Lyell’s syndrome: the cure comes from an off-label drug

For some years at the IDI in Rome, patients have been treated with a therapy initially indicated for psoriasis. Doctor Biagio Didona: “It is the best dermatological innovation of the last 10 years”

First described in 1956, the Lyell’s syndrome it is a serious skin disease almost always caused by taking drugs, which can even lead to death. But a promising discovery, which comes from the Immacolata Dermopathic Institute IDI-IRCCS in Rome, has already saved the lives of numerous patients. We asked the Dr. Biagio Didonadirector of the Center for Rare Dermatological Diseases at the IDI, to explain to us the main characteristics of this pathology and the discovery for which he was awarded during the last congress of the American Academy of Dermatology, which took place last March in San Diego.

Doctor Didona, to begin with, could you briefly describe Lyell’s syndrome?

Lyell’s syndrome is the most serious drug-induced illness known. It has a very low incidence, equal to one case in a million people every year and there is a slight prevalence in women. In Italy, with a population of around 65 million, we expect around 65 cases per year. It is caused mainly by anti-inflammatory drugs, antiretroviral drugs, allopurinol, antiepileptics and antibioticsto give just a few examples, and the risk increases in subjects suffering from autoimmune diseases, such as systemic lupus erythematosus, or with HIV. Usually the reaction occurs about seven days after taking the drug, but sometimes it can be slower and appear after 10, 15 or even 20 days.

And what are the main symptoms?

At the beginning there are general symptoms such as fever, burning skin and asthenia. Then skin lesions appear with the appearance of purple macules especially on the hands and feet, which can develop into blisters. Other symptoms progressively appear such as ulcerations and crusts in the mouth, eyes or genitals. The skin peels off as if burned, and in some cases, the disease can lead to serious systemic complications, including electrolyte imbalances, clotting disorders and breathing problems, which are the leading cause of death. Lyell’s syndrome has a very high mortality ratewhich is between 30 and 50% of those affected, with a rather rapid progression: generally speaking over days or weeks.

From a therapeutic point of view, how is Lyell syndrome treated?

It must be said, first of all, that the diagnosis is almost always clinical and relatively simple. There are confirmatory tests such as biopsy, but the patient must be treated immediately, even without waiting for the results. As far as therapy is concerned, since the discovery of the disease in 1956, only cortisone was used. Intravenous immunoglobulins were subsequently introducedwhich gave better results, and more recently cyclosporine was used, until we started using etanerceptan innovative drug that we introduced into the treatment.

Etanercept? Could you explain better?

It is a drug initially used for psoriasiswhich works by blocking a cytokine called TNF-alpha, which plays a crucial role in the pathogenesis of the disease. Here at IDI we have treated 33 cases of Lyell and, based on a severity score of 0 to 6, there should have been 16 deaths. Instead, only 2 patients died, very elderly ones, and not directly due to the syndrome. Today it is clear that etanercept not only reduces mortality but blocks the disease and shortens hospital stays. Symptoms begin to improve the day after taking the drug, then the pain disappears and patients recoveralthough in some cases the disease can leave consequences.

Is it for this discovery that you, doctor, have been personally rewarded?

Yes, this year the American Academy of Dermatology honored us at the annual conference held in San Diego. Our work was selected as the best in recent years and etanercept therapy was judged the best dermatological innovation of the last 10 years.

And what will you do now?

We will continue to treat patients with etanercept. We often receive calls from other hospitals, even children’s hospitals or those outside the region. We have achieved excellent results and I really think that this drug will become the first choice in the treatment of Lyell’s syndrome.