Class of drug	Drug	Dose
H₂-receptor antagonists	Cimetidine	400 mg twice daily
	Famotidine	40 mg daily
	Nizatidine	300 mg daily
	Ranitidine	300 mg daily
Proton pump inhibitors	Esomeprazole	20 mg daily
	Lansoprazole	30 mg daily
	Omeprazole	20 mg daily
	Pantoprazole	40 mg daily
	Rabeprazole	20 mg daily
Antacids	Aluminium hydroxide	10–20 mL 3 times daily
	Magnesium carbonate	10 mL 3 times daily
	Magnesium trisilicate	10–20 mL 3 times daily
	Aluminium and magnesium complexes	10 mL between meals and at bedtime
Others	Alginates and antacids	2 tablets twice daily
Others	Chelates and complexes, e.g. tripotassium, dicitratobismuthate, sucralfate	2 tablets twice daily

Nausea and vomiting

Many gastrointestinal conditions are associated with vomiting, but nausea and vomiting without abdominal pain are frequently non-gastrointestinal in origin, e.g. acute infections, CNS disease and drug ingestion.

• Early-morning vomiting is seen in pregnancy, alcohol dependence and in some metabolic disorders (e.g. uraemia).

• Large volumes of vomit suggest intestinal obstruction; faeculent vomit suggests low intestinal obstruction or the presence of a gastrocolic fistula, while projectile vomiting is due to gastric outflow obstruction.

• Chronic nausea and vomiting with no other abdominal symptoms usually have a psychological cause.

Treatment

Many patients require no therapy. Food is usually withheld and fluids only are allowed. With more persistent vomiting, IV fluids, e.g. 0.9% saline (p. 369), are given for dehydration and correction of electrolyte abnormalities. A naso-gastric tube is inserted if there is bowel obstruction.

• Hyoscine 300 mcg is the most effective drug for motion sickness.

• Antihistamines, e.g. cyclizine 50 mg oral/IM/IV 3 times daily, oral cinnarizine 15 mg and oral promethazine 25–75 mg, are also used for motion sickness and in nausea and vomiting with vertigo. Drowsiness and antimuscarinic side-effects, such as urinary retention, dry mouth, photophobia (dilatation of the pupil), confusion and constipation (p. 137), occur.

• Dopamine receptor antagonists

• Phenothiazines, e.g. prochlorperazine 10 mg oral 3 times daily, perphenazine 4 mg 3 times daily oral, trifluoperazine 2–4 mg oral in divided doses and chlorpromazine 10–25 mg orally 4–6-hourly, are useful for vomiting produced by drugs or surgery and in nausea associated with vertigo. Drowsiness, acute dystonic reactions and other extrapyramidal side-effects occur.

• Metoclopramide is given 10 mg 3 times daily orally or intravenously for all causes of vomiting, with high doses often given by intravenous infusion for cytotoxic drug-induced vomiting. It is a pro-kinetic agent with additional central effects.

• Domperidone 10 mg 3 times daily oral is predominantly used for cytotoxic drug-induced vomiting. It has few central effects, as it does not cross the blood–brain barrier easily. Side-effects of metoclopramide and domperidone include sedation and acute dystonia, although dystonia is less with domperidone. Both drugs should be avoided in pregnancy.

• Serotonin (5HT₃) antagonists are mainly used for cytotoxic drug-induced vomiting and post-operatively. Granisetron 1–2 mg is given 1 hour before cytotoxic treatment, then 2 mg daily. Ondansetron is given as 8 mg 1–2 hours before treatment, then 8 mg every 12 hours. Side-effects include constipation, headache and rash.

• Synthetic cannabinoid (nabilone 1 mg twice daily) is used for cytotoxic-induced vomiting refractory to other treatments. Side-effects include drowsiness, ataxia (these two can persist for 72 hours) and visual disturbance. Avoid in patients with a history of psychiatric disorder and in the elderly.

• Neurokinin receptor antagonist (aprepitant 125 mg 1 hour before chemotherapy, then 80 mg daily for 2 days) is used as an adjunct to dexamethasone and 5HT₃ treatment. Side-effects include gastrointestinal problems, headaches and dizziness. Do not use when the patient is breast-feeding.

Diarrhoea

Acute diarrhoea

Acute diarrhoea is very common and is usually due to dietary indiscretion, infectious agents, toxins or drugs, e.g. antibiotics, magnesium-containing antacids, or laxatives. It is usually self-limiting and ceases in 24–48 hours with no treatment.

• Watery diarrhoea. Viral infections with rotavirus, enteric adenovirus and norovirus are common and usually cause acute watery diarrhoea. Salmonella, Campylobacter and non-invasive Escherichia coli and Clostridium difficile may also cause watery diarrhoea.

• Bloody diarrhoea (dysentery). This can occur due to Shigella, Campylobacter, Salmonella, invasive E. coli subtypes and C. difficile.

• Investigations

• Stool culture. Salmonella, Shigella, Campylobacter and E. coli can all be detected on culture. Detection of viral particles requires electron microscopy, which is not performed routinely.

• Ova, cysts and parasites. Amoebiasis and giardiasis should be considered in returning travellers with diarrhoea.

• C. difficile toxin. C. difficile infection is associated with the use of broad-spectrum antibiotics and is a common cause of diarrhoea in hospitalized patients. It is diagnosed by the presence of toxin in stools.

• Flexible sigmoidoscopy. This may be useful in protracted cases to allow mucosal assessment and biopsy.

• Oral rehydration solutions (p. 59) containing glucose and electrolytes are useful to prevent dehydration. IV rehydration is generally required only in severe cases or in the very young and very old.

• Antidiarrhoeal drugs may impair clearance of the pathogen but can be given for symptomatic relief.

• Loperamide 2–4 mg 4 times daily is a non-absorbed opioid that stimulates receptors in the enteric nervous system to reduce peristalsis and fluid secretion. It has the advantage of being non-euphoria-inducing, has no antimuscarinic side-effects and dependence does not occur. Adverse effects include nausea.

• Codeine 30–60 mg oral 4 times daily acts in a similar way to loperamide but is systemically absorbed; opioid side-effects occur.

• Co-phenotrope 2 tablets 4 times daily contains an opioid (diphenoxylate) and an antimuscarinic agent (atropine) which reduces colonic motility. It has antimuscarinic side-effects (p. 134).

All produce constipation if given frequently.

• Specific therapy

• Antibiotic therapy. Most bacterial causes of diarrhoea are self-limiting (lasting only days) and antibiotics are not necessary. Quinolones (e.g. ciprofloxacin 500 mg twice daily) may decrease the severity and duration of symptoms.

• C. difficile. A course of 10–14 days of oral metronidazole 400 mg 3 times daily. Oral vancomycin 125 mg 4 times daily is used for resistant cases. Oral vancomycin and IV metronidazole are used in patients not responding to vancomycin and with life-threatening infections.

• Amoebiasis. Diagnosis is confirmed by the presence of trophozoites or cysts of Entamoeba histolytica in the stool, or by serum antibody tests. Treatment is with oral metronidazole 800 mg 3 times daily for 5–10 days or tinidazole oral 2 g daily for 2–3 days. Oral paromomycin 500 mg 3 times daily for 7 days or oral diloxanide furoate 500 mg 8-hourly for 10 days should be given to clear parasites from the bowel.

• Giardiasis. Diagnosis is clinical. Trophozoites of Giardia intestinalis in stool or duodenal aspirate are not usually found. Therapy consists of oral metronidazole 2 g a day for 3 consecutive days or tinidazole 2 g orally single dose.

Diarrhoea in patients with HIV infection

Chronic diarrhoea is a common symptom in patients with HIV infection (p. 96). Cryptosporidium is the commonest pathogen isolated. Other infective causes include cytomegalovirus, Mycobacterium avium and Giardia intestinalis. Stool culture with examination for ova, cysts and parasites should be performed, together with flexible sigmoidoscopy/colonoscopy and biopsy.

• Treatment should be directed at individual causes. Some suggest empiric therapy with metronidazole for Giardia. Non-infective causes of diarrhoea associated with HIV disease include a specific enteropathy, lymphoma and Kaposi’s sarcoma. All these conditions are less common with highly active anti-retroviral treatment (HAART).

Chronic diarrhoea

Chronic diarrhoea refers to diarrhoea of more than 4 weeks’ duration. It can be due to a variety of causes (usually non-infective) including inflammation (inflammatory bowel disease), drugs (metformin, statins), functional factors, malabsorption or cancer (change in bowel habit), the treatments for which are described elsewhere.

• Clinical features

• Steatorrhoea suggests excessive fat in the stool and is due to malabsorption and pancreatic disease.

• Bloody diarrhoea suggests active colonic inflammation and is most commonly due to inflammatory bowel disease.

• Watery diarrhoea is the most common presentation and encompasses the broadest range of diagnoses. When standard investigations have proved unhelpful, a 72-hour assessment of stool weights may be helpful. The stool weights per day are not normally performed but in general: < 250 g is normal (frequency of defecation is often interpreted as diarrhoea by patients with, for example, irritable bowel syndrome); between 300 and ∼800–900 g is probably organic (Crohn’s disease); > 1000 g may be due to laxative abuse or a neuroendocrine tumour, e.g. VIPoma, causing profuse watery diarrhoea.

• Investigations. These include rectal examination, sigmoidoscopy, stool culture and ova, cysts and parasites, followed by a colonoscopy or barium follow-through, depending on type of diarrhoea. Small bowel MRI is replacing barium follow-throughs.

• Treatment. Treatment is usually directed at the cause, but symptomatic treatment as above is appropriate whilst investigations are ongoing or when specific therapy has failed to provide relief.

Constipation

This term is used for the infrequent passage of stool (< 2 per week), straining > 25% of the time or passage of hard stools and incomplete evacuation. Headache, malaise, halitosis, abdominal bloating and discomfort are often attributed to constipation without any factual evidence.

Constipation can come on acutely and, in the older patient, may indicate an organic disorder. Chronic constipation lasting years is usually functional.

Local anal diseases, e.g. fissures or haemorrhoids, are associated with constipation, as are some drugs, e.g. opiates, antimuscarinics, calcium channel blockers (such as verapamil), antidepressants and iron, and systemic disorders, e.g. hypothyroidism, hypercalcaemia and diabetes mellitus.

Rectal examination, flexible sigmoidoscopy/colonoscopy or CT pneumocolon (barium enema is being used less) may be necessary to rule out structural diseases in recent-onset constipation.

Treatment

• Lifestyle changes. Lifestyle changes, including a high fluid intake and regular exercise, help. Dietary fibre is mainly non-starch polysaccharides (NSP), which are soluble or insoluble. Soluble fibre (e.g. psyllium, ispaghula, calcium polycarbophil — found in the flesh of fruits, vegetables and grains) is broken down and fermented by colonic bacteria, increasing stool bulk. Insoluble fibre (wheat bran, corn) also increases the bulk of stools but can sometimes make symptoms worse, e.g. wind. Dietary fibre should be increased to up to 30 g a day. This is achieved by increasing consumption of bread, potatoes, fruit and vegetables and reducing sugar intake in order to avoid an increase in total calories. Unprocessed bran added to food increases fibre but many find it unpalatable. Bulk-forming laxatives increase faecal mass, which stimulates peristalsis, and are of use in those individuals with small hard stools where dietary fibre cannot be sufficiently increased. Ispaghula husk 3.5 g twice daily or methylcellulose 1.5–3 g twice daily is used.

• Laxatives (Box 5.2)

• Osmotic laxatives are non-absorbable salts or carbohydrates that increase the amount of water retained in the large bowel and should be used as first-line drugs. Lactulose 15 mL twice daily is a semi-synthetic non-absorbed disaccharide. As a side-effect it can cause cramps and flatulence. Macrogols, inert polymers of ethylene glycol (1–3 sachets daily), are not fermented so gas is not formed and distension does not occur. Magnesium salts 5–10 g daily are dissolved in a glass of hot water before breakfast; they work in 2–4 hours.

• Stimulant laxatives increase intestinal motility and can consequently cause abdominal cramps. They are contraindicated in intestinal obstruction. Benign pigmentation of the colon (melanosis coli), colonic atony due to smooth muscle atrophy and damage to the myenteric plexus occur and so these drugs should not be used long-term. Bisacodyl 5–10 mg at night (tablets or suppositories), or dantron –co-danthrusate 1–2 capsules at night is indicated only in terminally ill patients (because of evidence of carcinogenicity in animal studies). Senna is given as 15–30 mg at night and increasing gradually.

• Lubiprostone is a bicyclic fatty acid, which opens chloride channels, increasing intestinal water secretion. It is used in the irritable bowel syndrome with constipation.

• Methylnaltrexone is an opioid antagonist and is effective in opioid-induced constipation without reducing the analgesic effect. It is given subcutaneously.

• Faecal softeners (e.g. liquid paraffin) can be given and arachis oil per rectum helps to soften impacted faeces.

• Bowel-cleansing solutions are used as pre-operative or pre-procedural regimens to empty the bowel. They should not be used routinely as laxatives. They are used in combination with a low-residue diet for the 48 hours prior to the procedure. They include sodium picosulphate 10 mg sachets; 2 sachets on the day before the procedure; a mixture of macrogols, sodium sulphate and bicarbonate 4 L 4–6 hours before the procedure; and magnesium carbonate mixture 2 sachets on the day before the procedure. Very elderly patients must be observed to avoid dehydration.

• Prucalopride is now used for resistant constipation.

• Biofeedback. For some patients chronic constipation is due to a failure of coordination of the process of defecation. Biofeedback has been shown to be of benefit in these patients and is used in some specialized centres.

Gastro-oesophageal reflux disease

Reflux is extremely common in the general population, causing mild indigestion and heartburn.

Heartburn is the major feature and is mainly due to direct stimulation of the hypersensitive oesophageal mucosa, but also partly caused by spasm of the distal oesophageal muscle. It is aggravated by bending, stooping or lying down and may be relieved by antacids. The patient may complain of a burning pain on drinking hot liquids or alcohol.

Regurgitation of food and ‘acid’ into the mouth occurs, particularly when the patient is bending or lying flat. Aspiration into the lungs, producing pneumonia, is unusual without an accompanying stricture, but cough and nocturnal asthma from regurgitation and aspiration can occur. The differential diagnosis of the retrosternal pain from angina can be difficult; 20% of cases admitted to a coronary care unit have gastro-oesophageal reflux disease (GORD).

• Prokinetic agents metoclopramide 10 mg 3 times daily and domperidone 10 mg 3 times daily are dopamine antagonists (for side-effects, see p. 644). They are occasionally helpful, as they enhance peristalsis and speed gastric emptying. Cisapride has been withdrawn because it increases the Q–T_c interval and the risk of arrhythmias.

• Surgery. Surgery should never be performed for a hiatus hernia alone. The properly selected case with severe reflux symptoms confirmed by pH monitoring and with oesophagitis on oesophagoscopy responds well to surgery. Repair of the hernia and additional antireflux surgery (e.g. a modified Nissen fundoplication) is performed laparoscopically. Results show an improvement in symptoms in up to 80% of cases. The indications for surgery are not always clear, as medical therapy with PPIs is so effective; a young patient requiring years of drug treatment is one common indication. Patients with oesophageal dysmotility unrelated to acid reflux do less well than those with proven reflux.

Non-erosive reflux disease (NERD)

These cases include patients with reflux symptoms. They often do not respond to a PPI. Patients are usually female and often the symptoms are functional (p. 167).

Complications

• Peptic stricture usually occurs in patients over the age of 60. The symptoms are those of dysphagia over a long period preceded by severe heartburn. Treatment is by dilatation of the stricture and a PPI is given to achieve anacidity. Occasionally, surgery for continued reflux is required. Intermittent dysphagia is more classical of a Schatzki ring than a peptic stricture.

• Barrett’s oesophagus. This occurs as a result of longstanding reflux (Fig. 5.1). It consists of columnar epithelium with intestinal metaplasia extending upwards into the lower oesophagus and replacing normal squamous epithelium. Barrett’s oesophagus (even short segment < 3 cm) is pre-malignant for adenocarcinoma. Risk factors for progression are male sex, age > 45 years, length of segment > 8 cm, early age of onset and duration of symptoms of GORD, the presence of ulceration and stricture and a family history. Dysplasia is patchy and biopsies from all four quadrants (every 2 cm) of the Barrett’s segment must be performed. There is some evidence that anti-reflux surgery leads to Barrett’s regression. Patients without dysplasia do not require surveillance. Low-grade dysplasia requires regular endoscopic surveillance. High-grade dysplasia is now treated with radiofrequency ablation using the HALO system or local endomucosal resection. Endoscopic ablation therapy with photodynamic therapy or laser is also used.

• Adenocarcinoma. Patients with weekly reflux symptoms were nearly 8 times more likely to develop adenocarcinoma than those without symptoms in one study. The greater the frequency, severity and the duration of reflux symptoms, the greater the risk.

Fig. 5.1 Barrett’s oesophagus. Endoscopic view showing a segment of columnar-lined oesophagus (arrowed)

Other oesophageal disorders

Achalasia

Achalasia is characterized by aperistalsis in the body of the oesophagus and failure of relaxation of the lower oesophageal sphincter (LOS) on initiation of swallowing.

The disease presents at any age with a long history of intermittent dysphagia for both liquids and solids, and regurgitation of food from the dilated oesophagus. Aspiration pneumonia may result. Severe retrosternal chest pain due to vigorous non-peristaltic contraction of the oesophagus occurs, particularly in younger patients.

• Barium swallow will show dilatation of the oesophagus, lack of peristalsis and often synchronous contractions. The lower end gradually narrows like a bird’s beak.

• Manometry shows aperistalsis of the oesophagus, as well as failure of relaxation of the LOS.

• Oesophagoscopy is necessary to exclude a small carcinoma at the lower end of the oesophagus.

Treatment

• Endoscopic balloon dilatation is performed to produce a sustained reduction of the LOS by disrupting the circular muscle with balloon dilatation under fluoroscopic guidance. Greater diameters of dilatation are used (30–40 mm) than for dilatation of peptic strictures. The risk of perforation is therefore higher and occurs in 3–5% cases. An effective symptom response occurs in 80% of patients; most patients require 2–3 dilatations over a 5-year period. Younger patients tend to have a shorter duration of response.

• Botulinum toxin acts to prevent the release of acetylcholine from peripheral nerves, thus inducing muscle paralysis. Although controversial, it can be injected quadrantically in 25 U aliquots at the squamocolumnar junction. Studies have shown reasonable response rates but the duration of response ranges between 7 and 11 months. This therapeutic option is attractive for elderly patients, as it is low-risk and easy to administer repeatedly.

• Heller’s surgical myotomy is a well-established surgical procedure and can now be performed with a minimally invasive laparoscopic approach. The duration of response is excellent, with 85–90% of patients describing a good symptomatic response at 5 years. Consequently, the surgical approach is often preferred in younger patients. The associated mortality is in the region of 1%. To prevent reflux, some surgeons combine this laparoscopic operation with a partial fundoplication (see below).

• Pharmacological therapy with smooth muscle relaxants such as calcium channel blockers (nifedipine) and nitrates can be given pre-prandially. They are less effective than other measures.

GORD is a common complication, with all successful treatments necessitating PPI therapy in most patients.

Diffuse oesophageal spasm

This disorder causes chest pain and dysphagia, is diagnosed by oesophageal manometry and is characterized by simultaneous non-peristaltic oesophageal contractions occurring after 20% or more swallows. Barium swallow may show a corkscrew appearance. Nutcracker oesophagus is a variant of diffuse oesophageal spasm characterized by very high-amplitude peristalsis (> 200 mmHg).

• Treatment. Sublingual nifedipine 10 mg 3 times daily should be tried initially. When the spasm is associated with GORD, acid suppression is given.

Rings and webs

A number of rings and webs have been described throughout the oesophagus that may cause dysphagia (difficulty in swallowing). They can usually be treated at endoscopy by dilatation.

Eosinophilic oesophagitis

This usually occurs in young white male patients who have a long history of dysphagia, food impaction, heartburn and oesophageal pain. Endoscopically there is mucosal furrowing, loss of vascular pattern and prominent circular folds. Histologically there is a characteristic infiltration with eosinophils (the oesophagus is usually devoid of eosinophils). The cause is unknown but there may be a personal or family history of allergic diseases. Food allergy may be a causative factor.

• Treatment is with a PPI, swallowing inhaled steroid preparations, e.g. fluticasone or oral steroids. Liquid budesonide is used.

Oesophageal infections

Infection is a cause of painful swallowing (odynophagia) and is seen particularly in the immunosuppressed, the debilitated, patients on antibiotics and those with AIDS. Oral lesions may make the diagnosis obvious, e.g. thrush, but endoscopy with cytology and biopsy is often necessary. Candida is treated with oral nystatin 400–600 000 U 4 times daily. Fluconazole 100 mg daily for 2 weeks is used for more severe cases and IV amphotericin B 0.3–0.5 mg/kg/day for systemic infection. Herpes simplex is treated with oral aciclovir 400 mg 5 times daily for 7 days but may require IV therapy 5 mg/kg 8-hourly for 5 days. Cytomegalovirus is treated with ganciclovir IV infusion 5 mg/kg 12-hourly. Prophylactic treatment with nystatin or amphotericin is required for all patients on large doses of immunosuppressive therapy.

Chemical oesophagitis

• Drugs, such as bisphosphonates, potassium, NSAIDs, aspirin and iron, can cause a variety of oesophageal disorders, e.g. oesophagitis, ulcers, erosions and strictures, presenting as odynophagia or dysphagia. An oesophagoscopy should be performed. Treatment depends on the lesion and stopping the offending drug if possible.

• Ingestion of household products (e.g. intentional or accidental in young children), such as bleach, toiletries and disinfectants, can cause corrosion of the mouth and of the pharyngeal and oesophageal mucosa. Gastric aspiration, lavage or dilution or neutralization of alkali is contraindicated. Careful upper gastrointestinal endoscopy is required to assess damage. Strictures occur in the long term. If there is life-threatening pharyngeal or laryngeal oedema, endotracheal intubation is necessary.

Oesophageal perforation or rupture

The commonest cause is endoscopic dilatation, usually of malignant strictures. Small lesions heal spontaneously (with nil by mouth and broad-spectrum antibiotics), but many require insertion of an oesophageal stent. Rupture can also occur after forceful vomiting, when it presents with severe chest pain and collapse. Treatment is surgical.

Peptic ulcer disease

Peptic ulcers are mainly due to Helicobacter pylori infection or non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin.

Helicobacter pylori

This is a spiral-shaped, Gram-negative, urease-producing bacterium. It is found in the gastric antrum and in areas of gastric metaplasia in the duodenum, in 95% of patients with a duodenal ulcer and 75% of patients with a gastric ulcer. H. pylori is also present in people with no ulcer disease and in up to 80% in people from developing countries. It can be identified by the following methods:

• Non-invasive:

• ¹³C urea breath test. The measurement of ¹³CO₂ in the breath, after ingestion of ¹³C urea, is very sensitive (98%) and specific (95%) for the presence of H. pylori.

• Serological tests. These detect IgG antibodies to H. pylori and are 80% sensitive and specific. They are used in diagnosis and in epidemiological studies. IgG titres may take up to 1 year to fall by 50% after eradication therapy and therefore are not useful for confirming eradication or the presence of a current infection.

• Stool immunoassay. The overall sensitivity is about 90% with a specificity of 95% for the presence of H. pylori.

• Invasive (endoscopy): Gastric biopsies are added to urea in a gel containing phenol red (CLO test). If H. pylori is present, the urease enzyme splits the urea to release ammonia, which raises the pH of the solution and causes a rapid colour change. Biopsies can also be cultured and sensitivities to antibiotics can be ascertained. H. pylori can be detected histologically.

Eradication therapy for H. pylori

Treatment is based on a PPI (omeprazole or lansoprazole) plus two antibiotics (from clarithromycin, amoxicillin, tetracycline and metronidazole) for 1 week. Because of metronidazole resistance in 20–50% and no resistance to amoxicillin, the preferred regimen was omeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg, all twice daily for 1 week.

With the increase in clarithromycin resistance many are now using quadruple therapy with omeprazole 20 mg × 2 daily, tripotassium di-citrate bismuthate 120 mg × 4 daily, tetracycline 500 mg × 4 daily and metronidazole 500 mg × 3 daily for 2 weeks. These should be taken 30 mins before a meal, antacids and milk avoided for half an hour before or after; patients should be warned that bismuth may blacken their tongue.

Reinfection after successful eradication occurs in < 1%. In developing countries, where compliance is often poor and antibiotic resistance high, failure of eradication is common.

Tinidazole or tetracycline is occasionally used in some regimens with antisecretory drugs and other antibiotics.

Treatment failures (< 10% with good compliance) are treated with bismuth plus a PPI plus two antibiotics for 2 weeks.

Aspirin and other NSAIDs

These drugs cause gastric mucosal damage in 50% of patients taking them regularly and ∼30% will have ulcers on endoscopy. Only 5% have symptoms and only 1–2% have a major problem, i.e. gastrointestinal bleed. In patients who develop problems, NSAIDs should be stopped and for established ulcers, a PPI should be prescribed. H. pylori eradication is unhelpful. When stopping NSAIDs is not possible, use an NSAID with low gastrointestinal side-effects at the lowest possible dose, e.g. ibuprofen 1–2 g daily, and prophylactic cytoprotective therapy, e.g. a PPI (omeprazole 20 mg daily) or misoprostol, which is a synthetic analogue of prostaglandin E1 and is given as 200 mcg 4 times per day. The main side-effects of this latter agent are diarrhoea and abdominal pain, and so it is not often used.

Prophylactic therapy

This is necessary for all high-risk patients, i.e. those over 65 years, those with a peptic ulcer history, particularly with complications, and patients on therapy with corticosteroids or anticoagulants. An alternative is to give a COX-2 NSAID, which causes less mucosal damage (p. 298), but long-term cardiovascular risk is a problem.

General measures for peptic ulcer disease

Stopping smoking helps ulcers heal. Eradication of H. pylori is judged on the relief of symptoms, except in patients with complications of peptic ulcer disease in whom eradication should be checked by a ¹³C urea breath test or stool immunoassay. A patient with a gastric ulcer should be re-endoscoped at 6 weeks to check healing and to exclude a malignant ulcer. Antacids are of no value for ulcer healing but may help pain relief. The choice depends on the formulation, side-effects and buffering capacity. For example, a compound alginate 15 mg 4 times a day may be given.

Complications of peptic ulcer

These include haemorrhage (p. 151).

• Perforation is becoming increasingly uncommon because of better medical therapy. Duodenal ulcers perforate more commonly than gastric ulcers, usually into the peritoneal cavity. Treatment is surgical and H. pylori should be eradicated.

• Gastric outlet obstruction is now uncommon but can occur due to duodenal ulcer oedema or subsequent scarring. There is projectile vomiting and a succussion splash may be demonstrated clinically. Metabolic alkalosis can occur due to loss of acid. Those with duodenal oedema may settle but the majority are treated with dilatation, stenting or surgery.

Gastrointestinal haemorrhage

Acute upper gastrointestinal bleeding

Haematemesis is the vomiting of blood from a lesion proximal to the distal duodenum. Melaena is the passage of black tarry stools; the black colour is due to altered blood — 50 mL or more is required to produce this. Melaena can occur with bleeding from any lesion in areas proximal to and including the caecum.

Unaltered or ‘maroon blood’ passed per rectum can be due to an upper gastrointestinal bleed if the bleed is massive.

Clinical approach to the patient

All cases with a recent (i.e. within 48 hours) significant gastrointestinal bleed should be seen in hospital. In many, no immediate treatment is required, as often there has been only a small amount of blood lost and the patient’s cardiovascular system can compensate for this. Approximately 85% of patients stop bleeding spontaneously within 48 hours.

Immediate management (Box 5.3)

This involves taking a rapid history to determine the likely aetiology of the bleeding and carrying out an examination. Note the age of the patient and make a rapid assessment of the haemodynamic state. Look for pallor, cold nose, tachycardia and low BP, i.e. ‘shock’, and also for evidence of co-morbidity, i.e. cardiac failure, ischaemic heart disease, renal and malignant disease or signs of chronic liver disease. Co-morbidity adversely effects outcome. Give oxygen to shocked patients. Take blood for Hb, U&E, LFTs, coagulation studies, and grouping and cross-matching.

Box 5.3 Management of acute gastrointestinal bleeding (see also Fig. 20.4)

• History and examination. Note co-morbidity

• Monitor pulse and BP half-hourly

• Take blood for haemoglobin, urea, electrolytes, liver biochemistry, coagulation screen, group and cross-matching (2 U initially)

• Establish IV access — 2 large-bore IV cannulae; central line if brisk bleed or if patient is elderly or has co-morbidities

• Give blood transfusion/colloid if necessary. Indications for blood transfusion are:

– Shock (pallor, cold nose, systolic BP < 100 mmHg, pulse > 100 bpm)

– Hb < 10 g/dL in patients with recent or active bleeding

• Oxygen therapy if hypoxic

• Urgent endoscopy in shocked patients/liver disease

• Continue to monitor pulse and BP

• Re-endoscope for continued bleeding/hypovolaemia

• Angiography if bleeding continues

• Surgery if bleeding persists

• Blood volume. The major principle is to restore the blood volume rapidly to normal. This can best be achieved by transfusion of blood via one or more large-bore 14–18 IV cannulae. A central venous catheter is useful in the severely shocked and elderly. It may be necessary to give a colloid, e.g. gelofusine, initially to a severely shocked patient whilst blood products are awaited. Occasionally, with a massive bleed, O negative blood can be given.

• Rate of blood transfusion must be monitored; the pulse rate and venous pressure are good guides to transfusion requirements.

• Anaemia does not develop immediately after a bleed as haemodilution has not taken place, and therefore the Hb level is a poor indicator of the need to transfuse. If, however, the Hb level is low (< 10 g/dL) and the patient has either bled recently or is actively bleeding, transfusion is usually necessary.

• Correction of coagulopathy. All anticoagulants, antiplatelet agents and NSAIDs should be stopped if possible. Significant coagulopathy should be corrected with fresh frozen plasma (FFP) (15 mL/kg) and cryoprecipitate (about 20 mL). IV vitamin K (10 mg) should be given if the coagulopathy is due to warfarin or liver disease, but as its action is delayed for up to 24 hours FFP is also usually required. Platelet infusion is indicated if the platelet count is < 50 × 10⁹/L.

• Naso-gastric tube insertion. Insertion of naso-gastric tube is not normally required. It is occasionally useful in confirming the diagnosis and ensuring an empty stomach prior to oesophagogastroduodenoscopy (OGD).

• Timing of upper gastrointestinal endoscopy. Whenever possible, OGD should be performed within 24 hours, as it allows diagnosis, risk stratification (Table 5.2) and early discharge. However, as the majority of upper gastrointestinal bleeds stop spontaneously, most patients can wait to have an OGD performed within normal working hours. Emergency endoscopy should be reserved for patients with a high likelihood of either persistent bleeding or recurrent bleeding. Rockall et al (Table 5.3) found the likelihood of rebleeding and mortality could be predicted on the basis of five factors and devised a simple scoring system to allow risk assessment. Although the full scoring system requires endoscopy, the first three factors can be used in isolation to provide an initial assessment to determine the need for emergency endoscopy. There should be a lower threshold for emergency endoscopy in patients with known or likely oesophageal varices (e.g., minor coffee ground vomit).

Table 5.2 Risk of recurrent bleeding in peptic ulceration

Endoscopic appearance	Risk
Active bleeding	55%
Visible vessel	45%
Adherent clot	20%
Flat spot	10%
Clean base	5%

Table 5.3 Rockall risk assessment score in non-variceal upper gastro-oesophageal haemorrhage

Management of specific acute upper gastrointestinal disorders

Mallory–Weiss tears (5% of diagnoses found on endoscopy for acute UGI haemorrhage)

These appear as linear mucosal tears at the gastro-oesophageal junction. They are often no longer visible by the time endoscopy is performed. Most patients stop bleeding spontaneously and early discharge within 24 hours is usually possible.

Oesophagitis (10%)

As described on p. 140, this should be treated with high-dose oral PPI therapy, e.g. omeprazole 40 mg daily.

Oesophageal varices (10%)

Oesophageal varices are portosystemic collaterals, which occur due to portal hypertension usually secondary to cirrhosis of the liver. In the upper gastrointestinal tract they occur most commonly at the gastro-oesophageal junction and the fundus of the stomach, although duodenal varices also occur occasionally.

Oesophageal varices are easily seen at endoscopy as blue/purple vascular swellings that form columns running the length of the oesophagus. They can be graded according to their number and size, with longer, larger columns being more likely to bleed. Microtelangiectasia on the surface of the varix, usually described as a cherry red spot, are also associated with an increased risk of bleeding. In contrast to upper gastrointestinal bleeds, in general, only 40% of variceal bleeds stop spontaneously and therefore urgent endoscopic intervention is required. Even in patients with cirrhosis, upper gastrointestinal bleeding can still be caused by peptic ulcers rather than varices.

• General management. Patients with variceal bleeding are often unstable and require admission to an ICU or HDU. CVP monitoring is frequently required, and endotracheal intubation for airway protection should be performed if there is agitation or a decreased conscious level.

• Pharmacotherapy

• Terlipressin 1–2 mg IV 4-hourly for 48 hours is an analogue of vasopressin and causes selective vasoconstriction of the splanchnic vasculature. This leads to a reduction in portal pressure and has been shown to reduce mortality from variceal bleeds. Side-effects include coronary ischaemia and myocardial infarction. Terlipressin should not be used in those with ischaemic heart disease.

• Octreotide 50–100 mcg bolus, then 25–50 mcg/hour for 3–5 days, a somatostatin analogue, has a similar effect to glypressin but does not have the same ischaemic side-effects.

• Antibiotics are needed for bacterial infections, which occur in one-third to two-thirds of patients with variceal bleeds. Patients with untreated bacterial infections have a higher risk of continued bleeding and recurrent bleeding. All patients with variceal bleeding should receive a broad-spectrum antibiotic (e.g. ciprofloxacin 500 mg twice daily or third-generation cephalosporin).

• Lactulose and phosphate enemas may be needed. Due to the increased production of ammonia caused by the digestion of blood, patients with cirrhosis frequently develop encephalopathy subsequent to a variceal bleed. Enemas with lactulose 10 mL 4 times daily and phosphate 1 twice daily are therefore commenced early in treatment.

• Endoscopic therapy

• Oesophageal banding. This is the first-line endoscopic treatment for oesophageal varices, both acutely and as secondary prophylaxis. A rubber band is placed via an endoscope over the varix, leading to its strangulation and necrosis. Bands are placed on each varix just above the oesophago-gastric junction (OGJ) and 5–8 bands can be applied before the endoscope must be removed in order to reload. Variceal banding has a higher success rate (85–95%) than injection sclerotherapy (80%) for the control of acute variceal bleeding and the rates of complications are lower. The procedure should be repeated every 2 weeks after the initial bleed until the varices are obliterated.

• Injection sclerotherapy. Injection of the sclerosant causes coagulation necrosis, followed by thrombosis with inflammation and scarring of the surrounding tissue, leading to variceal obliteration. The most commonly used sclerosant is ethanolamine (5%). Between 1 and 3 mL of sclerosant is injected into each varix just above the oesophago-gastric junction (OGJ). Necrotic ulcers are present in 90% of patients the day after injection and rates of complication with stricture formation and perforation are high (up to 20%).

• Balloon tamponade. A Sengstaken–Blakemore tube can be used as a temporizing measure for a maximum of 24 hours, when other interventions have failed or are not available. It consists of a tube with an oesophageal and a gastric balloon, which is placed either under direct vision or endoscopically via the mouth into the stomach. The gastric balloon is then inflated with either 500 mL air or 200–300 mL of water and 50 mL of radio-opaque water-soluble contrast depending on manufacturer’s recommendation. An X-ray is essential to check tube position. Gentle traction is applied to pull the gastric balloon against the gastro-oesophageal junction, compressing the bleeding vessels. Inflation of the oesophageal balloon above 35 mmHg is associated with a high incidence of oesophageal perforation and therefore is rarely done. It should only be used in ICU with sedation, and endotracheal intubation is required.

• Transjugular intrahepatic portosystemic shunt (TIPS). In this radiological procedure a guidewire is passed from the jugular vein into the liver; an expandable metal stent is then passed over the guidewire into the liver to form a channel between the systemic and portal circulations. This decompresses the portal system and is an effective treatment for uncontrolled or recurrent variceal bleeding. The principal side-effect is worsening encephalopathy.

• Surgery (used when all the forms of therapy described above have failed):

• Oesophageal transection — can be performed as an emergency procedure for uncontrolled bleeding.

• Shunt surgery — portocaval or distal splenorenal shunts can be performed as an elective procedure in those with recurrent variceal bleeding when other measures have failed.

Gastric varices

Gastric varices should be treated pharmacologically with terlipressin and antibiotics; endoscopic therapy with banding or sclerosants is usually ineffective. Endoscopic injection with tissue adhesive agents such as N-butyl cyanoacrylate (histoacryl) has been reported as being effective in up to 90% of cases. This liquid forms a hard polymer on contact with blood, which plugs the bleeding varix. TIPS should be considered early and surgery may be necessary.

• Prevention of recurrent variceal bleeding. The risk of recurrence is 60–70% over a 2-year period. Long-term measures to prevent this are:

• Oral propranolol. Give an adjusted dose to reduce the resting pulse rate by 25%. This will also prevent bleeding from portal gastrophy.

• Endoscopic treatment. Banding at 2-weekly intervals leads to obliteration of varices but follow-up is necessary as varices return (30–40% per year).

Patients with cirrhosis and varices who have not bled should be given propranolol.

Peptic ulcers (50%)

Gastric and duodenal ulcers are the commonest cause of significant upper gastrointestinal bleeding. The risk of continued bleeding and rebleeding can be predicted on the basis of the endoscopic appearance of the ulcer (Box 5.3). This in turn determines the required medical and endoscopic therapy.

Larger ulcers (> 2 cm) and those located on the lesser curve of the stomach and the posterio-inferior wall of the duodenal bulb also have a higher risk of rebleeding.

• Management

• Medical therapy. Stability of clot is favoured by a high gastric pH, with clot lysis occurring at a pH < 6. PPI therapy is more effective than H₂-antagonists in preventing recurrent bleeding. In ulcers with active bleeding, visible vessels or adherent clot, IV omeprazole 80 mg IV bolus followed by 8 mg/hour infusion reduces the rebleed rate to 7% compared to 23% with placebo. Most rebleeds occur within 72 hours and therefore the infusion should be continued for this period of time. For ulcers with a clean base or flat spot, an oral PPI is sufficient. H. pylori eradication therapy should be commenced immediately if a CLO test is positive (p. 144).

• Endoscopic therapy. Endoscopic therapy is not required for ulcers with a clean base or flat spot but should be attempted for those with active bleeding or a visible vessel. Adherent clot should be removed to expose any visible vessels. It is now agreed that bimodal therapy should be employed. Any two of the following should be used:

a) adrenaline (epinephrine) injection — 1 : 10 000 adrenaline injected quadrantically around the bleeding point (2–3 mL per injection)

b) thermal coagulation —with either heater probe or bipolar electrocoagulation

c) mechanical devices — endoscopically placed clips that can apply tamponade to the bleeding point.

When an initial attempt at endoscopic therapy fails, it is common to undertake a second procedure. However, the case should be discussed with surgical colleagues and preparations made for surgery should the patient rebleed.

• Therapeutic angiography. Options at angiography include selective intra-arterial vasopressin infusion or embolotherapy with micro-coils, gelatin or polyvinyl alcohol particles. Technical success rates of 50–90% have been reported. Therapeutic angiography is used when endoscopy fails to control the bleeding.

• Surgery. Due to improvements in endoscopic and medical therapy, the requirement for surgery for the treatment of bleeding peptic ulcers has declined dramatically over the last few decades. However, it is still occasionally required when other interventions have failed. Ligation of the bleeding vessel is performed.

Erosive gastritis and duodenitis (10–20%)

This should be treated with oral PPI therapy and H. pylori eradication if the CLO test is positive.

Oesophageal and gastric cancer (<4%)

Bleeding points on the tumour can be treated with similar endoscopic therapy to that employed for gastric and duodenal ulcers. Endoscopic therapy with argon plasma coagulation (APC) or NAG laser therapy may also be useful.

Prognosis

The mortality from gastrointestinal haemorrhage has shown little change from 5–12% over the years, despite many changes in management, mainly because of a demographic shift to more elderly patients with co-morbidity. The lowest mortality rates are achieved in dedicated medical/surgical gastrointestinal units. Early therapeutic endoscopy has not so far lowered mortality, although rebleeding episodes are reduced.

GI haemorrhage in specific circumstances

Bleeding after percutaneous coronary intervention (PCI)

This occurs in approximately 2% of patients undergoing PCI (who are on antiplatelet therapy), and has a high mortality of 5–10%. Urgent endoscopy should be performed with appropriate therapy, for example, for an ulcer. A PPI should be given intravenously. Management is difficult, as cessation of antiplatelet therapy has a high risk of acute stent thrombosis and also an associated high mortality. Using a risk assessment score (e.g. Rockall, p. 148), a reasonable approach is to stop all antiplatelet therapy in high-risk patients but to continue in low-risk ones. These patients should be under the combined care of a cardiologist and a gastroenterologist.

Acute lower gastrointestinal bleeding

Massive bleeding from the lower gastrointestinal tract is rare. Conversely, small bleeds from haemorrhoids occur very commonly. Massive bleeding is usually due to diverticular disease or ischaemic colitis (p. 166).

Initial management

Initial management is similar to that of upper gastrointestinal bleeding (p. 146). Additional immediate investigations are rectal examination, proctoscopy and sigmoidoscopy.

• Colonoscopy performed within 24 hours of presentation gives the best chance of making a diagnosis. A rapid bowel cleanser should be given first, either orally or via an naso-gastric tube, to ensure good visibility.

• Mesenteric angiography is useful both diagnostically and therapeutically. The mesenteric vessels are selectively cannulated and contrast is injected to look for extravasation into the gastrointestinal lumen. The minimum bleed rate required is 0.5 mL/min. Embolization of the bleeding vessel can be performed but carries the risk of bowel infarction. Intra-arterial infusions of vasopressin can also be given.

The majority of lower gastrointestinal bleeds settle with supportive management. However, surgical removal of the affected part of bowel is occasionally required.

Management of specific acute lower gastrointestinal disorders

Angiodysplasia

This refers to abnormal blood vessels most commonly found in the caecum and proximal ascending colon. They are also associated with Hereditary haemorrhagic telangiectasia (HHT), renal disease, von Willebrand’s disease and aortic stenosis. Treatment is usually endoscopic, with thermal modalities and argon plasma coagulopathy (APC). In HHT, hormonal therapy with oestrogen–progesterones (oestradiol 0.035–0.05 mg; norethisterone 1 mg twice daily) has also been tried but evidence for efficacy is conflicting. Side-effects include gynaecomastia and erectile dysfunction.

Meckel’s diverticulum

This is a congenital abnormality in the ileum, approximately 60 cm from the ileocaecal valve. It is usually symptomless but can ulcerate and bleed. Treatment is surgical removal.

Radiation proctitis

Radiation damage causing superficial vascular abnormalities can occur months to years after exposure to radiation therapy. In the rectum it causes proctitis and rectal bleeding. It is refractory to most treatments, although endoscopic APC therapy may be effective. Sucralfate enemas and also formalin swabs, inserted into the rectum for 2 mins, have also been tried.

Occult/chronic gastrointestinal bleeding

All men and post-menopausal women with iron deficiency anaemia should be investigated for possible blood loss from the gastrointestinal tract. The history and examination may indicate the most likely site of bleeding, but if no clue is available, it is usual to investigate both the upper and lower gastrointestinal tract endoscopically at the same session (’top and tail’).

Initial investigations

• Upper gastrointestinal endoscopy with duodenal biopsy — to exclude an upper gastrointestinal malignancy and coeliac disease.

• Colonoscopy — to exclude a colonic neoplasm.

If these investigations are normal, the patient can be treated with oral iron replacement therapy (p. 202) and only investigated further should anaemia recur.

Further investigations

• Small bowel follow-through is often the next investigation but diagnostic yield is low and many advocate proceeding straight to capsule endoscopy.

• Wireless capsule endoscopy involves swallowing a tiny video camera which is moved by peristalsis though the bowel and transmits images to a recorder carried on a belt.

• New enteroscopic techniques with a single and double balloon show a similar diagnostic yield to the wireless capsule.

• Radio-labelled red cell scan involves red blood cells labelled with ^99-technetium, which are given intravenously to the patient and passed into the gut at the point of bleeding. This is detected as a pool of tracer by a gamma camera but a minimum bleed rate of approximately 0.1 mL/min is required. If positive, this technique can localize the bleeding source in 80% of cases.

• Mesenteric angiography.

Treatment

Individual diagnoses are treated as appropriate.

Malabsorption

Coeliac disease

Coeliac disease (CD) is a chronic inflammatory response to the gliadin component of gluten in patients who are mainly DQ2/DQ8-positive. Gluten is contained in cereals, wheat, rye and barley. There is a loss of villi (villus atrophy) with crypt hyperplasia in the mucosa of the proximal small bowel and an increase in intra-epithelial lymphocytes. Coeliac disease can present at any age. Patients can be asymptomatic or present with non-specific tiredness and malaise or gross malnutrition. Routine blood tests showing anaemia, with a combination of iron, B12 or folate deficiency, is now a common presentation. Common gastrointestinal symptoms range from diarrhoea, steatorrhoea, abdominal bloating, mouth ulcers and angular stomatitis.

Investigations

These include:

• Anti-tissue tranglutaminase IgA antibodies. This cheap, quick ELISA technique has high sensitivity (85–100%) and specificity (97–100%). Levels return towards normal within 1–2 months of starting a gluten-free diet. The test is therefore useful in monitoring compliance.

• Anti-endomysial IgA antibodies. This immunofluorescence technique uses umbilical cord tissue and has high sensitivity (84–100%) and specificity (94–100%).

• IgA deficiency. IgA-deficient patients are 10–20 times more likely to develop coeliac disease and have false-negative serological tests.

• HLA DQ2/DQ8. A positive test demonstrates a high risk of having coeliac disease.

• Duodenal biopsies. Gastroscopy with four distal duodenal biopsies still represents the gold standard for diagnosis.

Management

All patients with coeliac disease should be referred to a dietitian for a gluten-free diet (GFD). The avoidance of gluten should be emphasized even in the asymptomatic patient because of the increased risk of osteoporosis and malignancy (which is reduced by a strict diet). Folate deficiency is present in 50% of patients and iron deficiency is common; initial replacement therapy is given. Most patients respond to a GFD; a few require corticosteroids or azathioprine. All patients diagnosed with coeliac disease should undergo a bone densitometry scan (dual energy X-ray absorptiometry, DEXA) to assess for osteoporosis, which should be treated with bisphosphonates (p. 324), and monitored yearly. Pneumococcal vaccination is necessary due to the occurrence of splenic atrophy.

Dermatitis herpetiformis is a gluten-sensitive enteropathy with a subepidermal, blistering rash, mainly on the extensor surfaces. It is treated with dapsone 50–200 mg and a gluten-free diet.

Tropical sprue

This condition presents with diarrhoea and malnutrition due to malabsorption of two or more substances (particularly of fat and vitamin B₁₂). It occurs in residents in and visitors to affected tropical areas. There is partial villous atrophy of the mucosa throughout the small bowel. The cause is unknown. Most patients improve on leaving the sprue area and taking folic acid 5 mg daily. Tetracycline 1 g daily for ∼6 months is required by patients with more severe symptoms.

Bacterial overgrowth

Bacterial overgrowth of the small bowel occurs when there is intestinal stasis due to a structural or motility abnormality of the gut. Examples include jejunal diverticulosis, post-surgical intestinal blind loops, intestinal strictures or fistulae, and motility abnormalities such as autonomic neuropathy secondary to diabetes and radiation enteropathy. The diarrhoea is due to bacterial deconjugation and dehydroxylation of bile salts. Bacteria also metabolize B₁₂, which can cause a macrocytic anaemia.

Investigations

Investigation is with a glucose-hydrogen breath test, in which an orally ingested glucose load is given and expired hydrogen measured. Metabolism of the glucose in the small intestine by bacteria causes a characteristic early rise in breath hydrogen. A barium follow-through or small bowel MRI will exclude a structural abnormality of the small bowel.

Treatment

Underlying structural abnormalities should be corrected if possible. Rotating 2-week courses of antibiotics, usually metronidazole 400 mg 3 times daily, co-amoxiclav 250–500 mg 3 times daily and ciprofloxacin 500 mg twice daily, form the mainstay of treatment.

Bile salt malabsorption

Bile salts are synthesized from cholesterol and conjugated with glycine or taurine in the liver. They are excreted via the biliary tree into the duodenum, where they solubilize lipids in micelles, allowing fat absorption. They are reabsorbed in the distal small intestine and are later re-secreted by hepatocytes. Bile acid malabsorption usually occurs in patients who have undergone ileal resection but it is also occasionally encountered as a primary condition. Diarrhoea occurs, as the failure to reabsorb bile salts in the ileum leads to their accumulation in the colon, where they cause diarrhoea by reducing water and electrolyte absorption and increasing colonic motility.

Investigations

The SeHCAT test involves administering a fixed dose of radio-labelled ⁷⁵Se-homochoyl taurine, a bile acid analogue. A percentage retention at 7 days is calculated, with normal individuals retaining more than 15%.

Treatment

Treatment is with colestyramine 4–8 g daily in water, which forms an insoluble complex with bile acids. It should be taken 1 hour after or 4–6 hours before other drugs, as it can interfere with absorption. It is unpalatable and poorly tolerated, and causes constipation.

Massive intestinal resection (short-bowel syndrome)

This most often occurs following resection for Crohn’s disease, mesenteric vessel occlusion, radiation enteritis or trauma. There are two common situations:

• Shortened small intestine ending at a terminal small bowel stoma. The major problem is sodium and fluid depletion, and the majority of patients with 100 cm or less of jejunum remaining will require parenteral supplements of fluid and electrolytes, often with nutrients. Sodium losses can be minimized by increasing salt intake, restricting clear fluids between meals and administering oral glucose–electrolyte mixture with a sodium concentration 90 mmol/L. Jejunal transit time can be increased and stomal effluent loss of fluids and electrolytes reduced by treatment with the somatostatin analogue octreotide 200 mcg SC 3 times daily, and to a much lesser extent with loperamide, codeine phosphate or co-phenotrope. There is no benefit to a low-fat diet, but fat assimilation can be increased on treatment with colestyramine and synthetic bile acids.

• Shortened small intestine in continuity with colon. Only a small proportion of these patients require parenteral supplementation of fluid, electrolytes and nutrients because of the absorptive capacity of the colon for fluid and electrolytes. Unabsorbed fat results in impairment of colonic fluid and electrolyte absorption, so patients should be on a low-fat diet. A high carbohydrate intake is advised, as unabsorbed carbohydrate is metabolized anaerobically to short-chain fatty acids (SCFAs), which are absorbed, stimulate fluid and electrolyte absorption in the colon and act as an energy source (1.6 kcal/g). Patients are often treated with colestyramine to reduce diarrhoea and colonic oxalate absorption.

Inflammatory bowel disease

Inflammatory bowel disease (IBD) comprises two major forms, Crohn’s disease and ulcerative colitis. Both are idiopathic, lifelong, inflammatory diseases of the gastrointestinal tract. Microscopic ulcerative, microscopic lymphocytic and microscopic collagenous colitis also occur.

• Crohn’s disease (CD) is characterized by chronic transmural granulomatous inflammation with a tendency to form strictures and fistulae. It can affect any part of the gastrointestinal tract, and often does so in discontinuity to form skip lesions. Most commonly it affects the terminal ileum and ascending colon (ileocolonic disease). CD is classified according to the site, extent and pattern of disease. These factors govern the clinical symptoms. Active CD characteristically produces the triad of abdominal pain, diarrhoea and weight loss, although the preponderance of each symptom (as well as malaise, fever and anorexia) will vary. Small bowel CD is often complicated by the development of luminal stenosis due to inflammatory or fibrotic strictures, leading to obstructive symptoms. Colonic CD is less often complicated by obstruction and tends to cause more severe diarrhoea. However, in contrast to ulcerative colitis, significant rectal bleeding is less common. Anal and perianal involvement is common.

• Ulcerative colitis (UC) is a more superficial inflammation than that of CD, and usually involves only the mucosa. It affects only the large bowel, although in rare cases there can be a ‘backwash ileitis’. UC usually involves the rectum (proctitis) but extends proximally in continuity to a varying extent, often to affect the whole colon (total colitis). Bloody diarrhoea is the characteristic symptom of ulcerative colitis. During severe acute attacks systemic features such as anorexia, fever and malaise are also common. There is an increased incidence of cancer with pancolitis of over 10 years’ duration.

Investigations

• Blood tests. Platelets, ESR and CRP are often raised in acute flares of CD but less so in UC. Low albumin levels occur with chronic active disease.

• Colonoscopy. This is useful both diagnostically and because it allows assessment of colitis and terminal ileal disease.

• Imaging

• Small bowel follow-through is useful for diagnosing and assessing small bowel CD, particularly small bowel strictures.

• CT enterography also detects pathology outside of the intestine.

• MR enterography is being increasingly used, as it does not involve radiation. Pelvic MRI is used to assess perianal fistulae in CD.

• Capsule endoscopy is a technique used to image the small bowel. It is useful in diagnosing small bowel CD when other tests have been negative, in assessing disease activity in known CD and in differentiating indeterminate colitis from CD.

• Labelled white cell scanning involves radio-labelled white cells that are taken up preferentially by areas of inflammation. This technique is most useful in assessing the extent of disease involvement.

• Plain abdominal X-ray is useful for assessing colonic dilatation in acute colitis and in excluding perforation.

Treatment

The aim of treatment is to induce and then maintain remission. It therefore depends on disease activity, with some treatment being used for acute flairs (corticosteroids), some for maintenance of remission (immunosuppressants) and some for both (5-aminosalicylates). All drug therapy has side-effects and patients should be warned of this and told to report any problems immediately to their doctor.

Drugs used in the treatment of IBD (Box 5.4)

Aminosalicylates

These comprise a range of different formulations, all of which deliver 5-aminosalicylate (mesalazine) in millimolar concentrations to the gut lumen. The site in the gastrointestinal tract at which the 5-ASA moiety is released determines the choice of agent.

• Formulations

These drugs should be prescribed with their proprietary names stated as the different formulations are not interchangeable.

• Oral preparations. These differ, depending on method of delivery.

a) Carrier molecules: sulfasalazine is from the older generation of aminosalicylates. The 5-ASA moiety is linked to a sulfapyridine carrier molecule and is released after splitting by bacterial enzymes in the large intestine. Olsalazine (a dimer of 5-ASA) and balsalazide (a prodrug of 5-ASA) are without the sulfapyridine carrier molecule and therefore lack the sulphonamide side-effects. They are recommended for use in disease affecting the descending and sigmoid colon.

b) pH-dependent release mechanisms/resin-coated: mesalazine. This type is recommended for use in colonic disease.

c) Time-controlled: 5-ASA microspheres are recommended for use in ileocolonic disease.

• Topical preparations. Mesalazine can be given as rectal suppositories to treat rectal disease (proctitis), and as liquid and foam enemas to treat sigmoidal and descending colonic disease (left-sided disease).

• Indications

• Maintaining remission. There is little evidence to support 5-ASA use as maintenance therapy in CD, but as these compounds are generally well tolerated with few adverse effects they are often prescribed. Aminosalicylates are effective in maintaining remission in patients with UC and are first-line therapy. There are also weaker data to suggest that long-term 5-ASA use may reduce the long-term increased risk of colorectal cancer in UC. There are little comparative data between 5-ASA compounds and most generally seem to be equally effective. Choice depends on tolerability, cost and disease distribution. Once-daily dosing is now advocated with several compounds as maintenance treatment. Regular topical use may be required in left-sided disease or proctitis.

• Active disease. There is little evidence to support the use of 5-ASA in acute CD. Mesalazine slow-release 4 g/day has been shown to be more effective than placebo in causing clinical improvement in patients with active Crohn’s ileocolitis but clinical significance is debatable. Sulfasalazine may be useful in the treatment of mild colonic CD. There is good evidence to support the use of 5-ASA in active UC. Either starting with or increasing to high-dose mesalazine (> 3 g/day) induces remission in 50% of patients with mildly/moderately active UC. The addition of 5-ASA enemas to high-dose oral 5-ASA has been shown to increase remission rates further. Suppositories 1 g once daily and enemas of mesalazine 1 g twice daily are useful in treating acute proctitis and left-sided disease.

• Adverse effects

• 5-ASA are generally well tolerated, with few adverse effects. Intolerance is 15%. Diarrhoea occurs in 3%, headache in 2%, nausea in 2% and rash in 1%. Renal impairment can rarely occur; blood disorders occur and patients should be advised to report unexplained bleeding, bruising or sore throat.

• Sulfasalazine has more adverse effects than other 5-ASA due to the sulfapyridine carrier molecule. These occur in 10–45%. Minor effects include headache, nausea and diarrhoea. Hypersensitivity reactions are rare but other major effects include rash, fever, agranulocytosis, pancreatitis, alveolitis and toxic epidermal necrolysis. Reversible sperm count reduction can occur in males.

Corticosteroids

Corticosteroids are potent anti-inflammatory agents that reduce the production of inflammatory cytokines and promote apoptosis in various inflammatory cell types.

• Formulations

• Oral preparations. Prednisolone is the most commonly used preparation. Budesonide is an oral steroid with a high first-pass metabolism. The low systemic availability leads to reduced systemic side-effects compared with oral prednisolone.

• IV preparations. Hydrocortisone is the IV steroid formulation most commonly used in IBD (100 mg 4 times daily).

• Topical preparations. Prednisolone is used as suppositories and liquid and foam enemas.

• Indications

• Maintaining remission. There is no role for steroids in maintaining remission.

• Active disease. Prednisolone 0.5–0.75mg/kg induces remission in approximately 60–80% patients with active CD. The starting dose is usually 40 mg orally once daily and it is then reduced by approximately 5 mg every 5–7 days. A more gradual dose reduction can be used for patients who have initially responded to prednisolone but have then relapsed on the lower doses. A starting dose of 60 mg is occasionally used for patients who have not responded to 40 mg, although the incidence of adverse events is significantly increased. Starting doses of < 15 mg are generally not effective. Budesonide is slightly less effective than prednisolone but is useful in moderately active terminal ileal/ascending colonic CD (3 mg 3 times daily) and, due to the lower frequency of long-term side-effects, longer courses can be given. IV steroids (hydrocortisone 100 mg 4 times daily) are used when the patient has either not responded to oral prednisolone or is so ill that hospital admission is required. Oral prednisolone induces remission in ∼80% of patients with active UC. Dosing is similar to that used in Crohn’s disease. Prednisolone can also be given topically in distal colitis and proctitis but is generally less effective than topical 5-ASA therapy. Sometimes topical 5-ASA and steroid therapy may be given in combination. As with CD, IV steroids are given to those who have not responded to oral steroids or who require hospital admission.

• Adverse effects (see Box 15.2, p. 585). Around 50% of patients report adverse effects with steroid use.

• Short term — acne, moon face, oedema, sleep disturbance, agitation, increased appetite, weight gain and impaired glucose tolerance.

• Long-term — associated with > 12-week use: osteoporosis and the rarer osteonecrosis of the femoral head, cataracts, myopathy and susceptibility to infection. DEXA scans for osteoporosis are performed every 2–5 years.

• Steroid withdrawal — adrenal insufficiency (p. 582) if not withdrawn gradually, myalgia and malaise.

Thiopurines

Thiopurines are purine antimetabolites that inhibit ribonucleotide synthesis, leading to T-cell apoptosis.

• Formulations

• Azathioprine and 6-mercaptopurine. Azathioprine is metabolized to mercaptopurine, which is in turn metabolized to 6-thioguanine, the principal active metabolite.

• Indications

• Maintaining remission. Thiopurines have been shown to be effective in inducing and maintaining remission in CD and UC. Azathioprine is usually given at a dose of 2 mg/kg and mercaptopurine 1–1.5 mg/kg, although this will depend on blood monitoring (see below). In a Cochrane review the odds ratio for maintaining remission in CD was 2.2, with a number needed to treat of 7. Thiopurines are used as a steroid-sparing agent in steroid-dependent and steroid-resistant CD and UC. There is no absolute rule as to when they should be started but they are used in patients who have required two or more courses of steroids in 12 months or those who have relapsed within 6 weeks of a previous course. The duration of use is not clear-cut, but current guidelines suggest that thiopurines should be used for 3–4 years and then discontinuation should be discussed with the patient if there are no signs of active disease.

• Active disease. Although thiopurines have been shown to be effective in active disease, the delay in onset of action (up to 3 months) limits their use as an immediate treatment.

• Adverse effects

• Minor: intolerance — up to 20% of patients develop myalgia, headache, nausea or diarrhoea, usually within 2–3 weeks of starting thiopurines. This usually resolves without stopping the drug.

• Major: profound leucopenia develops in 3% of patients. It can occur at any time during treatment, although it is commonest during the initiation phase. FBC monitoring is recommended, at least monthly for the first 2 months of treatment and 3–6-monthly thereafter. Leucopenia is commoner in individuals with deficiency of thiopurine methyltransferase (TPMT) activity, an enzyme involved in thiopurine metabolism. Many experts therefore advocate routine TPMT testing with 50% dose reduction in heterozygotes for TPMT activity and complete avoidance of use in homozygotes. Hepatotoxicity and pancreatitis occur in less than 5% of individuals. Liver biochemistry should be measured simultaneously with FBC.

Mycophenolate mofetil

This is an antiproliferative immunosuppressant agent and stops the proliferation of T- and B- lymphocytes. It is used in the same way as azathioprine.

Methotrexate

Methotrexate inhibits dihydrofolate reductase, an enzyme involved in purine synthesis and DNA/RNA synthesis.

• Indications

• Maintaining remission. Methotrexate 10–20 mg orally once weekly has proven benefit as a second-line steroid-sparing agent in CD (40% of patients steroid-free at 3 months). There is less evidence for its use in UC.

• Active disease. Slow onset of action (4–6 weeks) limits the use of methotrexate as a sole agent in the treatment of active UC or CD.

• Adverse effects

• Minor: nausea, vomiting, malaise, fatigue and stomatitis. (The latter is reduced by co-prescription of folic acid 5 mg orally, given 24 hours after the methotrexate.

• Major: Hepatotoxicity (fibrosis/cirrhosis) and leucopenia occur. Regular blood monitoring should be carried out weekly until the dose is stabilized, and then 3-monthly. Pneumonitis occurs rarely.

Ciclosporin

Ciclosporin, a calcineurin inhibitor, is a potent immunosuppressive agent preventing the clonal expansion of T-cell subsets.

• Indications

• Maintaining remission. Oral ciclosporin is occasionally used as maintenance therapy in chronic active UC.

• Active disease. IV ciclosporin 2 or 4 mg/kg/day is used as salvage therapy for patients with acute, severe UC whose only other therapeutic option is colectomy (p. 164). Initial response rates are ∼60%, although the percentage of patients avoiding colectomy in the longer term is lower (30–40%).

• Adverse effects

• Minor: occur in 30–50% and include tremor, paraesthesiae, malaise, headache and abnormal liver biochemistry.

• Major: occur in 0–15% and can be life-threatening. These include neurotoxicity, renal impairment and infections. Risk of seizure is increased in patients with a low cholesterol (< 3.0 mmol) or low magnesium (< 0.5 mmol) and a reduced dose or oral preparation can be used in these circumstances. Mortality rates of 2% are reported. BP, FBC, renal function and ciclosporin concentration (trough 100–200 ng/mL) should be measured during therapy.

Biological agents/cytokine modulators

Infliximab is a chimeric (human/mouse) monoclonal antibody against tumour necrosis factor-alpha. It has potent anti-inflammatory actions and although the precise mechanism is unknown in IBD it is likely to involve apoptosis of T-cells. Adequate resuscitation facilities should be available.

• Indications

• Maintaining remission. Regular 8-weekly maintenance infusions in both fistulizing and non-fistulizing CD are more effective then placebo in maintaining remission. Cost, however, may limit availability of this strategy. Antibodies can develop to infliximab, limiting its efficacy, and are more common with sporadic use than with maintenance infusions. Maintenance infusions have been shown to be effective in maintaining remission in UC but are less commonly used than in CD.

• Active disease. Around 80% of patients with inflammatory CD refractory to 5-ASA, corticosteroids and/or immunomodulators respond to IV infusions of infliximab 5 mg/kg at 0, 2 and 6 weeks. Expert advice should be sought. Around 70% patients with refractory fistulizing CD respond to a course of 3 infusions at 0, 2 and 6 weeks (5 mg/kg).

Between 50 and 70% of patients with chronic active refractory UC respond to infusions of 5 mg/kg at 0, 2 and 6 weeks, then 5 mg/kg every 8 weeks, although this is more controversial than in CD. Discontinue if there is no response after 1–2 doses. A single infusion of infliximab 5 mg/kg has also been shown to reduce colectomy rates in fulminant colitis compared to placebo and may be an alternative rescue therapy to ciclosporin.

• Adverse effects: Infusion reactions occur and respond to slowing infusion rate and treatment with antihistamines, paracetamol and corticosteroids. Patients should be monitored during infusions. Up to 60% of patients form antibodies against infliximab and this can shorten the duration of response and predispose to an infusion reaction. Risk from delayed hypersensitivity reactions increases if the drug-free interval is over 16 weeks. There is an increased incidence of infection and specifically disseminated TB. Active sepsis is therefore an absolute contraindication. All patients should be screened for TB, with history and CXR prior to treatment. Certain patients may require TB prophylaxis. Development of anti-dsDNA antibodies and lupus-like syndrome is a rare but recognized side-effect.

Adalimumab is a fully human IgG, anti-TNFα monoclonal antibody used for inducing and maintaining a clinical remission; it is given as for active CD as 160 mg at week zero and 80 mg at week 2, and 40 mg alternate weeks thereafter. Dose escalation to 40 mg weekly may be required in the longer term. Trials have shown similar efficiency to infliximab. Adalimumab is now being used as first-line biological therapy, as is infliximab.

Certolizumab pegol is a humanized anti-TNF Fab′ monoclonal antibody fragment; it is attached to polyethylene glycol. It is used for inducing and maintaining a remission in moderate to severe active CD as a second-line biological agent.

Natalizumab, a humanized monoclonal IgG₄ antibody that binds to α₄ integrin, is effective in inducing and maintaining remissions and is used as a second-line agent.

Antibiotics

Antibiotics alter bacterial flora. Their beneficial action is consistent with the hypothesis that inflammation in IBD is driven by an inappropriate reaction to bacterial flora.

• Indications

• Active disease. Both metronidazole 500 mg 3 times daily and ciprofloxacin 500 mg twice daily are established treatments for active perianal CD. They can be used in combination or in rotation for a relatively long course (4 weeks). Metronidazole has also been used to treat luminal CD, although it is now generally not recommended.

• Adverse effects. Peripheral sensory neuropathy can develop with long-term (> 4 weeks) use of metronidazole. Patients should avoid alcohol because of a disulfiram-like reaction causing facial flushing. For ciprofloxacin side-effects, see p. 83; for metronidazole, see p. 84.

Antidiarrhoeals

Antidiarrhoeals (p. 136) may be useful in certain patients but should not be used in patients with acute, severe disease.

Diet/lifestyle

• Smoking. All patients with CD should stop smoking.

• Diet. In general, patients with IBD should eat a normal diet and be encouraged to maintain a normal weight. Patients with small bowel strictures and symptoms of subacute obstruction should adhere to a low-residue diet.

• Probiotics and pre-biotics. Probiotics are live attenuated bacteria or bacterial products which, when ingested, modify the composition of the enteric flora. Pre-biotics are non-digestible food supplements that are fermented by host bacteria, stimulating their growth. Probiotics have been shown to be of benefit in pouchitis and may be useful in UC.

• Haematinics. Serum levels should be measured annually and replaced as necessary. Individuals with CD who have had a terminal ileal resection are at particular risk of B₁₂ deficiency.

• Indications — active Crohn’s disease. Elemental diets (p. 126), when given as the sole nutritional source, achieve similar rates of remission to oral steroids. In paediatric patients they are particularly useful as an alternative to steroids, which cause growth retardation.

• Adverse effects. Elemental diets are usually unpalatable and poorly tolerated.

Surgery

• Indications

• Maintaining remission. Surgery is not performed for quiescent disease but may be of use in relieving stricturing disease. Colectomy is sometimes recommended in patients with UC and high-grade dysplasia.

• Active disease. Surgery is generally only undertaken when other treatment options have failed, but nevertheless 80% of patients with CD will require an operation at some time during the course of their disease. The range of surgical options for CD is variable, reflecting the diverse nature of the disease. Local resection or stricturoplasty is performed for localized stricturing disease. Attempts are always made to preserve as much bowel as possible, as multiple operations may be required, which can culminate in intestinal failure (short bowel syndrome, p. 155) and a need for lifelong parenteral nutrition. Colectomy may be required for colonic disease but ileal recurrence is common. Abscess drainage and seton insertion are often required for perianal disease. Pan-proctocolectomy with ileo-anal pouch formation is the surgical procedure of choice for patients with UC that has proven refractory to medical therapy. This is usually performed as a two-stage operation, with initial removal of the colon with an ileostomy. The procedure is often performed semi-electively in individuals with chronic active disease but can be performed as an emergency for patients with toxic megacolon who are at risk of perforation. An ileo-anal pouch is then formed at further surgery some months later.

Pouchitis occurs in one-third of these patients with diarrhoea and bleeding. Treatment in severe cases is unsatisfactory but antibiotics for active disease (ciprofloxacin, metronidazole) and probiotics for maintenance of remission, e.g. lactobacilli, bifidobacteria, form the mainstay of treatment.

• Adverse effects. These are the same as for all abdominal surgery, although in addition patients with CD are at greater risk of forming post-operative fistulae.

Acute severe colitis

Acute severe colitis can occur in patients with UC and CD (but remember it can also occur with C. difficile infection). It presents with diarrhoea (> 6 stools/day), fever > 37.5° and tachycardia > 90 bpm. Investigations show an anaemia (< 10 g/dL), a high ESR and a low serum albumin (< 30 g/L). A plain abdominal x-ray can show a thin-walled dilated colon (> 5 cm, or 8 cm in caecum) that is gas-filled and contains mucosal islands (toxic megacolon) (Fig. 5.2). Daily X-rays are required, as perforation occurs, with a mortality of up to 25%.

Fig. 5.2 Plain abdominal X-ray showing toxic dilatation. The arrows indicate mucosal islands.

Treatment

Treatment is urgent and should be supervised by an experienced physician and colo-rectal surgeon. Fluid and electrolyte imbalance should be corrected. IV hydrocortisone 100 mg 4 times daily is given. If there is no response in 48–72 hours and the CRP continues to be elevated > 45 mg/L, a second-line agent is commenced. Ciclosporin 2 mg/kg IV, accompanied by enteral nutrition for 5–7 days, can be used as a bridge to try to avoid surgery. Infliximab is used similarly (p. 161). The decision to proceed to surgery is often complex. In general, surgery is required if there is a toxic megacolon which does not respond rapidly to medical treatment, or if second-line treatment fails. If C. difficile infection is the cause of the severe colitis, do not treat with steroids and use vancomycin.

Pregnancy and IBD

Women with inactive IBD have normal fertility. Active disease reduces fertility and increases the number of spontaneous abortions. Although the risk of exacerbations is not increased, if they do occur, they often occur in the first trimester and immediately post partum. Aminosalicylates, steroids and azathioprine are safe at the time of conception and pregnancy. Biological/cytokine modulators e.g. infliximab or adalimumab are thought to be safe in the first trimester. Methotrexate is completely contraindicated in pregnancy.

Colonic and anal disorders

Acute colonic pseudo-obstruction

Acute colonic pseudo-obstruction (Ogilvie’s syndrome) is a motility disorder characterized by massive colonic dilatation in the absence of an obstructing lesion. Around 90% of cases occur in association with other medical conditions such as sepsis or renal or respiratory failure, or after surgical procedures. Drugs, e.g. narcotic analgesics and tricyclic antidepressants, are often causative. The condition results in spontaneous perforation in 3–15% of cases, with an associated mortality of 40–50%.

Clinical features

Symptoms include abdominal distension, colicky pain, absolute constipation, and nausea and vomiting.

Investigations

• CT scan should always be used to exclude an obstructing lesion.

• A water-soluble contrast enema can both exclude obstruction and liquefy remaining stool.

• Colonoscopy can also be useful, both diagnostically and therapeutically (see below).

Management

• Conservative therapy resolves 75% of cases within 24–48 hours.

• Nil by mouth and a naso-gastric tube limit further gaseous distension and prevent vomiting, and mobilization measures include rolling the bed-bound patient regularly and encouraging the ambulatory patient to walk. Electrolyte disturbances (potassium, calcium, magnesium and phosphorus) should be corrected and medications, e.g. narcotics, antimuscarinics, sedatives or calcium channel blockers, should be stopped. Total parenteral nutrition is indicated in very protracted cases.

• Neostigmine, an inhibitor of cholinesterase given as an IV 2 mg bolus over 3–5 mins, leads to a resolution in 90% of cases. It can be repeated once if unsuccessful on the first occasion. Transient bradycardia can occur and patients should be monitored during drug administration.

• Endoscopic colonic decompression is indicated if the caecal diameter is > 9 cm or the patient has failed to respond to other therapies. It is technically difficult, with a perforation rate of 1–3%, but is initially successful in 70% of cases. Daily plain abdominal X-rays should be performed to detect recurrence.

• Surgery is indicated for those cases where there are signs of colonic perforation or when the patient has failed to respond to medical and endoscopic therapy and perforation is imminent (caecal diameter > 9 cm). Caecostomy is the procedure of choice.

Diverticular disease

Diverticula are pouches of mucosa that extrude through the colonic wall. They are almost ubiquitous in the Western world, possibly due to the low-fibre diet.

• Diverticulosis refers to the presence of diverticula and is asymptomatic.

• Diverticulitis refers to inflamed diverticula with associated intramural or extracolonic inflammation. It presents with left-sided abdominal pain and tenderness, as diverticula are commonest in the sigmoid colon in the developed world. A palpable tender mass may be present in the left iliac fossa. There may be altered bowel habit, and diverticulitis is usually associated with constipation. Patients may feel generally unwell and have a fever. Diverticula (particularly right-sided) are a cause of massive lower gastrointestinal bleeding (p. 152).

Investigations

• Blood tests. Diverticulitis is usually associated with a high white cell count and raised ESR and CRP.

• CT scan. This will show colonic wall thickening, diverticula and any pericolic collections and abscesses.

• Colonoscopy. Diverticula are usually diagnosed as a coincidental finding at colonoscopy. Colonoscopy is contraindicated if acute diverticulitis is suspected, due to the risk of perforation.

Treatment

Mild cases of diverticulitis can be managed with oral antibiotics (cefalexin 500 mg 3 times daily or ciprofloxacin 500 mg twice daily plus metronidazole 400 mg 3 times daily) and laxatives. Cases with systemic upset, fever and a raised white cell count should be admitted to hospital for bowel rest (patients are kept nil by mouth and hydrated with IV fluids — 0.9% saline with 20 mmol/L K⁺) and antibiotics (cefuroxime 750 mg IV 3 times daily and metronidazole 500 mg IV twice daily). Once the acute attack has resolved, patients may be given laxatives (ispaghula husk 1 sachet twice daily) to avoid constipation and to reduce the likelihood of further attacks. Surgical intervention is only required for complications such as abscess or fistula formation, perforation and repeated attacks.

Ischaemic disease of the colon (ischaemic colitis)

Occlusion of the branches of the superior or inferior mesenteric arteries, often in the older age group, commonly presents with sudden abdominal pain and the passage of bright red blood from the rectum, with or without diarrhoea. The lesion usually affects the splenic flexure and settles with conservative management. A few patients need surgery.

Perianal disorders

Haemorrhoids

Haemorrhoids are engorged veins at the ano-rectal junction. They develop due to excessive straining at stool and can prolapse. Rectal bleeding is usually bright red and seen separate to the stool in the pan or on the toilet paper; pruritus ani and perianal pain occur. Proctoscopy shows haemorrhoids classically in the 3, 7 and 11 o’clock position. Haemorrhoids can thrombose and become acute, painful, tense, bluish lumps in the perianal area. Other more serious causes of rectal bleeding should be excluded with flexible sigmoidoscopy.

• Treatment

• Local anaesthetic creams are often combined with corticosteroids. There are many different formulations available (e.g. dibucaine 0.5%, hydrocortisone 0.5%, aluminium acetate 3.5%, hydrocortisone 0.275% and lidocaine 5%).

• Stool softeners are given to reduce straining at stool.

• Oral analgesics may be required for thrombosed haemorrhoids (paracetamol 1 g 4 times daily).

• Injection with phenol (5%) under direct vision acts as a local sclerosant; band ligation can also be performed.

• Haemorrhoidectomy is reserved for cases where other measures have failed and symptoms are severe. Thrombosed haemorrhoids can be excised in severe cases.

Anal fissures

Anal fissures are acute tears in the skin lining the anal canal and are caused by the passage of hard stool. They usually heal in 2–3 weeks. They cause severe anal pain, particularly during defecation. On proctoscopy, fissures are usually seen as posterior elliptical tears. Local anaesthetic creams are available over the counter. Glyceryl trinitrate (0.4%) and diltiazem (2%) creams help to relax the sphincter spasm, facilitating healing. Laxatives in the form of stool softeners reduce symptoms.

Perirectal abscesses

These present as painful, indurated swellings in the perianal area. They can occur de novo or in association with inflammatory bowel disease. Examination under anaesthetic (EUA), MRI and endoanal US is used to outline the position and extent of the abscess. Surgical drainage is required for the majority, with antibiotics (cefuroxime 750 mg IV 3 times daily or oral cefalexin 500 mg 3 times daily and metronidazole 500 mg IV 3 times daily or 400 mg orally 3 times daily).

Perianal fistulae

These develop from perianal abscesses and present with chronic perianal discharge. Management of those associated with Crohn’s disease is described on p. 162. MRI scan and EUA are usually required, followed by surgical treatment, with 90% being either laid open or excised.

Functional gastrointestinal disorders

This term refers to a collection of overlapping disorders with symptoms attributable to the gastrointestinal tract but where no organic disease can be found. Investigations, if necessary, are performed to exclude relevant organic pathology, but many of the disorders can be diagnosed by the history alone. These disorders have been characterized by an international committee (Rome III 2006) into specific disorders but in clinical practice there is enormous overlap.

Functional oesophageal disorders (heartburn, chest pain of presumed oesophageal origin, dysphagia, globus)

Symptoms include heartburn (p. 139), chest pain and dysphagia. Dysphagia usually requires investigation with an endoscopy to exclude other oesophageal pathology. A barium swallow and oesophageal manometry help to exclude a motility disorder, e.g. achalasia. Globus describes an intermittent sensation of a lump in the throat.

Treatment

• PPI therapy (Table 5.1) may be beneficial in some patients, particularly those with heartburn (p. 59).

• Nitrates, e.g. GTN spray, and calcium channel blockers, e.g. buccal nifedipine 10 mg, occasionally help. A low-dose tricyclic antidepressant, e.g. amitriptyline 10 mg daily, has been shown to be effective in some patients, particularly those with associated depression. Antimuscarinic side-effects include constipation, dry mouth and urinary retention. Fatigue is also common and treatment should be taken at night.

Functional gastroduodenal disorders (dyspepsia, belching, nausea and vomiting, rumination syndrome in adults)

Dyspepsia is the second commonest functional disorder, causing upper abdominal discomfort, bloating, early satiety and nausea. Nausea is common in association with functional gastrointestinal disorders but vomiting is rare. Self-induced vomiting compatible with an eating disorder should be excluded. OGD is required in patients > 55 years of age with a short history or alarm features (p. 134). Nausea does not warrant investigation, particularly in the young and in patients with no alarm symptoms. Simple blood tests may help to reassure the patient.

Functional bowel disorders (irritable bowel syndrome, bloating, constipation, diarrhoea)

Irritable bowel syndrome (IBS) is the commonest functional gastrointestinal disorder, with 1 in 5 people in developed countries reporting compatible symptoms. Many patients do not fulfil all the criteria but this should not prevent the diagnosis being made. The usual symptoms are lower abdominal pain relieved by defecation, increased frequency of defecation (> 3 per day) or constipation (< 3 per week), a variable stool consistency, and bloating and wind. These symptoms can be classified separately as constipation-predominant, diarrhoea-predominant or mixed IBS. In addition, non-intestinal symptoms are common, e.g. painful periods, dyspareunia, urinary frequency, back pain, fibromyalgia, fatigue and insomnia.

Treatment

• Reassurance and explanation of the symptoms are often all that is required.

• Pharmacotherapy is largely symptomatic and depends on the predominant symptom.

• Antimuscarinics. These are thought to relax intestinal smooth muscle and reduce pain but have little effect on stool frequency. The most commonly used preparation is hyoscine butylbromide 10 mg 3 times daily. Dicycloverine hydrochloride 10–20 mg 3 times daily is used less frequently due to its greater side-effect profile. Antimuscarinic side-effects include constipation, urinary urgency and retention, dry mouth, and rarely transient bradycardia and arrhythmias. These drugs are contraindicated in closed-angle glaucoma, paralytic ileus, myasthenia gravis and prostatic enlargement.

• Antispasmodics. Those used to treat IBS include mebeverine 135 mg 3 times daily and peppermint oil 1–2 capsules 3 times daily. Side-effects: allergy has been reported rarely.

• Laxatives. Constipation-predominant IBS may respond to simple laxatives, which are available both on prescription and over the counter (p. 137). Bulk-forming laxatives may exacerbate symptoms of bloating and in this situation osmotic laxatives may be more beneficial.

• Antidiarrhoeal agents. These may be effective in diarrhoea-predominant IBS (p. 136).

• Tricyclic antidepressants. Low-dose tricylics, such as amitriptyline, have been shown to reduce symptoms in a number of randomized placebo-controlled trials. The mechanism of action is unknown but may involve a reduction in the sensitivity of enteral nerves. A meta-analysis indicated an odds ratio of 4 for benefit of these drugs compared to placebo. There is some evidence to suggest that they are more effective in diarrhoea-predominant IBS. Tricyclics are recommended for moderate to severe IBS with a predominant symptom of pain. They should be started at a dose of 25 mg. Doses < 30 mg seem most effective but the dose can be escalated to 100 mg if there is no response and providing they are tolerated. An attempt should be made to taper the dose after 12 months.

• Selective serotonin reuptake inhibitors. Good evidence to support their use is lacking. They should be reserved for when there is an active mood disorder or when tricyclics have failed. In constipation-predominant IBS, paroxetine 20 mg daily is helpful.

• Non absorbable antibiotics. Rifaximin has recently been shown to help IBS patients without constipation.

• Other drugs. 5HT4 agonists e.g. prucalopride improve colonic transit and can improve symptoms in constipation. Cisapride and tegaserod were withdrawn as they were not sufficiently GI selective in women and caused long QT syndromes. However the newer 5HT4 agonist, Prucalopride, is now licensed for the treatment of functional constipation and constipation predominant IBS. Probiotics (i.e. live or attenuated bacteria or bacterial products) and pre-biotics (i.e. non-digestible food substances that are fermented by host bacteria stimulating their growth) are also used. A trans-galacto-oligosaccharide pre-biotic has shown benefit in a small RCT. FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) are short-chain carbohydrates fermented in the colon, yielding large amounts of gas and causing bloating. Low-FODMAP diets have been helpful in some patients.

• Dietary therapy. Many patients find their symptoms are exacerbated by particular foods. The commonest identified are wheat-containing foods, dairy products, alcohol and excess fibre. Patients are often able to identify and exclude particular food types independently or can be referred to a dietitian for a more formalized exclusion diet.

• Cognitive therapy. Cognitive behavioural therapy (CBT), hypnotherapy and relaxation therapy have all been reported as effective in small trials of patients with IBS. Patients with anxiety and depression seem to benefit more from these therapies.

Pancreatic and biliary tract disease

Acute pancreatitis

In the developed world the majority of cases of acute pancreatitis are due to gallstones or alcohol. Rarer causes include drugs (e.g. azathioprine, corticosteroids), hyperlipidaemia and post-endoscopic retrograde cholangiopancreatography (ERCP) (5%). Severity ranges from mild self-limiting episodes to severe disease with extensive pancreatic and peripancreatic necrosis. Presentation is with upper abdominal pain, which is classically epigastric and severe, and radiates to the back; it is often accompanied by nausea and vomiting. Tachycardia, hypotension and oliguria are present in severe cases.

Investigations

• Serum amylase is elevated if measured within 24 hours of the onset of pain. A level three times the upper limit of normal is almost diagnostic. Serum lipase is used in a similar way in some centres.

• Ultrasound is a useful test to detect gallstones.

• Contrast-enhanced CT allows assessment of the degree of necrosis and detection of the complications of pancreatitis, such as collections and pseudocyst development. It should be performed in all patients with persistent organ failure or signs of sepsis 6–10 days after admission and repeated as necessary to assess progress.

Assessment of severity

Multiple factors are used to develop scoring systems (Table 5.4). The Ranson and Glasgow scoring systems have been developed to predict severe cases of pancreatitis with a sensitivity of 80%. The APACHE scoring system has also been used.

Table 5.4 Factors during the first 48 hours that predict severe pancreatitis *

Factor	Measurement
Age	>55 years
White cell count	>15 × 10⁹/L
Blood glucose	>10 mmol/L (>180 mg/dL)
Serum urea	>16 mmol/L (>45 mg/dL)
Serum albumin	<30 g/L
Serum calcium	<2 mmol/L (<8 mg/dL)
Serum LDH	>600 U/L
Serum aspartate transferase	>200 U/L
PaO₂	<8.0 kPa (60 mmHg)
CRP	>150 mg/L