Wild-type (senile) amyloidosis differential diagnosis

Jump to navigation Jump to search

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2]Syed Hassan A. Kazmi BSc, MD [3]

Overview

Wild-type (senile) amyloidosis can be differentiated from other conditions that present with heart failure, polyneuropathy, and organomegaly.

Differentiating Wild-type (Senile) Amyloidosis from other Diseases

Differentials Based on Cardiac Involvement (Heart Failure)

Wild-type (senile) amyloidosis should be differentiated from other causes of heart failure:

Differential Diagnosis History and Symptoms Physical Examination Laboratory Findings Imaging Findings
Cardiac amyloidosis
  • Elevated jugular pressure

Periorbital purpura: Often occurs with sneezing, coughing or with minor trauma. Indicates capillary involvement of AL type amyloidosis.

  • Macroglossia
  • Abnormal phonation
  • Hepatomegaly
  • Ascites may be present in the setting of heart failure
  • Valvular involvement murmurs of mitral and tricuspid regurgitation (systolic).


  • Normocytic mormochromic anemia
  • Serum free-light-chain assay positive
  • Increased BNP, ANP and β2 microglobulin
  • Voltage-to-mass ratio is more sensitive than EKG, 2D Echo and nuclear scanning alone
Cardiac sarcoidosis
  • Asymptomatic conduction abnormalities
  • Chest pain
  • Congestive heart failure symptoms:
    • Fatigue
    • Syncope
    • Dyspnea
    • Chest pain.
    • Irregular heartbeats
    • Palpitations
    • edema
  • Ventricular tachyarrhythmia
  • Heart block
  • Valvular regurgitation
  • Pericardial effusion
  • Constrictive pericarditis or temponade
  • Serum markers that have been reported as markers of sarcoidosis in general are:
    • Serum amyloid A (SAA)
    • Soluble interleukin-2 receptor (sIL-2R)
    • Lysozyme
    • Angiotensin-converting enzyme (ACE)
    • Gycoprotein KL-6
    • Hypercalcemia
    • Hypercalciuria
    • (noncaseating granulomas secrete 1,25 vitamin D)
  • Radionuclide examinations
    • Thallium‐201 scintigraphy
    • Gallium‐67 scintigraphy
    • Positron emission tomography
  • Magnetic resonance imaging
  • Samples of myocardium with sarcoidosis shows the following:
  • Non‐caseating, multinucleated giant cell granuloma in the subendocardium
  • Trichrome stain can show a dense band of collagen fibers, encasing aggregate of granulomas and inflammatory cells
ST Segment Elevation Myocardial Infarction
  • Chest pain with possible radiation to left arm and lower jaw
  • Squeezing, crushing chest pain
  • Sweating
  • Nausea and vomiting
  • Anxious patient in pain with diaphoresis
  • Signs of heart failure may be present
  • Arrhythmia
  • ST elevation, new left bundle branch block, and Q wave on EKG
  • Elevated cardiac biomarkers
  • Either complete or subtotal occlusion of an epicardial coronary artery on coronary angiography
  • Confluent hyperenhancement extending from the endocardium
Non ST Elevation Myocardial Infarction
  • Crushing, left-sided substernal chest pain or pressure that radiates to the neck or left arm
  • Same as ST-elevation MI
  • ST-segment depression or T-wave inversion on EKG
  • Elevated cardiac biomarkers
Pericarditis
  • Chest pain relieved by sitting up and leaning forward and worsened by lying down
  • Fever, anxiety, difficulty breathing
  • Pericardial friction rub
  • Signs of cardiac tamponade may be present
  • PR segment depression and electrical alternans on EKG
  • A flask-shaped, enlarged cardiac silhouette on CXR
  • Pericardial thickness of more than 4 mm on MRI
  • Pericardial effusion and cardiac chamber indentation or collapse on echo when cardiac tamponade is present
Alcoholic Cardiomyopathy
  • History of alcohol abuse
  • Fatigue, weakness, anorexia, palpitations, and shortness of breath on activity
  • Leg swelling and pedal edema
  • Signs of heart failure such as presence of S3 and S4 heart sounds, pedal edema, and jugular venous distension
  • Signs of alcoholic liver disease may be present
  • Elevated MCV and MCHC on CBC
  • Elevated LDH, AST, ALT, creatine kinase, gammaglutamyl transpeptidase, malic dehydrogenase, and alpha-hydroxybutyric dehydrogenase
  • Q waves and non specific ST and T wave changes on EKG
  • Cardiomegaly, pulmonary congestion, and pleural effusions on CXR
  • Left ventricular dilatation on echo


Differentials Based on Presentation As a Multi-Organ System Dysfunction Disorder


Organ System Involvement Differential Diagnosis Causes Clinical Features Laboratory Findings Gold Standard Test Therapy
Polyneuropathy
POEMS syndrome (Demyelinating)
Metabolic Syndrome (Axonal pathology)
Vitamin Deficiencies (Axonal Pathology)
Guillain-Barre Syndrome (Demyelinating)
  • Delayed F waves
  • Clinical diagnostic criteria (progressive weakness of more than two limbs, areflexia, and progression for no more than four weeks)
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (Mixed axonal and demyelinatiing)
  • EFNS/PNS criteria
  • Koski criteria
Multifocal Motor Neuropathy
  • Progressive, asymmetric, distal and upper limb predominant weakness
  • No significant sensory abnormalities
  • Areflexia
  • Clinical criteria (EFNS/PNS):
    • Slowly progressive or step-wise progressive, focal, asymmetric limb weakness; i.e., motor involvement in the motor nerve distribution of at least two nerves for > 1 month.
    • No objective sensory abnormalities except for minor vibration sense abnormalities in the lower limbs
Organ System Involvement Differential Diagnosis Causes Features Laboratory Findings Gold Standard Test Therapy
Organomegaly (Hepatosplenomegaly and Lymphadenopathy) Malaria
Kala-azar
Infective Hepatitis
Chronic Myelogenous Leukemia (CML)
Lymphoma
Primary (AL) Amyloidosis
  • Typical green birefringence under polarized light after Congo red staining (appears in red under normal light)
  • Congo red staining
  • Melphalan-prednisone/dexamethasone
  • Dexamethasone plus Cyclophosphamide-thalidomide
  • Stem cell transplantation
Gaucher's Disease
Organ System Involvement Differential Diagnosis Causes Features Laboratory Findings Gold Standard Test Therapy
Cardiac Failure Cardiac amyloidosis (AL and ATTRwt)
  • Monoclonal plasma cell proliferation
  • Extracellular amyloid fibril deposition
  • Fatigue
  • Dyspnea
  • Dizziness
  • Orthopnea
  • Peripheral edema
  • Weight loss due to cardiac cachexia
  • Ascites
  • Syncope on exertion
  • Transthyretin (ATTRwt) associated more common in African-Americans during sixth to seventh decade of life
  • Normocytic mormochromic anemia
  • Serum free-light-chain assay positive
  • Increased BNP, ANP and β2 microglobulin
  • Voltage-to-mass ratio is more sensitive than EKG, 2D Echo and nuclear scanning alone
  • Biopsy:
  • Diffuse deposition of amorphous hyaline material (nodular pattern - 8 to15 nm in diameter), in mesangium (weakly staining with periodic acid-Schiff (PAS)


  • Supportive care
  • Tafamidis
  • Melphalan-prednisone/dexamethasone
  • Dexamethasone plus Cyclophosphamide-thalidomide
Cardiac sarcoidosis
  • The causes are not fully known.
  • Over-reaction of the immune system after exposure to an infectious agent (bacteria or viruses), chemical, or allergen.
  • Excessive inflammation and the clustering of white blood cells.
  • Asymptomatic conduction abnormalities
  • Chest pain
  • Congestive heart failure symptoms:
    • Fatigue
    • Syncope
    • Dyspnea
    • Chest pain.
    • Irregular heartbeats
    • Palpitations
    • edema

Serum markers that have been reported as markers of sarcoidosis in general are:

  • Serum amyloid A (SAA)
  • Soluble interleukin-2 receptor (sIL-2R)
  • Lysozyme
  • Angiotensin-converting enzyme (ACE)
  • Gycoprotein KL-6
  • Hypercalcemia
  • Hypercalciuria
  • (noncaseating granulomas secrete 1,25 vitamin D)
  • Biopsy: samples of myocardium with sarcoidosis shows the following:
  • Non‐caseating, multinucleated giant cell granuloma in the subendocardium
  • Trichrome stain can show a dense band of collagen fibers, encasing aggregate of granulomas and inflammatory cells
  • Corticosteroid treatment
  • Antiarrhythmic treatment
  • Pacemakers and defibrillators
  • Cardiac transplantation
Hypertrophic obstructive cardiomyopathy


  • Echocardiography:
    • Left ventricular asymmetric hypertrophy
    • Parasternal long axis shows relationship of the septal hypertrophy and the outflow tract
    • Left ventricular diastolic dysfunction
    • SAM (systolic anterior motion) of the mitral leaflet
    • Mid-systolic closure of the aortic valve
    • Late peaking, high velocity flow in the outflow tract
    • Variability of obstruction with maneuvers (exercise, amyl nitrate inhalation, and post-PVC beats)
Alcoholic cardiomyopathy
  • Alcohol consumption


ST-elevation myocardial infarction
Pericarditis



References