Amyloidosis

Jenny Morrison Morning Report 8/3/2007

Amyloidosis
Infiltration of organs with the deposit of extracellular insoluble fibrillar protein.
Antiparallel beta-pleated sheet configuration on x-ray diffraction. Straight and unbranching fibrils 8-10 nm in width on EM. Binds Congo red leads to green birefringence under polarized light. Binds thioflavine T yellow-green fluorescence.

Congo Red Stains of Heart Infiltrated with Amyloid

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Amyloidosis- Subtypes
AL primary, Ig light chain deposits AA secondary, serum amyloid A deposits in chronic diseases with inflammation Dialysis beta-2 microglobulin Heritable multiple different mutations, ex. in TTR Senile Systemic Amyloidosis wt TTR Organ specific ex. Alzheimers disease

Clinical Manifestations of Amyloidosis

Renal proteinuria, nephrotic syndrome, renal failure
GI hepatomegaly +/- splenomegaly, bleeding, gastroparesis, constipation, malabsorption Neuro mixed sensory and motor peripheral neuropathy, autonomic neuropathy, bowel/bladder dysfunction, orthostatic hypotension, dementia

Clinical Manifestations of Amyloidosis

MSK pseudohypertrophy of muscles, macroglossia, arthropathy
Heme bleeding diathesis Pulm pleural effusions, parenchymal nodules, tracheobronchial infiltration (hoarseness, stridor, airway obstruction, dysphagia), rarely pulmonary HTN Skin waxy thickening, nodules/plaques, easy bruising, purpura

Amyloid Deposits in the Liver

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Cardiac Amyloidosis
Restrictive cardiomyopathy Right sided heart failure (both right and left sided pressures are elevated) Angina Syncope or pre-syncope Conduction disease Rarely, cardiac tamponade Hypotension Sudden death

Amyloid Deposits in the Heart

K. B. Shah, et al. Archives of Internal Medicine. 2006.

Amyloid Deposits in the Heart

K. B. Shah, et al. Archives of Internal Medicine. 2006.

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Diagnosis
Suspicion: unexplained heart failure, clinical picture (ex. proteinuria, hepatic dysfunction) TTE, EKG Tissue biopsy (abd fat pad, rectal, salivary gland, endomyocardium) Check pro-BNP, CE, SPEP, UPEP Consider bone marrow biopsy Evaluate for proteinuria, coagulopathy

Cardiac AmyloidosisPhysical Exam

Elevated JVP Hepatomegaly Edema Abnormal heart sounds, murmur Hypotension Signs of other organ involvement

Cardiac AmyloidosisEKG Findings

Low voltage- especially in contrast to degree of hypertrophy Conduction abnormalities (heart block)
Atrial fibrillation Pseudoinfarct patterns

Pseudoinfarct EKG Pattern

D. R. Booth, et al. Circulation. 1995.

AmyloidosisEchocardiographic Findings
LV and RV wall thickening LV (and RV) diastolic dysfunction Nondilated or small LV cavity Biatrial enlargement RV dilation Thickened aortic and mitral valves Increased echogenicity granular, sparkling appearance of the myocardium

Treatment
Treat underlying plasma cell disorder in AL or underlying infectious or inflammatory disorder in AA. Renal transplant or change dialysis mode for dialysis-related amyloidosis.
Hereditary liver transplantation +/concomitant heart and renal transplant

Amyloidosis: Take Home Points

Any organ system can be involved. Several different subtypes- look same under microscope but behave differently and are treated differently. Congo red stain apple-green birefring. Low voltage EKG but hypertrophy noted on TTE, restrictive pattern CM. think of cardiac amyloidosis.

References
Booth, D. R., et al. A Novel Variant of Transthyretin Associated with Autosomal Dominant Cardiac Amyloidosis in an Italian Family. Circulation. 1995. 91: 962-967. Gorevic, P. D. An overview of amyloidosis. UpToDate.com. Rajkumar, S. V. and M. A. Gertz. Advances in the Treatment of Amyloidosis. NEJM. 2007. 356: 2413-2415. Shah, K. B., et al. Amyloidosis and the Heart. Archives of Internal Medicine. 2006. 166: 1805-1813. Simons, M., et al. Amyloid cardiomyopathy. UpToDate.com.

Some pictures obtained from www.pathguy.com and www.chemo.net.

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