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Gastrointestinal Amyloidosis and Multiple Myeloma

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Fares Alahdab
Fares Alahdab
Fares Alahdab
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Shreyas Saligram at University of Pittsburgh
Shreyas Saligram
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Abstract and Figures

A 74-year-old female was admitted for evaluation of dyspnea at rest. She reported chronic abdominal pain, long-standing diarrhea and weight loss of 30 lbs over the course of the previous two years. Echocardiogram showed restrictive cardiomyopathy with normal ejection fraction. CT abdomen was unremarkable and mesenteric angiography ruled out mesenteric ischemia. Esophagogastroduodenoscopy (EGD) (Fig. 1) revealed friable mucosa of the duodenum and a biopsy demonstrated amyloid deposition (Fig. 2) and a positive Congo red stain (Online Fig. 3). Further lab workup showed elevated serum lambda free light chains and elevated serum β2-microglobulin. A decision for a bone marrow biopsy was made to exclude other plasmacytic dyscrasias, which revealed multiple myeloma (Online Fig. 4).Figure 1EGD revealing patchy mucosa with friability and active oozing from the second part of the duodenum (white arrows).Figure 2Duodenal biopsy showing amyloidosis (white arrow) and hyalinization of the thick-wall ...
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Gastrointestinal Amyloidosis and Multiple Myeloma
Fares Alahdab, MD
1,2
and Shreyas Saligram, MD, MRCP
3
1
University of Damascus Faculty of Medicine, Damascus, Syria;
2
Mayo Clinic, Rochester, MN, USA;
3
University of Kansas Medical Center,
Kansas City, KS, USA.
KEY WORDS: primary amyloidosis; multiple myeloma; gastrointestinal
amyloidosis.
J Gen Intern Med
DOI: 10.1007/s11606-014-2897-7
© Society of General Internal Medicine 2014
A74-year-old female was admitted for evaluation of
dyspnea at rest. She reported chronic abdominal pain,
long-standing diarrhea and weight loss of 30 lbs over the
course of the previous two years. Echocardiogram showed
restrictive cardiomyopathy with normal ejection fraction.
CT abdomen was unremarkable and mesenteric angiography
ruled out mesenteric ischemia. Esophagogastroduodenoscopy
(EGD) (Fig. 1) revealed friable mucosa of the duodenum and a
biopsy demonstrated amyloid deposition (Fig. 2) and a
positive Congo red stain (Online Fig. 3). Further lab workup
showed elevated serum lambda free light chains and elevated
serum β2-microglobulin. A decision for a bone marrow
biopsy was made to exclude other plasmacytic dyscrasias,
which revealed multiple myeloma (Online Fig. 4).
Light chain or primary amyloidosis is the most common
form of amyloidosis and is associated with plasma cell
dyscrasias.
1
Approximately 15 % of these patients have
concurrent multiple myeloma, and up to 31 % of them have
small bowel amyloidosis on autopsy.
2
Although the clinical
and endoscopic findings in gastrointestinal amyloidosis can
be nonspecific, histopathological patterns of amyloid
deposition are diagnostic.
3
Random gastrointestinal biopsies
are more sensitive and are diagnostic in 80 % of the cases.
4
Major causes of death in these patients are renal failure and
restrictive cardiomyopathy.
5
Conflict of Interest: The authors declare that they do not have a
conflict of interest.
Corresponding Author: Fares Alahdab, MD; 1919 3rd AVE NE,
APT 2., Rochester, MN 55906, USA (e-mail: Alahdab.fares@mayo.edu).
Figure 1. EGD revealing patchy mucosa with friability and active
oozing from the second part of the duodenum (white arrows).
Figure 2. Duodenal biopsy showing amyloidosis (white arrow) and
hyalinization of the thick-walled blood vessels with amyloid
deposition (black arrow).
Electronic supplementary material The online version of this article
(doi:10.1007/s11606-014-2897-7) contains supplementary material,
which is available to authorized users.
Received December 18, 2013
Revised March 18, 2014
Accepted May 5, 2014
REFERENCES
1. Sattianayagam PT, Hawkins PN, Gillmore JD. Systemic amyloidosis
and the gastrointestinal tract. Nat Rev Gastroenterol Hepatol.
2009;6:608–617.
2. Ebert EC, Nagar M. Gastrointestinal manifestations of amyloidosis. Am J
Gastroenterol. 2008;103:776–787.
3. Hokama A, Kishimoto K, Nakamoto M, et al. Endoscopic and histo-
pathological features of gastrointestinal amyloidosis. World J Gastrointest
Endosc. 2011;3:157–161.
4. Lovat LB, Pepys MB, Hawkins PN. Amyloid and the gut. Dig Dis.
1997;15:155–171.
5. PetreS,ShahIA,GilaniN.Reviewarticle: g astrointestinal amyloidosis—clinical
features, diagnosis and therapy. Aliment Pharmacol Ther. 2008;27:1006–1016.
Alahdab and Saligram: Gastrointestinal Amyloidosis and Multiple Myeloma JGIM
... Although the clinical and endoscopic findings in gastrointestinal amyloidosis can be nonspecific, histopathological patterns of amyloid deposition are diagnostic. [11][12][13] There are no specific drugs to control bleeding in amyloidosis. However, treating myeloma along with proton pump inhibitor may be helpful in preventing/controlling bleeding. ...
... Site of amyloidosis is difficult to predict, however close follow up and looking for non-specific GI complaints including abdominal pain, changes in bowel habits, overt gastrointestinal bleeding and complaints related to altered motility or symptoms of peripheral neuropathy, heart failure and renal insufficiency should evaluated at the earliest. 11,12 Abdominal symptoms can develop due myeloma therapy also. 15 High dose chemotherapy followed by autologous stem cell transplant provides long term control in patients with myeloma and AL amyloidosis. ...
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Amyloid Light chain (AL) amyloidosis is a rare disease, which is seen in approximately one-tenth of patients with multiple myeloma. We report a 52 years old male, who presented with complaints of anorexia and weight loss. He was diagnosed to have multiple myeloma-international staging score (ISS) Stage 3 and was started on VTD (Bortezomib, Thalidomide, and Dexamethasone) chemotherapy. Within 2 weeks of therapy, he had abdominal symptoms like abdominal pain, loose stools, vomiting and hematochezia. Imaging showed dilated proximal bowel loops with fluid filled contents and prominent vessels in rectum. Emergency surgical exploration revealed thickened proximal jejunum with blood clots in the lumen. Resection of proximal jejunum was done. Histopathological examination of resected specimen was suggestive of AL amyloidosis. Post-surgical resection of jejunum, patient had initial improvement followed by deterioration. He was discharged against medical advice as per relative’s request. Hence an index of clinical suspicion of amyloidosis must been present in all Multiple myeloma patients.
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Amyloidosis is a rare disorder, characterized by the extracellular deposition of an abnormal fibrillar protein, which disrupts tissue structure and function. Amyloidosis can be acquired or hereditary, and systemic or localized to a single organ, such as the gastrointestinal (GI) tract. Clinical manifestations may vary from asymptomatic to fatal forms. Primary amyloidosis (monoclonal immunoglobulin light chains, AL) is the most common form of amyloidosis. AL amyloidosis has been associated with plasma cell dyscrasias, such as, multiple myeloma. Secondary amyloidosis is caused by the deposition of fragments of the circulating acute-phase reactant, serum amyloid A protein (SAA). Common causes of AA amyloidosis are chronic inflammatory disorders. Although GI symptoms are usually nonspecific, histopathological patterns of amyloid deposition are associated with clinical and endoscopic features. Amyloid deposition in the muscularis mucosae, submucosa, and muscularis propria has been dominant in AL amyloidosis, leading to polypoid protrusions and thickening of the valvulae conniventes, whereas granular amyloid deposition mainly in the propria mucosae has been related to AA amyloidosis, resulting in the fine granular appearance, mucosal friability, and erosions. As a result, AL amyloidosis usually presents with constipation, mechanical obstruction, or chronic intestinal pseudo-obstruction while AA amyloidosis presents with diarrhea and malabsorption Amyloidotic GI symptoms are mostly refractory and have a negative impact on quality of life and survival. Diagnosing GI amyloidosis requires high suspicion of evaluating endoscopists. Because of the absence of specific treatments for reducing the abundance of the amyloidogenic precursor protein, we should be aware of certain associations between patterns of amyloid deposition and clinical and endoscopic features.
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The systemic amyloidoses are serious and potentially fatal disorders caused by deposition of autologous proteins in an abnormal fibrillar from. The clinical features are highly variable but gut involvement is common and random gastrointestinal biopsies are diagnostic in 80% of patients. Presentations include macroglossia, motility disorders, hemorrhage and pseudo-tumors, although amyloid can mimic almost any other gut pathology. Nonspecific mucosal abnormalities are common both radiologically and at endoscopy. Scintigraphy with serum amyloid P component demonstrates and quantifies the systemic amyloid deposits. Therapy that reduces the supply of the amyloid fibril precursor protein can markedly improve prognosis. Intensive nutritional support for malnourished patients, motility-enhancing drugs and octretide for motility disorders, and correction of clotting disorders in bleeding patients are important adjunctive treatments.
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Review article: Gastrointestinal amyloidosis - Clinical features, diagnosis and therapy
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Amyloidosis is one of the unusual diseases about which a physician may not think when it is affecting the patient. During the last three decades, there has been an enormous progress in the understanding of the chemical nature, classification, pathogenesis, clinical features, diagnostic measures and therapy of this disorder. To provide an updated review of amyloidosis affecting the gastrointestinal tract. Review of current medical literature. Amyloid proteins (irrespective of the type) can deposit in various parts of the gastrointestinal tract and liver resulting in symptoms of abdominal pain, dysmotility, diarrhoea, gastrointestinal bleeding, hepatomegaly and even portal hypertension with its associated complications. Definitive diagnosis can only be made by histological examination of the affected organ. Disease modifying treatment with high-dose chemotherapy followed by autologous stem-cell transplantation has shown promise. Liver transplantation is an option for a select group of patients. Suspicion of gastrointestinal amyloidosis in patients without known history of amyloidosis is difficult, but should be considered in those older than 30 years with unexplained diarrhoea, weight loss, autonomic dysfunction, malabsorption or proteinuria. While most gastrointestinal complications are managed symptomatically, causal therapy is reserved for a select few from various subtypes of this disorder.
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