Case Presentation:
A 58 year old female with a past medical history of diabetes mellitus and proteinuria presented with a chief complaint of profuse, non‐bloody diarrhea, post‐prandial epigastric pain, and a 20 pound weight loss over the past 3‐4 months. Physical examination was notable for tachycardia, mild hypotension and severe, pitting edema of the lower extremities. Laboratory studies revealed a non‐anion gap hyperchloremic metabolic acidosis, hypokalemia, severe hypoalbuminemia and a coagulopathy. Stool studies revealed no evidence of infection but were consistent with a protein‐losing gastroenteropathy. The patient’s symptoms were refractory despite aggressive symptomatic treatment.
A colonoscopy revealed only non‐specific inflammation but upper endoscopy biopsies revealed diffuse mucosal amyloid deposition. CT imaging of the chest and abdomen subsequently showed small bowel thickening and several lytic bone lesions. Serum and urine electrophoresis studies demonstrated monoclonal proliferation of free kappa light chains and biopsy of a bone lesion confirmed a diagnosis of multiple myeloma.
Discussion:
Amyloidosis is an infiltrative disease that results from deposition of improperly folded proteins into extracellular tissue and there are a variety of different subtypes. The most common is AL, primary amyloidosis, in which monoclonal immunoglobulin light chains produced by plasma cells are deposited. This subtype accounts for about 80% of amyloidosis cases, and of these about 10‐15% are associated with overt multiple myeloma. Other forms include AA and beta‐2 microglobulin, which are associated with chronic inflammatory conditions and dialysis respectively. Amyloidosis can target a variety of tissues, resulting in a widely variable clinical presentation. The most commonly affected sites are the kidneys, heart, nerves, muscle, and liver. The gastrointestinal (GI) tract can also be involved, although this occurs much more commonly in the AA form. In AL forms, only about 1% of patients have clinical GI symptoms. Manifestations of GI amyloidosis can be variable but include, GI bleeding due to friable mucosa, protein losing gastroenteropathy, dysmotility and malabsorption due to mucosal infiltration.
Therapy focuses on amelioration of GI symptoms as well as treatment of the underlying disease process. In addition to supportive care, there have been case reports documenting the effectiveness of corticosteroids and/or octreotide in reducing diarrhea. Notably, this has been found in patients with AA amyloidosis and has not been trialed in patients with AL amyloidosis.
Conclusions:
Chronic diarrhea has a broad differential diagnosis and the etiology can be challenging to elucidate. One rare cause is GI amyloidosis, which can present in a variety of ways. The key to making this diagnosis is to keep a high clinical suspicion, especially in patients at increased risk for amyloidosis with the systemic signs or symptoms associated with amyloidosis.
