Primary amyloidosis presenting as small bowel encapsulation

Department of Medicine, Division of Gastroenterology, 1Dalhousie University, Halifax, Nova Scotia; 2University of Calgary, Calgary, Alberta Correspondence: Dr Jennifer Jones, 129 Red Fern Terrace, Halifax, Nova Scotia B3S 1K9. Telephone 902-425-6339, fax 902-473-4067, e-mail joneskenyon@yahoo.ca Received for publication September 20, 2002. Accepted January 19, 2004 J Jones, G VanRosendaal, C Cleary, S Urbanski, RC Woodman. Primary amyloidosis presenting as small bowel encapsulation. Can J Gastroenterol 2004;18(3):169-172.

Patients frequently present with symptoms of acute or subacute small bowel obstruction (4).A preoperative diagnosis may be suggested by a number of imaging modalities including barium meal, ultrasonography and abdominal computed tomography (CT).Characteristic imaging features of SEP have been discussed in a number of papers (2,(5)(6)(7)(8)(9).Management has included surgical decortication and long term hyperalimentation depending on the symptom severity.Spontaneous resolution of symptoms with conservative therapy has also been reported (10).
We describe a 62-year-old man with small bowel encapsultaion as a first presentation of amyloidosis.To our knowledge, this is the first reported case of small bowel encapsulation as a result of primary amyloidosis.

CASE PRESENTATION
A previously healthy, 62-year-old man presented in July, 1997 with a three day history of nausea, bilious vomiting, mild abdominal distention and constipation.He lost 5.45 kg within the last two months.This man had no history of gastrointestinal pathology or abdominal surgery.
On examination the abdomen was slightly distended, bowel sounds were normal and the abdomen was soft with no tenderness or palpable mass.Abdominal x-rays revealed dilated loops of small bowel with air-fluid levels and a paucity of air in the rectum and right colon.He was admitted with a diagnosis of partial small bowel obstruction.Small bowel follow-through was normal and the patient was managed conservatively with symptom resolution over a one week period.
Eight weeks later the patient presented again with a three week history of epigastric abdominal discomfort, nausea and abdominal distension.Blood work showed a normocytic, normochromic anemia.The white blood cell count, vitamin B 12 and folate levels were normal.The platelet count was 222 × 10 9 /L.An antinuclear antibody was negative.Quantitative immunoglobins, lactate dehydrogenase, complement, C-reactive protein and beta-2 microglobulin were normal.A serum protein electrophoresis showed a monoclonal immunoglobulin (Ig) G, (3.7 g/L) with lambda light chain restriction.Urinalysis showed mild proteinuria.Urine protein electrophoresis showed a polyclonal and monoclonal IgG band, trace IgA, a kappa polyclonal band and a lambda monoclonal band.Vitamin D, calcium and prostate specific antigen were normal.Smooth muscle antibody was normal and albumin was 27 g/L.A CT scan of the abdomen and pelvis showed marked dilation of the proximal small bowel as well as a sharp change in caliber within the ileum in keeping with a chronic small bowel obstruction.
The patient underwent a laparotomy 18 days after admission.Intraoperatively the peritoneum was noted to be thickened and the small bowel was totally encased in an inflammatory 'peel'.The upper abdomen, liver, stomach and subdiaphragmatic areas were encased with some obliteration of the peritoneal cavity.The stomach and duodenum were grossly dilated.The encasing membrane was avascular and was easily removed from the small bowel.Once the membrane was removed, the small bowel was normal in appearance.
The histology of this membrane revealed bands of thickened collagen overlying the original peritoneal surface.A mild, nonspecific inflammatory, neutrophilic infiltrate was present.There were two distinct patterns of amyloid distribution, the first in the blood vessels and the second beneath a thickened peritoneal surface.This unusual pattern of deposition was present in the form of a thick band not associated with any recognizable anatomic structure.Also, the blood vessels in the proximity of this band contained amyloid suggesting that the patient had pre-existing systemic amyloidosis, developed chronic peritonitis and within chronically inflamed tissue had subsequent amyloid deposition.There was a layer of amorphous eosinophilic material lining the site of the original peritoneal surface, which stained congo red and demonstrated apple green birefringence.The amyloid also stained with cresyl violet (Figure 1).Immunohistochemical stains for kappa and lambda were negative within these amyloid deposits.Beta-2 microglobulin and beta amyloid stains were also negative.Potassium permanganate pretreatment eradicated the congo red positivity, suggesting that the amyloidosis was secondary in nature rather than primary.There was no evidence of malignancy or other systemic inflammatory disease.
Postoperatively, the patient's bowel habit normalized and his weight stabilized.Small bowel biopsies for amyloidosis showed extensive amyloid deposition in the distal duodenum.A bone marrow biopsy showed only a mild plasmacytosis (10%) via staining with antilambda antisera.An echocardiogram showed no changes consistent with amyloid infiltration or evidence of diastolic dysfunction.A skeletal survey was normal.
In January, 1998 the patient was seen in follow-up and was asymptomatic.The monoclonal protein measured 5.6 g/L.
Figure 1) Amyloid deposits seen between the collagen fibers of the peritoneal lining and in the walls of the capillaries.Cresyl violet stain.Original magnification ×200.
In 1999, the presence of mild microscopic (2+) proteinuria was observed along with an increase in the monoclonal protein to 6.2 g/L.No urinary electrophoresis was done.Over the course of the next 12 months he developed nephrotic range proteinuria and a renal biopsy confirmed the presence of amyloidosis.A two-dimensional echocardiogram revealed left ventricular wall hypertrophy with normal left ventricular function and no evidence of diastolic dysfunction.
In September, 2000 he underwent high-dose chemotherapy and an autologous stem cell transplant and made a good recovery.Six months post bone marrow transplant there remained a persistent monoclonal protein of 3.1 g/L along with nephrotic range proteinuria of 7 g in a 24 h period compared with a pretransplant level of 3.95 g in 24 h.He had no gastrointestinal symptoms.

DISCUSSION
Amyloidosis is a pathological process which encompasses a spectrum of diseases that result from extracellular deposition of pathologic fibrillar proteins (11)(12)(13).The three clinical forms of amyloidosis (primary [AL], familial and secondary) each differ in their pathogenesis (11).AL amyloidosis is associated with immunocyte dyscrasia and results from frequent amino acid substitutions in the light chain variable region leading to light chain destabilization and fibrillogenesis (14).
Clinical presentations vary depending on the organs involved.There are no documented cases of amyloidosis presenting as small bowel encapsulation.Mucosal, vessel wall and intramural involvement of the gastrointestinal (GI) tract are well recognized and may lead to intestinal ischemia, infarction, dysmotility and malabsorption (13).Symptoms of GI amyloid extend from the mouth to the anus and include macroglossia, diarrhea, constipation, fecal incontinence or rectal prolapse and dysphagia.Malabsorption occurs secondary to bacterial overgrowth, mucosal ischemia, pancreatic exocrine insufficiency or submucosal amyloid deposition.Dysmotility or antral amyloidoma may lead to gastric outlet obstruction.GI bleeding and intestinal infarction results from capillary and blood vessel involvement.Other GI manifestations include proteinlosing enteropathy and hepatosplenomagaly (13).
The changes observed in our patient were those of chronic peritonitis with extensive peritoneal fibrosis and mild, nonspecific inflammation.Of particular interest was the fact that this patient had two distinct patterns of amyloid distribution.This is a curious phenomenon in a patient not previously known to have systemic amyloidosis.This is an unusual pattern of amyloid distribution and amyloid deposition presenting in this manner has not been reported.The prognostic significance of this presentation is unclear.Traditionally, the clinical classification of patients into four groups: those with heart failure, nephrotic syndrome, peripheral neuropathy and other is useful for determining long term prognosis (15).Our patient has renal amyloidosis.Studies of patients undergoing dialysis have shown improvements in survival rates over the years, particularly in younger patients (15)(16)(17)(18)(19)(20).Age greater than forty years is a factor in determining survival (21,22).Isoniemi et al (22) showed slightly better results in 1989 and attributed them to the use of cyclosporin.However, the mortality was still high.
The goals of amyloidosis therapy include supportive measures as well as targeting the underlying defect.Our patient most likely has the AL variant.Numerous studies have shown superior efficacy of a combination of oral melphalan and prednisone when compared with treatment using colchicine, prednisone and/or melphalan (23,24).Despite these results, response rates are still low, with a survival increase from a median of six months to 12 months in those receiving chemotherapy.Patients must survive long enough to receive several cycles of melphalan before survival benefit occurs (11).Treatment with high dose intravenous melphalan plus autologous blood stem cell support has resulted in complete remission of the plasma cell dyscrasia and substantial improvement in amyloid-related organ disease (11).More recently, van Gamerer II et al (25) report a case series of 38 patients with AL amyloidosis treated with vincristine, doxorubicin and dexamethasone and high dose melphalan followed by autologous stem cell transplantation (ASCT).Six months after ASCT 78% of surviving patients showed a partial clonal response but none responded completely.Clinical condition improved in 675.After a median followup of 25 months, 75% of the study group were alive (25).Subsequent experience with ASCT in patients with AL has shown success (26,27).
To date (November 2003), there has been no recurrence of gastrointestinal amyloidosis in our patient.However, he has developed end-stage renal insufficiency.