatment, or when they first appear in a person who is over age 45 or who has other symptoms such as weight loss, because stomach cancer can cause similar symptoms. Also, when severe ulcers resist treatment, particularly if a person has several ulcers or the ulcers are in unusual places, a doctor may suspect an underlying condition that causes the stomach to overproduce acid.

An EGD, a form of endoscopy is carried out on patients in whom a peptic ulcer is suspected. By direct visual identification, the location and severity of an ulcer can be described. Moreover, if no ulcer is present, EGD can often provide an alternative diagnosis.

One of the reasons that blood tests are not reliable for accurate peptic ulcer diagnosis on their own is their inability to differentiate between past exposure to the bacteria and current infection. Additionally, a false negative result is possible with a blood test if the patient has recently been taking certain drugs, such as antibiotics or proton pump inhibitors.

The diagnosis of Helicobacter pylori can be made by:

– Urea breath test (noninvasive and does not require EGD);

– Direct culture from an EGD biopsy specimen; this is difficult to do, and can be expensive. Most labs are not set up to perform H. pylori cultures;

– Direct detection of urease activity in a biopsy specimen by rapid urease test;

– Measurement of antibody levels in blood (does not require EGD). It is still somewhatcontroversial whether a positive antibody without EGD is enough to warrant eradication therapy;

– Stool antigen test;

– Histological examination and staining of an EGD biopsy.

H. pylori

The breath test uses radioactive carbon atom to detect H. pylori. To perform this exam the patient will be asked to drink a tasteless liquid which contains the carbon as part of the substance that the bacteria breaks down. After an hour, the patient will be asked to blow into a bag that is sealed. If the patient is infected with H. pylori, the breath sample will contain radioactive carbon dioxide. This test provides the advantage of being able to monitor the response to treatment used to kill the bacteria.

The possibility of other causes of ulcers, notably malignancy (gastric cancer) needs to be kept in mind. This is especially true in ulcers of the greater (large) curvature of the stomach; most are also a consequence of chronic H. pylori infection.

If a peptic ulcer perforates, air will leak from the inside of the gastrointestinal tract (which always contains some air) to the peritoneal cavity (which normally never contains air). This leads to “free gas” within the peritoneal cavity. If the patient stands erect, as when having a chest X-ray, the gas will float to a position underneath the diaphragm. Therefore, gas in the peritoneal cavity, shown on an erect chest X-ray or supine lateral abdominal X-ray, is an omen of perforated peptic ulcer disease.

Endoscopic picture in peptic ulcer

Complications

Gastrointestinal bleeding is the most common complication. Sudden large bleeding can be life-threatening. It occurs when the ulcer erodes one of the blood vessels, such as the gastroduodenal artery.

Perforation (a hole in the wall) often leads to catastrophic consequences. Erosion of the gastro-intestinal wall by the ulcer leads to spillage of stomach or intestinal content into the abdominal cavity. Perforation at the anterior surface of the stomach leads to acute peritonitis, initially chemical and later bacterial peritonitis. The first sign is often sudden intense abdominal pain. Posterior wall perforation leads to bleeding due to involvement of gastroduodenal artery that lies posterior to the 1st part of duodenum.

Рerforation and Penetration are when the ulcer continues into adjacent organs such as the liver and pancreas.

Gastric outlet obstruction is the narrowing of pyloric canal by scarring and swelling of gastric antrum and doudenum due to peptic ulcers. Patient often presents with severe vomiting without bile.

Описание: 162_gastro

Cancer is included in the differential diagnosis (elucidated by biopsy), Helicobacter pylori as the etiological factor making it 3 to 6 times more likely to develop stomach cancer from the ulcer.

A major causative factor (60% of gastric and up to 90% of duodenal ulcers) is chronic inflammation due to Helicobacter pylori that colonizes the antral mucosa. The immune system is unable to clear the infection, despite the appearance of antibodies. Thus, the bacterium can cause a chronic active gastritis (type B gastritis), resulting in a defect in the regulation of gastrin production by that part of the stomach, and gastrin secretion can either be increased, or as in most cases, decreased, resulting in hypo- or achlorhydria. Gastrin stimulates the production of gastric acid by parietal cells. In H. pylori colonization responses to increased gastrin, the increase in acid can contribute to the erosion of the mucosa and therefore ulcer formation. Studies in the varying occurrence of ulcers in third world countries despite high H. pylori colonization rates suggest dietary factors play a role in the pathogenesis of the disease.

Another major cause is the use of NSAIDs. The gastric mucosa protects itself from gastric acid with a layer of mucus, the secretion of which is stimulated by certain prostaglandins. NSAIDs block the function of cycloxygenase 1 (cox-1), which is essential for the production of these prostaglandins. COX-2 selective anti-inflammatories preferentially inhibit cox-2, which is less essential in the gastric mucosa, and roughly halve the risk of NSAID-related gastric ulceration.

The incidence of duodenal ulcers has dropped significantly during the last 30 years, while the incidence of gastric ulcers has shown a small increase, mainly caused by the widespread use of NSAIDs. The drop in incidence is considered to be a cohort-phenomenon independent of the progress in treatment of the disease. The cohort-phenomenon is probably explained by improved standards of living which has lowered the incidence of H. pylori infections.

Although some studies have found correlations between smoking and ulcer formation, others have been more specific in exploring the risks involved and have found that smoking by itself may not be much of a risk factor unless associated with H. pylori infection.Some suggested risk factors such as diet, and spice consumption, were hypothesized as ulcerogens (helping cause ulcers) until late in the 20th century, but have been shown to be of relatively minor importance in the development of peptic ulcers. Caffeine and coffee, also commonly thought to cause or exacerbate ulcers, have not been found to affect ulcers to any significant extent. Similarly, while studies have found that alcohol consumption increases risk when associated with H. pylori infection, it does not seem to independently increase risk, and even when coupled with H. pylori infection, the increase is modest in comparison to the primary risk factor.

Gastrinomas (Zollinger Ellison syndrome), rare gastrin-secreting tumors, also cause multiple and difficult-to-heal ulcers.

Нe diagnosis is mainly established based on the characteristic symptoms. Stomach pain is usually the first signal of a peptic ulcer. In some cases, doctors may treat ulcers without diagnosing them with specific tests and observe whether the symptoms resolve, thus indicating that their primary diagnosis was accurate.

A gastroscopy, is carried out on patients in whom a peptic ulcer is suspected. By direct visual identification, the location and severity of an ulcer can be described. Moreover, if no ulcer is present, EGD can often provide an alternative diagnosis.

The diagnosis of Helicobacter pylori can be made by:

– Urea breath test (noninvasive and does not require EGD);

– Direct culture from an EGD biopsy specimen; this is difficult to do, and can be expensive. Most labs are not set up to perform H. pylori cultures;

– Direct detection of urease activity in a biopsy specimen by rapid urease test;

– Measurement of antibody levels in blood (does not require EGD). It is still somewhat controversial whether a positive antibody without EGD is enough to warrant eradication therapy;

– Stool antigen test;

Histological examination and staining of an EGD biopsy.

The possibility of other causes of ulcers, notably malignancy (gastric cancer) needs to be kept in mind. This is especially true in ulcers of the greater (large) curvature of the stomach; most are also a consequence of chronic H. pylori infection.

Younger patients with ulcer-like symptoms are often treated with antacids or H2 antagonists before EGD is undertaken. Bismuth compounds may actually reduce or even clear organisms, though the warning labels of some bismuth subsalicylate products indicate that the product should not be used by someone with an ulcer.^[21]

Patients who are taking NSAIDs may also be prescribed a prostaglandin analogue (Misoprostol) in order to help prevent peptic ulcers, which are a side-effect of the NSAIDs.

When H. pylori infection is present, the most effective treatments are combinations of 2 antibiotics (e.g. Clarithromycin, Amoxicillin, Tetracycline, Metronidazole) and 1 proton pump inhibitor (PPI), sometimes together with a bismuth compound. In complicated, treatment-resistant cases, 3 antibiotics (e.g. amoxicillin + clarithromycin + metronidazole) may be used together with a PPI and sometimes with bismuth compound. An effective first-line therapy for uncomplicated cases would be Amoxicillin + Metronidazole + Pantoprasole (a PPI). In the absence of H. pylori, long-term higher dose PPIs are often used.

Treatment of H. pylori usually leads to clearing of infection, relief of symptoms and eventual healing of ulcers. Recurrence of infection can occur and retreatment may be required, if necessary with other antibiotics. Since the widespread use of PPI’s in the 1990s, surgical procedures (like “highly selective vagotomy”) for uncomplicated peptic ulcers became obsolete.

Perforated peptic ulcer is a surgical emergency and requires surgical repair of the perforation. Most bleeding ulcers require endoscopy urgently to stop bleeding with cautery, injection, or clipping.

Ranitidine and famotidine, which are both H2 antagonists, provide relief of peptic ulcers, heartburn, indigestion and excess stomach acid and prevention of these symptoms associated with excessive consumption of food and drink. Ranitidine and famotidine are available over the counter at pharmacies, both as brand-name drugs and as generics, and work by decreasing the amount of acid the stomach produces allowing healing of ulcers.

Enteritis

Enteritis is inflammation of the small intestine.

Causes, incidence, and risk factors:

Enteritis is usually caused by eating or drinking substances that are contaminated with bacteria or viruses. The germs settle in the small intestine and cause inflammation and swelling, which may lead to abdominal pain, cramping, diarrhea, fever, and dehydration.

Enteritis may also be caused by:

– An autoimmune condition such as Crohn`s disease

– Certain drugs, including ibuprofen, naproxen sodium, and cocaine

– Damage from radiation therapy

The inflammation can also involve the stomach (gastritis) and large intestine (colitis).

Risk factors include recent family illness with intestinal symptoms, recent travel, or exposure to untreated or contaminated water.

Types of enteritis include:

– Bacterial gastroenteritis

– Campylobacter enteritis

E. coli enteritis

– Food poisoning

– Radiation enteritis

– Salmonella enteritis

– Shigella enteritis

– Staph aureus food poisoning

Symptoms:

The symptoms may begin hours to days after you become infected. Symptoms may include:

Abdominal pain

Diarrhea – acute and severe

Loss of appetite

Vomiting – rare

Signs and tests:

A stool culture may be done to determine the specific type of infection, however, this test may not always identify the bacteria causing the illness.

Unusual case of subacute intestinal obstruction due to eosinophilic enteritis with enteroliths

Campylobacter jejuni Enteritis

Treatment:

Mild cases usually need no treatment.

Antidiarrheal medication may delay the organism from leaving the digestive tract, and therefore may not be recommended.

Rehydration with electrolyte solutions may be necessary if dehydration occurs.

Persons with diarrhea (especially young children) who are unable to drink fluids because of nausea may need medical care and fluids through a vein.

Expectations (prognosis):

Symptoms usually go away without treatment in a few days.

Complications:

Dehydration

Prolonged diarrhea

Prevention:

– Always wash hands after using the toilet and before eating or preparing food or drink. You may also clean your hands with a 60% alcohol based product.

– Avoid drinking from unknown sources, such as streams and outdoor wells, without boiling the water first.

– Use only clean utensils for eating or handling foods, especially when handling eggs and poultry.

– Cook food completely and properly.

– Store food appropriately in coolers.

CROHN’S DISEASE –

A nonspecific chronic transmural inflammatory disease that most commonly affects the distal ileum and colon but may occur in any part of the GI tract.

Etiology and Epidemiology

The fundamental cause of Crohn’s disease is unknown. Evidence suggests that, a genetic predisposition leads to an unregulated intestinal immune response to an environmental, dietary, or infectious agent. However, no inciting antigen has been identified. Cigarette smoking seems to contribute to the development or exacerbation of Crohn’s disease.

Over the past few decades, incidence of Crohn’s disease has increased in Western populations of Northern European and Anglo-Saxon ethnic derivation, third-world populations, blacks, and Latin Americans. The disease occurs about equally in both sexes and is more common among Jews. Approximately one of six patients has at least one first-degree relative with the same disease or, less frequently, with ulcerative colitis. Most cases begin in patients < 30 yr, with the peak incidence in those aged 14 to 24 years.

Pathology

The earliest mucosal lesion of Crohn’s disease is crypt injury in the form of inflammation (cryptitis) and crypt abscesses, which progress to tiny focal aphthoid ulcers, usually located over nodules of lymphoid tissue. In some cases, these lesions regress; in others, the inflammatory process evolves with influx and proliferation of macrophages and other inflammatory cells, occasionally forming noncaseating granulomas with multinucleated giant cells.

Transmural spread of inflammation leads to lymphedema and bowel wall thickening, which may eventually result in extensive fibrosis. Development of patchy mucosal ulcers and longitudinal and transverse ulcers with intervening mucosal edema frequently creates a characteristic cobblestoned appearance. The attached mesentery is thickened and lymphedematous; mesenteric fat typically extends onto the serosal surface of the bowel. Mesenteric lymph nodes often enlarge. Transmural inflammation, deep ulceration, edema, muscular proliferation, and fibrosis cause deep sinus tracts and fistulas, mesenteric abscesses, and obstruction, which are the major local complications. Granulomas can occur in lymph nodes, peritoneum, the liver, and all layers of the rowel wall and are occasionally seen at laparotomy or laparoscopy as miliary nodules. Although pathognomonic, granulomas are absent in up to 50 % of patients and are therefore not essential to diagnose Crohn’s disease. They appear to have no definitive bearing on the clinical course.

Segments of diseased bowel are characteristically sharply demarcated from adjacent normal bowel (“skip areas”)—thus the name regional enteritis. Of all cases of Crohn’s disease, about 33% involve the ileum ileitis); about 45% involve the ileum and colon (ileocolitis), with a predilection for the right side of the colon; and about 15 % involve the colon alone (granulomatous colitis). Occasionally, the entire small bowel is involved jejunoileitis), and rarely, the stomach, duodenum, or esophagus. The perianal region is also affected in 1/4 to 1/3 of cases.

The spectrum of Crohn disease presentations includes (a) gastroduodenitis (7% of patients), (b, c) jejunoileitis and ileitis (33% of patients), (d) ileocolitis (45% of patients), and (e) colitis (15% of patients).

Symptoms, Signs, and Complications

Chronic diarrhea with abdominal pain, fever, anorexia, weight loss, and a right lower quadrant mass or fullness are the most common presenting features. However, many patents are first seen with an acute abdomen that simulates acute appendicitis or intestinal obstruction. About 1/3 of patients have a history of perianal disease, especially fissures and fistulas, which are sometimes the most prominent or even initial complaint. In children, extraintestinal manifestations frequently predominate over GI symptoms. Arthritis, fever of unknown origin, anemia, or growth retardation may be a presenting symptom, and abdominal pain or diarrhea may be absent.

The most common patterns of Crohn’s disease pathology are (1) inflammation characterized by right lower quadrant abdominal pain and tenderness; (2) recurrent partial obstruction caused by intestinal stenosis and leading to severe colic, abdominal distention, constipation, and vomiting; (3) diffuse jejunoileitis, with inflammation and obstruction resulting in malnutrition and chronic debility; and (4) abdominal fistulas and abscesses, usually late developments, often causing fever, painful abdominal masses, and generalized wasting.

Enterocutaneous fistulae in Chrohn’s disease

Obstruction; development of enteroenteric, enterovesical, retroperitoneal, or enterocutaneous fistulas; and abscess formation are common complications of inflammation. Intestinal bleeding, perforation, and small-bowel cancer develop rarely. When the colon alone is affected, the clinical picture may be indistinguishable from that of ulcerative colitis.

Endoscopic spectrum of Crohn disease includes (a) aphthous ulcerations amid normal colonic mucosal vasculature; (b) deeper, punched-out ulcers in ileal mucosa; (c) a single colonic linear ulcer; and (d) deep colonic ulcerations forming a stricture.

Extraintestinal manifestations are categorized as:

Complications that usually parallel the activity of the intestinal disease and possibly represent acute immunologic or microbiologic concomitants of the bowel inflammation: peripheral arthritis, episcleritis, aphthous stomatitis, erythema nodosum, and pyoderma gangrenosum. These manifestations may be reported by > 1/3 of patients hospitalized with inflammatory bowel disease. They are twice as common when colitis is present as when disease is confined to the small bowel. When extraintestinal manifestations occur, they are multiple in about 1/3 of patients. Disorders associated with inflammatory bowel disease but running an independent course: ankylosing spondylitis, sacroiliitis, uveitis, and primary sclerosing cholangitis. The genetic association of these syndromes and of Crohn’s disease (and ulcerative colitis) with the HLA antigen B27 is discussed under the extracolonic complications of ulcerative colitis, below. Complications that relate directly to disrupted bowel physiology: kidney stones from disorders of uric acid metabolism, impaired urinary dilution and alkalinization, and excessive dietary oxalate absorption; urinary tract infections, especially with fistulization into the urinary tract; and hydroureter and hydronephrosis from ureteral compression by retroperitoneal extension of the intestinal inflammatory process. Other bowel-related complications include malabsorption, especially in the face of extensive ileal resection or bacterial overgrowth from chronic small-bowel obstruction or fistulization; gallstones, related to impaired ileal reabsorption of bile salts; and amyloidosis, secondary to long-standing inflammatory and suppurative disease. Thromboembolic complications may occur, usually with severe disease activity, as a result of hypercoagulability associated with altered levels of clotting factors and platelet abnormalities.

Diagnosis

Crohn’s disease should be suspected in a patient with the inflammatory or obstructive symptoms described above and in a patient without prominent GI symptoms but with perianal fistulas or abscesses or with otherwise unexplained arthritis, erythema nodosum, fever, anemia, or stunted growth (in a child).

Laboratory findings are nonspecific and may include anemia, leukocytosis, hypoalbuminemia, and increased levels of acute-phase reactants reflected in elevated ESR, C-reactive protein, or orosomucoids. Elevated alkaline phosphatase and γ-glutamyltranspeptidase accompanying colonic disease often reflect primary sclerosing cholangitis.

Definitive diagnosis is usually made by x-ray. Barium enema x-ray may show reflux of barium into the terminal ileum with irregularity, nodularity, stiffness, wall thickening, and a narrowed lumen.

X-ray showing abnormal terminal ileum in Crohn’s disease

A small-bowel series with spot x-rays of the terminal ileum usually most clearly shows the nature and extent of the lesion. An upper GI series without small-bowel follow-through usually misses the diagnosis.

In advanced cases, the string sign may be seen with marked ileal strictures and separation of bowel loops. In earlier cases, x-ray diagnosis may sometimes be difficult, but air double-contrast barium enema and enteroclysis may show superficial aphthous and linear ulcers. In questionable cases, colonoscopy and biopsy may help confirm the diagnosis of Crohn’s colitis and allow direct visualization and biopsy of the terminal ileum. Upper GI endoscopy may identify gastroduodenal involvement in Crohn’s disease patients with upper GI symptoms. Although CT can detect extramural complications (eg, fistulas, abscesses, masses), it is not routinely needed for initial diagnosis. Ultrasound may help delineate gynecologic pathology in women with lower abdominal and pelvic pain.

Prognosis

Although spontaneous remission or medical therapy may result in a prolonged asymptomatic interval, established Crohn’s disease is rarely cured but instead is characterized by intermittent exacerbations. In the absence of surgical intervention, the disease never extends into new areas of small bowel beyond its initial distribution at first diagnosis. With judicious medical and, where appropriate, surgical therapy, most patients with Crohn’s disease function well and adapt successfully. Disease-related mortality is very low and continues to decrease.

GI cancer, including cancer of the colon and small bowel, is the leading cause of Crohn’s disease-related death. Patients with long-standing Crohn’s disease of the small bowel are at increased risk of small-bowel cancer, with bowel in continuity as well as in bypassed loops. Furthermore, patients with Crohn’s disease of the colon have a long-term risk of colorectal cancer equal to that of ulcerative colitis, given the same extent and duration of disease.

Approximately 70% of Crohn’s disease patients ultimately require surgery. Furthermore, Crohn’s disease is likely to recur even after resection of all clinically apparent disease.

The typical perianal skin tag of CD differs from the typical hemorrhoid tag

Treatment

No cure is known. Cramps and diarrhea may be relieved by oral administration up to 4 times a day (ideally before meals) of anticholinergics, diphenoxylate 2.5 to 5 mg, loperamide 2 to 4 mg, deodorized opium tincture 0.5 to 0.75 mL (10 to 15 drops), or codeine 15 to 30 mg. Such symptomatic treatments are safe, except in cases of severe, acute Crohn’s colitis, which may progress to toxic megacolon as in ulcerative colitis. Hydrophilic mucilloids (eg, methylcellulose or psyllium preparations) sometimes help prevent anal irritation by increasing stool firmness.

Sulfasalazine primarily benefits patients with mild to moderate colitis and ileocolitis but has some efficacy in ileitis as well. It may also maintain remission, although it has not been proven to prevent recurrence after surgery. (For details of sulfasalazine therapy, see Treatment under Ulcerative Colitis.)

Mesalamine (5-aminosalicylic acid), the active moiety of sulfasalazine, is available in several oral formulations designed to release in various segments of the small bowel and colon. It is especially useful in patients who are intolerant of sulfasalazine. In doses of up to 4 g/day, mesalamine is effective for inducing and maintaining remission and is showing considerable promise for inhibiting postoperative recurrence.

Corticosteroid therapy treats the acute stages of Crohn’s disease by dramatically reducing fever and diarrhea, relieving abdominal pain and tenderness, and improving the appetite and sense of well-being. Large doses of oral prednisone, 40 to 60 mg/day, should be given initially. The equivalent dose of hydrocortisone (200 to 300 mg) may be given by continuous IV drip to hospitalized patients with severe disease. The daily dose of prednisone is gradually reduced after a satisfactory response so that, after 1 or 2 mg, it is ≤ 10 mg.

Although as little as 5 or 10 mg/day of prednisone may help control symptoms in some patients, long-term therapy often does more harm than good. Corticosteroids should be avoided when obvious infections (eg, fistulas, abscesses) are present. In uncertain cases (eg, those with a tender, inflammatory mass), antibiotics should be given concurrently.

The new topically active corticosteroid budesonide can be given orally or as an enema and has low systemic bioavailability and thus reduced adrenal suppression. Controlled-release budesonide given orally induces remissions with somewhat fewer side effects than prednisolone, but it is not as effective as the conventional corticosteroid and seems no better than placebo in preventing relapses beyond 6 monthes.

Broad-spectrum antibiotics that are active against enteric gram-negative and anaerobic flora may help reduce disease activity in many patients but are most consistently effective for suppurative complications (eg, infected; fistula, abscess). Metronidazole 1 to 1.5 g/day is beneficial, especially in Crohn’s colitis, and is particularly useful for treating perianal lesions. Neuropathy manifested chiefly by paresthesias is a common, potentially serious side effect of long-term use; it is usually reversible when the drug is stopped. There is a high incidence of relapse after discontinuing the drug. Among other broad-spectrum antibiotics, ciprofloxacin has shown particular promise, but the results of multidrug antituberculous regimens have been mixed.

Immunomodulating drugs, particularly the antimetabolites azathioprine and 6-mercaptopurine, are effective as long-term therару. Azathioprine 2.0 to 3.5 mg/kg/day or 6- mercaptopurine 1.5 to 2.5 mg/kg/day orally significantly improves overall clinical status, decreases corticosteroid requirements, heals fistulas, and maintains remission for many years. However, these drugs often do not produce clinical benefits for 3 to 6 monthes and side effects of allergy, pancreatitis, and leukopenia must be watched for.

Methotrexate 25 mg IM or subcutaneously once/week benefits some patients with severe corticosteroid-refractory disease, even those who have failed to respond to azathioprine or 6-mercaptopurine. High-dose cyclosporine has demonstrated benefits in inflammatory and fistulous disease, but its long-term use is contraindicated by multiple toxicities. Infliximab, a monoclonal antibody that inhibits tumor necrosis factor, can be given I/V for moderate to severe Crohn’s disease (especially fistulous disease) refractory to other treatments; long-term efficacy and side effect remain to be determined. Other potential immunoregulatory treatments include inter-leukin-1 blockers, antibody to interleukin-12, anti-CD4 antibodies, adhesion molecule inhibitors, and down-regulatory cytokines These many experimental treatment approaches attest to the inadequacy of current: drug therapy for Crohn’s disease. Some patients with intestinal obstruction or fistulas have improved with elemental diets or hyperalimentation, at least over a short term, and children often achieve increased rates of growth. Thus, these measures may serve as preoperative or adjunc-tive therapy and may even be valuable as primary therapy.

Surgery.

Surgery is usually necessary for recurrent intestinal obstruction or intractable fistulas oг abscesses. Resection of the grossly involved bowel may ameliorate symptoms indefinitely but does not cure the disease. Sulfasalazine has not been shown to prevent postoperative recurrence, but mesalamine > 2 g/day may be effective. The recurrence rate, defined by endoscopic lesions at the anastomotic site, is > 70% at 1 year and > 85% at 3 years; defined by clinical symptoms, it is about 25 to 30% at 3 years and 40 to 50% at 5 years. Ultimately, further surgery is required in nearly 50% of cases. However, recurrence rates appear to be reduced by early postoperative prophylaxis with mesalamine, metronidazole, or possibly 6-mercaptopurine. Moreover, when surgery has been performed for specific complications or failure of medical therapy, most patients experience an improved quality of life.

Colitis

Colitis is a term used to describe inflammation of the colon. There are a variety of causes of colitis including infections, poor blood supply, and autoimmune reactions.

The colon is located in the abdominal cavity and is divided into the following parts: the cecum, the ascending colon, the transverse, the descending colon, the sigmoid, the rectum, and the anus. The right colon includes the cecum and ascending colon. The left colon includes the transverse segment to the sigmoid.

The colon (large bowel or large intestine) is responsible for collecting and storing the waste products of digestion. It is a long muscular tube that pushes undigested food towards the anus for eventual elimination as a bowel movement. Food is digested in the stomach into a liquid slurry that passes through the small intestine where the nutrients are absorbed into the body for use. When the liquid mixture enters the colon, it mixes with mucus and normal bacteria that reside in the colon. The wall of the colon has numerous layers. There is a smooth muscle layer that wraps the outside and is responsible for squeezing the undigested food through the length of the colon. The inner layer, or mucosa, comes into contact with the fluid and allows the absorption of water and electrolites, which helps to solidify the feces (poop). The mucosal layer is where the colon inflammation occurs and is responsible for the symptoms of colitis.

As with any other organ, the colon has a blood supply with arteries delivering oxygen rich blood and nutrients to it, and veins that drain carbon dioxide and lactic acid from it. Diseases that decrease blood supply can cause inflammation of the colon.

Colitis Causes

Inflammation of the colon can be caused by a variety of illnesses and infections. Some of the most common causes are discussed below.

Infectious Colitis

Viruses and bacteria can cause colon infections. Most are food-borne illnesses or “food poisoning.” Common bacterial causes include Shigella, E Coli, Salmonella and Campylobacter. These infections may cause bloody diarrhea and can result in significant dehydration.

Parasites such as giardia can cause significant diarrhea. The parasite can enter the body when infected water is swallowed. The source may be from recreational water such as rivers, lakes, and swimming pools. It may also be contaminated from a water well or cistern.

Pseudomembranous colitis is caused by the bacteria Clostridium difficile (C. difficile). This disorder is often seen in patients who have recently been taking antibiotics for an infection. The antibiotic alters the normal bacteria present in the colon and allows an overgrowth of the Clostridium bacteria. Clostridium bacteria produce a toxin that causes diarrhea. This is an infection, and often there is a fever present. The diarrhea is usually not bloody.

Ischemic Colitis

The arteries that supply blood to the colon are like any other artery in the body. They have the potential to become narrow due to atherosclerosis (just like blood vessels in the heart, which can cause angina, or narrowed vessels in the brain can cause a stroke). When these arteries become narrow, the colon may loose its blood supply and become inflamed.

The colon can also lose its blood supply for mechanical reasons. A couple of examples include volvolus, where the bowel twists on itself, or an incarcerated hernia, where a portion of the colon gets trapped in an outpouching of the abdominal wall, which prevents blood from flowing to the affected portion.

In individuals who are at risk for decreased blood flow to the colon, ischemic colitis can occur if the blood pressure falls. This may occur with dehydration, anemia, or shock.

Ischemia or lack of blood supply causes significant pain, fever, and bloody bowel movements.

Inflammatory Bowel Disease

There are two types of inflammatory bowel disease, ulcerative colitis, and Crohn’s disease.

Ulcerative colitis is thought to be an autoimmune illness in which the body’s immune system attacks the colon and causes inflammation. Ulcerative colitis begins in the rectum and may gradually spread throughout the colon. The signs and symptoms include abdominal pain and bloody bowel movements.

Crohn`s disease may involve any part of the digestive tract from the esophagus and stomach, through to the small and large intestine all the way to the rectum. It often has skip lesions, that is diseased areas are interspersed with healthy areas of tissue.

Microscopic Colitis

Two diseases make up this group of colon inflammation, collagenous colitis and lymphocytic colitis. In these diseases, the inflammation is caused when the colon wall becomes engorged with either collagen or lymphocytes. Watery, non-bloody diarrhea is the most common symptom.

This is an uncommon illness that is seen more frequently in older women. The cause is unknown but an autoimmune potential may exist.

Chemical Colitis

If chemicals are instilled into the colon, inflammation and damage can occur. One of the complications of an enema is inflammation of the mucosal lining of the colon caused by harsh chemicals.

Colitis Symptoms

Symptoms of colitis will depend upon the type of colitis that is present, but in general, colitis most often is associated with abdominal pain and diarrhea.

Other symptoms of colitis that may or may not be present include

Blood in the bowel movement may or may not be present. Diarrhea can sometimes cause hemorrhoids, which can bleed. However, blood with a bowel movement is not normal and the affected person should contact their health care practitioner or seek other medical care.

Tenesmus may exist; this is the constant urge to have a bowel movement.

The abdominal pain may come in waves, building to diarrhea, and then waning.

There may be constant pain.

Fever, chills, and other signs of infection and inflammation may be present depending upon the cause of colitis.

Diarrhea is a common symptom of colitis, and most episodes resolve in a matter of hours.

Medical care should be accessed if any of the following conditions exist:

persistent diarrhea, dehydration (symptoms of dehydration include lightheadedness; weakness; decreased urination; dry mouth, eyes, and skin; fever, significant abdominal pain, and/or blood in the bowel movement.

Colitis Diagnosis

The diagnosis of colitis begins with a thorough history by a physician or health care practitioner. Since the symptoms usually are abdominal pain and diarrhea, it is important to learn about the onset and duration of symptoms, and any other complaints or symptoms the patient may have. Since most causes of diarrhea are relatively benign and self-limiting, questions may be asked to search for some of the causes listed above.

An important concern is whether there is blood in the bowel movement (stool). While this may lead to the diagnosis of colitis, colon cancer is another important cause of blood in the stool, and this symptom should not be ignored (as mentioned previously, blood with a bowel movement or in the stool is not normal and should not be ignored).

Some questions asked of the patient may include:

1. the time of onset of symptoms,

2. the duration of pain,

3. the frequency of diarrhea, and

4. whether there are any other associated complaints.

Other questions may include lifestyle, especially if an infectious cause is being considered. Recent travel, unusual diet, or the use of noncommercial water (for example, drinking from a well or river water on a camping trip) may point the diagnosis to bacterial infections such as Shigella, Campylobacter,or parasite infections such as giardia. Recent use of antibiotics may direct the health care practitioner to consider Clostridium difficile as the cause.

The past medical history is also important to assess the risk factors for peripheral vascular disease or narrowing of the arteries. These include smoking, high blood pressure, high cholesterol, and diabetes. This may give direction to explore ischemic bowel as the cause for colitis.

Physical examination will focus on the abdomen. The physician will feel for areas of tenderness, for masses, or abnormally enlarged organs like the liver, spleen, and kidney.

While unpleasant, the rectal examination is of utmost importance. Using a finger, the physician feels inside the rectum, trying to find a mass or tumor. As well, the color and consistency of stool can be evaluated and if it is not grossly bloody, can be tested for occult blood (blood that is present but cannot be seen with the naked eye).

Vital signs are an important part of the physical examination. Temperature, blood pressure, pulse, and respiratory rate will help guide the direction of testing. If the vital signs are not stable, that is the blood pressure is low or the pulse rate too fast, a crisis may be imminent. The physician may need to intervene acutely and delay some of the diagnostic evaluation until the patient is stabilized. Orthostatic vital signs, where the blood pressure and pulse rate are taken both lying and standing may assist with detecting dehydration.

Laboratory

Blood testing will help assess the stability of the patient and look for potential issues associated with colitis.

A complete blood count (CBC) will assess the red blood cell count, the white blood cell count, and the number of platelets. The red blood cell count will help define the amount of bleeding. White blood cell counts elevate when the body is undergoing stress including the stress of infection. Platelets help blood to clot, so knowing the platelet number in a patient with bleeding is useful.

Electrolyte abnormalities can occur with diarrhea. Low sodium and potassium levels may be seen and may cause symptoms far removed from the initial colitis complaints.

Kidney function may be assessed by measuring the BUN (blood urea nitrogen) and creatinine levels..

Stool samples may be collected for culture, looking for infection as the cause of colitis. The history will assist the health care practitioner decide the tests to order and what cultures would be appropriate.

Colonoscopy

video Colonoscopy

If a specific cause of colitis is not readily apparent, then colonoscopy may be considered. A gastroenterologist will insert a long flexible camera into the anus and examine the full length of the colon. The appearance of the colon by itself may be enough to make the diagnosis. Biopsies (small pieces of tissue) may be taken from the lining of the colon and examined by a pathologist (a medical doctor specializing in the diagnosis of tissues) to help confirm the diagnosis. Microscopic colitis (lymphocytic and collagenous) can only be diagnosed with biopsy of the affected area.

Colonoscopy is an essential cancer screening test and is especially important for those patients who have had blood in their stool that cannot be explained by another diagnosis.

Imaging

Computerized tomography (CT) may be used to image the colon and the rest of the abdomen. Different types of colitis have distinctive patterns that may help a radiologist recognize a specific diagnosis. A CT scan may be ordered urgently if the history and physical examination performed by the health care practitioner leads to concern that an urgent or emergent problem exists that may require surgery

Typhlitis (Neutropenic Colitis)

On occasion a barium enema or other imaging tests may be used to evaluate the anatomy of the colon.

Colitis Treatment

Medical Treatment

The definitive treatment of colitis is dependent upon the cause. Many cases require little more than symptomatic care, including clear fluids to rest the bowel and medications to control pain. Some patients become acutely ill and will need intravenous (IV) fluids and other interventions to treat their illness.

Infections: Infections that cause diarrhea and colitis may or may not require antibiotics, depending upon the cause. Viral infections resolve with the supportive care of fluids and time. Some bacterial infections like Salmonella also do not need antibiotic therapy; the body is able to get rid of the infection on its own. Other bacterial infections like Clostridium difficile always require treatment with antibiotics.

IBD: Inflammatory bowel diseases (IBDs) like ulcerative colitis and Crohn’s disease, are often controlled by a combination of medications that are used in a step-wise approach. Initially, anti-inflammatory medications are used, and if these are less than successful, medications that suppress the immune system can be added. In the most severe cases, surgery may be required to remove all or parts of the colon and small intestine.

Ischemic colitis: Treatment of ischemic colitis is initially supportive, using intravenous fluids to rest the bowel and prevent dehydration. If adequate blood supply to the bowel isn’t restored, surgery may be required to remove parts of the bowel that have lost blood supply.

Diarrhea and abdominal pain: Most causes of colitis present with diarrhea and crampy abdominal pain. These symptoms are also found with mild illnesses like viral enteritis (inflammation of the colon). Initial treatment at home may include a clear fluid diet for 24 hours, rest, and acetaminophen (Tylenol) as needed for pain. Often symptoms resolve quickly and no further care is needed.

Loperamide (Imodium) is an effective medicine to control diarrhea. Acetaminophen or ibuprofen can be used for pain control.

Depending upon the cause of the colitis, medication may be prescribed to control or cure symptoms. Antibiotics may be helpful in colitis caused by some infections. Anti-inflammatory and immune suppression drugs can be used to control the symptoms of inflammatory bowel disease.

Colitis Surgery

Surgery may be required for ischemic colitis, Crohn’s disease, or ulcerative colitis, depending upon the severity of the illness and the response to more conservative non-surgical treatments.

In ulcerative colitis, removal of the colon cures the disease.

For other illnesses, usually the part of the colon that is at risk or damaged is removed.

Colitis Other Therapy

Diet: A clear fluid/liquid diet allows the colon to rest, since the fluid is absorbed in the stomach and none is passed into the colon to be processed as stool. Hydration: Adequate hydration is important because an individual can lose a significant amount of fluid with each diarrheal bowel movement. Aside from the daily fluid requirements, this excess loss needs to be replaced, otherwise dehydration will occur and potentially worsen the symptoms of abdominal pain and cramping.

IV fluids: Intravenous (IV) fluid may be required, especially if the patient cannot drink enough fluids by mouth. For some illnesses like ischemic colitis, in which blood flow to the bowel is already compromised, adequate hydration is a key element in treatment. Electrolyte replacement may be required in some patients who have significant dehydration.

For most individuals, infectious colitis is an isolated event, and once the symptoms and infection have cleared, no further care is needed.

For those with inflammatory bowel disease, the goal becomes symptom control instead of disease cure, since symptoms can occur over the course of a lifetime. Once the initial diagnosis is made, continued care with a primary care d octor and a gastroenterologist will be necessary. A long-term relationship with this treatment team may be able to lessen the frequency and intensity of future disease flare-ups.

Ischemic bowel disease does not happen in isolation, and a person that has poor circulation to the bowel likely has poor circulation elsewhere. Continued monitoring may be necessary to minimize the risk of future episodes.

Colitis Prevention

Infectious colitis remains a common ailment worldwide, affecting millions daily. The lack of clean drinking water and adequate sanitation are the main causes, leading to thousands of potentially preventable deaths each day. In developed countries, poor hand washing and poor kitchen hygiene allow the potential for infectious colitis. Prevention lies in cleanliness.

Inflammatory bowel diseases are difficult to prevent at the present time. The likely causes are heredity and perhaps an abnormal auto-immune response to an unknown stimulus in the body.

Since ischemic colitis is caused by narrowing of the blood vessels to the bowel, decreasing the risks for other types of circulatory problems such as peripheral vascular disease, heart attack, and stroke will also decrease the risk for ischemic colitis. The common risk factors are smoking and poor control of high blood pressure, high cholesterol levels, and diabetes.

Understanding the cause of a specific colitis has allowed more targeted therapy. For example, observation has replaced surgery to remove the colon as standard therapy for some people with ulcerative colitis, and limiting the use of antibiotics has decreased the number of resistant bacteria that can cause infectious diarrhea.

Worldwide, initiatives to increase access to clean water and adequate hygiene is perhaps the most important way to save lives.

ULCERATIVE COLITIS –

A chronic, inflammatory, and ulcerative disease arising in the colonic mucosa, characterized most often by bloody diarrhea.

Etiology and Epidemiology.

The cause of ulcerative colitis is unknown. Evidence suggests that a genetic predisposition leads to an unregulated intestinal immune response to an environmental, dietary, or infectious agent. However, no inciting antigen has been identified. The evidence for a specific microbial etiology for ulcerative colitis is even less convincing than for Crohn’s disease, and the familial tendency is less pro-nounced. Unlike in Crohn’s disease, current cigarette smoking appears to decrease risk. Like Crohn’s disease, ulcerative colitis may afflict people at any age, but the age-onset curve shows a bimodal distribution, with a major peak at ages 15 to 30 and a second smaller peak at ages 50 to 70; however, this later peak may include some cases of ischemic colitis.

Pathology.

Pathologic changes begin with degeneration of the reticulin fibers beneath the mucosal epithelium, occlusion of the subepithelial capillaries, and progressive infiltration of the lamina propria with plasma cells, eosinophils, lymphocytes, mast cells, and polymorphonuclear leukocytes. Crypt abscesses, epithelial necrosis, and mucosal ulceration ultimately develop. The disease usually begins in the rectosigmoid and may extend proximally, eventually involving the entire colon, or it may involve most of the large bowel at once. Ulcerative proctitis, which is localized to the rectum, is a very common and more benign form of ulcerative colitis. It is often refractory to treatment and undergoes late proximal spread in about 20 to 30% of cases.

Symptoms and Signs

Bloody diarrhea of varied intensity and duration is interspersed with asymptomatic intervals. Usually an attack begins insidiously, with increased urgency to defecate, mild lower abdominal cramps, and blood and mucus in the stools. However, an attack may be acute and fulminant, with sudden violent diarrhea, high fever, signs of peritonitis, and profound toxemia. Some cases develop following a documented infection (eg, amebiasis, bacillary dysentery).

When ulceration is confined to the rectosigmoid, the stool may be normal or hard and dry, but rectal discharges of mucus loaded with RBCs and WBCs accompany or occur between bowel movements. Systemic symptoms are mild or absent. If ulceration extends proximally, stools become looser and the patient may have > 10 bowel movements/day, often with severe cramps and distressing rectal tenesmus, without respite at night. The stools may be watery, may contain mucus, and frequently consist almost entirely of blood and pus. Malaise, fever, anemia, anorexia, weight loss, leukocytosis, hypoalbuminemia, and elevated ESR may be present with extensive active ulcerative colitis.

Complications

Bleeding is the most common local complication. Another particularly severe complication, toxic colitis, occurs when transmural extension of ulceration results in localized ileus and peritonitis. As toxic colitis progresses, the colon loses muscular tone and begins to dilate within hours or days. Plain x-rays of the abdomen show intraluminal gas accumulated over a long, continuous, paralyzed segment of colon—a result of lost muscle tone.

Toxic megacolon (or toxic dilation) exists when the diameter of the transverse colon exceeds 6 cm. The severely ill patient has a fever to 40° C (104° F), leukocytosis, abdominal pain, and rebound tenderness. This condition usually occurs spontaneously in the course of especially severe colitis, but some cases may be precipitated by overzealous use of narcotic or anticholinergic antidiarrheal drugs. Treatment must be given in the early stages, preferably before full-blown megacolon occurs, to avert dangerous complications (eg, perforation, generalized peritonitis, septicemia). With prompt, effective treatment, the mortality rate can be held at < 4% but may be > 40% if perforation occurs.

Major perirectal complications, such as those in granulomatous colitis (eg, fistulas, abscesses), do not occur.

The incidence of colon cancer is increased when the entire colon is involved and the disease lasts for > 10 yr, independent of disease activity. After 10 yr, the cancer risk in extensive colitis appears to be about 0.5 to 1%/yr. Although cancer incidence is highest in cases of universal ulcerative colitis, the risk is significantly increased with any extent of ulcerative colitis above the sigmoid. There is probably no higher absolute cancer risk among patients with childhood-onset colitis, independent of the longer duration of disease. The long-term survival after diagnosis of colitis-related cancer is about 50%, a figure comparable to that for colorectal cancer in the general population.

Regular colonoscopic surveillance, preferably during remission, is advised for patients whose disease duration (as 8 to 10 yr) and extent (beyond rectosigmoidal) place them at high risk of developing colon cancer. Endoscopic biopsies should be taken throughout the colon and reviewed by an experienced pathologist. Any grade of definite, confirmed dysplasia is a strong indication for colectomy because the likelihood of concomitant or imminent colorectal cancer may be as high as 80 %. In such cases, corroboratory pathologic interpretation is important to distinguish between definite neoplas- tic dysplasia and reactive or regenerative atypia secondary to inflammation. However delaying colectomy in favor of repeated follow-up surveillance is unwise if dysplasia is unequivocal. Pseudopolyps have no prognostic significance but may be difficult to distinguish from neoplastic polyps; thus, any suspicious polyp should undergo excision biopsy.

Extracolonic problems include peripheral arthritis, ankylosing spondylitis, sacroiliitis, anterior uveitis, erythema nodosum, pyoderma gangrenosum, episcleritis, and in children, retarded growth and development. Peripheral arthritis, skin complications, and episcleritis often fluctuate with the colitis whereas spondylitis, sacroiliitis, and uveitis usually follow a course independent of the bowel disease. Most patients with spinal or sacroiliac involvement also have evidence of uveitis, and vice versa.These latter conditions may precede the colitis by many years and tend to occur more commonly in persons with the HLA-B27 antigen.

Erythema nodosum on the skin

Pyоderma gangrenosum seen in UC

Episcleritis in UC

Minor changes in liver function tests are common, but clinically apparent liver disease occurs in only 3 to 5% of patients. Liver disease may manifest as fatty liver or more seriously as autoimmune hepatitis, primary sclerosing cholangitis, or cirrhosis. Primary sclerosing cholangitis (PSC) occurs in 5% of ulcerative colitis patients, most commonly in those who were young when the colitis began. PSC may precede symptomatic ulcerative colitis by many years and is mort reliably diagnosed by endoscopic retrograd-cholangiography than by liver biopsy. Some investigators believe that signs of subclinics ulcerative colitis, if systematically sought, could be found in all patients with PSC. Alate complication of ulcerative colitis-associated PSC is cancer of the biliary tract which may appear even 20 yr after colectomy. More than 50% of PSC and cholangiocarcinoma cases in Western countries occur in patients with Crohn’s disease or ulcerative colitis.

Diagnosis

The history and stool examination permit a presumptive diagnosis of ulcerative colitis that should always be confirmed by sigmoidoscopy, which provides a direct, immediate indication of disease activity. Total colonoscopy is not usually necessary before treatment and may be hazardous in active stages because of the risk of perforation. In early cases, the mucous membrane is finely granular and friable, with loss of the normal vascular pattern and often with scattered hemorrhagic areas; minimal trauma (friability) causes bleeding in multiple pinpoint spots.

VIDEO (Colonoscopy. Ulcerative colitis)

The endoscopic spectrum of ulcerative colitis includes (a) mucosal edema, erythema, loss of vasculature; (b) granular mucosa with pinpoint ulceration and friability; (c) regenerated (i.e., healed) mucosa with distorted mucosal vasculature; and (d) regenerated mucosa with typical postinflammatory pseudopolyps

The mucosa soon breaks down into a red, spongy surface dotted with many tiny blood- and pus-oozing ulcers. As the mucosa becomes progressively involved, the inflammation and hemorrhage extend into the bowel muscle. Large mucosal ulcers with copious purulent exudate characterize severe disease. Islands of relatively normal or hyperplastic inflammatory mucosa (pseudo-polyps) project above areas of ulcerated mucosa. Biopsies may be nonspecific and sometimes cannot exclude acute infectious (self-limited) colitis; however, features that suggest chronicity (eg, distorted crypt architecture, crypt atrophy, a chronic inflammatory infiltrate) support the diagnosis of ulcerative colitis. Even during asymptomatic intervals, the sigmoidoscopic appearance is rarely normal; some degree of friability or granularity almost always persists. There is loss of the normal vascular pattern, and biopsy shows evidence of chronic inflammation.

Plain x-rays of the abdomen sometimes help to judge the severity and proximal extent of the colitis by showing loss of haustration, mucosal edema, and absence of formed stool in the diseased bowel. Barium enema, like colonoscopy, is not usually necessary before treatment and may be hazardous in active stages because of risk of perforation. Later in the course of disease, however, the entire colon should be evaluated to determine the extent of involvement. Total colonoscopy is the most sensitive and widely used method, although barium enema can be informative. Barium studies show loss of haustration, mucosal edema, minute serrations, or gross ulcerations in severe cases. A shortened, rigid colon with an atrophic or pseudopolypoid mucosa is often seen after several years’ duration.

In this air-contrast radiograph of ulcerative colitis, the mucosal pattern is granular with loss of normal haustrations in a diffuse, continuous pattern.

Colonoscopy with biopsy is mandatory to evaluate the nature of a stricture. Biopsy may also help distinguish ulcerative colitis from Crohn’s disease if the inflammation is highly focal or if a granuloma is seen.

Prognosis

Usually, ulcerative colitis is chronic with repeated exacerbations and remissions. A rapidly progressive initial attack becomes fulminant iearly 10% of patients, with complications of massive hemorrhage, perforation, or sepsis and toxemia. Complete recovery after a single attack may occur in another 10%; however, there always remains the possibility of an undetected specific pathogen.

Nearly 1/3 of patients with extensive ulcerative colitis require surgery. Total proctocolectomy is curative: Life expectancy and quality of life are restored to normal, and the risk of colon cancer is eliminated.

Patients with localized ulcerative proctitis have the best prognosis. Severe systemic manifestations, toxic complications, and malignant degeneration are unlikely, and late extension of the disease occurs in only about 20 to 30%. Surgery is rarely required, and life expectancy is normal. The symptoms, however, may prove exceptionally stubborn and refractory. Moreover, because extensive ulcerative colitis may begin in the rectum and spread proximally, localized proctitis should not be definitively diagnosed until it has stayed localized for > 6 monthes. Localized disease that later extends is often more severe and more refractory to therapy.

Treatment

Avoiding raw fruits and vegetables limits mechanical trauma to the inflamed colonic mucosa and may lessen symptoms. A milk-free diet may help but need not be continued if no benefit is noted. An anticholinergic drug or loperamide 2.0 mg or diphenoxylate 2.5 mg orally 2 times a day to 4 times a day is indicated for relatively mild diarrhea; higher oral doses of loperamide (4 mg in the morning and 2 mg after each bowel movement) or diphenoxylate (б mg 3 times a day or 4 times a day), deodorized opium tincture 0.5 to 0.75 mL (10 to 15 drops) every 4 to 6 hours, or codeine 15 to 30 mg every 4 to 6 hours may be required for more intense diarrhea. These antidiarrheal drugs must be used with extreme caution in more severe cases

because they may precipitate toxic dilation.

In mild or moderate disease that does not extend proximally beyond the splenic flexure, remission may sometimes be achieved with a hydrocortisone enema instead of with oral corticosteroid therapy. Initially, hydrocortisone 100 mg in 60 mL of isotonic solution is given rectally once or twice/day. It should be retained in the bowel as long as possible; instillation at night, with the patient’s hips elevated, may prolong retention and extend distribution. Treatment, if effective, should be continued daily for about 1 wk, then every other day for 1 to 2 wk, then discontinued gradually over 1 to 2 wk. Because systemic side effects may occur as with oral corticosteroids, enema preparations of new corticosteroid analogs such as budesonide, which is topically potent but less systemically active, are becoming more widely used outside the USA.

Mesalamine may also be given by enema and is beneficial in many cases of refractory proctosigmoiditis and left-sided colitis. The standard dose is mesalamine 4 g in 60 or 10 mL of solution giveightly, although recent studies suggest that 1 g may be equally effective. Suppositories of mesalamine 500 mg are also effective in treating proctitis, or ever proctosigmoiditis, and are preferred by patients. After clinical and endoscopic remission has been established (usually within a few weeks), frequency of administration car be tapered, although a topical or oral long–term maintenance regimen is often required to prevent relapse.

More extensive mild or moderate disease as well as localized disease may respond to oral sulfasalazine. Because GI intolerance common, the drug should be given with food and, if necessary, in the enteric-coated form. To minimize common side effects (eg, nausea, dyspepsia, headache), dosage should initially be low (eg, 0.5 g orally 2 times a day) and gradually increased over several days to 3 to 6 g/day in divided doses. Reversible decreases in sperm count and motility may occur in up to 80% of men. More serious side effects (eg, blood dyscrasias; hemolytic anemia; paradoxical exacerbation of colitis, rarely, hepatitis) may prevent use of sulfasalazine.

Once remission is achieved, long-tem maintenance therapy with sulfasalazine 1 to 3 g/day is indicated to prevent relapse. The sulfapyridine component of sulfasalazine; interferes with folic acid absorption, so folate supplementation of 1 to 2 mg /day is generally recommended. Patients with chronic fecal blood loss may also require iron to prevent anemia. New oral analogs of sulfasalazine have been developed to eliminate the sulfapyridine moiety, which is responsible most of the common side effects, while allowing delivery of mesalamine to diseased reas of the small intestine and colon. Clinical trials have shown that olsalazine, a mesalamine dimer, is effective in treating mild-to-moderate colitis and maintaining remission. Like sulfasalazine, olsalazine depends on an azobond to prevent рrоxymal absorption of the mesalamine and to keep іt in the intestinal lumen until the azo- bond hydrolyzed and active mesalamine геleased by the enzymatic action of bacterial flora in the lower ileum and colon. Bacterial cleavage of the compound releases twice quantity of mesalamine without any sulfonamide. Another mesalamine-based azo compound, balsalazide, has also proven effective and has been approved in many countries.

Other forms of mesalamine have various delayed-release coatings. Asacol is monomelic mesalamine coated with an acrylic polymer whose pH solubility delays release of the drug until entry into the distal ileum and colon. Claversal and Salofalk (not available in the USA) are similar mesalamme preparations with a pH-dependent acrylic coating that allows release of the drug slightly more proximally. Pentasa is a mesalamine formulation encapsulated in ethylcel-lulose microgranules that provide timed release of drug much more proximally in the small bowel. The new mesalamine analogs have been shown to be effective in treatment of mild or moderately active disease and in maintenance of remission. Olsalazine is given in divided doses of 1.5 to 3.0 g/day; Asacol, 2.4 to 4.8 g/day; and Pentasa, 1.5 to 4.0 g/day.

Moderately severe disease in ambulatory patients usually requires systemic corticosteroid therapy. Relatively intensive therapy with oral prednisone 40 to 60 mg/day in either single or divided doses frequently induces dramatic remission. After 1 to 2 wk, the daily dose may be gradually reduced by about 5 to 10 mg/wk. Sulfasalazine (2 to 4 g/ day in divided doses) may be added when prednisone 20 mg/day is controlling the colitis; very gradual tapering and ultimate withdrawal of the corticosteroid may then be possible.

Severe disease, manifested by > 10 bloody bowel movements per day, tachycardia, high fever, or severe abdominal pain, requires hospitalization. If the patient had been receiving corticosteroid treatment > 30 days at the time of admission, hydrocortisone 300 mg/day should be given by continuous I/V drip. In patients who have not received recent corticosteroids, ACTH 75 to 120 U/day by continuous i/v drip has been reported to be a slightly more effective initial therapy, but adrenal hemorrhage is occasionally a complication. In either event, treatment is given for 7 to 10 days while the response is monitored by recording the nature and frequency of bowel movements. An initial abdominal x-ray should be obtained to assess the extent and severity of colonic involvement, and the patient must be observed closely for the development of toxic megacolon.

Unless dehydration resulting from diarrheal losses is imminent, use of hydrocortisone or ACTH in I/V 0.9% sodium chloride solution is not usually advised because edema is a frequent complication. Potassium chloride 20 to 40 mEq/L added to the I/V fluids usually helps prevent hypokalemia. Anemia may require transfusions. Parenteral hyperalimentation is sometimes used for nutritional support but is of no value as primary therapy; in fact, patients who can tolerate food will do better if they eat.

Oral prednisone 60 mg/day may be substituted after remission has been achieved with the 7- to 10-day course of parenteral treatment. A patient who remains well on the oral regimen for 3 to 4 days may leave the hospital, and the corticosteroid dosage may be gradually reduced at home under close medical supervision.

Immunomodulatory drugs.

Immunomodulatory drugs are acceptable for some patients with refractory or corticosteroid-dependent ulcerative colitis. Azathioprine and 6-mercaptopurine inhibit T-cell function, and a decline in the activity of both natural killer cells and cytotoxic T cells is correlated with a clinical response. The full benefit of azathioprine 2 to 3.5 mg/ kg/day or 6-mercaptopurine 1.5 to 2.5 mg/ kg /day may not be seen for 3 to 6 monthes because these drugs are slow-acting. Complications include pancreatitis (an absolute contraindication to continued use) and reversible neutropenia, which simply requires a lower dose with regular monitoring of WBC counts.

Cyclosporine has a rapid onset and is primarily indicated for acute severe ulcerative colitis unresponsive to high-dose IV corticosteroids. Continuous W infusion of cyclosporine can induce remission and avert surgery in about 80% of such cases. An additional 6 mo of treatment with oral cyclosporine, ultimately shifting to azathioprine or 6-mercaptopurine, may sustain longer-term remissions in 50 to 60% of cases. Because serious and even fatal complications (eg, renal toxicity, seizures, opportunistic infections) may occur, patients generally are not offered cyclosporine unless the safer curative option of colectomy is infeasible or inappropriate. Candidates for cyclosporine therapy should be referred to centers experienced in its use.

Toxic colitis is a grave emergency. As soon as signs of toxic colitis or impending toxic megacolon are detected, the following should be taken immediately: (1) discontinue all antidiarrheal drugs; (2) give nothing by mouth and pass a long intestinal tube attached to intermittent suction; (3) give aggressive I/V fluid and electrolyte therapy, with 0.9% sodium chloride, potassium chloride, albumin, and blood as needed; (4) give ACTH (adrenocorticotropic hormone) 120 U/day or hydrocortisone 300 mg/day by continuous I/V drip; and (5) give antibiotics (eg, ampicillin 2g I/V every 4 to 6 hours cefazolin 1 g I/V every 4 to 6 hours).

Having the patient roll over in bed from the supine to prone position every 2 to 3 hours may help redistribute colonic gas and prevent progressive distention. Passage of a soft rectal tube may also be helpful, but it must be done with extreme caution to avoid bowel perforation.

The patient must be watched closely for signs of progressive peritonitis or perforation. Percussion over the liver is important because loss of hepatic dullness may be the first clinical sign of free perforation, especially when peritoneal signs are suppressed by massive corticosteroid dosage. Abdominal x-rays should be obtained every 1 or 2 days to follow the course of colonic distention and to detect free or intramural air. If intensive medical measures do not produce definite improvement within 24 to 48 h, immediate surgery is required or the patient may die of perforation and attendant sepsis.

Emergency colectomy is indicated for massive hemorrhage, fulminating toxic colitis, or perforation. Subtotal colectomy with ileostomy and rectosigmoid closure is usually the procedure of choice because most critically ill patients cannot tolerate total proctocolectomy with abdominoperineal resection. The rectosigmoid stump may be electively removed later or may be used for ileoanal anastomosis with an intrapelvic intestinal reservoir, or pouch, with or without a rectal mucosectomy. In any event, the intact rectal stump should not be allowed to remain indefinitely because of the risk of disease activation and malignant degeneration. Elective surgery is indicated for mucosa dysplasia or clinically suspected cancer, for all symptomatic strictures, for growth retardation in children, or most commonly, for intractable chronic disease resulting in invalidism or corticosteroid dependence Rarely, severe colitis-related extraintestinal manifestations (eg, pyoderma gangrenosum) may also be indications for surgery. Total proctocolectomy permanently cures ulcerative colitis. Permanent ileostomy has been the traditional price of this cure, although various alternatives (eg, the continent ileostomy, pelvic reservoirs or pouches with ileoanal anastomosis) are now available. The physical and emotional burdens imposed by any form of colon resection must be recognized, and care should be taken to: see that the patient receives all the instructions and psychologic support that are necessary before and after surgery.