PRACTICAL GASTROENTEROLOGY • APRIL 200374

Diarrhea in Gastrointestinal Amyloidosis: A Case Reportand Review of the Literature

A CASE TO REMEMBER

Sammy Ho, M.D., Gastroenterology Fellow, Department of Gastroenterology, Hepatology and Nutrition, WinthropUniversity Hospital, Mineola, NY. Kavita R. Kongara, M.D., Attending Physican, Director, Gastrointestinal Diag-nostic Motility Center and Women’s Center for Gastroenterology, Winthrop University Hospital, Mineola, NY.

Amyloidosis is characterized by the accumulation of an insoluble amyloid protein in theextracellular space of many different tissues. It is a multisystem disorder and clinicalinvolvement of a single organ is rare. Diagnosis is established by histologic demonstra-tion of amyloid protein in affected tissues. The gastrointestinal tract is frequentlyinvolved in amyloidosis. Common presenting symptoms include abdominal pain,weight loss, anorexia, nausea, vomiting, diarrhea, and rarely obstruction. Although thegastrointestinal complications may result in significant morbidity, they are usually notthe cause of death, which is most often due to renal failure, restrictive cardiomyopathy,or ischemic heart disease. We report a case of gastrointestinal amyloidosis in an elderlygentleman who presented with diarrhea and weight loss.

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Sammy Ho Kavita R. Kongara

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A CASE TO REMEMBER

Diarrhea in Gastrointestinal Amyloidosis

T he incidence of amyloidosis is about twelve casesper million population per year (1). Althoughrenal disease in the form of nephrotic syndrome

and congestive heart failure with restrictive cardiomy-opathy are the most common presentations, 30 to 60percent of patients with amyloid experience gastroin-testinal symptoms (2). Amyloid associated dysmotilitymay be presented as intestinal pseudo-obstruction ordiarrhea. We report an interesting case of an elderlymale who presented with diarrhea and weight loss as amanifestation of gastrointestinal amyloidosis.

CASE REPORTA 78 year old male presented with a six month historyof fatigue, anorexia, and diarrhea. The patientdescribed the diarrhea as approximately eight loosebowel movements per day. Previous medical historyincluded hypertension and monoclonal gammopathyof undertermined significance (MGUS). On review ofsystems, it was noted that the patient also had a 15pound weight loss, exertional dyspnea, and frequentsyncopal episodes. He denied any sick contacts orrecent travel. Surgical history included drainage of asubdural hematoma secondary to a fall three monthsprior. Family history was noncontributory. He was anex-smoker and drank one beer a day.

On presentation, the patient was noted to haveorthostatic hypotension. Physical examinationrevealed a cachetic elderly gentleman with a largetongue, three plus edema in the lower extremities, anddiffuse hyporeflexia.

The patient was mildly anemic and EKG showedlow voltages on all anterior limb leads. Twenty-fourhour urine collection revealed proteinuria within thenephrotic range (4g/24hr). Colonoscopy was unre-markable and an upper endoscopy was done withexamination to mid-jejunum (130cm). Areas of flat-tened mucosa was noted (Fig. 1). Biopsy tissuerevealed increased submucosal deposits, congo redstain confirmed amyloidosis (Fig. 2).

The patient experienced numerous syncopalepisodes during the admission. Pulmonary status alsodeteriorated, requiring mechanical ventilation. Heexpired due to multi-system organ failure shortly afterthe diagnosis of amylodosis.

DISCUSSIONThe biochemical description of each type of amyloid isrepresented by two letters: “A” for amyloid, followedby a second letter specifying the type of amyloid. Theamyloid derived from immunoglobulin light chains iscalled AL. Although more than ten different types ofamyloid are described in the literature, AL (primary),AA (secondary or reactive), AF (familial), and AH(hemodialysis-related) amyloid account for 90% of allcases of amyloidosis producing GI symptoms (3). Themost common causes of reactive amyloidosis arerheumatoid arthritis, inflammatory bowel disease, andfamilial Mediterranean fever. Gastrointestinal diseaseis present in as many as 60% of patients with reactiveamyloidosis (4). On the other hand, GI involvementappears to be less common in AL amyloidosis.

Clinical Syndromes of GI AmyloidosisGastrointestinal complaints are common in patientswith amyloidosis, even if the chief complaint is notalways GI related. Typical presenting symptoms includeabdominal pain, weight loss, fatigue, and anorexia.Amyloid-associated dysmotility may be manifested asintestinal pseudo-obstruction, diarrhea, or achalasia. Inour case presentation, the patient presented with diar-

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Figure 1. Area of flattened mucosa in the mid-jejunum.

rhea. Diarrhea in patients with amyloidosis is oftensevere. It is thought to be due to a combination of auto-nomic neuropathy, amyloid infiltration of the submu-cosa resulting in malabsorption, and bacterial over-growth (4). Recent reports of the efficacy of somato-statin analogue in cases of refractory diarrhea suggestthat a secretory mechanism may be involved (5).

Systemic amyloidosis affects every part of the gas-trointestinal tract from the mouth to the anus.Macroglossia occurs in 20% to 50% of primary amy-loid patients and causes difficulties with speech, mas-tication, and deglutition (2). Patients with esophagealinvolvement usually present with dysphagia andsymptoms of esophageal reflux. In their study of 30patients with systemic amyloidosis, Rubinow, et aldescribed abnormal esophageal manometric findingsinvolving the lower esophageal sphincter, the body ofthe esophagus, or both in 63% of patients (6). Patientswith gastric involvement can present with gastropare-sis, epigastric pain, gastric outlet obstruction, pepticulceration, hematemesis, and melena. Korelitz andSpindell reported in primary amyloidosis that at initialassessment, 5% of patients had a gastric ulcer, 7%hematemesis, 9% tumor, and 20% nausea and vomit-ing related to amyloid deposition (7). Liver involve-ment varies considerably in amyloidosis. Detectablehepatomegaly occurs in 33% to 50%, but markedabnormalities of liver serology are rare (2).

Interestingly, some patients who ultimately showclinical evidence of primary amyloidosis present withmonoclonal gammopathy of undetermined signifi-cance (MGUS). It has been reported that three to fourpercent of patients with MGUS eventually developsymptoms related to amyloidosis (8).

Endoscopic FeaturesCharacteristic endoscopic findings in GI amyloidosisinclude erosions, ulcerations, polypoid protrusions,and fine granular appearance. In their review of endo-scopic findings in amyloid, Tada, et al found that finegranular appearance and polypoid protrusions to be themost common endoscopic features of GI amyloidosis(9). However, biopsy should be done in every casebecause grossly normal mucosa does not preclude his-tologic evidence of amyloid.

DiagnosisBarium radiography is of limited diagnostic utility,since the changes that may be seen, such as dilatationof the small bowel or colon, are not specific for amy-loidosis. The definitive diagnosis of gastrointestinal

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Diarrhea in Gastrointestinal Amyloidosis

Figure 2a. Endoscopic biopsy stained with hematoxylin andeosin. Note the arteriolar wall hyalination and thickening ofsmall vessel media.

Figure 2b. Apple-green birefringence of the amyloiddeposits when observed under polarized light.

PRACTICAL GASTROENTEROLOGY • APRIL 200378

amyloidosis requires histological confirmation. Tada,et al found small bowel biopsy to have the highest sen-sitivity for amyloid (100%), followed by biopsy ofcolon, stomach, and esophagus (9). Overall, endo-scopic biopsies of the upper GI tract are more sensitivethan those from the lower GI tract—86% versus 80%(9). By comparison, rectal biopsy and abdominal fataspiration have a reported sensitivity of 75% to 85%(10). The amyloid fibrils can be identified by theircharacteristic appearance on the electron microscopyand by their ability to bind Congo red, leading toapple-green birefringence under polarized light.

TreatmentsChemotherapy has been useful in the treatment of ALamyloidosis. Two major trials, which used slightly dif-ferent regimens of intermittent oral melphalan andprednisone, have confirmed the efficacy of this ther-apy over no therapy or therapy with colchicine alone.The response rate is low, however, with an increase insurvival of approximately 6 months in those receivingchemotherapy (11). Patients must also live longenough to receive several cycles of melphalan before asurvival benefit occurs.

Although the gastrointestinal complications mayresult in significant morbidity, they are not usually thecause of death. Therapy is directed at symptomaticcontrol of the gastrointestinal manifestations and at theunderlying disease. Those who are malnourished orunable to tolerate feeding due to dysmotility may ben-efit from total parenteral nutrition. Patients with gas-troparesis can be treated with reglan. Octreotideacetate has been shown to be very effective in treatingpatients with diarrhea due to GI amyloidosis. This may

indicate that a secretory mechanism is involved. Othertreatment options being tested now are thalidomideand TNF receptor antagonists (Embrel) (1).

There has been a recent vast increase in the under-standing and treatment of patients with amyloidosis.Early diagnosis is essential for the optimal effect oftreatment on patient survival and quality of life. In thefuture, it is hoped that clinicians will diagnose early,treat promptly, and halt the progress of an almost uni-formly fatal disease. ■

References1. Khan MF, Falk RH. Amyloidosis. Postgrad Med Journal,

2001;77:686-693.2. Friedman S, Janowitz HD. Gastrointestinal disorders and sys-

temic disease, Part I. Gastroenterolgy Clinics, 1998;27(3):596-614.

3. Lee JG, Wilson JA, Marcia R, et al. Gastrointestinal Manifesta-tions of Amyloidosis. Southern Medical Journal, 1994;87(2):2432-2447.

4. Camilleri M. Gastrointestinal amyloidosis. [Up to Date web site].2001. Available at: http://www.uptodate.com. Accessed Oct 22,2002.

5. Yam LT. Octreotide for diarrhea in amyloidosis. Annals of Inter -nal Medicine, l991;115(7):577.

6. Rubinow A, Burakoff R, Cohen AS, et al. Esophageal manome-try in systemic amyloidosis: A study of 30 patients. AmericanJournal Med, 1983;75:951.

7. Korelitz BI, Spindell LN. Gastrointestinal amyloidosis: Report ofa case and review of the clinical and radiological aspects. Journalof Mt Sinai Hospital, 1958;23:683.

8. Kyle RA. Monoclonal gammopathy of undetermined signifi-cance. [Up to Date web site] 2001. Available at: http://www.upto-date.com. Accessed Oct 22, 2002.

9. Tada S, Lidda M, Iwasshita A, et al. Endoscopic and biopsy find-ings of the upper digestive tract in patients with amyloidosis.Gastrointest Endoscopy, 1990;36: 10-14.

10. Kim DD, Ryan JC. Gastrointestinal Manifestations of SystemicDiseases. In: Sleisenger and Forddtran’s Gastrointestinal andLiver Diseases, 7th ed. Saunders, 2002:507-537.

11. Skinner M, Anderson J, Simms R, et al. Treatment of 100 patientswith primary amyloidosis: a randomized trial of melphalan, pred-nisone, and colchicines versus colchicines only. American Jour -nal of Med, 1996;100:290.

A CASE TO REMEMBER

Diarrhea in Gastrointestinal Amyloidosis

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