When to Suspect a Diagnosis of Amyloidosis

Acta Haematol. 2020;143(4):304-311. doi: 10.1159/000506617. Epub 2020 Apr 27.


Amyloidosis is a group of complex diseases caused by extracellular deposition of pathological insoluble fibrillary protein in organs and tissues and may result in severe organ dysfunction. Despite the etiological heterogeneity of systemic amyloidosis, the clinical manifestations of the different forms of amyloidosis largely overlap and depend upon the effected organ. The signs and symptoms that should raise suspicion for the potential diagnosis of amyloidosis are usually nonspecific; therefore, establishing the diagnosis is difficult, and early diagnosis requires clinical suspicion. Light chain (AL) amyloidosis may present with highly specific signs such as macroglossia and periorbital purpura, but these signs are insensitive. Amyloidosis is still underdiagnosed, even though treatments are now available and are effective in improving patient's survival and quality of life. Cardiac amyloidosis is the major determinant of survival, and the earlier it is detected the better the survival. All MGUS patients should be routinely screened for AL amyloidosis by a focused history and physical examination and routine assessment of urine albumin. The aim of this review is to provide clinicians with knowledge about the signs and symptoms that raise the suspicion of amyloidosis, bearing in mind the importance of early diagnosis of this disease.

Keywords: AL amyloidosis; ATTR amyloidosis; Misdiagnosis.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amyloidosis / diagnosis*
  • Amyloidosis / etiology
  • Amyloidosis / metabolism
  • Amyloidosis / therapy
  • Animals
  • Diagnosis, Differential
  • Disease Susceptibility
  • Humans
  • Immunoglobulin Light-chain Amyloidosis / diagnosis
  • Immunoglobulin Light-chain Amyloidosis / etiology
  • Immunoglobulin Light-chain Amyloidosis / metabolism
  • Immunoglobulin Light-chain Amyloidosis / therapy
  • Male
  • Middle Aged
  • Organ Specificity
  • Phenotype