The only other medical history was childhood asthma. There was a family history of Crohn \200\231s disease, but no other family history of gastrointestinal disease. On examination, he was fit and well, with a body mass index of 25kg/m2. His hands, skin, an d abdomen were normal, with no tremor, normal speech, no goiter, and no abdominal findings. Investigations showed: Barium swallow: there was no structural abnormality in the hypophar- ynx or esophagus and n o stricture. There was transient hold up of a swallowed marshmallow. The gastro-oesophageal junction opened normally. Gastroscopy: esophagus, stomach and duodenum looked normal. Oesophageal, gastric and duoden al biopsies were taken. Questions 27a) What is the differential diagnosis? 27b) By examining the oesophageal biopsy (Fig. 27.1 in the central colored section), what is the diagnosis? 27c) What changes could be present on endoscopy in this condition? 27d) What is the treatment of this condition? 27e) What is the prognosis? This page intentionally left blank OXFORD CASE HISTORIES 180 Answers 27a) What is the differential diagnosis? The differential diagnosis is: Eosinophilic oesophagitis Peptic stricture from gastro-oesophageal reflux Achalasia Muscle disorders Muscular dystrophies Hyper or hypothyroidism Myasthenia gravis Oesophageal involvement in systemic conditions (e.g. scleroderma) Oesophageal spasm. Intermittent dysphagia in a young adult over many years (particularly with an episode of fo od impaction), should raise the possibility of eosinophilic oesophagitis. This becomes more likely with a personal or family history of allergic disorders. It should always be consid ered in the differential diagnosis of chronic unexplained dysphagia, but has been recognize d only relatively recently. The barium swallow is usually normal, but strictures of varying length and diameter can occur. Distinguishing eosinophilic oesophagitis from gastro-oesophageal reflux disease can be diff icult, but the latter only causes food impaction if a mechanical stricture (which should be visible on barium swallow) is present. It is notable that a proton pump inhibitor relieved reflux symp- toms in this patient, but did not relieve dysphagia. Dysphagia due to severe oesophagitis without a stricture is not that uncommon, but the sensation is relieved by aci d suppression. Achalasia should be considered, but several features make the diagno- sis unlikely. Patient s with achalasia tend to have dysphagia for both sol- ids and liquids. Furthermore, chest p ain occurs in up to half of patients, and 60 \200\22390% describe regurgitating undigested foods during or shortly after a meal. The barium swallow might also be expected to show fea tures of achalasia given the 2-year history. The typical feature of achalasia on barium swa llow is the \200\230bird \200\231s beak \200\231 appearance of the gastro-oesophageal junc tion, due to the non-relaxing sphincter, and sometimes associated with a dilated esophagus. Fluoroscopy during the swallow may reveal decreased peristalsis. At endoscopy, there may b e a transient resistance to the passage of the endoscope through the gastro-oesophageal jun ction CASE 27 181 that is recognized by an experienced endoscopist alert to the potential diagnosis. Muscular disorders must not be overlooked, but often are at first presentation. There are t hree categories to consider. The first is mus- cular dystrophy: two uncommon forms of muscu lar dystrophy involve the striated muscles of the pharyngo-oesophageal region. Dystrophia m yotonica is a familial disease characterized by myopathic facies, myotonia, swan neck, musc le wasting, frontal baldness, testicular atro- phy, and cataracts. Oculopharyngeal dystroph y is a syndrome that presents later in life with ptosis and dysphagia, with a dominant pat- tern of inheritance. The second category is hyperthyroidism or hypo- thyroidism, which can also affect striated musculature. The third muscle disorder is myasthenia gravis, which is a disorder of the motor end plate, affecting the striated oesophageal musculature with cli nical manifestations that resemble the myopathies. The characteristic fea- ture is fatigue during repeated effort, with successive attempts to swal- low (pharyngo-oesophageal transfe r) causing more symptoms as the meal progresses. Systemic conditions such as scleroderma, polymyositis, or mixed con- nective tissue disease can involve the esophagus. Other findings such as sclerodactyly, telangiectases or weaknes s, are generally detected in conjunction with symptoms of dysphagia. Oesophageal spasm generally presents with retrosternal chest pain, with episodes lasting fo r minutes or hours. Intermittent dysphagia occurs in 30 \200\22360% of patients. A barium s wallow can reveal a \200\230corkscrew Fig. 27.1 (see color plate 12) Mid-oesophageal biopsy from a patient with dysphagia and a n ormal esophagus at endoscopy. OXFORD CASE HISTORIES 182 esophagus \200\231, due to dysfunctional circular muscle contractions that in extreme situa tions trap barium between powerfully contracted segments. The endoscopic appearance is norm al. 27b) By examining the oesophageal biopsy (Fig. 27.1 in the central color section) what is the diagnosis? The diagnosis is eosinophilic oesophagitis. The diagnosis hinges on histopathological evide nce of eosinophils infiltrating the oesophageal mucosa. It is well recognized that other di seases are associated with eosinophilic infiltration of the esophagus, including gastro-oes ophageal reflux, but with a lesser degree of eosinophilic infiltrate. For diagnosis of eosi nophilic oesophagitis, the eosinophilic infiltration in the squamous epithelium should exce ed 20 eosinophils/high power field at x400 mag- nification. Mid-oesophageal biopsies should be the standard of care for patients with dysphagia and a normal endoscopy. 27c) What changes could be present on endoscopy in this condition? Typical endoscopic findings of eosinophilic oesophagitis include mucosal longitudinal linea r furrows, a corrugated appearance or plaque-like exu- dates, friability of the oesophageal mucosa ( \200\230cr pe-paper \200\231 mucosa), and strictures of variable length. Most pa tients appear to have a normal esophagus at endoscopy, so the endoscopist should be encoura ged to take biopsies. 27d) What is the treatment? Corticosteroids, either topical or systemic, are generally effective. Initial treatment sho uld be swallowed fluticasone (220 g dose x four puffs, swallowed with a minimal amount of water twice daily, instructing patients not to eat or drink for 2 hours after each dose). C ontinue ther- apy for 6 weeks, if there is a response. Recurrent symptoms are best treated with the same dose, but for a longer period. If there is no initial response, systemic cort icosteroids (prednisolone 40mg/day, tapered over 6 weeks) should be considered. Elimination diets: although eosinophilic oesophagitis appears likely to be an allergic diso rder, identifying the triggering allergens (food or environmental) is labor intensive and u nproductive. Patients may have multiple allergies, making it difficult to comply with aller gen-avoidance or food restriction. Pediatric patients are often treated with an elimina- ti on or liquid diet and improve, but they comply with food restriction better than adults. CASE 27 183 Oesophageal dilatation: patients with eosinophilic oesophagitis are at increased risk for m ucosal tears and perforation after oesophageal dilata- tion. Medical treatment of eosinophi lic oesophagitis decreases the risk of strictures. Dilatation should be carried out only in patients who fail medical therapy and have severe dysphagia. New therapies such as anti-IL5 monoclonal antibody therapy are evolving. 27e) What is the prognosis of this condition? Untreated, patients with eosinophilic oesophagitis may develop stric- tures, with weight lo ss, food impaction, or even perforation. After patients are successfully treated, it is lik ely that 25 \200\22340% will have relapse of their symptoms. The long-term outcome for pati ents with eosino- philic oesophagitis who have been treated and the proportion that require multiple courses of treatment is unknown. There have been no cases of oesophageal malignan cy observed in association with eosinophilic oesophagitis. Further reading Attwood SE, Lamb CA (2008). Eosinophilic oesophagitis and other non-reflux inflammatory con ditions of the esophagus: diagnostic imaging and management. Best Pract Res Gastro; 22: 639 \200\22360. Basavaraju KP, Wong T (2008). Eosinophilic oesophagitis: a common cause of dysphagia in young adults? Internat J Clin Pract; 62:1096 \200\223107. Ferguson DD, Foxx-Orenstein AE (2007). Eosinophilic esophagitis: an update. Dis esophagus; 20: 2 \200\2238. OXFORD CASE HISTORIES 184 Case 28 A 44-year-old French woman presented to the emergency department with severe, acute right u pper quadrant pain, and was referred to the gastroenterol- ogy registrar on call. The pain had developed shortly after her evening meal, was constant, and radiated through to her bac k. She had vomited once. On specific questioning it appeared that she had had some back pai n in the preceding days. She was being treated for autoimmune liver disease with prednisolone 40mg/day. This had bee n started 3 days before, when her ALT increased. She had a 30-pack/year smoking history, bu t rarely drank alcohol. At the time of referral she had already had intravenous morphine for the pain. Her pulse wa s 104bpm, blood pressure 127/82mmHg, temperature 36.1 C, and respiratory rate 36/min. Her abdomen was at that time tender in the right upper quadrant, but nowhere else. There was no tenderness on per- cussion, but there was generalized involuntary guarding. She could not lie flat, because this exacerbated the pain. Investigations showed: 9/L, platelets 179 x109/L mol/L Hb 14g/dL, WCC 13.82 x10 Na 134mmol/L, K 4.0mmol/L, creatinine 84 mol/L, ALT 260 IU/L, ALP 508 IU/L, albumin 41g/L Bilirubin 25 CRP 5mg/L Amylase 73 IU/L. Questions 28a) What is the differential diagnosis? Consider the factors that complicate the patient \200\231s assessment. 28b) What common conditions need excluding, and what uncommon medical conditions should be kept in mind? 28c) What investigations should be requested on admission? 28d) Discuss the medical management of the underlying condition. 28e) Discuss potential complications and the further management of this patient. This page intentionally left blank OXFORD CASE HISTORIES 186 Answers 28a) What is the differential diagnosis? Consider the factors that complicate the patient \200\231s assessment. The differential diagnosis includes Biliary colic (and associated complications) Peptic ulcer (and associated complications) Mesenteric ischaemia Acute pancreatitis with a normal amylase Peritonitis with features obscured by corticosteroids Ruptured ectopic pregnancy. The patient has presented with acute, postprandial, right upper quadrant (RUQ) pain, locali zed tenderness, and generalized guarding, without percussion tenderness. Postprandial pain is characteristic of biliary colic due to passage of a stone into or through the cystic duc t, peptic ulcer, and mesenteric ischaemia. Guarding is not a feature of any of these condi- tions if they are uncomplicated. Vomiting commonly occurs with biliary colic, but our pati ent had had an ultrasound scan 6 months before, which had shown no gallstones. Acalculous c holecystitis is very rare; RUQ tenderness (Murphy \200\231s sign) with a thickened gallblad der wall in the absence of stones is suggestive. Acute cholangitis is characterized by RUQ abdominal pain, jaundice, and fever usually with rigors (Charcot \200\231s triad). Our pati ent had neither jaundice nor fever. Mesenteric ischaemia is unlikely in a young patient, bu t characteristically presents with severe pain and a paucity of signs. Our patient had no r isk factors for arterial thromboembolism. Acute pancreatitis presents with upper abdominal pain that may radiate to the back, and may be associated with peritonism. Acute pancreatiti s with a (relatively) normal amylase can occur in patients with chronic pancreatitis and li ttle glandular function, commonly caused by alcohol. Our patient had no risk factors for pa ncreatitis. Acute symptoms justify an anatomical approach to differential diag- nosis, but the generali zed guarding indicates peritonitis. Perforation of a hollow organ is the usual cause. Pepti c ulcer perforation usually leads to instantaneous pain and peritonism, due to acid in the peritoneal cavity. The chemical irritation caused by acid causes pain, before bacterial per i- tonitis supersedes. In contrast, peritonitis which develops (for example) after iatrogen ic perforation during colonoscopy may take hours to develop, because the colonic pH is neut ral. Diverticulitis or appendi- citis are other potential causes, but perforation is usuall y preceded by a CASE 28 187 typical clinical syndrome. Small bowel tumors or diverticula may also perforate, but are ra re. In any woman in their reproductive years, an ectopic pregnancy needs to be considered. Localized pain may be fol- lowed by rupture, with ensuing peritonitis. This is usually asso ciated with hypotension and anemia, due to hemorrhage. A pregnancy test should be carried o ut. Other gynecological causes include pelvic inflammatory disease, which may cause RUQ pai n if complicated by the Fitz \200\223Hugh \200\223 Curtis syndrome, and ovarian torsion, wh ich presents with abdominal pain (albeit lower abdominal pain) and vomiting. Acute renal co lic gen- erally presents with pain at the renal angle, which radiates to the groin, is seve re, and is associated with vomiting. The assessment of this patient was complicated by the fact that she had received an opioid analgesic just before referral, which masked signs of peritonism. She was also on high-dose corticosteroids, which can also mask signs of peritonitis. The underlying autoimmune hepat itis was a red herring and not responsible for her acute symptoms. It does not cause acute liver distension to provoke capsular pain. 28b) What common conditions need excluding and what uncommon medical conditions should be kept in mind? Three common medical conditions causing severe abdominal pain (including peritonism) are di abetic ketoacidosis, lower lobe pneumonia, and an acute coronary syndrome. All can cause ab dominal pain, are treatable, and carry serious consequences for the patient if missed. Uncommon medical causes of acute abdominal pain are acute por- phyria, familial Mediterrane an fever, acute angio-oedema, and heavy metal poisoning. Addison \200\231s disease, althoug h it can cause chronic abdominal pain, does not present as an acute abdomen. These should b e suspected if initial investigations do not reveal the cause. The acute porphyrias include acute intermittent porphyria, variegate porphyria and heredita ry coproporphyria. They are caused by geneti- cally determined deficiencies in various enzy mes involved in the synthe- sis of heme. In the UK, acute intermittent porphyria is the mos t common type. A deficiency in hydroximethylbilane synthetase (HMB-synthetate) underlies th e condition. People affected by this condition are heterozy- gous for the affected gene and have half-normal levels of HMB-synthesate. Acute attacks are precipitated by substances th at induce the rate-limiting (hepatic) enzyme, involved in heme synthesis, aminolaevulinic a cid syn- thetate (ALA-synthetase). This enzyme is the first in the heme-biosynthetic pathwa y, upstream of HMB-synthetase. The list of precipitant drugs that should be avoided is long and may be found in the British National OXFORD CASE HISTORIES 188 Formulary or on the European Porphyria Initiative website (www.porphy- ria-europe.org). Ste roid hormones seem to be particularly important, because attacks do not occur before pubert y. Hormonal contraceptives should be avoided. Premenstrual attacks are similarly related to endog- enous progesterone, but surprisingly, pregnancy usually poses no prob- lem, indicat ing a beneficial metabolic factor. Acute attacks of porphyria may also be precipitated by a reduction in caloric intake, as wi th acute illness, dieting or fasting. Abdominal pain is the most prominent manifestation. T he pain is usually diffuse and con- stant. Fever and abdominal tenderness are unusual, and inflammatory markers are usually normal. Other features of an acute attack include constipa tion, mental symptoms of anxiety, confusion, paranoia, depres- sion, and hallucination. Sym pathetic over-activity manifests with tachy- cardia or dysrrhythmias. Peripheral neuropathy is not universally present in acute attacks, and skin lesions do not occur. The diagnosis of an acute attack is made by demonstrating elevated levels of urinary porphobilino- gen. N ormal urinary porphobilinogen during an acute attack effectively excludes acute intermitten t porphyria as the cause of acute symptoms. Fecal porphyrins are usually normal (in contras t to variegate porphyria and hereditary coproporphyria). Urinary ALA is increased, although levels may be normal in the absence of an acute attack. In these circum- stances the diagn osis is based on detecting HMB-synthesase deficiency in erythrocytes. Acute porphyria is managed in the first instance symptomatically with opioid analgesia, ant iemetics, and sedatives. Intravenous glucose (300g/day) may be effective in milder cases bu t intravenous haematin is more effective and should be started without delay and continued for 4 days. Haem arginate or haem albumin may also be used. In the long term there is an in creased risk of hypertension, renal disease, and hepatocellular carcinoma. Familial Mediterranean fever (FMF) is the prototype of the heredi- tary periodic fever synd romes and is especially common in people of Jewish, Italian, Turkish, Armenian, or Arab dec ent. Acute attacks start early in life, are always associated with a fever, and are accompa nied by abdominal pain in 90%. Abdominal pain may vary from mild general- ized pain, to sev ere pain with peritonism and ileus. Amyloidosis (AA) is a late complication, which occurred commonly before colchicine was shown both to prevent this and reduce the frequency of atta cks. Acute angioedema is bradikinin mediated. and may be due to a hereditary CASE 28 189 C1 esterase deficiency or due to the development of autoantibodies (acquired) against C1 es terase. Attacks of colicky abdominal pain with episodes of laryngeal oedema are characteris tic. Urticaria is not a feature. Therapy with attenuated androgens is effective as prophyla xis. In some settings -aminocaproic acid is also used. Heavy metal poisoning with arsenic , lead, mercury or cadmium may all be associated with abdominal pain. A thorough occupation al history is important. In the acute setting a urine heavy metal assay is the investigatio n of choice. Chelating agents are available for all but cadmium. 28c) What investigations should be requested on admission? Urine dipstix helps exclude diabetic ketoacidosis. An erect chest radio- graph and abdomina l radiograph are mandatory. The chest radiograph may indicate pulmonary consolidation and s hould reveal intraperitoneal air if present. An abdominal radiograph (which need not be an erect movie) may show the distended bowel loops of an ileus. Pancreatic calcification (indi cating underlying chronic pancreatitis) should be sought. Calcified gallstones are present in only 10% of patients with gallstones, so gall- stones are rarely seen on plain radiograp hy. In contrast, most renal stones are radio-opaque and may be visible on plain radiography . Our patient \200\231s pain, however, was not typical of renal colic. An ECG is necessary to exclude myocardial ischaemia. Blood tests including biochemistry, inflammatory markers, and full blood count will reveal electrolyte abnormalities, liver function derange- ment (due to the passage of a gallstone) , evidence of inflammation or infection, and may show changes of underlying chronic disease . Our patient had a normal CRP, with a mildly elevated leucocyte count. Mild leucocytosis m ay result from underlying infection, although the CRP is usually markedly elevated. It is w orth noting that if done early, the CRP may be normal, because there is a lag in CRP respon se. Mild leucocytosis may be caused by the prednisolone therapy in this patient, or result from pain, which causes demargination of leucocytes in the periphery, through catecholamine release. Metabolic stress (as with diabetic ketoacidosis) can cause a leucocytosis, even w ithout underlying infection. Liver func- tion tests were unhelpful in our patient, as they were already elevated because of the autoimmune hepatitis. Acute pancreatitis (in the absen ce of a chronic component) was effectively excluded by the normal serum amylase. The normal serum albumin and hemoglobin are consistent with an acute event. OXFORD CASE HISTORIES 190 A chest radiograph showed lucency under the right hemi-diaphragm (Fig. 28.1). A lateral dec ubitus abdominal radiograph was requested (car- ried out after the patient had been positio ned on her left side for 10 min), which showed a locule of air above the liver (Fig. 28.2). A surgical opin- ion was sought. At the time of surgical review, the opioid analgesia had worn off and the patient clearly had peritonism. A CT scan of the abdomen revealed free air above the liver and in the porta hepatis (Fig. 28.3). The site of visceral perforation was not evident, but peptic ulcer perforation was thought to be the most likely diagnosis. The patient was taken to theater and a small perforated duodenal ulcer was identified and trea ted with simple closure using an omental patch. 28d) Discuss the medical management of the underlying condition. While gastric acid secretion plays a central role in peptic ulcer disease (PUD), because ul ceration occurs during increased acid secretion and healing occurs during acid suppression, pepsin contributes to ulceration. Impairment of mucosal protection mechanisms, including d isruption of the integrity of the mucous gel layer, reduced bicarbonate production, impaire d blood flow, and mucosal repair also contribute. Helicobacter pylori, NSAID use, and acid- hypersecretory states are the main risk fac- tors for the development of PUD. Zollinger \200\223Ellison syndrome, due to a gastrinoma with excess gastrin secretion, may cause mult iple ulcers, but is very rare. H. pylori stimulates acid and pepsin production; both H. pyl ori and NSAIDs impair mucosal defense. NSAIDs do so partly through Fig. 28.1 This erect chest radiograph shows elevation of the right hemidiaphragm, with subt le subdiaphragmatic radiolucency (arrow). The gastric air bubble is clearly visible on the left. Note that this is a poor inspiratory movie, and lung fields should be interpreted wit h caution. CASE 28 191 Fig. 28.2 A lateral decubitus movie of the abdomen showing a locule of air above the liver (arrow) and the same lucency over the liver, further to the right, below the diaphragm. inhibition of prostaglandin synthesis. Other risk factors that contribute to the developmen t of PUD are psychological stress, smoking, other drugs such as potassium chloride, bisphos phonates, corticosteroids or mycophenolate mofetil, and advancing age with concomitant decl ine in prostaglandin levels. Certain chronic conditions are associated with an Fig. 28.3 A CT scan at the level of the porta hepatis showed a small amount of free gas ant erior to the liver (large arrow) and gas locules in the porta hepatis (small arrow). There is free intra-abdominal fluid, mainly in the perihepatic region, which tracked inferior to the porta hepatis, right paracolic gutter, and pelvis on further sections. Note the irregul ar liver contour, in keeping with chronic liver disease. OXFORD CASE HISTORIES 192 increased risk of PUD, including chronic lung disease, renal failure, and liver cirrhosis. Duodenal ulceration is the most common form of PUD in the West and is associated with H. py lori in >95%. Gastric ulceration may also be associated with H. pylori in up to 70% of case s in early studies, but is now more commonly caused by NSAID ingestion. Although most PUD m ay be explained by either H. pylori or NSAIDs, recent series from the USA report that neith er H. pylori, nor a history of NSAID use could explain up to a third of gastric and duodena l ulcers. The reliability of this finding may be affected by inaccurate history taking rela ted to NSAID use and/or unreliable testing procedures for H. pylori. Even so there is a sub set of PUD in which a cause is not found. Before the first effective antisecretory therapy with H2 blockers, the mainstay of therapy for recurrent or complicated PUD was surgery. Gas tric surgery for PUD has almost vanished since the advent of proton pump inhibitor (PPI) th erapy and the discovery of H. pylori. Eradication of H. pylori is indicated if found in a patient with PUD. Eradication of H. pyl ori alone (Table 28.1) effectively heals and pre- vents recurrent H. pylori-associated PUD. Treatment with an antisecre- tory drug alone heals, but does not prevent recurrence unless treatment is continued. The combination of eradication therapy and acid suppres- sion is s uperior to acid suppression alone in healing duodenal ulcers, but not necessarily with gast ric ulcers. The main benefit of H. pylori eradication therapy is to prevent recurrent ulceration. Follo wing H. pylori eradication, recurrence of PUD is reduced Table 28.1 Helicobacter pylori eradication therapy for low-risk patients* First-line \200\223 7 days treatment >90% eradication rate. Usual reason for failure is po or adherence and not bacterial resistance Omeprazole 20mg or lansoprazole 30mg twice daily Amoxicillin 1g twice daily or (if penicillin allergic) metronidazole 400mg twice daily Clarithromycin 500mg twice daily Second-line \200\223 14 days treatment (if failure of first-line) Omeprazole 20mg or lansoprazole 30mg twice daily Amoxicillin 1g twice daily or (if penicillin allergic) clarithromycin 500mg twice daily Metronidazole 400mg twice daily Patients with dyspepsia in the community, or gastritis at endoscopy with no ulceration or o ther complications. CASE 28 193 to <10%, compared with 60 \200\22370% if eradication therapy is not given. Maintenance ther apy with a PPI is indicated for those patients who have to use long-term NSAIDs (rheumatolo gical diseases, or aspirin for ischaemic heart disease). Misoprostil, a prostaglandin E ana log, is effective at reducing recurrence of NSAID-induced gastric ulceration. At a dose of 800 g/day, the recurrence rate was 4% at 12 weeks with continued NSAID therapy, compared w ith 65% on placebo in one study. This compares favorably with a PPI, but misoprostil is ass ociated with more side effects. Another strategy to manage patients with PUD who need long-term NSAIDs is to use a differen t analgesic. Selective COX-2 inhibitors are associated with a lower incidence of gastrointe stinal side effects, although several agents have been withdrawn from the market because of increased cardiovascular side effects. Other novel NSAIDs include cyclo-oxygenase-inhibiti ng nitric oxide donators, which maintain mucosal blood flow while inhibiting cyclo-oxygenas e, and are under development. Following the diagnosis of a peptic ulcer, most often by endoscopy, standard treatment incl udes acid suppression for 4 weeks (esomepra- zole 40mg, lansoprazole 30mg, daily omeprazole 20mg, or pantoprazole 40mg) for duodenal ulcers and 8 weeks for gastric ulcers, together w ith eradication therapy (Tables 28.1 and 28.2). Medication is best taken 30 min before brea kfast to ensure maximal acid suppression, since this coincides with the time of maximal num ber of active binding sites. At the time of endoscopy, biopsies for H. pylori should be tak en. Before PPI therapy has been started, a rapid urease test can be carried out on mucosal biopsies. If the patient is already on a PPI, histopathological examination of biopsies is necessary. Empirical eradication therapy for H. pylori can be justified in the case of duod enal ulceration, since these are almost always associated with infection. A positive test r esult for any ulcer allows confirmation of H. pylori as the cause and is best practice in v iew of the possibility of a non-H. pylori ulcer and the small percentage of alterna- tive a etiologies. Patients with H. pylori can be classified into low risk and high risk groups. Low risk Dyspepsia in the community Antral or body gastritis at endoscopy, with no ulceration or other complications. OXFORD CASE HISTORIES 194 Table 28.2 Helicobacter pylori eradication therapy for high-risk patients* 1st line \200\223 7 days treatment As above for low risk patients 2nd line \200\223 14 days treatment (after failure of 1st line) Omeprazole 20mg or lansoprazole 30mg twice daily Metronidazole 400mg twice daily Amoxicillin 1g twice daily or (if allergic to penicillin) clarithromycin 500mg twice daily De-Noltab 2 twice daily 3rd line \200\223 14 days treatment (after failure of 1st and 2nd line) Omeprazole 20mg or lansoprazole 30mg twice daily Metronidazole 400mg twice daily Tetracycline 500mg three times daily De-Noltab 2 twice daily 4th line \200\223 14 days treatment (generally reserved for patients with a MALT lymphoma on specialist advice Omeprazole 20mg or lansoprazole 30mg twice daily De-Noltab 2 twice daily Plus TWO antibiotics not used before e.g. rifabutin, tetracycline or levofloxacin. Contact microbiology for patient specific advice History of PUD; patients who continue to need NSAIDs, have peptic ulcers, or MALT lymphoma. High risk Low-risk patients who continue to need NSAIDs Peptic ulcers, particularly if bleeding MALT lymphoma. A second endoscopy to confirm ulcer healing is only necessary for gastric ulcers, 8 weeks a fter diagnosis. Multiple biopsies should be taken at the edge of the ulcer or healed area t o exclude underlying malignancy, which may be present in 1% of gastric ulcers. Duodenal ulc ers are almost never malignant, and require neither biopsy nor repeat endoscopy. 28e) Discuss the potential complications and further management of this patient Complications of PUD include hemorrhage, perforation, and gastric outlet obstruction. The m ost common of these is hemorrhage. 15% of peptic ulcers bleed, and the risk increases with age. Hemorrhage may occur without preceding symptoms in 20% of cases. The risk of recurrent hemorrhage is reduced by eradication of H. pylori. Testing for H. pylori in acute upper ga strointestinal hemorrhage is hampered by a high CASE 28 195 false-negative rate for the rapid urease test. The urea breath test is inap- propriate in t he circumstances. Management of a bleeding ulcer first involves appropriate resuscitation, then endoscopic therapy (injection of adrenaline, heater probe application, or endoscopic c lipping). Two modalities are best used: adrenaline injection plus one other. Successful end oscopic haemostasis is only then followed by high-dose intravenous therapy with a PPI. The Hong Kong regimen of intravenous omepra- zole 80mg followed by 8mg/hour for up to 72 hours, reduces the rate of re-bleeding. The mechanism may be related to inhibition of thromboly- sis at a higher gastric pH, with the formation of stable clot. Failure to establish haemost asis endoscopically requires surgical intervention, or radiographic embolization of a bleed ing vessel. Perforation of a peptic ulcer is the most common complication after hemorrhage. Up to 7% of peptic ulcers perforate. Penetration refers to direct extension of an ulcer into an adjace nt organ, as opposed to free intraperitoneal perforation. A perforated peptic ulcer require s surgery. With the availability of acid suppression and eradication therapy, an omental pa tch (simple closure of the defect) is the procedure of choice. Eradication of H. pylori is highly effective at preventing recurrent duode- nal ulcer perforation, and makes long-term acid suppression unneces- sary. The most important prognostic factor determining outcome is time to diagnosis and appropriate surgery. Delayed diagnosis (>24 hours) is associated with significant reduction in survival and a hi gh index of suspicion needs to be maintained, espe- cially for patients on corticosteroids or of advanced age, when clinical features of peritonitis may be masked. Any acutely ill el derly patient without a clinically identifiable explanation for their condition needs thoro ugh evaluation of the abdomen, with appropriate radiological imaging. Conversely, it is wor th noting that cocaine may be associated with duodenal ulcer perforation, which should be c onsidered when per- foration presents in young patients. Gastric outlet obstruction occurs in up to 2% of patients with PUD. It may be inflammatory, presenting acutely with oedema in the duodenal bulb obstructing the gastric outlet, which may resolve with medical therapy. More commonly it is chronic, due to recurrent ulceration with fibrosis, causing a fixed stenosis of the gastric outlet. This is an indication for pn eumatic (balloon) dilatation in conjunction with appropriate medical therapy (acid suppress ion and eradication therapy). If unsuccessful, a definitive surgical procedure is warranted . OXFORD CASE HISTORIES 196 PUD is occasionally refractory to medical therapy. A refractory ulcer is defined as an ulce r of >5mm that does not heal after appropriate PPI therapy (above). Missed H. pylori infect ion, continued NSAID ingestion and Zollinger \200\223Ellison syndrome need to be considered . Our patient had a diagnosis of visceral perforation made within 4 hours of presentation, an d was appropriate for surgery, which was suc- cessful. Eradication therapy was prescribed, but since it was thought to be associated with prednisolone for her autoimmune liver diseas e, PPIs were continued long term. Confirmation of successful eradication of H. pylori would normally be achieved by a breath test 4 weeks after ces- sation of therapy, but because of the need to continue PPI therapy, a repeat endoscopy and mucosal biopsy for histopathology was arranged 8 weeks after surgery. Further reading Behrman SW (2005). Management of complicated peptic ulcer disease. Arch Surg; 140: 201 \200\2238. Kocer B, Surmeli S, Solak C, Unal B et al. (2007). Factors affecting mortality and morbidit y in people with peptic ulcer perforation. J Gastroenterol Hepatol; 22: 565 \200\22370. Medicines Advisory Committee. Oxford Radcliffe Hospitals (2009). Adult guidelines: 1) Prescribing proton pump inhibitors, 2) Helicobacter pylori eradication. Medicines inform ation leaflet. Oxford Radcliffe Hospitals NHS Trust; 2(6). Yuan Y, Padol IT, Hunt RH (2006). Peptic ulcer disease today. Nat Clin Pract Gastroenterol Hepatol; 3: 80 \200\2239. CASE 29 197 Case 29 A 50-year-old male university science lecturer presented for follow up with his gastroenter ologist. He had previously had recurrent acute pancreatitis with four episodes over a perio d of 3 years, each with a marked increase in serum amylase. The last attack was a year ago. He denied drinking any alcohol. A cholecystectomy had been carried out after his second at tack of pancreatitis. He reported some postprandial fullness and 4kg weight loss. He had no other medical history and was on no medication. Examination was normal. Investigations showed: 9/L, platelets 145 x 109/L Hb 14.0g/dL, WCC 5.6 x 10 mol/L mol/L, AST 40 IU/L, ALT 40 IU/L, ALP 60 IU/L, Na 135mmol/L, K 4.1mmol/L, urea 3.5mmol/L, creatinine 75 Bilirubin 15 GGT 35 IU/L, albumin 40g/L Amylase normal CA 19.9 normal A CT of the abdomen carried out 2 years previously had shown a pseudocyst in the head of th e pancreas. Follow-up CT of the abdomen is illustrated (Fig. 29.1 and 29.2). An endoscopic ultrasound (Fig. 29.3) was carried out to characterize the lesion. This showe d a very large cystic dilatation of the main pancreatic duct. There were multiple papillary projections. The main pancreatic duct was grossly dilated. A \200\230fish-mouth \200\231 papilla was also seen (Fig. 29.4 in the central colored section). Questions 29a) What are the causes of recurrent acute pancreatitis? 29b) What is the differential diagnosis of the above lesion? Describe how to differentiate between these diagnoses. 29c) How would fine-needle aspiration assist in diagnosis of this lesion? 29d) How should this patient be managed? OXFORD CASE HISTORIES 198 Fig. 29.1 CT scan. Fig. 29.2 CT scan. Fig. 29.3 Endoscopic ultrasound. MPD: main pancreatic duct CASE 29 199 Fig. 29.4 (see color plate 13) Papilla at ERCP. Mucin extruding (small arrow) from the dist orted papilla (large arrow). OXFORD CASE HISTORIES 200 Answers 29a) What are the causes of recurrent acute pancreatitis? Any cause of acute pancreatitis may lead to further episodes if it is not corrected. The hi story and conventional diagnostic tests including blood tests for calcium and triglycerides , abdominal ultrasound to look for gallstones, MRCP, and CT scan of the abdomen, generally detect the cause of recurrent episodes of pancreatitis in 70% of cases. Endoscopic ultrasou nd may detect small stones in the common bile duct missed at ultrasound or MRCP. In view of the potential complications from ERCP (see Case 9), ERCP is now rarely an appropriate diag nostic investigation, although may be an appropriate therapeutic intervention. Causes of recurrent pancreatitis are shown in Table 29.1. 29b) What is the differential diagnosis of the above lesion? Describe how to differentiate between these diagnoses Based on the CT and endoscopic ultrasound findings, the main differen- tial diagnoses in th is case are: \200 Pancreatic cystic neoplasm: papillary mucinous neoplasm Mucin-producing tumors: intraductal (IPMN) and mucinous cystic neoplasm (MCN) Serous cystadenoma (SCA) Inflammatory pseudocyst, secondary to previous pancreatitis Cystic adenocarcinoma. Although inflammatory pseudocysts are more commonly associated with episodes of acute pancr eatitis, it is important to exclude non-inflammatory cystic lesions that can cause acute pa ncreatitis, because they can have a risk of malignant transformation. This lesion is most likely to be intraductal papillary mucinous neoplasm (IPMN). IPMN is a cystic neoplasm arising from the pancreatic duct, with mucin-producing epithelium. The CT s can and endoscopic ultra- sound (Figs 29.1 \200\22329.3) show that the main pancreatic duct is markedly dilated and has papillary-type projections. Solid nodules in the wall of the p ancreatic duct and the \200\230bright \200\231 sonographic features of mucin were seen. A \200\230fish-mouth \200\231 papilla, with mucin extruding from the ductal orifice, is char acteristic of intraductal papillary mucinous neoplasm (Fig. 29.4). These lesions have a hig h risk of malignant transformation and can present with acute pancreatitis that is often re current. They are commonly misdiagnosed as the far more common \200\230pseudocysts \200 \231. CASE 29 201 Table 29.1 Causes of recurrent pancreatitis Mechanical Congenital Pancreatic divisum, annular pancreas Acquired Gallstones (most frequent aetiological factor) Microlithiasis (<2mm in diameter and usually seen at endoscopic ultrasound and ERCP) Gallbl adder sludge (usually seen on ultrasound) Common bile duct macrolithiasis