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A review of published studies has identified 12 classes of drugs that can cause Raynaud’s disease – a condition where small arteries that supply blood to the skin constrict in response to cold. It suggests the condition may be more common as a drug side effect than previously thought.
A hand covered in snow

The reviewers identified 12 classes of drug that can give rise to Raynaud’s disease – a condition that affects the extremities, such as the fingers, causing numbness and pain in response to cold.

Reporting in the British Journal of Clinical Pharmacology, the reviewers also explain how they identified various underlying mechanisms through which the different drugs lead to Raynaud’s disease, also known as Raynaud’s phenomenon or Raynaud’s syndrome.

Lead author Dr. Charles Khouri, of the Grenoble University Hospital Centre in France, says:

“Beyond chemotherapies and beta-blockers, well known to induce Raynaud phenomenon, insights are currently emerging from a wide variety of drug classes through new pathophysiological pathways.”

Raynaud’s disease is a disorder that affects skin blood vessels, mostly in the fingers and toes. The blood vessels narrow more than normal in response to cold temperatures or stress. The blocked blood flow can cause numbness and pain.

There are two kinds of Raynaud’s disease: primary and secondary. Primary Raynaud’s disease is the more common form and happens on its own; it is most common in women and people living in cold places.

The secondary form of Raynaud’s disease happens along with some other health problem or in reaction to drugs. It can also affect workers who use vibrating equipment like jackhammers or who are exposed to certain chemicals.

‘Variety of underlying mechanisms’

The authors explain that drug-induced Raynaud’s disease has long been linked to use of certain drugs, such as chemotherapy drugs used in cancer treatment or beta-blockers used to treat angina, heart failure and high blood pressure.

Fast facts about Raynaud’s disease

  • People of all ages can have Raynaud’s disease
  • It may run in families, but more research is needed
  • The condition is quite easy to diagnose with simple tests.

However, Dr. Khouri and colleagues note that the evidence about drug-induced Raynaud’s disease is not clear, with confusion surrounding each drug’s effect and underlying mechanism. Also, new information is emerging from individual and small groups of cases.

As such, they conducted a systematic review of papers published since 1946 in English and French.

They identified 12 classes of drugs responsible for Raynaud’s disease, with a “variety of underlying mechanisms such as increased sympathetic activation, endothelial dysfunction, neurotoxicity or decreased red blood cell deformability.”

The reviewers note that two cancer chemotherapy drugs – cisplatin and bleomycin – were the ones most likely to be associated with Raynaud’s disease, followed by beta-blockers.

Cisplatin (brand names Platinol-AQ and Platinol) is used in the treatment of bladder, ovarian and testicular cancers. Bleomycin (Blenoxane) is used to treat a range of cancers, including penile cancer, cervical cancer and some types of lymphoma.

The authors also mention that more recent evidence suggests “a possible involvement of tyrosine kinase inhibitors (TKI), through an unknown mechanism.”

TKIs are drugs that stop cancer cells growing by blocking enzymes. There are many different approved types of TKI, targeting different enzymes and used to treat different kinds of tumors.

Meanwhile, Medical News Today recently learned that an “antifreeze protein” found in ticks and that protects them from freezing temperatures also prevents frostbite in mice.