Case Presentation: 73 year old male veteran with hypertension and stroke presents with progressive anasarca and dyspnea. The patient’s blood albumin level was < 1 g/dL, and his urine protein to creatinine ratio was > 5.5 grams per day, leading to a diagnosis of nephrotic syndrome. Renal biopsy revealed Immunoglobulin Light-Chain (AL) Amyloidosis. He responded well to diuresis. A Positron Emission Tomography (PET) scan demonstrated marked Fludeoxyglucose F18 (FDG) uptake in the left ventricle and bilateral kidneys. Bone marrow biopsy showed diffuse infiltration with abnormal plasma cells. The patient received his first cycle of CyBorD (cyclophosphamide, bortezomib, dexamethasone) therapy.He required re-admission 1 month later for anasarca. Electrocardiogram was notable for low voltage, and Cardiac Magnetic Resonance Imaging (MRI) revealed patchy areas of subendocardial delayed enhancement, thought to be consistent with early cardiac amyloidosis. Soon after, the patient was hospitalized for multiple episodes of syncope, with a decline in his hemoglobin level from 10 to 7.9g/dL. He had orthostatic hypotension out of proportion to that expected from anemia. He was arrhythmia-free. Behavioral modifications for orthostasis were initiated. Endoscopy showed an arterial-venous malformation in the distal esophagus, gastritis, duodenitis, and friable colonic lesions. Amyloid deposits were identified throughout the biopsy specimens. The patient’s multi-systemic involvement disqualified him from hematopoietic stem cell transplant. The patient was subsequently hospitalized three more times for gastrointestinal (GI) bleeding, and twice for volume overload with a large pleural effusion.
Discussion: Amyloidosis is a diverse group of diseases characterized by deposition of amyloid particles (misfolded peptide aggregates oriented in a beta-sheet structure which leads to apple-green birefringence with Congo red staining). The most common form of systemic amyloid (with the most severe prognosis) is Light-Chain (AL) Amyloidosis which derives from clonal plasma cells. It is characterized by cardiac and kidney dysfunction, but can also result in orthostatic hypotension, peripheral neuropathy, GI bleeding, and dysmotility. GI manifestations occur most frequently in the AL subtype. In one study, nearly 20% of patients reported GI symptoms, half of whom had biopsy-proven GI amyloidosis. Involvement of the GI tract indicates a poor prognosis, with a mean survival time of 8 months. In cases where the diagnosis of systemic amyloidosis is uncertain and GI features are present, duodenal biopsy is of the highest yield.Amyloidosis causes generalized autonomic failure and small fiber neuropathy. This patient’s predominant neuropathic symptom was orthostasis which contributed to syncope. Other autonomic symptoms that can also present are dry eyes and mouth, abnormal sweating, urinary symptoms, and erectile dysfunction. Small fiber neuropathy presents with pain, paresthesia, and numbness in extremities.
Conclusions: Hospitalists may be the first providers to recognize the laboratory findings and variable symptoms of this systemic disease. Organ damage is typically irreversible; therefore the primary goal is to slow the accumulation of amyloid particles. Early diagnosis is critical. This patient has been hospitalized 10 times in the past 12 months. While he retains a good functional status, the hospitalist team continues to actively discuss with the patient his goals of care.
