Case Presentation: Patient is a 76 year-old male with a significant background of ischemic heart disease with reduced ejection fraction, pyloric and duodenal ulcers, and chronic kidney disease attributed to chronic glomerulonephritis (not biopsy-proven). He presented with hematemesis and melena. Esophagogastroduodenoscopy revealed multiple gastric ulcers that were negative for Helicobacter pylori. Histology from the gastric biopsy showed amyloid deposits on Congo Red stain. Laboratory results revealed progressive chronic kidney disease with estimated glomerular filtration rate deteriorating from normal to 6ml/min over 2 years. On admission, patient had fluid overload and symptomatic uremia requiring initiation of hemodialysis. During his stay, there were episodes of recurrent bradycardia and paroxysmal atrial fibrillation, triggering concerns of cardiac amyloidosis. Stress echocardiogram was unable to confirm cardiac involvement due to pre-existing poor cardiac function, and cardiac magnetic resonance imaging was not performed due to his poor renal function and resultant risk of nephrogenic systemic fibrosis. Investigations for recurrent hypoglycaemia revealed severe hypothyroidism and adrenal insufficiency. Despite adequate replacement of levothyroxine and hydrocortisone, episodes of postural hypotension raised the suspicion for autonomic neuropathy. Abdominal fat pad biopsy was negative for amyloidosis and patient declined bone marrow testing. Subsequent repeat gastric biopsy sent for mass spectrophotometry confirmed AA (secondary) amyloidosis.
Discussion: This case demonstrates the varied presentation and multi-systemic involvement of AA amyloidosis. Patient presented with gastrointestinal bleeding, rapidly progressive renal failure, multiple endocrinopathies, with possible autonomic neuropathy and cardiac involvement. It also highlights the challenges in diagnosis of cardiac amyloidosis in patients with pre-exiting heart disease and poor renal function. There was difficulty in initially determining the type of amyloidosis, mainly AL (primary) amyloidosis versus AA (secondary) amyloidosis. Management would differ between giving a bortezomib-based regimen versus control of the underlying inflammatory disease. AL amyloidosis was not strongly considered as there was no evidence of plasma cell dyscrasia in the myeloma studies and absence of lymphoplasmacytic infiltrates in the gastric biopsy sample. Hence, there was no strong indication to give systemic bortezomib-based treatment. Moreover, the demonstration of loss of affinity for Congo Red after incubation of gastric tissue sections with potassium permanganate classically supported a secondary type of amyloidosis. The diagnosis of AA amyloidosis was confirmed by mass spectrophotometry of a subsequent gastric tissue sample.
Conclusions: Physicians need to be aware of the multi-systemic involvement of amyloidosis, evaluate for relevant organ involvement, and coordinate care between multiple healthcare disciplines. Characterizing the type of amyloidosis is crucial to guide appropriate management and the mainstay of diagnosis is via tissue biopsy. This case demonstrates that abdominal fat pad biopsy can be falsely negative in systemic amyloidosis, and alternative biopsy sites from clinically involved organs should be sought if suspicion remains high. Limitations for evaluation of cardiac amyloidosis needs to be acknowledged in the presence of pre-existing poor heart and renal function.