Diagnosis

Amyloidosis

Etiology

Cause [skh]

1. Primary amyloidosis -> AL amyloidosis (immunoglobulin light chain amyloidosis):

   A plasma-cell dyscrasia characterized by an autonomous proliferation of plasma cells with an overproduction of a monoclonal insoluble Ig protein. It usually affects the heart, kidneys, liver and nerves.

2. Secondary amyloidosis (AA amyloidosis):

   Result of chronic infection or inflammatory disease: Rheumatoid arthritis, Juvenile chronic arthritis, Ankylosing spondylitis, Psoriasis, Still disease, Behcet syndrome, Familial Mediterranean fever, Crohn disease, Leprosy, Osteomyelitis, Tuberculosis, Chronic bronchiectasis, Castleman disease, Hodgkin disease, Renal cell carcinoma, Colorectal cancer, Lung cancer, Bladder cancer, Cryopyrin-associated periodic syndromes. It most commonly affects the kidneys, liver and spleen.

3. Hereditary amyloidosis (familial amyloidosis):

   Autosomal dominant disease. It most commonly happens when a protein (transthyretin) made by the liver is abnormal. Often affects the nerves, heart and kidneys.

4. Wild-type amyloidosis (senile systemic amyloidosis):

   It occurs when the transthyretin protein made by the liver is normal but produces amyloid for unknown reasons. Wild-type amyloidosis tends to affect men over age 70 and often targets the heart. It can also cause carpal tunnel syndrome.

5. Localized amyloidosis:

   This type of amyloidosis often has a better prognosis than the varieties that affect multiple organ systems. Typical sites for localized amyloidosis include the bladder, skin, throat or lungs. Correct diagnosis is important so that treatments that affect the entire body can be avoided.

Pathophysiology [v7f]

Insoluble amyloid protein production -> accumulation -> organ failure. Common site of deposition and organ failure: heart, kidneys, gastrointestinal system, nervous system, joints, liver, spleen, pancreas, respiratory system, and skin.

Epidemiology

Incidence per 100.000 [v7f][8t9][sss]

Prevalence per 100.000 [v7f][8t9][sss]

Approach

• Blood test

• Urine test

• ECG

• Ultrasound cor

• Bone marrow biopsy

• Tissue biopsy

Treatment

1. Primary AL amyloidosis: daratumumab (a monoclonal antibody (mAb) that binds to CD38 on the surface of plasma cells, causing apoptosis), hyaluronidase, cyclophosphamide, bortezomib, and dexamethasone. Autologous stem cell transplantation (ASCT) is performed in those with an incomplete response to drug therapy.

2. Secondary amyloidosis (AA amyloidosis): treatment of the underlying disease, Colchine, Dimethylsulfoxide, Anticytokine therapy, cytotoxic immunosuppressive agents, clearance of amyloid deposits, stabilisators/binders

3. Hereditary amyloidosis/Wild-type amyloidosis: reducing transthyretin synthesis, stabilization of transthyretin protein, or elimination of the main source with liver transplantation.

Differential diagnoses

Alopecia, Angina pectoris, Carpal tunnel syndrome, Cutis verticis gyrata, Heart failure, Mastocytosis, Multiple myeloma, Myocardial infarction, Nephrotic syndrome, Peripheral neuropathy, Pseudoxanthoma elasticum, Renal failure, Scleredema, Sebaceous hyperplasia, Xanthomas