5.1 SYMPTOMATOLOGY OF GASTROINTESTINAL DISEASES 515

usually cause mild, intermittent dysphagia with solids. Steady pro- Chapter 5.1 gression of severity over a period of weeks is ominous, as it is usually due to malignant obstruction. The dysphagia of achalasia normally Symptomatology of occurs with almost every meal and is frequently associated with regurgitation. Typically, the dysphagia of diffuse oesophageal spasm gastrointestinal diseases is associated with crushing retrosternal pain and occurs episodically From contributions to OTM3 by J. Dent, and between episodes there is total freedom from dysphagia. D. P. Jewell, L. A. Turnberg, and Regurgitation D. G. Thompson Regurgitation is the effortless appearance of material in the pharynx without prior nausea, often misdiagnosed as vomiting. It is usually of small volume, but can be disabling. Symptoms should be evaluated Dysphagia and other symptoms of critically to differentiate true vomiting from regurgitation. The re- gurgitation of reflux disease is typically episodic, but in severe cases oesophageal disease it can occur after every meal. It changes little in pattern over months Indigestion-like symptoms arising from the to years. Regurgitation is usually a prominent symptom in achalasia, oesophagus occurring several times a week with gradual worsening over months In the great majority of patients these symptoms arise from oeso- to years. phageal mucosal irritation by refluxed gastric juice, ingested irritants Chest pain and pain on swallowing (odynophagia) or damage to the mucosa caused by infective agents. Reflux disease is overwhelmingly the most common cause (see Chapter 5.3 and Oesophageal pain from both mucosa and muscle typically occurs OTM3, Chapter 14.6). retrosternally and may radiate into the arms or jaw. Not infrequently, Heartburn is an episodic, lower retrosternal/epigastric burning pain the pain pattern is indistinguishable from cardiac pain if it is not that radiates upwards, sometimes to as high as the pharynx or jaw. clearly linked in time to swallowing. Reflux may also induce lower retrosternal or epigastric burning Association of severe retrosternal pain with dysphagia points ff without radiation, or a poorly localized lower chest/upper abdominal strongly towards di use oesophageal spasm or achalasia, but absence discomfort or unease. Pain tends to occur after food and is provoked of this association does not rule out these diagnoses. Resolution of by large, fatty, or highly spiced meals, by bending or stooping, or pain during high-level acid suppression suggests that the pain is reflux heavy physical exertion, and relieved by antacids. induced. Consistent lack of tight association of chronic chest pain Damage to the oesophageal mucosa from causes other than gastro- with exertion makes an oesophageal more likely than a cardiac source. oesophageal reflux can lead to similar symptoms. Hypersensitivity of the oesophageal mucosa can be ‘primary’ (irritable oesophagus) or Vomiting due to damage by infection, irradiation, or by injury induced by Vomiting is a common symptom of many disorders. The clinical drugs or other substances. circumstances will often help in diagnosis of the cause. If it is in the Dysphagia morning soon after waking it is characteristic of pregnancy, alcoholism, and metabolic disturbances such as uraemia. Vomiting associated The term implies a sensation of mechanical difficulty with movement with psychological disorders usually occurs during or soon after a of food from the mouth to the stomach. High and low dysphagia meal. Pyloric canal ulcers may also cause vomiting immediately after should be distinguished, as their investigation and causes differ. With a meal. Delayed vomiting (more than 1 h after a meal) is the usual high dysphagia, oral, pharyngeal or upper oesophageal structural pattern associated with peptic ulcer, gastric carcinoma, gallbladder abnormalities or motor dysfunction are the causes. The patient has disease, and intestinal obstruction. Projectile vomiting is often seen difficulty with ejection of boluses from the mouth, takes many in pyloric stenosis and is said to occur in patients with raised swallows to clear a normal-sized bolus, and usually coughs and intracranial pressure. splutters due to aspiration. With low dysphagia, successful swallowing The content of the vomitus may provide some diagnostic clues. is followed by a sensation of food hold-up. The surface location of ‘Vomiting’ of undigested food suggests that it is regurgitation sec- the sensation of obstruction is an unreliable indication of the site of obstruction. ondary to achalasia, an oesophageal stricture, or a pharyngeal di- Solid boluses are most likely to cause symptoms because they verticulum. Intestinal contents in the vomitus suggest intestinal require more propulsive force than liquids. Association of dysphagia obstruction or ileus and the vomit usually has a faecal odour. Bilious with swallowing of hard boluses above a particular size is strongly vomiting characteristically occurs after gastric surgery. Altered blood ff suggestive of a fixed narrowing, either due to extrinsic compression (‘co ee grounds’) is of obvious significance. or oesophageal stricture. Oesophageal obstruction is confirmed by Patients who are vomiting because of delayed gastric emptying regurgitation of saliva and other oesophageal contents, and inability may show gastric distension on physical examination and a succession to swallow further boluses. Bolus impaction at an oesophageal stenosis splash may be present. Visible peristalsis may be seen in patients with can lead to secondary painful oesophageal spasm. gastric-outlet or intestinal obstruction. Psychogenic vomiting is not uncommon and mainly affects women. Duration, progression, and frequency There is often a long history (e.g. vomiting associated with school Typically, the dysphagia of motor disorders will have been present for examinations). Vomiting normally occurs after a meal but can usually many months or years at presentation. Non-specific motor disorders be suppressed until the patient reaches a bathroom or lavatory. It is 516 GASTROENTEROLOGY 5 frequently a feature of bulimia nervosa (see Chapter 14.8). The depends, then, on that patient’s normal bowel habit. A change to an diagnosis should be recognized quickly and extensive investigation increased frequency or looser consistency becomes suspicious without should be avoided. the need to define whether the patient has diarrhoea or not. Cyclical vomiting occurs in children and is characterized by re- Another source of difficulty arises in the distinction between current attacks of severe vomiting, which may last for several days. what patients and what doctors perceive as diarrhoea. Patients with The onset is sudden and may be associated with headache, abdominal carcinoma of the rectum, for example, may complain of diarrhoea pain, and, occasionally, fever. The syndrome usually starts before the when they pass blood and mucus, but may still pass normal formed age of 6 years and the frequency of the attacks varies from more than stools. Faecal incontinence may also give rise to diagnostic difficulties. one a month to one or two each year. The cause is unknown. Organic Many patients are reluctant to complain of incontinence, to which disease, especially intracranial pathology, must be excluded. Most some social stigma is attached, and would rather complain of children gradually improve with increasing age and the attacks usually diarrhoea. stop by the end of puberty. These observations emphasize that definitions of diarrhoea should not be slavishly adhered to and that a careful history is essential for Abdominal pain accurate diagnosis. Pain from specific viscera Diagnosis Oesophageal disorders are unlikely to cause abdominal pain. Pain Diagnosis of acute infective diarrhoeal illnesses is usually straight- from the stomach and duodenum is usually midline in the epigastrium forward and rests on a history of recent onset, perhaps with nausea, or in the right upper quadrant, but may be felt in the back. Small- fever, and systemic upset. Staphylococcal ‘food poisoning’ will develop intestinal pain is central and midline, usually colicky, and radiating soon after ingestion of the offending food and may be severe but into the back. Colonic pain can be felt centrally, along the line of the short lived. Viral gastroenteritis is usually milder, often without colon, or in the hypogastrium. It is often poorly localized but systemic upset and lasts 2–3 days. Salmonella, Shigella, and Campy- frequently radiates into the back or into the thighs. Pain from the lobacter can cause more severe disease with fever and prostration. gallbladder and bile duct is colicky and is felt in the right upper Abdominal pain is a more prominent feature of Campylobacter while quadrant. Characteristically it is also felt in the back, between the the presence of blood and mucus in the stool suggests shigellosis or, scapulae or in the right shoulder tip. Pancreatic pain is epigastric and occasionally, salmonellosis. midline, radiates into the back, and is often made better by curling More difficulty is found with chronic, persistent, or intermittent up and aggravated by lying flat. diarrhoeal disease. In these cases an effort should be made to dis- tinguish diarrhoea of large bowel and small bowel origin. Large bowel Diagnosis diarrhoea will tend to occur maximally on waking in the morning, The major features of the pain to be determined are site, intensity, be associated with pain relieved by defecation and perhaps ac- character, timing, and aggravating and relieving factors. Associated companied by the passage of mucus. The presence of red blood in symptoms, such as bowel disturbance, vomiting, heartburn, and the stools of a patient with diarrhoea is a clear pointer towards a urinary and gynaecological symptoms must be elicited. Physical large bowel origin. Diarrhoea of small bowel origin does not occur examination may reveal areas of abdominal tenderness, rebound at any particular time and pain is not usually relieved by defecation. tenderness, and rigidity. Abdominal distension or visible peristalsis A pale fatty stool, without fresh blood or mucus clearly indicates must be looked for. Organ enlargement and the presence of masses small bowel disease. must be excluded. A rectal examination is essential. The hernial Associated symptoms such as anorexia and weight loss will suggest orifices should be carefully examined and the abdomen should be significant organic disease while long continued diarrhoea, perhaps auscultated for bruits. General examination may reveal the presence for many years, without weight loss or systemic upset might indicate of fever, tachycardia, jaundice, weight loss, or anaemia. an irritable bowel syndrome. Intermittency of diarrhoea, precipitated Investigation of abdominal pain will be directed by the clinical by stress, would point towards a functional bowel disturbance while findings. However, in cases of chronic pain it is not usually possible weight loss despite a good appetite should suggest thyrotoxicosis. A to make a firm clinical diagnosis as the symptom complexes of many high proportion of patients with diarrhoea are being treated for diseases overlap, for example gastric ulcer, gastric carcinoma, duodenal another disease and many of the drugs used are found to be responsible ulcer, gallstones, or irritable bowel syndrome. Radiological and endo- for the diarrhoea. Particular culprits are antihypertensive agents scopic investigations will therefore often be necessary. The diagnosis including
-blockers, diuretics, antacids, and antibiotics. Patients who of specific disorders is dealt with in the appropriate sections. drink large volumes of beer should not be surprised if they have loose stools but some come to the doctor complaining of diarrhoea. The presence of skin rashes, mouth ulcers, ‘conjunctivitis’, or perianal Diarrhoea disease, should alert one to the possibility of an underlying in- Usually diarrhoea is thought of in terms of frequency of evacuation flammatory bowel disease particularly Crohn’s disease. and consistency of stool, but it is not easy to set the limits beyond In addition to a full clinical examination a point should be made which diarrhoea may be said to occur. For example, a patient who of inspecting the stool and performing a rectal examination. is habitually constipated might complain of diarrhoea when his bowel frequency reaches twice per day and he would be right to do so as it Investigation might indicate serious bowel disease even though some arbitrarily The investigation of a patient with persistent diarrhoea will depend defined frequency of bowel evacuation has not been reached. A clinical on the history which may point towards a large or small bowel decision as to whether a given patient has diarrhoea or not usually origin. Stool culture and sigmoidoscopy should be performed early, 5.1 SYMPTOMATOLOGY OF GASTROINTESTINAL DISEASES 517 particularly in patients suspected of large bowel disease. Sig- Table 1 Causes of constipation moidoscopy with fibreoptic instruments is becoming increasingly Inadequate dietary fibre and fermentable carbohydrate used and it is often possible to examine the whole of the left side of Immobility, disinclination to defaecate the colon with little bowel preparation. The barium enema is less ...... valuable Organic obstruction: Where clinical features suggest small bowel disease evidence for ...... Neoplasm deficiency of nutrients should be sought, and a faecal fat or xylose ...... Diverticular disease tolerance test may then be indicated. A radiological examination of ...... the small bowel and a jejunal biopsy will provide indicators of Crohn’s disease underlying disease...... Metabolic diseases: ...... Persistent diarrhoea Hypothyroidism ...... ffi There remains a di cult group of patients in whom diarrhoea persists Hypercalcaemia but in whom all investigation has proved unhelpful. It is useful in ...... Extrinsic neurological diseases: such patients to admit them to hospital and make some simple ...... measurements of stool output. Patients with stool outputs of less Spinal cord and sacral-nerve disease ...... than about 400 g/day, and who complain of diarrhoea for which no Pudendal nerve damage cause has emerged on investigation, should be suspected of having ...... Parkinson’s disease an irritable bowel syndrome or anal incontinence. In others the ...... complaint of diarrhoea is made because of frequency of defecation, Chronic intrinsic neuromuscular disease of the colon: ...... although the amount of stool may be normal. The problem is then Hirschprung’s disease due to ‘irritability’ of the rectosigmoid or a defect in the reservoir ...... Chronic pseudo-obstruction function of the lower bowel...... In patients who have large volume of diarrhoea ([1 litre/day) the Systemic sclerosis ...... major differential diagnosis lies between an osmotic or a secretory Diabetic neuropathy cause...... Drug therapy: Measurements of stool osmolality, and sodium and potassium ...... concentrations are then useful. In a secretory diarrhoea the stool Opiates ...... osmolality is close to the calculated total stool ionic concentration, Anticholinergic agents including antidepressants ([Na+] + [K+]) × 2. On the other hand, in osmotic diarrhoeas, in ...... Iron therapy which some other non-absorbed solute is causing the diarrhoea, the ...... measured stool osmolality is considerably higher than the calculated Functional constipation total ionic concentration. A further test which helps differentiate these causes is to observe the effect on the diarrhoea of a 24–48-h fast. Osmotic diarrhoeas are markedly reduced by fasting but secretory lifelong disability, which usually indicates an intrinsic colonic neuro- diarrhoeas continue unabated. muscular disorder. The most common causes of constipation are Osmotic diarrhoea is most commonly caused by disaccharidase shown in Table 1. deficiency or occasionally by an osmotic purgative such as magnesium sulphate in a surreptitious purgative abuser. In chronic secretory History diarrhoea a search may be made for very rare peptide-secreting It is important to obtain a measure of the frequency, consistency, tumours, such as the pancreatic islet adenoma of the Verner–Morrison and volume of the stools. Infrequent desire to defecate suggests slow syndrome which can be revealed by detecting raised plasma peptide transit through the colon, while inability to expel faeces suggests concentrations. More common, but more difficult to detect, is the obstructed defecation. patient who is surreptitiously taking laxatives. The condition may be Sudden onset of constipation in a previously fit individual is a suspected when diarrhoea is severe and repeated investigation, often serious symptom and suggests intestinal obstruction, particularly if in several hospitals, has not revealed a cause. A previous psychiatric accompanied by increasing abdominal pain. Alternatively, con- history, the presence of hypokalaemia, and the detection of melanosis stipation since childhood, with slow deterioration in function with coli are useful clues. Once suspected it is a simple matter to search time, almost certainly indicates a progressive neuromuscular de- for the offending purgative in the patient’s locker and perform a generative disorder of the colon. Between these two extremes lie the screening test of urine and/or faeces for laxatives. most common modes of presentation. A dietary history is mandatory because the quantity of dietary fibre and fermentable carbohydrate ingested is the strongest determinant of faecal weight and defecatory Constipation frequency. The development of progressive obstruction of the colon Concepts of what constitutes constipation vary between societies and must always be considered in adults, particularly those in whom the individuals. In western Europe, passage of stool by normal individuals risk of colon cancer is high. A change in stool diameter together with ranges between two to three times per day to two to three per week. the presence of blood in the stool can be indicators of malignant Three-quarters of the population pass approximately one stool per rectal obstruction. Metabolic diseases, in particular hypothyroidism, day. Constipation ranges in its presentation from an acute onset, hypercalcaemia, and diabetes with autonomic neuropathy, should which is usually taken to suggest organic obstruction, to a chronic always be considered. Chronic constipation in young women who 518 GASTROENTEROLOGY 5 are otherwise well is characteristically worse during the latter phases Table 2 Causes of gastrointestinal bleeding of the menstrual cycle and also exacerbated by pregnancy. Inflammatory Consumption of constipation-inducing medication such as opiates Oesophagitis; gastritis; peptic ulcer; Crohn’s disease; ulcerative colitis; and anticholinergic agents, including antidepressants, must be ex- enterocolitis—infective, ischaemic, radiation cluded...... A family history of constipation suggests a chronic neuromuscular Mechanical disease of the colon. Hiatus hernia; Mallory–Weiss tears; Meckel’s diverticulum; diverticulosis coli Clinical examination ...... The presence of hard faeces palpable in the colon is a useful con- Neoplasms Carcinoma; polyps—single, multiple; leiomyoma; carcinoid firmatory sign. Gross abdominal distension is unusual, except in ...... individuals with severe megacolon due to colonic muscle disease or Vascular in those with psychiatric disorders and a severe disinclination to Varices; hereditary telangiectasia; angioma; aortointestinal fistula; defecate. mesenteric thrombosis or embolus; arteritis Examination of the perineum and anus is mandatory. A rough ...... guide to pelvic-floor dysfunction is obtained by examination of the Systemic perineum in the left lateral position while the patient either strains Chronic renal failure; thrombocytopenia; coagulation defects; or coughs. Absence of normal pelvic descent suggests an abnormality connective tissue disorders; dysproteinaemia of pelvic-floor relaxation. The visible descent of the perineum to the level of the ischial tuberosities after straining or coughing indicates Table 3 Causes of upper gastrointestinal bleeding and their frequency damage to neuromuscular control of the pelvic floor, which is often accompanied by rectal mucosal prolapse. Inspection of the anus for Cause Frequency (%) fissures or fistulae, is also important, as local anal pain on attempted Duodenal ulcer 35 defecation is a powerful inhibitor of stool expulsion. A rectal ex- ...... Gastric ulcer 20 amination and proctosigmoidoscopy should also be used to exclude ...... organic disease of the rectum, to inspect the mucosa for melanosis Acute gastric erosions/haemorrhagic gastritis 18 ...... coli, which is often an indicator of chronic laxative abuse, and to Mallory–Weiss tear 10 confirm the presence of solid faeces...... Gastric carcinoma 6 ...... Management Oesophageal varices 5 ...... In the vast majority of patients with simple constipation, the addition Other 6 of poorly absorbed dietary carbohydrate is usually successful. Laxatives can be additionally prescribed if dietary modification fails, beginning with agents such as lactulose. gastrointestinal bleeding. Rare causes include vascular abnormalities Specific stimulant laxatives can be tried in those individuals in (telangiectasia, angiomas), leiomyoma, haemophilia, throm- whom defecation remains a problem despite bulking agents. These bocytopenia, Ehlers–Danlos syndrome, pseudoxanthoma elasticum, drugs act directly on the neuromuscular apparatus of the colon and and rupture of the aorta into the duodenum. The role of aspirin in stimulate faecal expulsion. They should only be used chronically with initiating bleeding from whatever cause is still controversial. All the great reluctance. Enemas may be useful in obtaining colonic clearance anti-inflammatory drugs may be associated with bleeding. of impacted faeces and as a prelude to longer-term laxative use. In Assessment intractable cases, regular, intermittent enemas may be the only way When possible, the patient should be questioned about dyspepsia, of managing the problem. vomiting, alcohol, drugs, previous episodes of bleeding, and jaundice. In young persons with severe symptoms and slow transit, where Pulse, respiratory rate, blood pressure, and the state of the peripheral the life-style is severely impaired, subtotal colectomy can be of great circulation must be assessed. Specific signs to look for are those of benefit. chronic liver disease, iron deficiency, telangiectasia, and malignancy. Blood should be taken for cross-matching and for determination Acute gastrointestinal bleeding of haemoglobin, haematocrit, platelet count, and prothrombin time. The major causes of acute bleeding from the gastrointestinal tract are Management listed in Table 2. Intravenous saline should be given initially but, occasionally, uncross- matched blood (blood group O, rhesus negative), albumin, or plasma Acute upper gastrointestinal bleeding expanders may be required. Central venous-pressure lines should be This presents as haematemesis and/or melaena. It is very rare for inserted into all patients over 65 years of age and into younger patients lesionsdistaltotheligamentofTreitztocauseahaematemesis.However, who show signs of a compromised blood volume (tachycardia in excess brisk bleeding may occur from a proximal lesion, for example oe- of 100/min; postural fall in systolic blood pressure of >20 mmHg). sophagealvarices,withouthaematemesisandpresentasmelaena.Upper Transfusion should begin with whole blood in order to raise the gastrointestinal bleeding can be severe enough to cause the passage of haemoglobin to at least 10 g/dl. In general, 1 unit of blood raises the dark-red blood per rectum, which may cause diagnostic confusion. haemoglobin by 1 g/dl in an adult. Half-hourly observations of pulse, Table 3 shows the approximate frequency of lesions causing upper respiratory rate, and blood pressure are instituted, although these can 5.2 THE MOUTH AND SALIVARY GLANDS 519 be reduced in frequency once bleeding has stopped. The use of a Endoscopic management nasogastric tube is controversial as it adds to the discomfort of the The methods used range from the injection of sclerosants, coagulation patient, it may cause fresh bleeding, and can cause erosions that may by diathermy or heater probes to Nd:YAG laser therapy and ex- be confusing at subsequent endoscopy. Repeated nasogastric aspiration perimental methods of placing sutures or staples over the bleeding as a means of detecting a recurrent bleed is less sensitive than vessel. The most readily available technique is the injection of sclero- observing the pulse rate. The use of intravenous H2-antagonists in sants. the acute stage is common practice but there is little evidence to Course and progress support this. The overall mortality of upper gastrointestinal bleeding is about There may be some role for H2-antagonists in patients in intensive care to prevent acute bleeding from stress ulcers or from gastric 8–12 per cent and has remained constant since the 1960s. One of the erosions but intragastric instillation of antacids may be a more major factors contributing to this apparent lack of progress is the effective measure. increasing age of the population. So far, there is no evidence that early diagnosis by endoscopy or recourse to early surgery have greatly For patients bleeding from oesophageal varices, further procedures altered the overall prognosis, but it is now possible to predict which may be necessary (see Chapter 5.3). patients with gastric or duodenal ulcers are at particular risk from Diagnostic procedures rebleeding. The presence of a clot or a visible vessel at the base of Once bleeding has stopped, and the patient is in a good haemodynamic the ulcer has been shown to predict a high risk. It is possible that in state, the diagnosis of the cause of the bleeding can begin. Emergency this subgroup of patients, mortality may be reduced by an aggressive endoscopy or barium meals while the patient is still bleeding often interventional approach. reveal little more than the fact that the stomach is full of blood. However, diagnostic procedures should be done within 24 h of bleed- Further reading ing because erosions and tears can heal rapidly. Langman, M.J.S. (1985). Upper gastrointestinal bleeding: the trials of trials. The investigation of choice is upper gastrointestinal endoscopy as Gut, 26, 217–20. this will reveal tears and acute erosions of the stomach or duodenum Rutgeerts, P., Gevers, A.M., Hiele, M., Broekaert, L., and Vantrappen, G. that may frequently be missed radiologically and allows biopsies of a (1993). Endoscopic injection therapy to prevent rebleeding from peptic gastric ulcer or a tumour if found. ulcers with a protruding vessel: a controlled comparative trial. Gut, 34, If a gastric or duodenal ulcer is found, the endoscopist should 348–50. record whether there is active bleeding, whether a visible vessel can be seen in the base of the ulcer, or whether the ulcer crater is covered by a clot. These signs of recent bleeding have a very high predictive Chapter 5.2 value for rebleeding. Angiography should be reserved for patients with continuing bleed- ing in whom no cause has been found at endoscopy. It is useful in The mouth and salivary glands detecting angiomas, duodenal or ileal varices, bleeding from Meckel’s T. Lehner diverticulum or non-specific ulcers of the ileum, and small-bowel tumours. If emergency surgery is being considered, endoscopy may be indicated immediately, best performed under anaesthetic before sur- Dental caries and sequelae gery. The other possible indication for emergency endoscopy is when Aetiology oesophageal varices are suspected, as the patients may be bleeding Caries is an infection caused by aggregation of bacteria on the tooth from mucosal lesions such as erosions or peptic ulcers. The subsequent surface. Prevalence is greatest in children and young adults affecting management will obviously differ according to the endoscopic find- the occlusal surfaces and the enamel of the approximal surfaces of ings. teeth. An increasing prevalence of root caries occurs later in life. The development of dental caries requires: (a) the presence of cariogenic Indications for surgery bacteria capable of rapidly producing acid below the critical pH All patients presenting with acute upper gastrointestinal bleeding (4.1) for dissolving enamel, and (b) sugar in the diet that favours must be assessed by a physician and surgeon together. The indications colonization of these bacteria and that can be metabolized by them for surgery will depend on the cause of bleeding; if from an erosive to form acid. Among cariogenic organisms (Streptococcus mutans, gastritis, surgery should be avoided if possible as the surgeon may Streptococcus sanguis, Lactobacillus acidophilus, L. casei, and Ac- have to do a total gastrectomy. Bleeding from a carcinoma is rarely tinomyces viscosus) S. mutans is the most efficient. Sugar substrate for severe and continuous enough to require emergency surgery. The these organisms include starch, sucrose, glucose, fructose, and lactose. management of bleeding varices is considered elsewhere (see Chapter Of these the most important is sucrose. The major polysaccharide is 5.3 and OTM3, Chapter 14.6). dextran. For peptic ulcers, early surgery can be recommended once initial resuscitation has been achieved. This is particularly so for elderly Pathology patients if there is continuous bleeding resulting in transfusion in The enamel becomes demineralized and plaque bacteria penetrate excess of 6 pints. Bleeding to the point at which the central venous along the enamel prisms. Once the dentine is reached, destruction pressure cannot be maintained is a clear indication. Patients with by decalcification and proteolysis of the dentine is rapid. The pulp recurrent bleeds should also be recommended for early surgery. reacts by an acute inflammatory response that results in necrosis. 520 GASTROENTEROLOGY 5

Eventually, infection and toxic materials spread from the root-canal Gingival and periodontal disease opening to the tissues around the apex of the tooth and induce periapical inflammatory changes, which may terminate in an acute Aetiology or chronic abscess or a chronic granuloma. A dental abscess shows A mild inflammation of the gingiva (gum) and slight destruction of a mixed bacterial infection with a variety of streptococci, staphylococci, the collagen of the periodontal membrane are found in most adults. and other organisms. Advanced destruction of the periodontal membrane, including the There are two principal immunological mechanisms of protection supporting bone, is found in about half of the middle-aged or older against caries. One involves salivary IgA antibodies, the other involves population. A close association has been found between accumulation all the humoral and cellular components elicited by systemic im- of bacterial plaque and gingivitis. During this process a change occurs munization. Antibodies, complement, polymorphonuclear leucocytes, from a predominantly Gram-positive coccal form of plaque to a lymphocytes, and macrophages pass from the gingival blood vessels complex population of filamentous organisms, spirochaetes, vibrios, to the gingival domain of the tooth. and Gram-negative cocci. Of the Gram-positive organisms, Ac- tinomyces viscosus appears to be involved in the development of Clinical features gingivitis. Gram-negative organisms, essential in the development of Toothache is made worse by any hot or cold drink or food, affects periodontal disease include Porphyromonas gingivalis, Actinobacillus the patient especially at night-time, and may radiate to the face and actinomycetemcomitans, Capnocytophaga spp., and some spirochaetes. ear. If relief is not sought death of the dental pulp and the development Dental plaque may calcify, especially in adults and the elderly, to of an acute swelling due to an abscess or cellulitis follows. With an produce calculus, often found on the lingual surface of the lower acute abscess the inflammatory exudate may penetrate through the incisors and the buccal surface of the upper molars. Chronic gingival bone to the soft tissues; oedematous swelling of the face increases, inflammation may persist for many years and breakdown of the and if the upper canine is involved may spread to the eyelid. The periodontal membrane, with loss of the supporting bone, may follow. regional lymph nodes are tender and enlarged, there may be fever This is known as periodontitis (‘pyorrhoea’), and is the most important and some malaise. cause of loss of teeth after the age of 40. Much less commonly a cellulitis may give rise to a spreading infection along the fascial planes, especially of the submaxillary and Pathology sublingual spaces. The inflammatory exudate may occasionally spread Periodontitis is a progressively destructive process leading to loss of into the loose connective tissue of the glottis causing oedema and teeth. The immunological processes are complex, with the protective– respiratory obstruction. The attendant brawny swelling of the neck destructive mechanisms of lymphocyte and macrophage functions, and floor of the mouth, difficulty in swallowing, trismus, fever, and antibodies, and complement activation. Repair, with collagen form- malaise is referred to as Ludwig’s angina. An alternative chronic ation and destruction of the tissues, eventually leads to loss of support course is the development of a chronic pulpitis, granuloma, abscess, of the teeth. ff and eventually cyst around the apex of the o ending tooth, and these Clinical features may proceed without symptoms or only slight discomfort. The symptoms of chronic gingivitis or periodontitis are usually so Treatment mild that they often go unnoticed but there may be discomfort in ffi The principles of treatment are to remove the caries, apply a non- teeth, bleeding of gums and associated halitosis, di culty on eating, irritant dressing to protect the pulp and restore the tooth with a looseness of teeth, and occasionally abscess formation. filling. If the pulp is damaged irreversibly it will have to be extirpated Differential diagnosis and root-canal therapy instituted. The alternative is extraction of the Chronic gingivitis can be differentiated from acute ulcerative gingivitis offending tooth. A dental abscess is effectively dealt with by extraction, by the sudden onset, malaise, characteristic halitosis, pain, and ul- but if the tooth is to be saved, the pus is drained by an intraoral incision ceration of the gingiva in the latter. Herpetic gingivostomatitis occurs and/or establishing drainage through the root canal. Antibiotics are predominantly in children and again the onset is acute, with fever, useful in acute abscesses and phenoxymethylpenicillin, 250 mg four malaise, pain, and ulceration of the gingiva and oral mucosa (see times a day for about 7 days, is adequate. Cellulitis should first be below). Desquamative gingivitis may cause difficulties in differential treated by intramuscular benzylpenicillin, 1 MU four times a day. diagnosis and the points to bear in mind are that the attached gingiva The swelling should then be incised and extraction of the tooth under shows diffuse erosive areas and evidence of bullous lesions may be general anaesthesia should take place as soon as the patient’s condition found in the oral mucosa. permits it. Prevention of dental caries is best practised by plaque removal, Treatment and by limiting the intake of sugar. The type of toothpaste used Plaque and calculi should be removed by regular scaling of the teeth. matters less than the method of tooth brushing, although fluoride in Prevention involves careful tooth brushing, with the aid of plaque- toothpaste decreases the incidence of caries in children by up to disclosing solutions and regular use of dental floss and wood points. ff 40 per cent. Water fluoridation is the most e ective public-health Deep periodontal pockets can be treated by root planing, gingival preventive measure. curettage, or surgically. Differential diagnosis Toothache occasionally needs to be differentiated from sinusitis and Viral, bacterial, and fungal infections neuralgia. An abscess or cellulitis caused by dental caries can be Primary herpetic gingivostomatitis, recurrent herpetic infection (cold (rarely) confused with mumps. sores), Herpes zoster infection, herpangina, hand, foot, and mouth 5.2 THE MOUTH AND SALIVARY GLANDS 521 disease, oral manifestations of AIDS, and oral candidiasis are discussed Table 1 Classification of oral ulcers in Section 16 of this textbook (see also OTM3, pp. 1846–65). Recurrent oral ulcers Bacterial infections Minor, major aphthous, and herpetiform Behc¸et’s disease Acute (necrotizing) ulcerative gingivitis (Vincent’s gingivitis; ...... acute fusospirochaetal gingivitis) Microbial infection Aetiology Primary and recurrent herpes simplex infection It is caused by an infection, although the organisms responsible are Herpes zoster infection Acute ulcerative gingivostomatitis disputed. Evidence is accumulating in favour of a mixed, bacterial Tuberculosis pathogenesis of Gram-negative organisms (fusobacteria, veillonella, Syphilis bacteroides, leptotrichia), which may be responsible for the lesions ...... Neoplastic ulcers by their endotoxin activity. A number of predisposing factors are recognized; poor oral hygiene, accumulation of dental bacterial plaque, Carcinoma Leukaemia defective restorations, and pericoronitis are most important. The ...... disease is seen more commonly in young adults and smokers. Haematological disorders Pathology and clinical features Anaemia Neutropenia, agranulocytosis The gum undergoes an acute inflammatory reaction, leading to necrosis ...... of the epithelium and thrombosis of the small blood vessels. The clinical Dermatological disorders picture is thesudden onset of painful, bleeding gumsand a characteristic Erosive lichen planus foul breath. There is a rise in temperature, regional lymphadenitis, Pemphigus Benign mucous membrane pemphigoid anorexia, and significant malaise. Oral examination reveals necrotic, ff Erythema multiforme and Stevens–Johnson syndrome punched-out ulcers, a ecting predominantly the interdental gingiva. Reiter’s syndrome At times there are shallow necrotic ulcers affecting the oropharyngeal ...... Granulomatous disorders mucosa, which shows diffuse erythema (Vincent’s angina). Histiocytosis X Diagnosis Wegener’s granulomatosis This disease is often confused with primary herpetic stomatitis, but ...... Iatrogenic agents in this patients are usually younger and their breath lacks the distinct foul quality of ulcerative gingivitis. Direct examination of a smear Drug allergy Drug-induced agranulocytosis from the lesion reveals a large number of spirochaetal and fusiform Cytotoxic drugs organisms, with a decrease in the mixed bacterial flora. Radiotherapy ...... Treatment Trauma Metronidazole 200 mg by mouth three times daily for 3–4 days is Denture, teeth, or foreign body very effective. Phenoxymethyl penicillin, 250 mg four times daily for Chemical a week is equally effective. Hydrogen peroxide mouthwash, and a variety of peroxyborate preparations are also useful.

Cancrum oris (noma) is highly infective. Gumma and leucoplakia are the typical oral This is a rapidly spreading gangrene of the lips and cheeks, mostly manifestations of the tertiary stage. A gumma starts as a swelling of confined to children in parts of tropical Africa. It is thought to be the palate, tongue, or tonsils; it undergoes necrosis and results in a an extension of acute ulcerative gingivitis when associated with other painless, punched-out, deep ulcer, with a ‘wash-leather’ floor. The diseases, especially measles. Cancrum oris is very rare in the United lesion may heal with scarring, or give rise to perforation. Leucoplakia Kingdom, but can be seen in terminal stages of leukaemia, especially usually affects the dorsum of the tongue as an irregular, diffuse white when treated by cytotoxic, anti-inflammatory, and immuno- patch that cannot be rubbed off. suppressive drugs. Tuberculosis Oral ulceration Oral tuberculosis is rare. Commonly, the presenting feature is a The main causes are listed in Table 1. Only some merit more painful ulcer or a firm small swelling. Ulcers may be single or multiple, description here. but they are usually large, with a depressed floor and some induration of the base. Diagnosis is based on microscopy and culture and a Recurrent oral ulcers biopsy of the lesion. Oral tuberculosis responds readily to specific chemotherapy. Aphthous ulcers are common with a prevalence varying between 10 and 34 per cent (Plate 1). The aetiology is not known but there is Syphilis recent evidence suggesting a T-cell response to a peptide within the The chancre of the primary stage may present on the lip or tongue sequence of heat shock protein. While emotional stress may influence as a painless, small, firm nodule that breaks down and forms an ulcer the pattern of the disease, it is unlikely to be the direct cause. A with raised indurated edges. The regional lymph nodes then show family history is often present and the highest incidence of ulcers is discrete, rubbery enlargement. In the secondary stage, shallow, recorded in siblings in whom both parents have recurrent aphthous snail-track ulcers may affect the tonsils, tongue, or lips, and the saliva ulcers. In some female patients there is a relationship between the 522 GASTROENTEROLOGY 5 ulcers and menstrual period; the onset of ulceration may coincide Bullous lesions with puberty, or the ulcers may develop only after the menopause and often disappear during pregnancy. Pemphigus vulgaris (see also Section 11) This may present in the mouth, which is involved at some stage of Pathology the disease in most patients (Plate 2). Painful, fluid-filled blisters or An early intense lymphomonocytic infiltration, especially with a bullae burst within a few hours, resulting in shallow ulcers. These perivascular distribution, is a constant histological finding. This is persist for weeks or months, but new lesions recur. Oral manifestations followed by a polymorphonuclear infiltration and a significant increase may persist for many months, without overt ill-health but skin lesions, in the number of CD4 and CD8 subsets of T cells, Langerhans cells, malaise, and loss of weight may occur at a later stage. The lesions and macrophages. can be differentiated from recurrent aphthous ulcers by the presence Clinical features of bullae and when these ulcerate the edges lack the well-defined character of aphthous ulcers. The most important diagnostic test is About 80 per cent of recurrent oral ulcers are of the minor type; and the presence of acantholytic cells on microscopic examination of are found more frequently in women than men. Soreness 1–2 days direct scrapings from the lesion and a biopsy must always be taken. before ulceration increases in severity especially on eating. The ulcers Pemphigus must be differentiated from pemphigoid and dermatitis are round or oval, and enlarge in size, although they remain well herpetiformis (see below). A less severe and rare variant of pemphigus under 1 cm. They have a yellow floor with a slightly raised margin vulgaris is pemphigus vegetans. Vegetation may be found on the oral and often marked surrounding erythema and oedema. The common mucosa and lips, and histological examination shows intraepithelial sites of involvement are the mucosa of the lips and cheeks and margin abscesses containing numerous eosinophils. of the tongue, and the ulcers last 4–14 days. The rate of recurrences varies from 1 to 4 months and is usually irregular. Treatment Major aphthous ulcers are less common. Pain can be severe so that Prednisolone is given initially in doses of 40–60 mg/day and gradually patients find it difficult to eat and often lose weight. Ulcers may reduced to the minimal dose that will prevent formation of new enlarge to some 3 cm, may number as many as 10 and can mimic a lesions. The required dose may be reduced by adding azathioprine carcinomatous lesion. In addition to the lips, cheeks, and tongue, the in a dose of 200 mg/day. Treatment with corticosteroids must be soft palate and tonsillar region are commonly involved. Healing may maintained for life and has completely changed the prognosis of the take 10–40 days and recurrences are so frequent that the patient disease. suffers from continuous ulceration. The prevalence of major aphthous ulcers is raised in ulcerative colitis. A striking association has been Benign mucous membrane pemphigoid (see also found in smokers who give up the habit and develop recurrent Section 11) aphthous ulcers. This rare disease affects women twice as often as men, usually over Herpetiform ulcers may affect any part of the mouth. They account the age of 40 years. for less than 10 per cent of recurrent oral ulcers and are much more Bullous lesions involve the oral mucosa, conjunctiva, and skin common in females. Patients present with pain on eating and talking, around the genitals and orifices, but in some patients only the mouth and often with dysphagia; malaise and loss of weight can be prominent. is involved. The bullae rupture within a day or two leaving erosions The lesions persist for 7–14 days and commonly new ulcers appear and ulcers. The gingiva is commonly involved, giving rise to persistent before the previous crop has healed. pain, bleeding, and a diffuse, raw, fiery red lesion. The oral lesions It is important to differentiate both aphthous and herpetiform usually heal without scaring unlike those of the conjunctiva. ulcers from those found in iron, folate or vitamin B12 deficiency. The disease persists, often with exacerbations and remissions, over Ulcers relating to coeliac disease respond to a gluten-free diet. The many years. It is differentiated from pemphigus vulgaris on clinical shallow necrotic ulcers of agranulocytosis or neutropenia tend to grounds but only a biopsy examination will establish the diagnosis. persist at one site. Ulcers due to denture trauma are usually localized There are no acantholytic cells and the bullae are subepithelial and to the mucosa covering the mandibular and maxillary alveolus and not suprabasilar. Autoantibodies can be detected, in less than half the the buccal and lingual sulci. patients, binding to the basement membrane of epithelium and not The differential diagnosis from pemphigus, benign mucous mem- to the interepithelial substance. The disease should be differentiated brane pemphigoid, and erythema multiforme will be described below. from linear IgA disease, and dermatitis herpetiformis. Treatment Treatment Topical corticosteroids in aphthous ulceration are most effective if If the disease is confined to the mouth, topical corticosteroids are application is started during the prodromal phase, but later may often adequate but with involvement of other sites, systemic corti- reduce the severity and duration of ulceration. The most useful costeroids are indicated. preparations are triamcinolone in orabase; hydrocortisone sodium succinate, 2.5 mg per tablet; and betamethasone, 0.5 mg per tablet. Erythema multiforme (see Section 11) The tablets are kept in the mouth, or the ointment is applied to the The mouth can be affected without skin involvement. Painful, ex- ulcers, three to four times daily. Systemic prednisolone has to be tensive erosions and ulcers have a predilection for the palate, tongue, resorted to occasionally in patients with major aphthous ulcers. and cheeks (Fig. 1 and Plate 3). The gum may show extensive erosions, Topical tetracycline is the drug of choice in suppressing herpetiform which tend to bleed. Haemorrhagic crusting of the lips is often seen. ulcers, but is also useful in controlling some major aphthous ulcers. The Stevens–Johnson syndrome is a rare variant. The powder from a 250 mg capsule is dissolved in 10 ml of water If an offending agent is not found, the lesions may recur over and kept in the mouth four times daily. many years. The diagnosis of oral lesions without skin manifestation 5.2 THE MOUTH AND SALIVARY GLANDS 523

fuse and result in a diffuse, somewhat smooth, shiny white plaque which may be difficult to differentiate from leucoplakia. In bullous lichen planus a bulla is rarely seen, presumably because it bursts to produce ulcers. In erosive lichen planus there may be large shallow ulcers up to 3 cm in size, surrounded by white striae and papules. Except for discomfort, difficulties with eating, and occasionally loss of weight, there are no general manifestations and the regional lymph nodes are not enlarged, except with secondary infection. Lichen planus may affect only the gum, inducing a diffuse, fiery-red gingivitis and scattered erosions. The striae and papules are sufficiently distinctive to differentiate lichen planus from other lesions, without the need for a biopsy, but the diffuse hypertrophic variety can be confused with leucoplakia. Erosive lichen planus may very occasionally lack the distinctive striae, and then erythema multiforme and benign mucous membrane (a) pemphigoid should be excluded. Both systemic and discoid lupus erythematosus can present in the mouth as erosions, surrounded by a keratinized margin. Treatment In the absence of symptoms, hypertrophic lichen planus does not require treatment. Topical corticosteroids are usually effective in erosive lichen planus and suppress the striae and papules of the hypertrophic variety. Triamcinolone in orabase ointment applied four times a day is useful in localized lesions, but betamethasone 0.5 mg tablets are more effective, kept in the mouth three times daily. The lesions recur almost invariably, and corticosteroids may have to be applied with every relapse. In a very small number of patients, carcinomatous transformation, especially in the erosive type of lichen planus, can take place.

(b) Leucoplakia White patches of the oral mucosa that cannot be removed by scraping Fig. 1 Erythema multiforme: (a) haemorrhagic crusted upper lip; (b) diffuse erosion of the palate. are referred to as leucoplakia (Plate 5). Among identified causes are physical and chemical agents, smoking, and microbial infections (Candida, syphilis, AIDS); some cases are congenital or hereditary. A can be very difficult. The clinical features to note are the very extensive cause cannot be found in about half the cases. The microscopical erosions affecting the palate, tongue, cheeks, and gingiva and the features show a spectrum of changes; at the benign end is epithelial haemorrhagic crusting of the lips. An association with drugs or keratosis alone, followed by hyperplasia and then epithelial atypia at microbial infection is helpful. A biopsy can exclude pemphigus and the premalignant end. The lamina propria shows in parallel an erosive lichen planus. Behc¸et’s disease is an important differential increase in mononuclear cells, especially plasma cells. Carcinoma in diagnosis. situ is the least common histological finding. Clinical features Treatment The white patches vary from a soft, slightly thickened mucosa, ff Any o ending drug or infection should be eliminated. The oral lesions involving a small or very large mucosal surface, to hard, irregular often respond to topical tetracycline. white plaques with intervening normal, erosive, or ulcerated sites. The latter (speckled leucoplakia) has a greater propensity to carcinomatous Lichen planus (see Section 11) transformation. Any part of the oral mucosa or gum may be involved. Many patients with oral lichen planus do not have skin lesions. Frictional keratosis is usually found along the occlusal line of buccal Mouth lesions may remain symptomless for years. Some patients mucosa and presents as a linear white patch of even consistency. complain of a furry thickening of the mucosa and others of pain or Smoker’s keratosis shows a characteristic distribution of the soft and bleeding from the gums on eating. There are three types of oral lichen adjacent hard palate, as keratinized papules with central red dots. planus: hypertrophic, erosive, and bullous (Plate 4). The hypertrophic The distribution is due to involvement of the palatal mucous glands variety is most common and is usually seen in all three types. There and the red dots are the openings of the ducts. It is usually caused are white striae and minute papules, most commonly affecting the by pipe smoking, but cigarettes may also cause diffuse keratosis, posterior part of the buccal mucosa, lips, and dorsum of tongue, affecting most commonly the cheeks. Congenital and hereditary though the palate, gum, and floor of the mouth can also be involved. leucokeratosis shows diffuse, soft, white plaques, often with a folded The striae criss-cross giving rise to a fine lacy or fern-like pattern, surface. The lesions tend to be symmetrical; they affect the floor of and less commonly a honeycomb or annular patter. The striae may the mouth. 524 GASTROENTEROLOGY 5

All leucoplakias should be biopsied, except smoker’s keratosis of than twice as many men as women are affected. The incidence has the palate, as even small lesions have at times proved to be early been decreasing over the last four decades. The cause is unknown, carcinomas. It is also essential to find out the degree of epithelial but smoking and alcohol have been implicated, and it is pipe or cigar atypia as this affects the prognosis. Direct examination of scrapings smoking that have been associated with oral cancer. There is some can be helpful in the presence of hyphae of candida; cultures should evidence that Treponema pallidum, Candida albicans, human also be set up for candida. Serological tests are essential in the papilloma virus, and human immunodeficiency virus (HIV), may diagnosis of syphilitic leucoplakia. directly or indirectly influence the development of carcinoma. Among the predisposing lesions, leucoplakia is the best known. Submucous Treatment fibrosis is another precancerous condition and is found predominantly Smoker’s keratosis is reversible in many instances. Frictional keratosis in India and Sri Lanka. It seems to be related to eating chillis and can also be cleared, if some local cause of irritation is removed. possibly betel-nut chewing, and affects the palate, buccal mucosa, Candidal leucoplakia should be treated with topical antifungal drugs. and tongue. Syphilis should be managed by a course of penicillin. Leucoplakia showing evidence of epithelial atypia should be excised and Pathology occasionally a skin graft may be required. Squamous cell carcinoma in the mouth is usually a well-differentiated Most important is long-term follow-up, so as to detect in time the keratinizing neoplasm invading the surrounding tissue. Poorly differ- development of an incipient carcinoma. About 5 per cent of all entiated and anaplastic oral carcinomas are much less frequent. Spread leucoplakias undergo malignant changes and this figure increases to by local invasion and lymph node metastasis occurs at a late stage. about 30 per cent in leucoplakias showing histological evidence of Clinical features epithelial atypia. Malignancy is more commonly associated with The lesion may comprise a lump or an ulcer that is resistant to speckled leucoplakia as well as syphilitic leucoplakia. Congenital or healing and gradually enlarging in size. There may be little pain hereditary leucokeratosis were thought to be free of malignant changes, initially, but later discomfort and occasional bleeding may occur. although recently a few cases with carcinomatous transformation Cancer of the tongue may give rise to local pain and earache. A dry have been reported. mouth may be found in the early stages. Ulcers have a raised and often everted edge, and induration at the base. Any part of the mouth Benign neoplasms, cysts, and can be involved but the lips (usually the lower lip) and tongue developmental and inflammatory lesions of are most common, each accounting for about 25 per cent of oral carcinomas. The floor of the mouth, gingiva, cheek, hard and soft the soft tissues palate, and oropharynx may account for about 10 per cent. Some There are numerous benign neoplasms and soft tissue lesions of the patients may have two or even multiple carcinomas. Metastasis may mouth. These include papilloma, fibroma, lipoma, neurofibroma, occur to the submandibular or upper cervical lymph nodes, and haematoma, pigmented naevus, lymphangioma, denture granuloma, occasionally to the submental nodes. A biopsy is essential for any fibrous polyp, pregnancy tumours, mucus retention, and extravasation long-standing or indurated lesion. cysts. Soft-tissue tumours present as painless, slow-growing swellings Adenocarcinoma of the small salivary glands may also present as affecting any part of the mouth. Fibrous polyps are the most common a lump of the soft palate, lips, or cheeks and only a biopsy will and result from trauma or irritation from rough edges of carious establish the diagnosis. Carcinoma in situ is rare in the mouth, but teeth. Most of the tumours are sessile, some are pedunculated, and it may present as a diffuse, erythematous, somewhat velvety lesion, others flat and pigmented. They are usually symptomless except for affecting the mucosa of one-half of the soft palate or cheek. bleeding from hamartomas and giant-cell reparative granulomas. Treatment Definitive diagnosis depends on histological examination but a Surgical excision of the lesion and a margin of adjacent tissue may papilloma can be recognized by its firm, small, keratinized, finger- be extended if necessary to block dissection of the regional lymph like processes. Lymphangiomas are soft swellings, which may cause nodes. Radiotherapy is an alternative, commonly used in primary considerable enlargement of the lip or tongue. Hamartomas are flat treatment of cancer of the lip, in inoperable cases, or with recurrent or nodular red lesions that may blanch when compressed; they are carcinoma following surgery. Cytotoxic drugs have also been used occasionally confused with pregnancy tumours, which are rather with variable results. vascular granulomatous swellings of the gingiva. Giant-cell reparative granulomas are also very vascular, maroon-coloured lesions ori- Course and prognosis ginating from the gingiva. Denture granulomas can be readily re- The 5-year survival rates differ considerably with the anatomical site. cognized from their relation to the flange of a denture. Mucous Carcinoma of the lip has by far the best prognosis, and the 5-year retention or extravasation cysts are small, often bluish swellings survival rate is about 80 per cent. The figures for carcinoma of the affecting the lips or cheeks. tongue range from 25 to 35 per cent, floor of the mouth 20 to 40 per Surgical excision, with a margin of normal tissue at the base of the cent, cheek 30 to 50 per cent, and oropharynx, palate, and gingiva lesion, is usually indicated. Pregnancy tumours, however, commonly at about 25 per cent. regress spontaneously. Only the giant-cell reparative granuloma has a tendency to recur after excision. Salivary gland diseases Oral carcinoma Xerostomia (dry mouth) Carcinoma of the mouth accounts for about 2 per cent of all cancers Dry mouth is common can be caused by anxiety and emotional stress. in Britain. The prevalence increases after the age of 45 years and more Antihistamines, phenothiazines, antihypertensive agents, diuretics, 5.2 THE MOUTH AND SALIVARY GLANDS 525 and preparations containing atropine are well recognized causes. Some the affected gland and careful digital palpation along the course of diseases affect the salivary glands directly, e.g. Sjo¨gren’s syndrome and the salivary duct will localize the calculus. This may vary in size from sialadenitis. It may be impossible to eliminate the cause. In such a small grain to a concretion 10–20 mm in length. The localization cases, palliative measures include frequent sips of water, meticulous of a stone in a duct should be confirmed by radiographs and the oral hygiene, early treatment or preferably prevention of candidiasis presence of calculi in the gland can be diagnosed only by radiography. by topical nystatin or amphotericin B. Some prefer glycerine, others If the calculus is near the orifice of the duct it can occasionally be carboxymethylcellulose as a lubricant, and the latter can be taken as teased out, otherwise surgical removal is indicated. a solution or aerosol (Glandosane). A mucin preparation can also be helpful as a spray or as a lozenge (Saliva Orthana). Salivary gland tumours A variety of epithelial tumours affects the salivary glands. In the Sialadenitis parotid, the commonest is the pleomorphic adenoma or mixed salivary Bacterial or viral infections and rarely allergic reactions may cause tumour (74 per cent) followed by adenocarcinoma (12 per cent), inflammation of the salivary glands, giving rise to acute, chronic, and adenoma (8 per cent), muco-epidermoid tumour (3 per cent), and allergic sialadenitis, and recurrent parotitis. Ascending acute infection acinic cell tumour (2 per cent). Only pleomorphic adenoma will be of the parotid (Staphylococcus aureus, Streptococcus viridans or S. considered here. pneumoniae) used to be a common complication in elderly post- operative patients. Acute parotitis may also follow the use of drugs Pleomorphic adenoma causing xerostomia. The most common cause of acute parotitis is This originates from epithelial cells of the ducts, acini, or myoepithelial mumps. Salivary glands are sometimes affected by HIV infection, cells which proliferate in duct-like structures, sheets, and cords, within with an enlargement of the parotid glands. Chronic sialadenitis is a connective tissue stroma, which may show mucous, cartilaginous, usually associated with duct obstruction and usually affects the or hyaline appearance. The lesion is encapsulated, although satellite submandibular gland. Recurrent sialadenitis may be associated with tumours are often found outside the capsule. The tumour is usually a decreased salivary flow causing retrograde infection. found in adults and the parotid is most commonly affected, followed Clinical features by the submandibular gland and rarely the sublingual. The minor glands can also be affected, most frequently in the glands of the The usual presenting symptom in acute cases is a painful swelling in palate, lips, and cheeks. The tumour presents as a small, painless one of the parotid glands of an elderly patient. Commonly the patient swelling, which may take years to enlarge and is not attached to has a low-grade fever, oedema of the cheek, some trismus, and a the overlying skin or mucosa. Adenocarcinoma, mucoepidermoid purulent discharge may be expressed from the duct opening. In carcinoma, and adenoid cystic carcinoma may mimic pleomorphic chronic sialadenitis there are usually features of duct obstruction of adenoma in its slow growth, and can often be differentiated only on one of the submandibular glands. There is pain and swelling in the histopathological examination. submandibular or retromandibular region, with a reddened duct Treatment is by excision with a margin of normal tissue, as the orifice discharging pus. Recurrent parotitis presents as an acute pain tumour is radio-resistant. If left untreated the tumour may enlarge and swelling of one or both parotid glands, with erythema of the to a grotesque size. A small proportion may undergo carcinomatous duct orifices and pus discharging from them. There may be an transformation. The tumour has a bad record for recurrences after associated fever and malaise. Recurrences vary from weeks to months excision, thought to be due to residual satellite tumours outside the and after repeated attacks the affected gland may remain enlarged. capsule. There is little difficulty in the differential diagnosis between acute parotitis in the elderly and mumps in the healthy young subject. Discharging pus should be cultured. Recurrent parotitis can cause Neoplasms, cysts, developmental lesions, difficulties; sialography may show sialectasis and duct dilatation. In and dystrophies of the bones and teeth chronic sialadenitis there is usually clinical or radiological evidence of calculus and sialography may show duct dilatation. A number of such lesions can arise in the jaws including benign and A variety of granulomatous diseases may rarely affect the salivary malignant neoplasms, cysts and tumours of dental origin, dental glands, such as sarcoidosis, tuberculosis, syphilis, and actinomycosis. malformations and various osteodystrophies. They are described Allergic sialadenitis is also rare and to determine the allergic agent briefly in OTM3 (pp. 862–3). can be difficult. Treatment Halitosis In acute, chronic, or recurrent sialadenitis, appropriate antibiotics There are four possible sources of halitosis: the mouth, nasopharynx, should be used but surgical drainage may also be necessary. Oral lungs, and the gastrointestinal tract. Altered blood round the gum hygiene is also important. There is no special treatment for mumps. may be the most important oral cause, and this may be associated with In chronic sialadenitis the cause of obstruction, such as a calculus, debris or pus from gingivitis and periodontal pockets. A characteristic should be removed. The treatment of recurrent parotitis is more halitosis is found in acute ulcerative gingivitis. Chronic tonsillitis may difficult and if antibiotics do not control the disease, surgical in- be responsible for halitosis but atrophic rhinitis causing ozena is tervention should be considered. probably the most important cause to be excluded. Occasionally, respiratory tract infections may cause halitosis and a variety of Salivary duct obstruction due to calculus gastrointestinal disorders have been associated with bad breath but The presenting symptoms are a sudden unilateral swelling and pain with little evidence. Frequently all these sources of halitosis may be of the gland related to eating. Examination reveals a soft swelling of excluded without finding a cause. 526 GASTROENTEROLOGY 5

Possible reflux Further reading disease Bouquot, J.E., Weiland, L.H., and Kurland, L.T. (1988). Leukoplakia and carcinoma in situ synchronously associated with invasive oral/ Diagnosis oropharyngeal carcinoma in Rochester Minn., 1935–1984. Oral Surgery, Clearcut history History indeterminate no alert symptoms or alert symptoms Oral Medicine, Oral Pathology, 65, 199–207. Greenspan, D. and Greenspan, J.S. (1996). HIV related oral disease. Lancet, 348, 729–33. Mild–moderate Troublesome Function Endoscopy for tests diagnosis Lehner, T. (1992). Immunology of oral diseases. Blackwell Scientific symptom intensity symptom Publications, Oxford.

Lozada-Nur, F., Gorsky, M., and Silverman, S. (1989). Oral erythema Low-middle No Oesophagitis multiforme: clinical observations and treatment of 95 patients. Oral Assessment level trial of therapy oesophagitis of Surgery, Oral Medicine, Oral Surgery, 67, 36–40. severity Williams, D.M. (1989). Vesiculobullous mucocutaneous disease: pemphigus Good Poor vulgaris. Journal of Oral Pathology and Medicine, 18, 544–53. response response Williams, R.C. (1990). Periodontal disease. New England Journal of Medicine, 322, 373–82. Endoscopy to Tailored and Maintain assess severity titrated therapy

Fig. 1 Principal decision paths for management of reflux disease.

Chapter 5.3 Symptoms Heartburn is most important, but presentation may be with less- Diseases of the oesophagus specific patterns of dyspepsia or with regurgitation, haematemesis, and dysphagia due either to stricture or oesophageal body motor J. Dent dysfunction. Reflux-induced respiratory symptoms of hoarseness, persistent cough, and bronchospasm may predominate. Gastro-oesophageal reflux disease Diagnosis and assessment of severity Gastro-oesophageal reflux occurs to some degree in everybody and The history is pivotal for diagnosis because of the extremely high should only be considered a disease when it gives rise to significant prevalence of reflux-induced symptoms and the lack of a definitive, symptoms or complications. An abnormally high level of episodic inexpensive, diagnostic test for reflux disease. Endoscopy is the only exposure of the distal oesophagus to gastric contents is the most test that can give sensitive recognition and grading of oesophagitis, and important functional defect. In most patients this is due to abnormal reliable diagnosis of oesophageal columnar metaplasia. Mechanically neural control of the sphincter and oesophageal body. In the majority significant peptic stricture, gastric cancer, and chronic duodenal and of patients most reflux occurs during the day, predominantly after gastric ulcer are also diagnosed with high sensitivity. The value of food, but in those with severe oesophagitis nocturnal reflux and its endoscopy is enhanced by the histological diagnosis of endoscopic resultant acid exposure become important. Hiatus hernia is probably biopsy and cytology brushings. Barium swallow and meal is insensitive an important amplifier of defects of sphincter function and oeso- for diagnosis of oesophagitis and cannot grade it, but other pathology phageal clearance. In a small and ill-defined minority of patients, such as gastric ulcer and oesophageal stricture is demonstrated with apparently normal levels of reflux induce typical symptoms, pre- reasonable sensitivity. Barium swallow has an important role in the sumably because of oesophageal sensitization by a primary oeso- investigation of mechanisms of troublesome dysphagia, in recognizing phageal mucosal sensory defect. extrinsic oesophageal compression, and in the assessment of ana- tomically complex hiatus hernia. Oesophageal function tests (pH Oesophagitis monitoring, manometry, and radioisotope transit testing) may be helpful and are discussed in OTM3 (p. 1865). Steps needed for Excessive mucosal exposure to acid and pepsin leads to distal diagnosis are shown in Fig. 1). oesophageal ulceration in between one-third to one-half of patients Symptoms and the presence and severity of oesophagitis show poor with symptomatic reflux. The extent of ulceration varies from tiny correlation but the response of symptoms to low and medium levels patches of erosion to circumferential, extensive ulceration in a of therapy (see Table 1 and below) gives an indirect approximation small minority. Peptic stricture and/or oesophageal columnar of severity and helps to determine further action. metaplasia (Barrett’s oesophagus) are typically only associated with severe oesophagitis. Oesophageal adenocarcinoma is the main Tailoring and grading therapy significance of columnar metaplasia and is dealt with later. Table 1 provides a framework. The lowest effective dose of any agent Oesophageal columnar metaplasia also carries the risk of deep, should be used in long-term therapy. Endoscopic findings allow the benign oesophageal ulceration in the metaplastic segment. appropriate initial approach. Therapy is then graded upwards or Occasionally, such ulcers erode into mediastinal structures or the downwards in order to find the lowest that is effective. Initial high- pleural space often with a fatal outcome. Bleeding from oesophagitis level medical therapy is likely to confirm the diagnosis, but is relatively is relatively common, but rarely life threatening. expensive and uninformative about the best long-term approach. 5.3 DISEASES OF THE OESOPHAGUS 527

Table 1 Levels of antireflux therapy of oesophageal-body peristalsis (see below). Peptic stricturing is managed by a combination of peroral dilatation and healing of Low: antacids, non-drug measures ...... oesophagitis by either medical or surgical means. Middle: normal-dose H2-receptor antagonists, cisapride and Oesophageal columnar metaplasia (Barrett’s oesophagus) is in- sucralfate, ?bethanechol ...... creasingly recognized as a consequence of oesophagitis (see below). Upper: 2–4 × normal ranitidine dose, × 2 normal famotidine dose Respiratory disease may be the result of either direct aspiration of omeprazole 10 mg, lanzoprazole 15 mg refluxed gastric contents, or from the reflex effects of gastro-

Combination of cisapride and standard-dose H2-receptor antagonists oesophageal reflux. Proof of an association between coexistent reflux ...... ffi Highest: antireflux surgery, omeprazole 20 mg, lanzoprazole 30 mg and respiratory disease is often di cult. Regurgitation is the main problem in a small subgroup of patients who usually present complaining of ‘vomiting’. Vigorous medical Initial low–medium-level therapy has the disadvantage of giving less therapy sometimes controls the problem, but more often antireflux useful diagnostic information and often, slow relief of symptoms, but surgery is the only effective management. it is relatively inexpensive and will usually identify patients with severe Reflux is an important cause of non-cardiac chest pain (see below). oesophagitis by their lack of response. Non-drug measures and antacids Idiopathic achalasia and achalasia-like The efficacy of these approaches is often overrated. Most useful are states avoidance of large meals and provocant foods, drinks, and physical activities. The benefits to reflux disease of stopping smoking, losing These disorders are characterized by absent or incomplete relaxation weight, and raising the bedhead are more debatable. Antacid may be of the lower oesophageal sphincter and impairment of oesophageal- effective in controlling heartburn. body peristalsis. Idiopathic achalasia accounts for most cases and has an annual incidence of approximately 1–2/200 000; it affects all ages, Acid suppression but is most common in early to mid-adult life. The syndrome is This treatment is highly efficacious. Proton-pump inhibitors have a also seen in Chagas’ disease, occasionally in the intestinal pseudo- special place, because of their overall efficacy in the control of acid obstructive syndrome, as a manifestation of paraneoplastic neural secretion. Long-term acid suppression maintains patients free of dysfunction, and secondary to oesophageal amyloidosis. Impairment symptoms and oesophagitis indefinitely, but withdrawal is usually of inhibitory neural control of the distal oesophagus is the common associated with prompt relapse. The maintenance dose appears to be abnormality, produced by neural damage at several sites; evidence of the same as the lowest effective healing dose. There have been concerns myenteric inhibitory neurone degeneration is probably most im- about the safety of long-term acid suppression but to date, follow- portant. up of patients treated continuously for 5 or more years has shown no evidence of any important ill-effects. Symptoms Dysphagia with solids is the most common symptom. Regurgitation Motility stimulants is also prominent. The regurgitated material tastes bland because it Cisapride has a medium level of efficacy for both short- and long- never enters the stomach. Cramping chest pain occurs in some term management. The principal effect appears to be on oesophageal patients during the early, hypercontracting phase of the disorder. acid clearance. Weight loss may occur. In some patients, symptoms remain static for many years, but in others there is a progression with increasing Other agents regurgitation, when respiratory problems secondary to aspiration can ffi Sucralfate, which is of medium-level e cacy, is believed to act by become a major feature. protecting the oesophageal mucosa from chemical injury. Bethanechol Dilatation varies from a minor change to a grossly enlarged, colon- stimulates salivation and oesophageal contraction; at best it has only like oesophagus. Barium swallow shows a gastro-oesophageal junction ffi medium e cacy. Various formulations that include some mucosa that tapers smoothly to a closed sphincter, with occasional spurts of coating or protective agent combined with antacid are probably no flow into the stomach (Fig. 2). In the absence of dilatation, a barium better than antacid alone. swallow is usually reported as normal. Oesophageal manometry is Combination therapy the only sensitive method for demonstration of the motor dysfunction, and is especially important in patients with no radiological ab- Cisapride and H -receptor antagonists in combination gives moderate 2 normality. The important differential diagnosis is of malignancy of results, but is a relatively unattractive option given the high efficacy the gastric cardia. Endoscopy with biopsy and computed tomography of monotherapy with proton-pump inhibitors. scanning are helpful in this context. Antireflux surgery In skilled hands, antireflux surgery is very effective with a small Treatment (about 0.5 per cent) mortality. Laparoscopic antireflux surgery is an Calcium antagonists and
-adrenergic agonists compare poorly with important advance. mechanical disruption of the sphincter. Oesophagomyotomy (la- paroscopic or thoracoscopic) is effective but associated with a 5–10 per Management of complications cent risk of troublesome gastro-oesophageal reflux. Balloon dilatation Dysphagia secondary to peptic stricture needs to be distinguished from often needs to be repeated, and in some hands fails in up to 40 per the more common dysphagia due to defective triggering and control cent of patients, and carries a risk of perforation of about 5 per cent. 528 GASTROENTEROLOGY 5

Non-cardiac chest pain Chest pain resembling cardiac pain may arise from oesophageal disorder such as reflux or spasm and may then respond well to appropriate therapy. Monitoring of oesophageal pH and mobility studies can be helpful but no clear diagnosis emerges in as many as 50 per cent of cases. In them, anxiolytics and antidepressants may be effective particularly in those in whom there is continuing anxiety about a cardiac origin of pain.

Miscellaneous motor disorders (see OTM3, Chapter 14.6) Peristaltic pressure waves may exceed 250 mmHg (hypertensive peri- Fig. 2 Achalasia. Barium-filled dilated oesophagus; intact mucosa in distal stalsis, nutcracker oesophagus) and can produce central cardiac pain. achalasic segment. There are many other manometrically defined motor abnormalities associated or not with reflux, spasm, diabetes, or other autonomic Prognosis dysfunction. ‘Non-specific motor disorder’ is characterized by mul- If treatment is applied before the development of major dilatation, tipeaked swallow-induced contractions in the distal oesophagus. results are excellent, but achalasia carries an increased risk (ranging Hypocontraction causes deranged transit and mild intermittent dy- from 2 to 7 per cent) of oesophageal carcinoma. The average interval sphagia particularly for solids. Prokinetic drugs may improve con- from diagnosis of achalasia to development of carcinoma has been tractions but symptoms are rarely sufficient to warrant long-term estimated as 28 years. Some clinicians therefore recommend periodic treatment. screening endoscopy. Oesophageal muscle diseases Diffuse oesophageal spasm Systemic sclerosis involves the smooth muscle of the oesophagus in as Episodic chest pain and/or dysphagia may result from spastic con- many as three-quarters of patients (see Chapter 10.13). Primary tractions of the distal half of the oesophagus in the absence of any striated muscle disorders (such as dermatomyositis, polymyositis, precipitating structural stenosis. There may be an underlying disorder inclusion body myositis, muscular dystrophy, and myasthenia gravis) of neural control but evidence for this is lacking and the aetiology is may present with high dysphagia in association with oropharyngeal unknown. dysfunction. Symptoms Sliding hiatus hernia Virtually all patients have episodic, crushing, central retrosternal pain; About 90 per cent of hiatus hernias are of this type in which the cardiac ischaemia is often the first diagnosis. Intermittent dysphagia gastro-oesophageal junction is displaced upwards into the thorax, occurs in about two-thirds of patients and leads to temporary aban- giving a simple pouch of intrathoracic stomach. Symptoms of gastro- donment of eating until symptoms abate—usually over about 30 min, oesophageal reflux are the only ones of significance. These should be but episodes of oesophageal obstruction can last for several hours. treated along conventional lines (see above). As many patients with In the majority, episodes occur less than once a month, but in severe hiatus hernia are asymptomatic, its demonstration should not be cases these may occur several times a week, or each time food taken as diagnostic of reflux disease. intake is attempted. Full-blown dysfunction is usually absent during investigation, but in a minority, there is asymptomatic motor dys- Rolling hiatus hernia function. Barium swallow then shows trapping of beads of contrast In this disorder, part of the stomach herniates through the hiatus in the distal oesophagus—‘the corkscrew oesophagus’—or sustained alongside a normally situated gastro-oesophageal junction. This pat- obliteration of the distal oesophageal lumen. Manometry may show tern of herniation may narrow the exit from the herniated pouch intermittent, simultaneous, prolonged, and vigorous oesophageal con- into the main stomach cavity. Some rolling hernias are also associated tractions interspersed with normal swallow-induced peristalsis. Re- with displacement of the gastro-oesophageal junction above the hiatus laxation of the lower oesophageal sphincter is normal. The diagnosis (mixed hernias). Obstruction and distension of the pouch causes is made from the history and the exclusion of other problems. Most upper abdominal discomfort and can progress to strangulation. Gast- important among these is Schatski ring (see below). ric volvulus may obstruct the gastro-oesophageal junction. Both of these complications have a very high mortality and demand urgent Treatment surgery. Elective surgery is normally recommended to reduce and There is no specific therapy. Nitrites, nitrates, and calcium antagonists anchor rolling hiatus hernias in order to reduce these risks. may reduce symptoms; but reassurance is the most important measure. In the rare case of frequent, disabling spasm, long oesophagomyotomy Schatski ring (B ring) and other rings and webs can give good relief. There is no consistent progression of dysfunction The Schatski ring is a short luminal stenosis at the gastro-oesophageal and associated symptoms over time. Reports of progression to ach- junction (Fig. 3). The cause is unknown. With mechanically significant alasia are probably explained by early spastic achalasia having been rings, intermittent dysphagia occurs on eating solids. Episodes of misdiagnosed. bolus obstruction are not unusual, with associated chest pain caused 5.3 DISEASES OF THE OESOPHAGUS 529

Table 2 Common causes of medication-induced oesophageal injury

Severe injury—high risk Occasional injury Slow-release potassium chloride Ascorbic acid Non-steroidal anti-inflammatory agents Mexiletine Tetracycline Slow-release theophylline Quinidine Captopril Phenytoin Less severe injury—high risk Zidovudine Many antibiotics Iron supplements

Boerhaave’s syndrome Straining and vomiting can cause oesophageal rupture, most often in the left lower third. Spillage of the gastric contents into the pleural space causes shock and chest and upper abdominal pain with radiation to the back, left chest, or shoulder. The chest radiograph becomes abnormal only some hours after rupture. Surgical repair and drainage Fig. 3 Schatzki ring: thin, 2–4 mm in height, annular constriction at gastro- are usually necessary, and if this is delayed beyond 24 h, mortality is oesophageal junction; best shown on prone-oblique views. very high. Traumatic perforation by powerful oesophageal contractions. Failure to recognize a Schatski This may complicate oesophageal instrumentation. Perforation is ring frequently leads to the incorrect diagnosis of oesophageal spasm. suggested by the development of chest or epigastric pain directly The diagnosis requires an expert radiologist. Disruption of the ring after instrumentation, sometimes with dyspnoea. Pneumothorax and by peroral dilatation or endoscopic diathermy or laser is very re- surgical emphysema are diagnostic. Broad-spectrum antimicrobials warding. Other short oesophageal stenoses are due to peptic stricture, should be given on suspicion. The choice between conservative and muscular rings, and cervical webs, with (Plummer–Vinson syndrome) surgical management should be based on the individual circumstances. or without iron-deficiency anaemia. Increasingly, instrumental perforation is being managed non-sur- gically with nasogastric suction, antimicrobials, and intravenous Oesophageal diverticula and pseudodiverticula nutrition. Wide-mouthed, multiple diverticula are characteristic of scleroderma Caustic ingestion oesophagus. In other cases, diverticula occur in the mid and distal This is addressed in OTM3, Chapters 8.3.1 and 8.3.5. parts, probably caused by ‘blow-outs’ secondary to hypercontraction motor disorders. It is rare for these to cause symptoms. They are best Medication-induced oesophagitis left undisturbed because leakage is common after surgical removal. Medications known to have an especially high risk for oesophageal Multiple intramural out-pouchings of barium are characteristic of damage are listed in Table 2. Symptoms are those of oesophagitis intramural pseudodiverticulosis, which appears to be due to dilatation with stricturing. Such injury is the most likely cause of oesophagitis of submucosal gland ducts by an unknown process. and/or benign stricture at the level of the aortic arch, where pills can lodge. Injury at the distal oesophagus, the other common site of Extrinsic oesophageal compression hold-up, is often misdiagnosed as due to reflux disease. This is a relatively common cause of dysphagia, mainly from malignant Chemotherapy causes oesophageal disease in several ways. It may mediastinal lymphadenopathy. Other causes include a grossly enlarged impair mucosal defences, reducing resistance to damage from other heart, aortic aneurysm, or congenital vascular abnormalities such as agents, and increase susceptibility to infective oesophagitis from an aberrant right subclavian artery. immune suppression. Oesophageal transit and acid clearance may be impaired through neurotoxic effects of some agents. Fistulation or perforation may occur through cytotoxic effects on malignancy in Mechanical, chemical, and radiation trauma the oesophageal wall. Mallory–Weiss tear These mucosal tears extend across the gastro-oesophageal junction Oesophageal neoplasms and are normally induced by vigorous straining associated with Squamous cell carcinoma is the commonest oesophageal neoplasm. vomiting. Bleeding is the only consequence of significance. In 10 per Adenocarcinoma usually arises in association with columnar meta- cent of cases, bleeding is severe enough to cause hypovolaemia. The plasia, or Barrett’s oesophagus. Other oesophageal tumours are rare history is usually characteristic, but a definitive diagnosis requires but include melanoma, lymphoma, carcinoid, leiomyosarcoma, small endoscopy. Continued bleeding usually responds to endoscopic in- cell carcinoma, adenoid cystic carcinoma, and pseudosarcoma. Benign jection or electrocoagulation, vascular embolization, or vasopressin tumours include leiomyomas, lipomas, granular cell tumours, and infusion. Very rarely, surgery is needed to underrun a persistently squamous cell papillomas. The disorders are described in Chapter bleeding artery in the base of the tear. 5.20 and in OTM3 (pp. 1874–6 and Chapter 14.6). 530 GASTROENTEROLOGY 5

Table 3 Major causes of infective oesophagitis

Pathogen Management Remarks Immunocompetent patients Candida albicans Topical/oral antifungals By far most common Herpes simplex Acyclovir if severe Unusual; may denude mucosa Varicella zoster Acyclovir if severe In association with chickenpox/herpes zoster Bacteria Rare in well individuals ...... Immunocompromised patients Candida albicans Systemic antifungals Most common; oral disease almost diagnostic Cytomegalovirus Prophylaxis and treatment with Part of systemic infection ganciclovir or foscarnet Sepiginous → giant ulcers distal half Herpes simplex Prophylaxis and treatment with Circumscribed ulcers, raised edges → coalescence acyclovir or foscarnet Oral lesions. Tuberculosis Conventional From miliary and local spread Gram-positive cocci, Gram- IV antibiotics Often with systemic infection negative bacilli Syphilis Conventional Associated with tertiary syphilis elsewhere → inflammatory stricture

Infective oesophagitis Chapter 5.4 Viral oesophagitis can cause major haemorrhage. Infective oeso- phagitis can damage the full thickness of the oesophageal wall and Peptic ulceration lead to stricturing. Diagnosis is often aided by the setting. Cutaneous or oral disease can suggest what is happening in the oesophagus. J. J. Misiewicz and R. E. Pounder Endoscopy is the diagnostic method of choice. Mucosal appearances and the distribution of oesophageal lesions can be virtually diagnostic. In addition, biopsies and brushings allow histological diagnosis and Duodenal ulcer identification of infectious agents. The more important causes are Duodenal ulcer is a distinct break in the mucosa of the duodenum, summarized in Table 3. almost invariably in the duodenal bulb, but occasionally more distal. The ulcer may be superficial, or may penetrate to the serosa. Other non-neoplastic mucosal diseases Aetiology Rarely, Crohn’s disease can cause indolent, craggy ulceration and/or stricturing of the oesophagus. Oesophageal sarcoidosis can also mimic It is not known why patients develop duodenal ulceration, nor why Crohn’s disease. Other diseases affecting the oropharynx and oeso- the clinical course is characterized by episodes of intermittent relapse. phagus include epidermolysis bullosa, Behc¸et’s disease, lichen planus, The characteristics of the disease appear to be changing towards a pemphigus vulgaris, bullous pemphigoid, benign mucous membrane less severe form: why this should be so is not known. The strongest (cicatricial) pemphigoid, and drug-induced disease (Stevens–Johnson aetiological association is with infection of the gastroduodenal mucosa ff syndrome and toxic epidermal necrolysis). Chronic, and less fre- by Helicobacter pylori, which has important e ects on gastric function. quently, acute graft-versus-host disease may cause severe oesophageal Eradication of the bacterium leads to healing and dramatic decrease problems through mucosal desquamation or mural damage. Resultant in the incidence of relapse. H. pylori is an important aetiological stricturing shows considerable variation in appearances. factor in several other diseases of the foregut, including chronic gastritis, gastric ulceration, gastric cancer, mucosal associated lymph- Further reading oid tissue lymphoma, and Me´ne`trier’s disease. Quigley, E.M.M. (1997). Gastro-oesophageal reflux disease—spectrum or Acid and pepsin continuum? Quarterly Journal of Medicine, 90, 75–8. Although the presence of acid and pepsin is essential for the appearance Tytgat, G.N.J. (1995). Long term treatment for reflux oesophagitis. New of a duodenal ulcer it is probably only one of several aetiological England Journal of Medicine, 333, 1148–50. factors operating in most patients. Ulceration is thought to be related to an imbalance between the damaging effects of acid and pepsin and mucosal defences. As a group, patients with duodenal ulcer secrete more acid than healthy people. Five factors may account for the tendency to hypersecrete acid and pepsin: (a) increased parietal cell mass; (b) increased stimulation of acid secretion; (c) increased parietal cell sensitivity to stimulants; (d) decreased inhibitory control of acid secretion; and (e) Helicobacter pylori induced hypergastrinaemia. Several of these abnormalities (hypergastrinaemia, raised basal and 5.4 PEPTIC ULCERATION 531 stimulated acid output, decreased inhibitory drive mediated by Number of patients somatostatin, hyperpepsinogenaemia) disappear after eradication of 772 323 86 H. pylori. 100 Cimetidine 400 mg The abnormalities of acid output and gastrin release described twice daily above are subtle, difficult to investigate, and based on evidence 84% 80 collected from an intensive study of few subjects: it is uncertain Cimetidine whether they apply to all patients with duodenal ulcer. Much less is 400 mg at night 74% known about the importance of pepsin secretion, while knowledge 60 of factors affecting mucosal defence and integrity is fragmentary. Gastric emptying 40 Placebo The pH in the duodenal lumen is lower more frequently and for 34% longer periods in patients with duodenal ulceration than in controls. 20 These patients empty food from their stomachs faster so that after a

ff of patients in remission Percentage meal there is less food available to bu er secreted acid as it passes 0 into the duodenum, where acid is neutralized by bicarbonate. Patients 024681012 with duodenal ulcer do not have a gross defect of pancreatic alkaline Months of maintenance treatment secretion, but the alkaline secretions of the duodenal mucosa are Fig. 1 Maintenance treatment of duodenal ulcer with cimetidine: results of suboptimal. double-blind trials from 22 centres (from the data of Burland, W., Hawkins, B., and Beresford, J. (1980). Ulcerogenic drugs Postgraduate Medical Journal, 56, 173). Corticosteroids, aspirin, and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly thought to be ulcerogenic, but the evidence Some 50 per cent of patients who die from a peptic ulcer are unaware that they cause chronic duodenal (or gastric ulcer) is not convincing. of their ulcer at the time of their fatal admission. The cause of ulcer Anti-inflammatory agents can damage the gastric mucosa and are pain is not clear: it is not always directly related to intraduodenal used to produce ulcer models in experimental animals for the testing acidity, but is rapidly relieved by antacids. of drugs. Extrapolation from these models to humans should be Nausea and vomiting are relatively unusual, unless there is severe viewed with a certain amount of scepticism. However, the incidence of pain or pyloric stenosis. Posterior penetration into the pancreas may consumption of NSAIDs is high among patients with gastrointestinal cause mid-back pain, or pancreatitis. Major complications are rare; bleeding, or perforation. perhaps occurring in 1 per cent per year. Haemorrhage may cause Psychological factors haematemesis and/or melaena, or iron-deficiency anaemia. Per- Stress is often invoked as an important cause of duodenal ulcer. foration causes acute, severe pain, collapse, and peritonitis. Chronic (as opposed to acute) stress is difficult to measure. Case– Duodenal ulceration is a condition of spontaneous relapses and control studies suggest that patients with duodenal ulcer may be remissions. The change in the clinical picture from relapse to remission more stressed than controls exposed to similar events. can be remarkable. It is therefore unwise to make decisions about surgery during a relapse. Clinical trials show that within a year of Epidemiological factors treatment using a gastric acid antisecretory drug, 66 per cent of those Duodenal ulceration may affect 10–15 per cent of many populations. receiving a placebo will have had a symptomatic relapse (Fig. 1), and The prevalence is subject to marked geographic variation; for example, approximately one-third of asymptomatic patients have recurrent it is much more common in Scotland and northern England than in ulcers when examined by endoscopy. Some patients suffer only a southern England; it is more common in the south of India than the single episode of ulceration, while in others the illness is progressive, north. Men are affected more than women, but the incidence is with rare remissions and severe complications. Spontaneous healing increasing in women, particularly after the menopause. In India and of duodenal ulcer may be delayed, and relapses are earlier and more Africa the prevalence is higher in populations who eat a low-residue frequent in patients who either continue to smoke cigarettes or take diet. There are weak associations with smoking, alcohol, and anti- NSAIDs. inflammatory drugs. It is possible that there is a genetic predisposition; ulcers are more common in close family members, patients with Diagnosis blood group O and non-secretors of blood-group substances in the Duodenal ulcer cannot be diagnosed by clinical history, because saliva. similar symptoms occur in other diseases (gastric ulcer, gastric cancer, Virtually all patients are infected with H. pylori, but there are many or the irritable bowel syndrome). The patient often points to the who are colonized by it but who do not develop an ulcer. The epigastrium as the site of the pain, but this is not reliable. Physical prevalence of this organism seems to be determined by socio-economic examination may show epigastric tenderness, but is otherwise un- factors and the infection is usually acquired in childhood. helpful, unless there is severe pyloric stenosis, when visible gastric peristalsis and a succussion splash are present. Clinical picture and natural history The diagnosis is established by radiology or endoscopy. A barium The main symptom of duodenal ulceration is pain, classically epi- meal, preferably air-contrast, will show deformity of the duodenal gastric, related to food, and occurring during the night, but there cap, but the differentiation between scarring, mucosal folds, and an can be great individual variation. Indeed, severe ulceration to the active ulcer crater is less certain. Fibreoptic endoscopy is the best point of perforation or haemorrhage can be virtually symptomless. method of diagnosis. Even then, pyloric stenosis with retention 532 GASTROENTEROLOGY 5 of gastric contents, mucosal oedema, haemorrhage, or incomplete inspection of the base of duodenal cap can all cause the ulcer crater to be missed. Previous therapy may make the diagnosis more difficult or impossible. Duodenal ulcers are usually single, circular areas of discrete ulceration resembling oral aphthous ulcers, usually with a creamy yellow base. The fasting plasma gastrin concentration should be measured in patients with severe or ectopic ulceration, or in those with continuing ulceration after adequate medical treatment or surgery, to exclude the Zollinger–Ellison syndrome. Serological and salivary tests for specific antibodies to H. pylori have been used to screen young dyspeptic patients. This approach needs further validation.

Chronic benign gastric ulcer Ulcers can occur anywhere in the stomach, but most develop on the lesser curvature at the junction between the acid-secreting mucosa and that of the antrum. Special care must be taken to exclude malignancy in antral ulcers. Pre-pyloric ulcers resemble duodenal ulcers endoscopically and are best managed similarly. Aetiology Approximately 80 per cent of benign gastric ulcers are associated with H. pylori infection. There is also an association with NSAID medication. The gastric mucosa is probably injured by the com- bination of gastric acid, reflux of duodenal contents, and by H. pylori colonizing the antral epithelial cells. Patients with gastric ulcer tend Fig. 2 Benign gastric ulcer demonstrated by air-contrast barium meal; to reflux their duodenal contents, a tendency that is aggravated by mucosal folds reach the rim of the ulcer crater. smoking cigarettes. Gastric-emptying time tends to be prolonged and retention of contents predisposes to ulceration. Gastric ulceration was once a disease of young women but it is now common in both genders, in older age groups, and in patients excreted by the kidney. Cimetidine very occasionally causes coma in of low socio-economic class. severely ill people. Omeprazole is not generally available for in- travenous use. Erosive ulcers can also develop in patients taking Clinical picture and diagnosis NSAIDs or excess alcohol. Patients typically present with epigastric pain. Although ex- acerbations of discomfort after meals, remitting pain, weight loss, and a long history are common, a confident diagnosis must not Non-ulcer dyspepsia (functional dyspepsia) be made on clinical evidence alone. Many patients are asymptomatic Dyspepsia is common, but only a small proportion of sufferers have until they present with a complication such as acute or occult organic disease. Ulcer-like symptoms, bloating with early satiety gastrointestinal haemorrhage, or perforation. Up to a half of the (dysmotility dyspepsia) or features suggesting reflux are common. patients develop recurrence. Diagnosis can be continued by double Dysmotility dyspepsia may respond to motility-stimulating agents, contrast barium meal (Fig. 2) or endoscopy. The latter allows such as cisapride. Reflux dyspepsia merges into gastro-oesophageal biopsy and brush cytology, which is essential to exclude early reflux disease. Medical treatment of ulcer-like dyspepsia is un- carcinoma. satisfactory in that response to gastric acid suppressants, or to erad- ication of H. pylori, is unpredictable. The prevalence of H. pylori in patients with functional dyspepsia is similar to that of the general Acute erosive ulceration population. Multiple superficial ulcers may develop in the oesophagus, stomach, or duodenum of acutely stressed patients, particularly after major trauma, extensive burns, or during shock or hypoxia. The main Duodenitis damage appears to be due to mucosal ischaemia and hypoxia. This This is an ill-defined condition, characterized at endoscopy by in- type of ulceration usually presents with haemorrhage some days flamed, haemorrhagic, and friable duodenal-cap mucosa; duodenal after the initial insult, which may be aggravated by coagulopathies biopsies show acute inflammatory changes. Erosions may be present associated with the primary disorder. H2-receptor blockers can prevent and symptoms then may be indistinguishable from those of duodenal the ulceration and haemorrhage. The recommended maximum doses ulcer and may be complicated by haemorrhage. Most patients are are cimetidine (400 mg) or ranitidine (50 mg) intravenously 6-hourly, treated as if they have a duodenal ulcer; many will be colonized by preferably as a continuous infusion. In the presence of renal in- H. pylori, but the effect of eradicating this organism on duodenitis sufficiency the dose should be decreased, as the drugs are mainly has not been fully studied.