Prof. Piotr Kuna: Polish patients with rare eosinophilic diseases deserve a higher level of medicine

What is the cause of the rare eosinophilic diseases EGPA and HES, and how long does it take to diagnose them?

The nature of these diseases is unknown. In a study at the Mayo Clinic in Rochester of 1,500 people who had elevated eosinophil counts above 1,500, only 1 percent of them, or 1 in 100, had acute or chronic eosinophilic leukemia, or eosinoproliferative disease. In contrast, the rest had either HES or EGPA. This shows that the incidence of these diseases is much higher than leukemia, which we immediately suspect as we have a lot of white blood cells. And that's not true. It's not immediately leukemia. Where does it come from? Suspicions vary. Genetic anomalies, viral or other infections, environmental factors that modify cell proliferation, or allergies, or hypersensitivity reactions more broadly said. The fact is that in Poland, morphology is very rarely evaluated for eosinophils. Often, even when I see a blood count test, they just don't mark the composition of white blood cells. And white blood cells are, after all, lymphocytes, neutrophils, eosinophils, basophils. Sometimes monocytes are still added to that. So what we are really missing is good diagnostics. Second, these patients, both with EGPA and hyperoeosinophilic syndrome, present with very different symptoms. Of course, they are most often noted from the respiratory side, but they can also be neurological symptoms, skin symptoms, cardiovascular symptoms. There is no single, specific symptom. Taking into account these two elements, when eosinophils in peripheral blood are rarely evaluated, and the variety of clinical symptoms, the average time from the onset of this disease to full diagnosis is about 7 or even up to 10 years Of course, it depends on which doctor the patient goes to, and whether it is an experienced doctor who understands the issues, or whether they are family doctors who often have no experience, because these are very rare diseases.

You said about the non-specificity of the symptoms. So what is the course of these diseases? What do these diseases have in common, and can they lead to disability and premature death?

As for typical symptoms, the most common initial symptom of EGPA is bronchial asthma and asthma is diagnosed. Later, during the development of this disease, eosinophilia appears. Little, this asthma is a variable disease, it has periods of severity and remission. During a certain period, the asthma seems to disappear, but there is still eosinophilia. Then additional symptoms related to vasculitis develop, because EGPA is eosinophilic vasculitis. And this is confirmed with a biopsy. These lesions can be in different organs, not only in the lungs. They can also be in the skin, in the nervous system, in the kidneys, in the heart. In contrast, the second disease is hypereosinophilic syndrome (HES). In its case, the first symptoms, interestingly enough, usually involve the skin. They are urticaria and inflammation of the skin. Then there are also symptoms from the respiratory system and peripheral nervous system. In the case of EGPA, we can also often speak of complaints not only from the lower respiratory tract, but also chronic inflammation of the nasal mucosa and sinuses.

And what about the impact on quality of life, the induction of disability, and, well, what is the mortality rate from these diseases?

I rely on studies, of which there are not many. They apply to selected populations. It looks like if we diagnose EGPA or HES and don't treat it, half of the patients die within three years. That is, the mortality rate for diseases with high eosinophil levels is higher than for most cancers, and I want to emphasize this strongly. This is due to the fact that there are errors in treatment. As long as we know the cancer, we know how to treat it. And here we often don't know it. In recent years, there have been new standards, recommendations, new treatments. This has greatly improved the results of this treatment. Today I can say that if we recognize the disease, give the correct treatment, more than 90 percent of patients survive 9-10 years.

What treatments are used for these conditions today? What do patients have access to and what is the full therapeutic range?

Until now, the primary chronic treatment has been the administration of systemic steroids. In recent years, many papers have been published on the fact that steroids administered orally, intravenously or intramuscularly, unfortunately, increase our risk of complications greatly, and serious ones at that, such as a fourfold increased risk of sepsis and embolic-thrombotic disease (that is, embolism, which also has a high risk of mortality), diabetes, hypertension, myocardial damage obesity, cataracts, glaucoma and many other diseases. Steroids used chronically unfortunately help some diseases, but harm something else. Immunosuppressive treatment, the kind used in autoimmune diseases or cancer, has been added, but this too is not a safe treatment. It also carries risks. So I can say that there was a certain compromise - severe disease, strong drugs, but drugs that are also toxic. I recently spoke with a prominent oncologist. I asked him why do cancer patients die? He replied: you know, most often they die because they have complications from the drugs. Literally. People don't know about it, and it needs to be talked about. The patient needs to be informed that the treatment they are receiving has certain benefits, but also certain risks. The doctor's role is to balance these proportions. At the moment, new therapies have emerged. These are biologic drugs, targeting cytokines that are responsible for the growth, maturation of eosinophils and the release of toxic proteins from them. And, as it turns out, blocking these cytokines causes the number of these cells to drop in patients with hiereosinophilic syndromes, to decrease to normal levels. These toxic cells are gone, there are no granulomas, and the disease remains in remission or under good control. Yet, when these drugs are discontinued, of course the disease returns.

Are these therapies available to Polish patients, or is it a challenge to make them available?

These drugs are registered by the European Medicines Agency and are available in most European Union countries. In the United States, this treatment has been used for several years. The Polish medical community, the Polish Society of Allergology has also applied to the Ministry of Health for support in reimbursing these drugs. I have also been active in this area through the Society for Rare Diseases, because these are rare diseases. The number of EGPA or HES people in Poland is only a few hundred. This is really not a lot. We are waiting for the decision of the Minister of Health. As far as I know, the opinion of the Agency for Health Technology and Tarification is positive, so I hope that this year this therapy will also become available for patients with HES and EGPA. I would like to emphasize that HES and EGPA are two diseases that have the same mechanism. They may have slightly different consequences afterwards. But it is often the case that one disease turns into the other, and this is also very important, because we cannot separate these diseases and treat them completely differently. They should be treated exactly the same. And here there are problems, because as far as I know, the Ministry has the idea to separate these diseases and not put them in one drug program. I am a doctor, and I know one thing: that we should always treat a disease according to its mechanism, what causes the disease, and not according to what organ it affects. This is a higher level of medicine. I believe that Polish patients deserve this higher level of medicine.