Systemic amyloidosis: A rare presentation of mesenteric angina

Can J Gastroenterol Vol 16 No 10 October 2002 683

BRIEF COMMUNICATION

Systemic amyloidosis: A rarepresentation of mesenteric

angina

Christopher N Andrews MD1, Jack N Amar MD FRCPC2, Malcolm MM Hayes MBChB FRCPC3, Robert A Enns MD FRCPC2

1Department of Medicine, University of British Columbia, and Departments of 2Gastroenterology and 3Pathology, St Paul’s Hospital, Vancouver,British Columbia

Correspondence and reprints: Dr Robert A Enns, Department of Gastroenterology, St Paul’s Hospital, #300-1144 Burrard Street, Vancouver,British Columbia V6Z 2A5. Telephone 604-688-7017, fax 604-689-2004, e-mail [email protected]

Received for publication June 10, 2002. Accepted August 15, 2002

CN Andrews, JN Amar, MMM Hayes, RA Enns. Systemicamyloidosis: A rare presentation of mesenteric angina. Can JGastroenterol 2002;16(10):683-685.

A 64-year-old man presented with an eight-month history ofincreasing postprandial epigastric pain and a 15 kg weight loss.Computed tomography of the abdomen, panendoscopy andmesenteric angiography failed to explain the cause of thepatient’s mesenteric angina. Systemic amyloidosis involvingintestinal small vasculature without larger arterial involvementwas diagnosed at autopsy after the patient died of an asystolic car-diac arrest. Mesenteric angina without evidence of ischemicenteritis or pseudo-obstruction is a rare manifestation of amyloi-dosis.

Key Words: Abdominal pain; Amyloidosis; Ischemia; Mesentery

Infarctus mésentérique : manifestation rare del’amylose généralisée

RÉSUMÉ: Un homme de 64 ans est venu consulter pour des douleursépigastriques postprandiales se faisant de plus en fortes depuis huit mois etune perte de poids de 15 kg. Une tomodensitométrie de l’abdomen, unepanendoscopie et une angiographie du mésentère n’ont pas permis decerner la cause de l’infarctus mésentérique. Finalement, une amylosegénéralisée touchant les petits vaisseaux sanguins de l’intestin mais pas lesgrosses artères a été diagnostiquée à l’autopsie après que le patient eu suc-combé à un arrêt cardiaque par asystole. L’infarctus mésentérique en l’ab-sence d’entérite ischémique ou de pseudo-obstruction est unemanifestation rare de l’amylose.

Amyloidosis is a disease characterized by the accumula-tion of various insoluble fibrillar proteins (amyloid) in

extracellular tissue. These fibrils are made of low molecularweight subunits of a variety of normal serum proteins andaccumulate in amounts sufficient to impair normal organfunction (1).

Systemic amyloidosis can affect any part of the gastroin-testinal (GI) tract from the mouth to the anus, and can also

cause hepatic and pancreatic disease. Clinical manifesta-tions are numerous; this report describes an unusual case ofsystemic amyloidosis presenting as mesenteric angina.

CASE PRESENTATIONA 64-year-old black man who immigrated to Canada fromthe Caribbean in 1965 was well until 10 months beforeadmission, when he suffered a left hemispheric cerebral vas-

Andrews.qxd 10/15/2002 4:24 PM Page 683

cular accident with a mild residual deficit. Investigationsrevealed atrial fibrillation; therefore, he was started on abeta-blocker and anticoagulated with warfarin. He was nottaking any other medications.

Two months later, he developed anorexia associatedwith increasing epigastric pain. The pain would typicallystart 30 to 60 min after ingestion of solids or liquids, andwould remit between meals. High calorie liquids seemed tocause more pain than did water or tea. He was treated withan acid suppression agent by his family physician with norelief. The pain was severe enough that the patient hadstopped eating on many occasions, and he lost approxi-mately 15 kg over the next six months. He denied any diar-rhea, melena, hematochezia, steatorrhea, dysphagia, refluxor fever. He had occasional episodes of nonbloody vomitingin the 10 days before admission. He was admitted to hospi-tal for further investigation.

On examination, he appeared adequately nourished. Hewas normotensive, with a regular pulse of 80 beats/min, andwas afebrile. Cardiac and respiratory examinations wereunremarkable with the exception of a soft systolic murmur atthe left sternal border. There were no stigmata of chronicliver disease. Abdominal examination revealed no abnormalities. Digital rectal examination revealed guaiac-positive stool but was otherwise unremarkable.

Laboratory investigations revealed a normocytic anemiawith hemoglobin of 100 g/L. Electrolytes, urea, creatinine,aspartate aminotransferase, alanine aminotransferase andamylase levels were within normal ranges. Gamma glu-tamyltranspeptidase was elevated at twice normal, and lac-tate dehydrogenase was slightly elevated. There was apersistent unconjugated hyperbilirubinemia between 23µmol/L and 39 µmol/L (normal less than 20 µmol/L), and itwas questioned whether the patient had Gilbert’s syn-drome. Serum protein electrophoresis showed low albuminat 27 g/L (normal 35 g/L to 48 g/L) and low total protein at47 g/L (normal 60 g/L to 80 g/L) but was otherwise normal.Serum lactate was initially slightly elevated at 2.5 mmol/L(normal 0.5 mmol/L to 2.1 mmol/L), but normalized on sub-sequent readings following rehydration.

Tumour markers carcinoembryonic antigen and CA19were not elevated. Urinalysis showed no proteinuria. Bloodcultures were negative. His electrocardiogram was reportedas normal sinus rhythm with no new changes comparedwith previous readings.

Chest radiography revealed a trace of pleural fluid, butwas otherwise normal. Abdominal ultrasound showed noabnormalities. Computed tomography of the abdomen withcontrast showed a normal liver, gallbladder, spleen, pan-creas, adrenal glands and lung bases.

With no obvious explanation for the patient’s epigastricpain, endoscopic investigations were undertaken.Gastroscopy revealed some patchy erythema in the body ofthe stomach, which was not felt to be a significant source ofthe patient’s abdominal pain and weight loss. Biopsy sam-ples revealed Helicobacter pylori gastritis. Small bowel

appearance was normal on enteroscopy. Colonoscopy wasunremarkable except for a small cecal polyp with a benignappearance. The patient was pain free during all endoscop-ic investigations.

A 99mTc-Disofenin biliary scan demonstrated good hepa-tocyte function with patent cystic and common bile ducts.Barium small bowel follow-through examination was nor-mal, with no evidence of obstruction or ileus.

Mesenteric angiography was performed. This revealedwidely patent celiac axis and superior and inferior mesen-teric arteries, with no evidence of atherosclerosis. Therewas no evidence of peripheral stenoses or emboli.

With still no cause found for the patient’s ongoing pain,it was elected to perform endoscopic retrograde cholan-giopancreatography. An 8 mm gallstone was found in themid-common bile duct. Sphincterotomy and the stoneextraction, unfortunately, did not improve his pain. It wasthought that a cholecystectomy and/or laparotomy mightbe the next step because the exhaustive work-up had failedto reveal any clear cause for the patient’s pain and weightloss, which continued in hospital. Two days later thepatient experienced sudden onset shortness of breath, wentinto asystolic cardiac arrest and died despite resuscitationattempts.

Autopsy subsequently revealed severe diffuse systemicamyloidosis resulting in virtual obliteration of small- tomedium-sized arterial and venous vessels throughout thebody, including in the the mesentery and bowel wall. Therewas no evidence of bowel infarction premorbidly.

Extensive amyloid deposition was also found in mostorgans, including myocardium, kidneys, liver, bladder andbrain (the apparent cause of his previous stroke). There wasno evidence of multiple myeloma, underlying chronicinflammatory disease or lymphoproliferative disorder.Review of antemortem gastric biopsies revealed a nonsignif-icant amount of amyloid. Cause of death was ascribed to acardiac arrhythmia secondary to amyloid-induced car-diomyopathy.

DISCUSSIONFour major types of amyloid and several less common formshave been described (1,2). Primary amyloidosis (AL), themost common form, results from fibril formation from frag-ments of monoclonal antibody light chains and is associat-ed with multiple myeloma in up to 20% of patients (1). Theremainder of AL patients have an idiopathic etiology.Secondary (reactive, or AA) amyloidosis fibrils are com-posed of fragments of the acute phase reactant serum amy-loid A, and occur most frequently as a complication ofchronic inflammatory diseases, such as rheumatoid arthritis,tuberculosis and occasionally inflammatory bowel disease.Other common types are familial and hemodialysis-relatedforms.

Diagnosis of amyloid is established by Congo red stain-ing of a tissue specimen, which imparts a characteristicgreen birefringence when viewed with polarized light (1).

Andrews et al

Can J Gastroenterol Vol 16 No 10 October 2002684


Immunofixation tests are available to identify the AL amy-loid subtype, the most common form. This testing was notperformed in this patient, so the specific amyloid type is notknown. However, because chronic inflammatory diseasewas not clinically suspected nor found on autopsy, his fami-ly history was negative for amyloid-like disease, and he wasnot on hemodialysis, it suggests that the patient had themost common, idiopathic AL form.

Whether amyloidosis is systemic or localized, the severi-ty of the organ dysfunction is mostly a determinant of thebiochemical properties of the specific amyloid protein (2).GI disease is present in up to 60% of patients with AA, butis less common in AL amyloidosis (3). A retrospectivereview from the Mayo Clinic (Rochester, Minnesota) foundthat only 8% of 769 patients with AL amyloidosis had GIinvolvement on biopsy (4). Of patients with biopsy-provenGI amyloidosis, the most common sites of amyloid deposi-tion are the duodenum (100%), stomach (95%), colorec-tum (91%) and esophagus (72%) (5).

Clinically, although autopsy results have shown GIinvolvement in most patients with amyloidosis, symptomsare surprisingly rare (6). Symptoms can result from amyloiddeposition in the autonomic nervous system or from directinfiltration of the GI tract itself. Described syndromesinclude: GI bleeding (from ulcers, nodularity or polypoidlesions) (5), malabsorption (1,7), chronic dysmotility (pre-senting as dysphagia, gastroparesis, constipation or pseudo-obstruction) (3), protein-losing gastroenteropathy (8),

intestinal obstruction from amyloid tumours (9) and intes-tinal perforation (10).

Abdominal pain as a major symptom in GI amyloidosis isless common. In the above mentioned article by Menke(4), of 59 patients with gastric amyloidosis, only eight weresymptomatic; none described abdominal pain. Lee et al (7)reviewed 40 patients with amyloidosis, of whom 12 (30%)had abdominal pain, but only two of them had pain as theirchief complaint.

This patient described classic mesenteric ischemia symp-toms with postprandial abdominal pain 30 to 60 min aftereating, that remitted when the stomach was empty. Hedeveloped a fear of eating and subsequently lost 15 kg.These symptoms arise from decreased splanchnic blood flowusually as a result of atherosclerotic disease, with multiplelarge vessel stenoses. This patient had widely patent largerarteries but virtual obliteration of smaller mesenteric vascu-lature from amyloid deposits, giving a normal angiographicpicture but identical symptoms.

Additionally, although ischemic colitis has beendescribed as a result of amyloidosis (7), this patient had noevidence of ischemia on enteroscopy or full colonoscopy.This constellation of symptomatology and normal radi-ographic, endoscopic and angiographic findings is noveland has not been reported to our knowledge. Mesentericangina symptoms, though rare, should be considered oneof the protean manifestations of gastrointestinal amyloi-dosis.

Systemic amyloidosis: A presentation of mesenteric angina

Can J Gastroenterol Vol 16 No 10 October 2002 685

REFERENCES1. Sipe JD, Cohen AS. Amyloidosis. In: Fauci AS, Braunwald E,

Isselbacher KJ, eds. Harrison’s Principles of Internal Medicine, 14thedn. New York: McGraw-Hill, 1998:1856-60.

2. Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med 1997;337:898-909.

3. Friedman S, Janowitz HD. Systemic amyloidosis and thegastrointestinal tract. Gastroenterol Clin N Am 1998;27:595-614.

4. Menke DM, Kyle RA, Fleming CR, et al. Symptomatic gastricamyloidosis in patients with primary systemic amyloidosis. MayoClin Proc 1993;68:763-7.

5. Tada S, Iida M, Iwashita A, et al. Endoscopic and biopsy findings ofthe upper digestive tract in patients with amyloidosis. GastrointestEndosc 1990;36:10-4.

6. Gilat T, Revach M, Sohar E. Deposition of the amyloid in thegastrointestinal tract. Gut 1969;10:98-104.

7. Lee JG, Wilson JAP, Gottfried MR. Gastrointestinal manifestationsof amyloidosis. South Med J 1994;87:243-7.

8. Suzuki C, Higaki S, Nishiaki M, et al. 99mTc-HAS-D scintigraphyin the diagnosis of protein-losing gastroenteropathy due to secondaryamyloidosis. J Gastroenterol 1997;32:78-82.

9. Baldewijns M, Ectors N, Verbeeck G, et al. Intermittentsubobstruction and cholestasis as complications of duodenal amyloidtumours. Gastroenterol Clin Biol 1995;19:218-21.

10. Thaler W, Schatzer G, Eder P, Fichtel G. Amyloidosis – an unusualcase of recurrent intestinal bleeding and sigmoid perforation: Casereport with review of the literature. Int J Colorectal Dis 1999;14:297-9.


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Systemic amyloidosis: A rare presentation of mesenteric angina