Last reviewed: 24 Jan 2021
Last updated: 26 Oct 2018



History and exam

Key diagnostic factors

  • presence of risk factors
  • jugular venous distention
  • lower extremity oedema
  • periorbital purpura
  • macroglossia

Other diagnostic factors

  • fatigue
  • weight loss
  • dyspnoea on exertion
  • paraesthesia
  • claudication
  • nausea
  • abdominal cramps
  • alternating bowel habit
  • light-headed/orthostatic hypotension
  • submandibular salivary gland enlargement
  • hepatomegaly
  • shoulder pad sign
  • diffuse muscular weakness
  • sensory neuropathy
  • Tinel's sign
  • Phalen's manoeuvre

Risk factors

  • monoclonal gammopathy of undetermined significance (MGUS)
  • inflammatory polyarthropathy
  • chronic infections
  • inflammatory bowel disease
  • Castleman's disease
  • familial periodic fever syndromes

Diagnostic investigations

1st investigations to order

  • serum immunofixation
  • urine immunofixation
  • immunoglobulin free light chain assay
  • bone marrow biopsy

Investigations to consider

  • tissue biopsy
  • immunohistological studies of amyloid deposits
  • mass spectrometry
  • immuno-electron microscopy
  • genetic testing
  • serum amyloid P (SAP) scintigraphy scan
  • FBC
  • comprehensive metabolic profile
  • 24-hour urine collection
  • serum troponin level
  • B-type natriuretic peptide
  • beta-2-microglobulin
  • ECG
  • echocardiogram
  • Doppler echo with strain
  • cardiac MRI

Treatment algorithm


Morie A. Gertz

Seidler Jr. Professor of Medicine

Consultant in Hematology

Chair Emeritus of the Department of Medicine

Mayo Distinguished Clinician

Mayo Clinic College of Medicine




MAG declares that he has received honoraria from Celgene Corporation, Prothena Corporation Plc, Onyx Pharmaceuticals, Alnylam, and Ionis Pharmaceuticals. MAG is also an author of several references cited in this monograph.

Peer reviewersVIEW ALL

Associate Professor of Medicine


Program for Multiple Myeloma and Related Diseases

Princess Margaret Hospital





DR has been reimbursed by Millennium Pharmaceuticals, Inc and Johnson and Johnson, the manufacturers of bortezomib, for attending several conferences, for speaking at educational meetings, and for consulting work. She has also been reimbursed by Celgene, the manufacturer of lenalidomide and thalidomide, for attending several symposia and serving as a speaker.

Assistant Professor of Medicine and Oncology

Division of Hematology/Oncology

Wayne State University School of Medicine

Barbara Ann Karmanos Cancer Institute




JZ declares that he has no competing interests.

Use of this content is subject to our disclaimer