Sickle cell: Hydroxyurea and leg ulcers

Tola Dehinde

In recent weeks, I’ve been writing about the various research available for the treatment and management of sickle cell disease. One of the treatments I mentioned was hydroxyurea.

Today, I want to revisit this topic because I had a very negative experience with it.

A couple of years ago, my consultant, with my consent, decided to put me on this so-called “wonder drug.” I knew many people in the sickle cell community who had been taking it for over 10 to 20 years, and they all had positive things to say about it.

So, when my consultant encouraged me to try it, I did some research to understand the possible side effects of hydroxyurea, as it is primarily a cancer drug.

I found studies suggesting that hydroxyurea could affect white blood cells and even increase the risk of leukaemia.

Unfortunately, within two weeks of starting the medication, my leg began to swell. I went to the haematology day unit, saw a doctor, and was prescribed antibiotics because they thought it might be an infection.

However, despite using the antibiotics, my ankle only worsened. After a few weeks, I returned to the day unit and this time, I informed the doctor that I was taking hydroxyurea.

After consulting with his superiors, he advised me to stop taking it. Sadly, by that time, it was too late—the swelling had turned into a wound that took months to heal.

I’m planning to write a book about my experience and the treatments that worked for me, in the hope of helping others. Unable to sleep at night, I began researching hydroxyurea and leg ulcers.

There is a lot of medical research and literature available on this topic, and I’d like to share some of my findings with you.

Since its approval for the treatment of sickle cell disease in 1998, hydroxyurea has been extensively studied.

Before the U.S. Food and Drug Administration approved hydroxyurea for treating adults with SCD, most treatments were supportive, focusing on managing symptoms with red blood cell transfusions, pain relief, antibiotics, and intravenous fluids.

There were no approved therapies to modify the underlying disease process.

Hydroxyurea remains the only approved treatment that can alter the course of the disease, though repeated blood transfusions can greatly reduce its severity, and haematopoietic stem cell transplantation offers a potential cure.

Hydroxyurea’s effectiveness in treating SCD is largely due to its ability to increase foetal haemoglobin.

One study highlights an unexpectedly high risk of leg ulcers when hydroxyurea is used to treat sickle cell disease.

Although the exact cause remains unclear, older patients and those with a history of SCD-related ulcers seem to be at greater risk.

This suggests that hydroxyurea may interact with small vessel abnormalities, contributing to the development of ulcers. Interestingly, both stopping or reducing the dosage of hydroxyurea can sometimes be enough to heal these ulcers.

Therefore, it’s important to monitor any skin changes closely during hydroxyurea treatment in SCD patients.

Since hydroxyurea treatment may be linked to several skin-related side effects, particularly in patients with sickle cell disease who often need lifelong care, we conducted a study to assess the risk of these adverse skin reactions.

Our findings indicate that hydroxyurea has caused ulcers primarily in patients with a history of SCD-related ulcers, suggesting that the drug might interact with existing vascular abnormalities.

Therefore, extra caution is necessary when prescribing hydroxyurea to SCD patients, especially those who have had ulcers before or those who are older. While most of the skin reactions reported were mild, some were severe or even life-threatening, which led to the discontinuation of hydroxyurea.

The severe cases included the development of painful leg ulcers or skin cancers like cutaneous squamous cell carcinoma in 9% and 3% of the cases, respectively.

The use of hydroxyurea has been linked to the development of ulcers, particularly in patients with a history of sickle cell disease ulcers. This suggests that hydroxyurea may interact with existing vascular issues.

Extra caution is advised when prescribing hydroxyurea to SCD patients who have had ulcers before, as well as to older patients with SCD. Several skin-related side effects can occur in patients treated with hydroxyurea.

While most of these reactions are mild, some can be severe or even life-threatening, leading to the discontinuation of hydroxyurea.

Among the more severe cases, nine per cent of patients developed painful leg ulcers, and three per cent developed cutaneous squamous cell carcinomas.

Unlike in myeloproliferative disorders, where hydroxyurea is typically prescribed for a few years to mostly middle-aged white patients, in SCD, it is often prescribed for life to young Black patients.

Ulcers were considered to be caused by hydroxyurea if they, one, appeared or worsened during treatment while SCD was inactive and two, had no arterial or venous underlying cause and did not respond to repeated blood transfusions, and either disappeared or significantly improved after stopping or reducing hydroxyurea.

Given the lifelong use of hydroxyurea in individuals with SCD, it became important to assess its risks.

In one study, where a single dermatologist systematically examined all SCD patients on hydroxyurea at a specific centre, leg ulcers attributed to hydroxyurea were found in 29 per cent of the patients treated.

Research also shows that higher levels of foetal haemoglobin are associated with a lower incidence of leg ulcers, while hydroxyurea has been linked to a higher risk of these ulcers.

Only a few drugs are known to cause ulcers at sites far from where they are administered, and the exact cause of hydroxyurea-induced ulcers remains unknown.

The specific mechanisms behind hydroxyurea-induced ulcers are not yet understood. Additionally, the expert panel expressed concerns about the potential adverse effects of hydroxyurea on spermatogenesis in men receiving the drug at therapeutic doses.

If you would like to get in touch with me about Sickle cell, do so via my email address: [email protected]. And do check out my blog: https://www.dailylivingwithsicklecell.com/. My book on Sickle Cell – How to Live with Sickle Cell and my other books are available for purchase on www.amazon.com.