Amyloidosis Symptoms Diagnosis Prognosis and Treatment

Amyloidosis

Amyloidosis is deposition of insoluble amyloid fibrils in extracellular spaces of organ and tis­sues due to abnormal protein folding.

metabolic disorders resulting from the insidious deposition of protein-containing fibrils (amyloid) in tissues,

diseases characterized by extracellular deposition of insoluble protein fibrils in organs and tissues

clinicalCoronary Angiography -Indications of Coronary Arteriography (Angiography). Read more ... » manifestations of amyloidosis are enormously varied, and the diseaseCoronary Angiography -Indications of Coronary Arteriography (Angiography). Read more ... » may mimic many other conditions ranging from nephrotic syndromeMetabolic,Insulin Resistance Syndrome X Causes Symptoms. Read more ... » (when kidneys are infiltrated) or congestive heartCoronary Angiography -Indications of Coronary Arteriography (Angiography). Read more ... » failure (myocardial deposition),to dementias (brain involvement) .

Amyloidosis Classification

• is based on the nature of precursor plasma proteins that form fibril deposits :
  • ›Dialysis-related: Deposition of fibrils derived from-microglobulin; predilection for osteoarticular structures
  • ›Heritable or familial (AF): Many different types of variant plasma proteins form amyloid deposits beginning in midlife; most common form is caused by mutations of transthyretin (ATTR)
  • ›Organ-specific amyloidosis: Deposition isolated to 1 organ, resulting in specific syndromes; most common is Alzheimer disease caused by cerebral amyloid plaques:
  • ›Primary (AL): Plasma cell dyscrasia; deposition of protein derived from immunoglobulin light chain fragments
  • ›Secondary or reactive (AA): Complicates chronicChronic Hepatitis Classification viral hepatitis Clinical features and Treatment. Read more ... » infections or inflammatory diseases; deposition of serum amyloid A(SAA) protein
  • ›Senile systemic amyloidosis: Deposition of otherwise normal (wild-type) transthyretin in myocardium and other sites seen in elderly
  • Localized amyloidosis: Results from local amyloid deposits in tracheobronchial tree, urinary tract, or skin, which are also derived from monoclonal light chains, but not due to underling systemic plasma cell disorder

Amyloidosis may be :

• · Systemic amyloidosis
• ·Localized or organ limited amyloidosis. Systemic amyloidosis may be :
• · Neoplastic
• · Inflammatory
• · Genetic
• · Iatrogenic.
• Localized amyloidosis may be associated with ag­ing, diabetes.
  • There is no systemic involvement. ,

Nomenclature of Amyloidosis

• The first letter is A for amyloid deposits and then a letter for protein designation like.
• AL – amyloidosis involving immunoglobulin light chains.

Systemic Amyloidosis

• AL or Primary Idiopathic Amyloidosis
  • Most common form of Systemic Amyloidosis is AL.
  • It is associated with multiple myeloma in some cases.
• AA Amyloidosis
  • Secondary, reactive or acquired.
  • Occurs as a complicationHyperglycemic Hyperosmolar State (HHS) Acute Complication Of DM. Read more ... » of chronic inflammatory dis­ease.

Precipitating diseases

• · TuberculosisLeprosy Hansen's Disease types Causes of leprosy sign and Symptoms With Treatment. Read more ... »
• · Osteomyelitis
• · Leprosy.
• Familial causesCoronary Angiography -Indications of Coronary Arteriography (Angiography). Read more ... » of AA amylo‘dosis
  • Familial Mediterranean feverThyrotoxic crisis or Thyroid storm. Read more ... » (FMF), Familial cold ur­ticaria (FCU).
  • Colchicine blocks FMF and AA amyloidosis. HeredofamiAcute Myocardial Infarction (AMI) Causes PATHOPHYSIOLOGY and Etiology. Read more ... »lial amyloidosis:
  • Less common, presents as: – Neuropathy – NephropathyDiabetic Nephropathy and Renal complications of DM (Diabetes Mellitus). Read more ... »
  • - CardiomyopathyCardiomyopathy Clinical features Etiology Diagnosis Dilated Hypertrophic Restrictive cardiomyopathy with Treatment. Read more ... »
  • - HepatomegalyAlcoholic Liver Disease Diagnosis CAGE criteria and Treatment. Read more ... »
  • - Dementia.

Localized amyloidosis

• 1. Polypeptide hormoneAnterior Pituitary Hormones and Disorders. Read more ... »-derived amyloidosis – Cal­citonin, prolactin, insulinHyperglycemic Hyperosmolar State (HHS) Acute Complication Of DM. Read more ... » can lead to amyloido­sis.
• 2. Localized corneal amyloidosis.
• 3. Localized cardiovascular amyloidosis – from atherometous plaques, aortic media, atrial natri­uretic factor AANF.
• 4. Associated with Alzheimer’s disease – Beta amy­loid protein is found in Alzheimer’s disease and Down’s syndrome.
• 5. Prion diseases – Prions are a class of infectious protein responsible for a group of neurodegene­rative disease causing encephalopathy. Ex- Kuru, Creutzfeld-Jakob disease, and fatal insomnia.

Senile systemic amyloidosis

• It is cardiacCoronary Angiography -Indications of Coronary Arteriography (Angiography). Read more ... » amyloidosis with systemic involvement.
• Proteinuria
• Peripheral neuropathies Dementia
• Cognitive dysfunction Hepatomegaly
• KidneyDiabetic Nephropathy and Renal complications of DM (Diabetes Mellitus). Read more ... » enlargement Splenomegaly Cardiomegaly.

Renal involvement

• · Mild proteinuria
• · Frank nephrosis
• · Microscopic hematuriaDIAGNOSIS and Investigations OF SECONDARY HYPERTENSION. Read more ... »
• · Progressive azotemia
• · Rarely hypertensionHyperthyroidism or THYROTOXICOSIS Causes, Symptoms and Diagnosis. Read more ... »
• · Death.

Heart

• · Heart failureHeart Failure Causes Symptoms NYHA classification with Heart Failure Treatment. Read more ... »
• · Low voltage ECGCoronary Angiography -Indications of Coronary Arteriography (Angiography). Read more ... »
• · Conduction defects
• · AR, MR
• · Pericarditis with effusion
• · Restrictive CM P.

Liver

• · Portal hypertensionPortal Hypertension Clinical Features Symptoms Diagnosis and Treatment. Read more ... »
• · Hepatomegaly.

Spleen

• • Spler:lOmegaly.

Skin

• · Non pruritic lesions
• · Raised papules or plaque in axilla or inguinal regions
• · Racoon syndrome – periorbital ecchymoses (re­sembling the face of a racoon).

Gastrointestinal tract

• · Obstruction, ulceration, malabsorption, GI
• haemorrhage
• · Thick tongue – macroglossia.

Nervous systemCoronary Angiography -Indications of Coronary Arteriography (Angiography). Read more ... »

• · Peripheral neuropathy
• · Postural hypotensionHyperglycemic Hyperosmolar State (HHS) Acute Complication Of DM. Read more ... »
• · Adie’s pupil (a tonic pupil along with weak or absent tendon reflexes in the lower extremities, a benignPheochromocytoma Clinical Features Diagnosis Treatment. Read more ... » disorder seen in healthy, young women due to dysautonomia
• · Urinary incontinence.
• Other causes of Adie’s pupil are Shy-Drager syndrome, segmental hypohidrosis, diabetes, amyloidosis.

Endocrine

• · ThyroidHyperthyroidism or THYROTOXICOSIS Causes, Symptoms and Diagnosis. Read more ... » enlargement
• · Amyloid infiltration of adrenalHypothalamic, Pituitary And Other Sellar Masses. Read more ... » gland, pituitaryHypothalamic, Pituitary And Other Sellar Masses. Read more ... » gland and pancreas.

Joints and muscles

• · Symmetric arthritis of small joints
• · Muscle hypertrophy – shoulder pad sign
• · Carpal tunnel syndrome.

Respiratory system

• · Amyloidosis of lungs, bronchi, larynx, trachea
• · May resemble a neoplasm
• · May need excision.

Hematopoietic system

• • Deficiency of clotting factors.

Amyloidosis Risk Factors

• •Depends on type of systemic amyloidosis:
  • Untreated chronic inflammatory diseases (AA)
  • Untreated chronic infections (AA)
  • Underlying plasma cell dyscrasia (AL)
  • Long-term hemodialysisDialysis Indications Complications and Dialysis for Renal Failure. Read more ... »
  • Heredity (AF/AA)
  • Age (senile systemic/Alzheimer)

Amyloidosis DIAGNOSIS

• · Biopsy of abdominal fat, renalDiabetic Nephropathy and Renal complications of DM (Diabetes Mellitus). Read more ... » or rectal biopsy
• · Congo-red staining shows green birefringence with polarizing microscope.

Amyloidosis PROGNOSIS

• • Death can occur if untreated.

Amyloidosis TREATMENT

• Genetic counseling Hemodialysis
• Kidney transplant
• Liver transplantation Stem cell transplantation Melphalan Iododoxorubicin
• Colchicine – prevents acuteCoronary Angiography -Indications of Coronary Arteriography (Angiography). Read more ... » attacks.

First Line TREATMENT of Amyloidosis

• •Primary AL
  • Precautions with melphalan: Bone marrow suppression, cytopenias, infections
  • Melphalan and high-dose dexamethasone for patients who cannot tolerate HCT
  • High-dose melphalan followed by hemopoietic cell transplant (HCT): Improves quality of life and even result in remission in some cases
• •Secondary AA:
  • Control of underlying inflammatory disease: Consider anticytokine therapy for autoimmune diseases
  • Colchicine: for familial Mediterranean fever

Second Line TREATMENT of Amyloidosis

• •Primary AL
  • Precautions: Neutropenia, thrombocytopenia, rash, fatigueFatigue diagnosis medicine and treatment. Read more ... »
  • Lenalidomide with dexamethasone
  • Bortezomib with dexamethasone