Unusual Cause of Tarry Stool: What Do You Think?

Question: A 52-year-old man, who was in good health, presented with a 4-month history of tarry stool, abdominal pain, and weight loss. The patient denied history of inflammatory bowel disese and recent antibiotic use. His abdomen was soft, with mild periumbilical tenderness. There was no organomegaly. Laboratory studies showed red blood cell count 3.02 × 1012/L (normal range 4.3–5.8 × 1012/L), leukocyte count 6.57 × 109/L (normal range 3.5–9.5 × 109/L), platelet count 347 × 109/L (normal range 125–350 × 109/L), hemoglobin 66 g/L (normal range 130–175 g/L), aspartate transaminase 15 U/L (normal range 15–40 U/L), alanine transaminase 7 U/L (normal range 9–50 U/L), total serum protein 49 g/L (normal range 65–85 g/L), and serum albumin 27 g/L (normal range 40–55 g/L). Urine tests were normal. Esophagogastroduodenoscopy was normal, with multiple biopsies showing no abnormality in histopathology. Colonoscopy revealed patchy erythema throughout the colon without active hemorrhage (Figure A). Eight biopsies were taken from the ascending colon, transverse colon, descending colon, and sigmoid colon. Contrast-enhanced abdominal computed tomography showed thickened and dilated ileal loops (Figure B). A double-balloon retrograde enteroscopy revealed numerous patchy areas of denuded and ulcerated ileal mucosa (Figure C), the outline of which was graphically outlined with methylene blue staining (Figure D). Four biopsies were taken from the ileum. Screening was negative for serum tumor markers and the following autoantibodies: anti–double-stranded DNA, anti-nuclear antibody, anti-SSA/Ro, anti-SSB/La, anti–liver/kidney microsomal type 1, anti–Scl-70, anti–smooth muscle antibody, anti–U1-snRNP, anti-mitochondrial antibodies, anti-SmD1, cytoplasmic anti-neutrophil cytoplasmic antibody, and peri-nuclear anti-neutrophil cytoplasmic antibody. Electrocardiography and chest computed tomographic (CT) scan were normal. Biopsies of the colon and small intestine (hematoxylin and eosin staining) revealed the findings shown in Figure E. What is the most likely diagnosis? What would you do next? See the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. The differential diagnosis in this 52-year-old man with a 4-month history of tarry stool, abdominal pain, and weight loss includes ischemic enteropathy, inflammatory bowel disease, gastrointestinal lymphoma and tuberculosis, and systemic autoimmune diseases. In this patient, colonoscopic findings of patchy erythema suggested ischemic colitis. The CT scan ruled out mesenteric artery stenosis and major vessel disease; however, small vessel disease and slow flow state could not be excluded. Histologic evaluation of biopsy specimens showed the deposition of homogeneous, amorphous, and acidophilic material, mainly in the mucosal layer (Figure F). Congo red staining showing both the orange and the typical apple-green birefringence under distinct intensities of polarized light (Figures G and H) confirmed amyloidosis. Colonic amyloidosis may mimic ischemic colitis.1Trinh T.D. Jones B. Fishman E.K. Amyloidosis of the colon presenting as ischemic colitis: a case report and review of the literature.Gastrointest Radiol. 1991; 16: 133-136Crossref PubMed Scopus (29) Google Scholar It is important to assess the underlying etiology of amyloidosis. Transthyretin immuno-peroxidase stain was negative. The patient had positive serum and urine immuno-fixation electrophoreses with visible M-spike. Bone marrow biopsy revealed plasma cells accounting for 17% with binuclear characteristics, which confirmed the diagnosis of smoldering multiple myeloma. Next, one should evaluate the extent of amyloid deposits in various organs. Cardiac evaluation revealed elevated serum hyper-sensitive cardiac troponin T (76 pg/mL; normal range 0–14 pg/mL) and N-terminal pro–B-type natriuretic peptide (4420 pg/mL; normal range 0–14 pg/mL), marked thickening of left ventricles, and a mild circumferential pericardial effusion on echocardiography (Figure I), also confirming the diagnois of cardiac amyloidosis.2Falk R.H. Quarta C.C. Echocardiography in cardiac amyloidosis.Heart Fail Rev. 2015; 20: 125-131Crossref PubMed Scopus (54) Google Scholar Amyloidosis may cause extracellular tissue deposition of insoluble proteinaceous material, which is a rare disorder of protein metabolism.3Sattianayagam P.T. Hawkins P.N. Gillmore J.D. Systemic amyloidosis and the gastrointestinal tract.Nat Rev Gastroenterol Hepatol. 2009; 6: 608-617Crossref PubMed Scopus (78) Google Scholar Gastrointestinal involvement is uncommon in multiple myeloma–associated amyloidosis with clinically significant manifestations of both intestine and colon.4Antonini F. Goteri G. Macarri G. Bleeding localized amyloidosis of the colon.Dig Liver Dis. 2014; 46: e13Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Multiple myeloma should be considered in patients with disorders that are known to be associated with amyloidosis.5Alahdab F. Saligram S. Gastrointestinal amyloidosis and multiple myeloma.J Gen Intern Med. 2015; 30: 261-262Crossref PubMed Scopus (1) Google Scholar Clinical features of gastrointestinal amyloidosis mainly include bleeding, malabsorption, protein-losing enteropathy, dysmotility, and pseudo-obstruction.6Lim A.Y. Lee J.H. Jung K.S. et al.Clinical features and outcomes of systemic amyloidosis with gastrointestinal involvement: a single-center experience.Korean J Intern Med. 2015; 30: 496-505Crossref PubMed Scopus (35) Google Scholar This patient presented with colonic symptoms, and systematic work-up confirmed amyloidosis of the colon and heart. Our patient received daratumumab with bortezomib, cyclophosphamide, and dexamethasone, which have demonstrated significantly improved outcomes in patients with amyloidosis.7Palladini G. Milani P. Merlini G. Management of AL amyloidosis in 2020.Blood. 2020; 136: 2620-2627Crossref PubMed Google Scholar Four 21-day cycles of 1.3 mg/m2 bortezomib, 20 mg dexamethasone, and 300 mg/m2 cyclophosphamide was followed by 16 mg/kg daratumumab combined with bortezomib, cyclophosphamide, and dexamethasone once weekly for 16 weeks. Finally, 16 mg/kg daratumumab was administered once weekly for 8 weeks, then every 2 weeks for 16 weeks, and then every 4 weeks. Clinical and serologic improvement after therapy was rapid for the patient, with 1.5 years of survival thus far (Figure J). Autologous stem cell transplantation was not recommended for the patient owing to potentially lethal cardiac amyloidosis.