cutaneous amyloidosis at insulin injection site

Last edited 09/2020 and last reviewed 07/2021

nsulins (all types): risk of cutaneous amyloidosis at injection site

• Insulin-derived amyloidosis is a specific form of localised cutaneous amyloidosis composed of insulin fibrils. It is likely caused by insulin accumulation at the injection sites, especially if these sites are used for repeated subcutaneous injections
• a European review considered cases of insulin-derived cutaneous amyloidosis reported in patients treated with all types of insulin. Some were identified by either histological examination, computerised tomography, or a combination of these. Presence of insulin in the amyloid was recognised by immunohistochemical analysis and in a single case further validated by mass spectrometry
• in many of the cases initially analysed of the review, this resulted in poor glycaemic control (hyperglycaemia and hypoglycaemia)
• evidence showed in many cases patients were routinely injecting into the same sites repeatedly rather than rotating injection sites. When outcome of glycaemic control was reported, most patients recovered after they began to use a proper site-rotation technique
• in the UK, up until the end of July 2019, 2 reports of cutaneous amyloidosis in patients receiving insulin therapy have been received via the MHRA’s Yellow Card Scheme
• European review was not able to estimate the frequency of cutaneous amyloidosis in patients using insulin from the data available, but reports have been received only very rarely.

The literature suggests that cases of cutaneous amyloidosis may be under-reported and misdiagnosed as lipohypertrophy (a common increase in fat cells due to growth factor effect of insulin)

• both conditions are characterised by lumps in the skin. However, where lipohypertrophy lesions are lobular and regress after stopping insulin injection, amyloid lesions are more solid and firm, do not regress quickly, and usually require surgical excision to treat.

While amyloid lesions can delay insulin absorption and affect glycaemic control if used as a site for administration, the skin changes are thought to be localised. Although some cases of cutaneous amyloidosis were reported as of a serious nature, they were mostly reported as such due to hospital admission to resect amyloid lesion. Aside from impact on glycaemic control, no other complications have been recognised.

Patients who inject insulin at the same site regularly are at an increased risk of developing cutaneous amyloidosis at the injection site and consequently may have poor diabetes control due to lack of insulin absorption due to the amyloid mass. To prevent or reduce this, patients should be advised to rotate injection sites within the same body region.

There is a risk of hypoglycaemia in patients that suddenly change injection site from an area with cutaneous amyloidosis to an unaffected area (for example, changing the injection site from the torso to the leg). Patients should therefore carefully monitor blood glucose after changing injection site and consider adjusting the dose of insulin or antidiabetic medication to avoid hypoglycaemia, as needed.

• injection of insulin (all types) can lead to deposits of amyloid protein under the skin (cutaneous amyloidosis) at the injection site
• cutaneous amyloidosis interferes with insulin absorption, and administration of insulin at an affected site can affect glycaemic control
• remind patients to rotate injection sites within the same body region to reduce or prevent the risk of cutaneous amyloidosis and other skin reactions (for example, lipodystrophy)
• consider cutaneous amyloidosis as a differential diagnosis to lipodystrophy when a patient presents with subcutaneous lumps at an insulin injection site
• advise patients:
  • that insulin may not work very well if they inject into an affected ‘lumpy’ area
  • to contact their doctor if they are currently injecting insulin into a ‘lumpy’ area before changing injection site since a sudden change may result in hypoglycaemia
  • to monitor carefully blood glucose after a change in injection site and that dose adjustment of insulin or other antidiabetic medication may be needed
• report serious adverse drug reactions associated with insulin to the Yellow Card scheme

Reference:

• MHRA (September 23rd 2020). Insulins (all types): risk of cutaneous amyloidosis at injection site.