Nejm 2007;356:2361 (AA type); 2002;346:1786, 1818; 1997;337:902

Cause:Deposition of short-chain proteins in many parts of the body; several proteins are responsible for such deposition: AL, AA, AF, AH, AP

AL: An immunoglobulin light chain amyloidosis (primary type): patients with B- or plasma cell disorders like multiple myeloma or Waldenström’s; idiopathic

AF: Abnormal familial protein subunit found in affected families, usually present in middle or late life as myocardiopathy or neuropathy (Nejm 1997;336:466)

AA: Amyloidosis (secondary type) associated w SAA protein, an acute phase reactant: collagen vascular diseases, Crohn’s disease, cystic fibrosis, iv drug use, chronic infections (tbc, familial Mediterranean fever, osteomyelitis, etc)

AH: A ₂-microglobulin accumulated in serum of dialysis pts

AP: normal serum protein

Pathophys:Infiltration of organs by protein; in all types: kidney, liver, spleen, gi tract, skin; in AL type, predominantly: vessels, heart, marrow, lung infiltration with hemoptysis, joints (synovium), peripheral nerves, factor X deficiency, pancreatic islets (in myeloma, light chains taken up by macrophages, then excreted into interstitium where polymerized—Nejm 1982;307:1689)

Sx:Exertional muscle pain (due to arteriole infiltration and ischemia); fatigue; carpal tunnel syndrome

Si:Hepatosplenomegaly; raised skin plaques, if rubbed results in purpura, “greasy nose syndrome” (amyloid infiltration); “shoulder pad” deposition associated with arthropathy (Nejm 1973;288:354); RA-like acute arthritis; “scalloped pupils” in familial type (Nejm 1975;293:914); macroglossia (AL type only; sensory and autonomic neuropathy)

AA type amyloidosis may revert, esp the nephrotic syndrome, with rx of the primary disease (Nejm 1970;282:128)

Functional asplenia, nephrotic syndrome, CHF, water-losing nephropathy (r/o DI and postobstructive syndrome), factor X deficiency, which rx with splenectomy (Nejm 1981;304:827); peripheral or polyneuropathy (Nejm 1991;325:1482); atrial thrombi and embolization (Nejm 1992;327:1570)

Lab:

Path:Rectal or other tissue bx shows protein infiltration with green birefringence on polarizing scope exam with Congo red staining; in AA type, Congo red affinity can be leached out by K-permanganate unlike AL type. Normal-appearing skin will be positive in about half of all patients with either type.

Urine:24-h protein >3 gm and thus nephrotic

Xray:Chest shows cardiomegaly if cardiac infiltration. Serum amyloid P scan (Nejm 1990;323:508)

Rx:

AA type, rx primary disease

AL rx with melphalan + stem cell transplant, 40% 1-yr cure (Nejm 2004;140:85). Plasma exchange helps neuropathies (Nejm 1991;325:1482)

AF type, liver transplant (Ann IM 1997;127:618)

in cardiomyopathy, avoid calcium channel blockers and digoxin (Am J Cardiol 1985;55:1645)