short presentation on amyloidosis. main chunk taken from CMDT 2019

1. AMYLOIDOSIS
Dr. Muhammad Nabeel
PGT MU-I HFH

2. Learning Objectives
• What is amyloidosis ?
• Types
• Diagnosis
• Treatment
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3. Case Scenerio
• At his first visit with a hematologist, a 68-year-old Caucasian man
states that he has been diagnosed with amyloidosis, but he is unsure
of which type. The diagnosis was made after he developed peripheral
sensory neuropathy, tongue enlargement, and intestinal
malabsorption. He also reports recent onset of dyspnea and
orthopnea.
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4. What is Amyloidosis?
• Extracellular deposition of insoluble protein.
• Fibrils of specific protein involved.
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5. Types of Amyloidosis
• Systemic Amyloidosis
• Localized Amyloidosis
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6. Systemic Amyloidosis
• AL amyloidosis (Primary amyloidosis)
Occurs in plasma cells disorders.
Lights chains are produced in abundance.
Some misfold into AL proteins and build up in various tissues.
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7. Systemic Amyloidosis
• AA Amyloidosis (Secondary Amylodosis)
Serum amyloid A (acute phase reactant).
Occurs when there is prolonged inflammation.
SAA misfolds and end up accumulating in various tissues.
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8. Systemic Amyloidosis
• ATTR Amyloidosis
Transthyretin protein (TTR).
If normal it causes senile systemic amyloidosis.
If mutated it causes familial amyloid cardiomyopathy.
Organs affected are heart, peripheral and autonomic nerves.
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9. Systemic Amyloidosis
• AB₂M Amyloidosis
Beta 2 Micro-globulin .
Produced rheumatological manifestation in patients on long term HD.
accumulates in synovial membranes and bones.
Usually presents with carpel tunnel syndrome, persistant joint effusion,
spondyloarthropathy or cystic bone lesions
Visceral B₂M accumulation ocassionally occurs.
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10. Systemic Amyloidosis
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11. Localized Amyloidosis
• Alzheimer’s Disease
Neurodegenerative disease.
Beginning with memory impairment and spreading to language
and visuospatial deficits.
Aẞ peptide accumulate outside neurons in form of plaques.
Interfere with neuron to neuron signaling.
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12. Localized Amyloidosis
• Cerebral Amyloid Angiopathy
Cystatin C accumulates in the walls of vessels.
Weakens the walls of blood vessels.
Increased risk of hemorrhage.
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13. Localized Amyloidosis
• AIAPP Amyloidosis
Islet amyloid polypeptide (amylin)
Occurs in T2DM
Amylin aggregates in between B-cells of pancreas.
Causes damage and death of B-cells.
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14. Diagnosis of Amyloidosis
• Biopsy
Fat pad biopsy
Biopsy of the involved organ
• Congo red stain
• Polarized light
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15. Diagnosis of Amyloidosis
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16. Diagnosis of Amyloidosis
• AL Amyloidosis
Immuno-fixation of serum or urine
Assay for free light chains
Increase percentage of plasma cells in bone marrow (5-30 %)
Flow cytometry
Immuno-histochemical staining
In situ hybridization for LC mRNA
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17. Treatment of Amyloidosis
• No effective way to remove amyloidosis.
• Supportive care
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18. Treatment of Amyloidosis
• AL Amyloidosis
Cyclic oral malphan with prednisolone.
Cyclic oral malphan with dexamethasone.
High dose intravenous malphan followed by autologous stem cell transplant.
Organ transplant followed by HDM/SCT.
Thalidomide and lanalidomide.
Protease inhibitor Bortezomib.
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19. Treatment of Amyloidosis
• AA Amyloidosis
Treat underlying inflammatory or infectious disease.
TNF and IL-1 antagonist.
Eprodisate, interferes with the interaction of AA amyloid with GAG.
Colchecine in dose of 1.2-1.8 mg/day is an appropriate treatment in familial
Mediterranean fever.
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20. Treatment of Amyloidosis
• ATTR Amyloidosis
Orthotopic liver transplant.
• AB₂M Amyloidosis
No specific treatment
Cessation of dialysis after renal allograft may alleviate the symptoms
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21. Treatment of Amyloidosis
• Alzheimer’s Disease
Care giver support.
Pharmacological treatment for slowing down the congnitive detoriation.
Cholinesterase inhibitors ( donepezil, rivastigmine and glantamine).
NMDA glutamate receptor blocker (mamantine).
Ginko biloba extract.
For depression SSRIs are used.
Seizures should be controlled by appropriate anticonvulsant.
Atypical antipsychotics for neuropsychiatric symptoms.
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22. MCQ
• Which of the following would be the best test to confirm whether this
patient has AL amyloidosis?
Congo red staining of fat pad aspirate
Serum and urine protein electrophoresis with immunofixation
Echocardiography
κ/λ Immunostaining of tissue amyloid deposits
Transthyretin mutation analysis
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