Amyloidosis

AL (amyloid light chain) amyloidosis — the primary form — is a systemic disease resulting from an underlying plasma cell dyscrasia, causing deposition of misfolded amyloid light chain proteins across organs and progressive organ damage. Hereditary amyloidosis, the term now recommended over the older label ‘familial amyloidosis’, is a much rarer alternative cause.

Demographics

Most patients are 50–70 years old at diagnosis. Associated with multiple myeloma, B-cell malignancies, and cytogenetic abnormalities (14q translocations, 13q deletion). Agent Orange exposure is a possible risk factor.

Clinical features

Fatigue, weight loss, weakness and dyspnoea are common presenting complaints, usually with one organ’s dysfunction predominating:

• Renal (50% at diagnosis): ankle swelling, peripheral oedema, pleural/pericardial effusions, orthostatic hypotension symptoms.
• Cardiac (25% at diagnosis): exertional dyspnoea, peripheral oedema, orthostatic hypotension, weight gain.
• Peripheral/motor neuropathy: muscle weakness, paraesthesia, numbness.
• Autonomic neuropathy: altered bowel habit, early satiety, anhidrosis.
• GI: weight loss, diarrhoea, chronic nausea, hepatomegaly, rectal bleeding.
• May also see macroglossia, thickened skin/soft tissues, lymphadenopathy, claudication.

Investigations — organ-involvement criteria (International Society of Amyloidosis)

Organ	Criteria
Heart	BNP >332; mean wall thickness on echo >12mm
GI tract	Direct biopsy confirmation with symptoms
Kidney	24hr urine protein >0.5g/day, mainly albumin
Liver	Span >15cm; ALP ≥1.5× upper limit of normal
Lung	Interstitial pattern on X-ray; direct biopsy
Nerve	Peripheral: symmetric lower-extremity sensorimotor neuropathy. Autonomic: gastric-emptying disorder, voiding dysfunction, pseudo-obstruction

Management

• Diagnosis is generally confirmed by biopsy of affected tissue.
• Refer for specialist (haematology) management.
• Treatment goal is to suppress the underlying plasma cell dyscrasia, eliminating the supply of amyloidogenic protein.
• First-line, newly diagnosed AL amyloidosis: subcutaneous daratumumab (anti-CD38 monoclonal antibody) combined with cyclophosphamide, bortezomib and dexamethasone (dara-CyBorD) — now the first FDA-approved, standard-of-care regimen, following the ANDROMEDA trial (superior major-organ-deterioration-free survival vs CyBorD alone, HR 0.47). This has superseded the older approach of chemotherapy/stem cell transplant and high-dose corticosteroids plus immunomodulators alone as a starting regimen — those remain options for later lines or where daratumumab is unsuitable (registry: andromeda-daratumumab-al-amyloidosis-2021; verified 2026-07-23).