Info

- ECG and echocardiography: low voltage ECG; echo shows concentrically thickened ventricles, normal to small cavities and a normal or mild reduction in ejection fraction.

- SAP (serum amyloid protein) scan: radiolabelled serum amyloid P component allows detection and quantification of amyloid deposits and assessment of extent of organ involvement by scintigraphy. (In UK contact National Amyloidosis Centre at UCLMS Royal Free Hospital, London Campus).

Differential diagnosis

Exclude MM (as above), reactive (AA) amyloidosis (history of chronic inflammatory disorder) and familial amyloidosis (family history).

Prognostic factors

Poor prognostic features:

• Multisystem involvement.

2 Jaundice.

• High total body amyloid load on SAP scan.

Management

Aims: suppress underlying plasma cell neoplasia and paraprotein production to reduce further deposition of amyloid and permit regression resulting in improvement in organ dysfunction.

Supportive care

• Nephrotic syndrome: loop diuretic + salt ± fluid restriction.

• Renal failure: peritoneal or haemodialysis if required; rigorous control of hypertension.

• CCF: diuretic + ACE inhibitors if tolerated; digoxin hypersensitivity common; calcium channel blockers and |3-blockers contraindicated; cardiac transplantation should be considered in appropriate patients.

Chemotherapy

• Melphalan ± prednisolone: slow response rate; consider for patients not eligible for HDT; prolongs median survival in a randomised trial vs. colchicine (but survival only 12-18 months).

• VAD: induces a more rapid response than M&P; suitable initial therapy in those patients eligible for HDT; caution with vincristine in neuropathic patients and adriamycin in those with CCF; dexamethasone alone may produce responses.

• High dose melphalan and autologous PBSCT: improves organ function in up to 60% of survivors; up to 40% procedure related mortality; Note: stem cell mobilisation associated with mortality and morbidity due to cardiac complications (avoid cyclophosphamide), oedema and splenic rupture (low doses of G-CSF recommended); better tolerance of HDT if <2 organ systems involved; younger patients with good performance status and good renal and cardiac function do best; cardiac involvement or elevated creatinine poor prognostic factor; reduce melphalan dose to 100-140mg/m2 in high risk patients; GI haemorrhage a frequent complication; HDT should be undertaken in trial context.

• Allogeneic SCT: few patients have been treated; complete resolution has been reported.

Follow-up

Response to therapy should be monitored by quantitation of the serum or urine paraprotein (or serum free light chains); SAP scintigraphy; ECG, echocardiography and assessment of other organ dysfunction should be reviewed every 6 months.

Prognosis

• Median survival 1-2 years; 4-6 months if CCF at diagnosis.

• Most common cause cardiac: progressive congestive cardiomyopathy or sudden death due to VF or asystole.

• Others succumb to uraemia or other complications.

Other causes of amyloid

Acquired

• AA amyloid: reactive systemic amyloidosis associated with chronic 291 inflammatory diseases e.g. rheumatoid arthritis, TB; due to AA fibrils derived from serum amyloid A protein (SAA).

• Senile systemic amyloidosis due to transthyretin deposition.

• Endocrine amyloidosis, associated with APUDomas.

• Haemodialysis associated amyloidosis, localised to osteoarticular tissues or systemic due to |32-microglobulin deposition.

• Non-familial Alzheimer's disease, Down syndrome due to |3-protein.

• Sporadic Creutzfeldt-Jakob disease, kuru due to prion protein deposition.

• Type II diabetes mellitus due to islet amyloid polypeptide.

Hereditary

• Numerous syndromes with characteristic patterns of peripheral or cranial neurological involvement or visceral or cardiac involvement due to a variety of proteins.

• Familial Alzheimer's disease due to a |3-protein.

• Familial Mediterranean fever due to AA derived from SAA.

BCSH/UKMF Guideline. Guidelines on the dignosis and management of AL amyloidosis. ^ http://www.bcshguidelines.com

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