Introduction to diagnosis of Amyloidosis

Some combinations of symptoms may cause doctors to suspect a diagnosis of amyloidosis. These are known as “red flags” for amyloidosis.

Red flags include unexplained, progressive worsening in:

  • kidney function
  • protein in the urine
  • swollen ankles
  • shortness of breath on exertion
  • fainting
  • heart failure with poor response to standard treatments
  • tingling, pain and altered sensation in the hands and feet- “glove and stocking neuropathy”
  • changes in bowel habit- diarrhoea or constipation

Unfortunately these are all very common complaints, especially in the elderly.

In most cases these complaints are not due to amyloidosis.

However, doctors treating patients with these symptoms should perform appropriate investigations to rule out amyloidosis especially if:

  • the “red flag” symptoms and signs listed above occur together without obvious cause
  • there is a paraprotein or free light chains detected in the blood or urine
  • there is a longstanding inflammatory disease
  • there is a family history of amyloidosis

No blood test is diagnostic of amyloidosis but some test results can raise or support the suspicion. The diagnosis of amyloidosis may be confirmed (or may be eliminated) by taking a biopsy and performing an SAP scan.

When doctors in the UK suspect amyloidosis, they should refer patients to the NAC so that the diagnosis can be confirmed or ruled out.

a)      Suspicion of AL amyloidosis usually arises when there is detection of a paraprotein or of free light chains in the blood or urine, as well as symptoms of organ dysfunction that could be caused by AL amyloidosis.

If a patient feels well and just has paraprotein or free light chains detected in the blood or urine, then AL amyloidosis is highly unlikely, as most such patients just have MGUS and merely require regular follow up by their GP. Many of these patients should undergo further tests such as bone marrow examination and X-rays, to rule out myeloma.

b)      Suspicion of AA amyloidosis usually arises if a patient with a longstanding inflammatory condition develops symptoms of organ dysfunction that could be due to amyloidosis.

c)      Suspicion of hereditary amyloidosis usually arises if a person with a family history of amyloidosis develops symptoms of organ dysfunction that could be due to amyloidosis. Suspicion of hereditary amyloidosis in a patient without a family history of known amyloidosis usually arises late in disease, due to the rare nature of these conditions and the vague nature of the complaints.

e)      Suspicion of wild type ATTR amyloidosis usually arises when an elderly patient with heart failure responds poorly to conventional therapy and has characteristic findings on ECG and echocardiography. Until recently this diagnosis was often missed. In recent years doctors have realised that this diagnosis is actually far more common than was previously believed. Cardiologists are therefore more likely to make the diagnosis than they were in the past.

In the video below, the staff of the NAC pathology laboratory explain how their work contributes to diagnosis and typing of amyloidosis: