February 29 is not only the rarest date of the year, but also the International Day for Rare Diseases. Many do not have a very good idea of what kind of ailments they are. What unites them and how do they differ, how do people suffering from them live and are treated, how realistic is it to find them in oneself and what to do in this case? We talked about rare diseases with the chief freelance specialist-pulmonologist of the Ministry of Health Sergei Avdeev, MD, Corresponding Member of the Russian Academy of Sciences.
What are rare diseases
In the most general sense, rare diseases are those that affect only a small proportion of people in any region. There is no single list of rare diseases approved for the whole world; they can differ from country to country. EURORDIS (European Organization for the Study of Rare Diseases) estimates the total number of such diseases at about six to eight thousand, depending on the method of counting. Moreover, each disease affects a different number of people - from a few to millions.
The list of rare diseases, so to speak, is dynamic: scientific research adds about two dozen to it every month. What are these diseases? Their names may sound unusual: for example, leucinosis, aka maple syrup syndrome; or, say, cat cry syndrome.
However, if you look a little further, there is nothing funny here. Maple syrup syndrome is a severe congenital metabolic disorder that got its name from its characteristic feature - the unusual sweet smell of urine. Patients suffer from developmental delay, frequent vomiting, hypoglycemia, and low blood pressure.
In babies with feline cry syndrome, crying due to defects in the larynx resembles a meow. By the end of the first year of life, this symptom passes, but developmental delay, heart and internal organ defects, decreased muscle tone and a characteristic appearance - a moon-shaped face, deformed ears, wide-set eyes and a raised upper lip appear.
Progeria is sometimes referred to as Benjamin Button Syndrome. Surely you have seen photographs of children who already at the age of 10-12 years look like very old people: with progeria, changes occur in internal organs and skin associated with premature aging.
One of the most common diseases in this group is idiopathic pulmonary fibrosis (IPF), a lung pathology in which the median survival is two to five years. The most unpleasant thing is that in the early stages, the disease may be asymptomatic, and many patients associate shortness of breath, fatigue and coughing with physical exertion later with age-related changes and do not attach importance to symptoms.
The reasons for the development of most rare diseases are not known today. These include most genetic diseases as well as some infectious or autoimmune diseases. There are some factors that increase their risk (for example, smoking), but in general, there is currently no way to effectively prevent orphan diseases.
The diagnosis of rare diseases is making significant headway. Hundreds of such diseases can already be recognized by various methods. Sometimes these are specific biochemical markers, sometimes immunological, sometimes genetic analysis or high-precision computed tomography is required.
Patient registers are the tools for studying rare ailments. The main problem is that the doctor, to whom the patient comes with nonspecific complaints, suspects something rare and correctly sends the person for examination.
How rare are rare diseases
Despite the fact that a relatively small percentage of people are ill with each of these diseases, in total it turns out that this share is very large: for example, for the European Union it is at least 6-7% of the population. There are about three million people with IPF alone in the world, and in total from rare diseases, according to experts, about 300 million can suffer in the world.
Some of the rare diseases are not severe, but many are serious, chronic, life-threatening diseases. Patients often require complex, expensive treatments. These, as they are also called, orphan diseases, orphan diseases, are deprived of the opportunity to develop complex treatment regimens and drugs necessary for their therapy due to the high cost of such developments and the small number of potential buyers.
Such scientific and medical research creates an urgent need for government support, which, alas, is often more leisurely and limited than the survival of patients allows. On average, one to two years pass from the onset of the development of the disease until the diagnosis is made to a patient with IPF, and every day the opportunity for the effectiveness of treatment decreases. After diagnosis, the average life expectancy of such a patient is approximately two to three years.
Unfortunately, for most rare diseases, there is no way to completely cure or prevent them (but there are exceptions, the most famous of which is perhaps phenylketonuria). As a rule, the efforts of scientists and doctors are aimed at improving the quality of life of patients with such diseases and maximizing its duration.
In Russia today there is no single register of all patients with orphan diseases. These include those whose incidence is at the level of one person in 10 thousand, and, for example, patients with IPF in the country, according to experts, are at least 10 thousand people, and another dangerous rare disease, systemic scleroderma - at least 15 17 thousand people. These figures were announced at an event dedicated to the problems of orphan diseases, which took place in Moscow on February 25 this year.
At the same time, the level of detection of rare diseases is still very, very far from perfect, therefore the real total number of patients is always higher than the officially declared one. According to some estimates, the total number of Russians suffering from rare diseases is more than a million people.
Why do we write about them today
At the initiative of EURORDIS, the official date for the Day of Rare Diseases is February 29, but in common years, events dedicated to it are held on the 28th. The wider the prevalence of the disease, the more often doctors have a quick and correct diagnosis, patients and their families - to suspect that something is wrong, and to find out how to get treatment and support.
We talked with Sergey Avdeev about orphan diseases, attitudes towards patients and domestic developments in this area. Sergey Nikolaevich made a significant contribution to the treatment of rare diseases - in particular, he developed and introduced into medical practice methods for the diagnosis and treatment of such pathologies as idiopathic pulmonary fibrosis, interstitial pneumonia, lymphangioleiomyomatosis.
Sergey Nikolaevich, how do you get people interested in this topic at all? Rare diseases, so to speak, are a very unprofitable thing - for the pharmaceutical industry, for the bureaucratic apparatus. At the same time, it is clear that drugs must be created, funds must be allocated for patients
- This is really a problem, because there are diseases that either do not have any therapy, or therapy is true, real, effective. How to interest? First of all, it is worth thinking not only about the profits of pharmaceutical companies, but also about the social aspects of the problem. In recent years, solutions have been created for very small groups of patients, that is, for extremely rare diseases.
For example, take Fabry disease, a hereditary disease where effective therapy is available. There are very few patients, but therapy exists. Therefore, we must say that every disease requires attention, every suffering person deserves treatment for this disease. Let's just proceed from universal human values, not economic ones.
How different are the approaches to the treatment and diagnosis of orphan diseases in our country and abroad? Is there something that we have delivered better, or, on the contrary, that it would be worth taking into service?
- Thanks to the exchange of information, we are now in a common field, differences in approach to business disappear. The methods are becoming more or less universal throughout the world. From the point of view of diagnosis, from the point of view of treatment, I cannot say that there are huge differences somewhere. The approaches are very similar, at least in those countries where medicine is quite developed. Russia is the country where, I think, from the point of view of medicine, everything is just fine. Of course, there are a lot of problems in poor and remote regions.
Do young doctors and scientists go to the field of rare diseases?
- They do not come to this area, they are already within the framework of any profession. For example, here I am a pulmonologist, my field of activity is respiratory diseases. Our most frequent illnesses are asthma and pneumonia. But there are such rare diseases of the respiratory system as lymphangioleiomyomatosis, pulmonary alveolar proteinosis. And such patients turn to, they need help. A professional should be able to help patients not only with the most common diseases, but with everyone, everyone deserves attention.
And what happens to the qualifications of doctors in the "lower link". Relatively speaking, a district pulmonologist in a polyclinic?
- Previously, we had only a few professional journals, not enough manuals and medical books. About 15-20 years ago, a doctor improved his qualifications every five years, at a mandatory retraining. Today, there are all the opportunities for continuous and continuing education. If a doctor wants to be a professional - we have people who want to reach the very heights - then there is only one approach: continuous training, continuous education. And today there are all the possibilities for this.
Are there any resources where a doctor can come to improve his skills in the field of rare diseases?
- Of course, there are resources. Any professional community has its own interests in terms of rare diseases. The Russian Respiratory Society, that is, pulmonologists, has a register of patients with lymphangioleiomyomatosis, a register of people with idiopathic pulmonary fibrosis. Together with cardiologists, we are dealing with such a rare disease as pulmonary arterial hypertension.
There are educational programs, there are clinical guidelines, at all major medical events, new information on rare diseases constantly appears, despite the fact that they are rare. For example, at the events of the Russian Respiratory Society, there are constant analyzes and presentations dedicated to rare diseases.
To the question of such events: at a recent event hosted by Boehringer Ingelheim, antifibrotic drugs were discussed for people with orphan lung diseases.Are there any domestic developments in this branch of rare diseases? Are there any breakthroughs in Russian science and medicine?
- For antifibrotic therapy - probably not. In the list of antifibrotic drugs, which are registered in all countries, there are only two drugs. They were created by huge multinational companies, and only these two drugs are used everywhere. Perhaps, in our country, there are searches for such drugs, perhaps they are conducting research. But these studies are not yet visible to me as a clinician. As a rule, we begin to notice such studies in the second and third phases.
But if we talk about - I don't know how about breakthrough, let's say, about new things in drug therapy, then we have such. In the field of antiviral drugs, triazavirin is a good example. Cardiologists probably have more such examples than we do; they have their own Russian-made antiarrhythmic drugs, which are very effective.
If we talk about rare diseases and pulmonology, we can cite as an example such a drug as tigerase, used in the treatment of cystic fibrosis, from the pharmaceutical company Generium. This is a huge achievement: they are capable of producing biosimulants for drugs such as omalizumab (a monoclonal antibody against immunoglobulin E). There are very few, if any, pharmacological solutions of this kind. This is the most complex bioengineered biological preparation. That is, in Russia there are still teams and companies that are capable of doing this.
If you suspect you or someone close to you have such a disease, how not to waste time? Not all first line doctors are so conscientious, and often the district therapist can only offer fluorography. What to do?
- The answer suggests itself - consultation with a qualified specialist in a good place, in a good center. Unfortunately, this can only be provided by large centers of our country, such as Moscow, Petersburg, Novosibirsk, Krasnoyarsk, Irkutsk … In general, there is no single institution that would deal with rare diseases - that is why they are rare. All these diseases are subdivided by profile, so it all depends on the symptoms, depending on which you need to be guided, for example, at the Institute of Cardiology, the Institute of Neurology, and so on.
We say that all these are very expensive things. Is funding for the treatment of patients with such rare diseases and developments in this area improving over the years?
- Of course, there is a lot more to wish for and achieve, but if we talk about rare diseases, then there are a number of orphan diseases that are still financed at the state level. We have a list of orphan diseases, there used to be a list of seven nosologies, today there are 14 of them, the so-called high-cost diseases - for which people are provided with a certain drug therapy.
Well, there are these 14 nosologies, which, although intermittently, are provided financially. But what about a person with a rare disease that is not on the list of diseases covered by government programs?
- Well, here's an example of pulmonary hypertension. There are two similar problems. Idiopathic pulmonary arterial hypertension is on the list of rare diseases, and all treatment is funded by the state, from the federal budget. Another disease is chronic thromboembolic pulmonary hypertension, a disease similar in symptoms and course, but not on this list. We are trying with all our might to ensure that she was included in the list, but so far this has not happened.
What are the ways out of the situation? Obtaining a disability group, then the patient will have access to the drug according to the ONLS system. The most important thing is that the patient does not abandon the social package (it includes drugs paid for by the budget and free for a patient with a disability, prescribed by a doctor.In case of refusal from the social package, a person loses the right to free medicines, but receives a small increase in his pension. - Approx. ed.). Unfortunately, many refuse the social package, winning an additional 700 rubles a month.
How can help for people with rare diseases be improved? What do you think can be changed?
- We need to change the system of providing our patients. If I were responsible for this, there would be more diseases in the list of orphan diseases, which are completely covered by drugs at the expense of the state. I would like more of these diseases to be recognized at the official level. Then all the other problems on the way to the drug in patients would be less. As for the rest, as for the fundamental transformations of the system, somewhere there is insurance, somewhere a state guarantee - there is no single way and cannot be.
What advice can be given to patients and their relatives to improve their emotional state after diagnosis, during treatment?
- Talk to a specialist. Today it is a universal recipe. There is no need to keep all the questions to yourself or search for answers on the Internet. A health care professional can advise on both treatment and nutrition, as well as behavior. Of course, a person who first encountered his diagnosis can go to a psychotherapist for emotional support, but professional clarification from a specialist should be put first.
Has the qualitative composition of patients with rare diseases changed over the period of your practice? You know, it is often said about some diseases that they have become "younger" - are there any such examples? Have any orphan diseases become less common?
- On the contrary, I would say that the patients have become older. Take the same cystic fibrosis - unfortunately, before it was a fatal disease and not so many patients lived to be at least 20 years old. Thanks to modern methods of therapy, the average age of patients with cystic fibrosis in our country is approaching 40 years. But I cannot name orphan diseases that would become less common.
Has there been a general increase in the number of patients with rare diseases in general, and if so, how can this be explained? Are there any factors, maybe the environment?
- Yes, it is. The basic factor here is improved diagnostics. Our understanding of the processes and diagnostic methods are becoming more and more perfect, and, accordingly, there are also more identified patients with rare pathologies.
What advice can you give to a person living in a big city? Take, for example, the recent "black sky regime" in Krasnoyarsk. Is it possible to keep your lungs healthy? Does this influence increase the risk of developing orphan diseases?
- Unfavorable ecology is a risk factor for many diseases - both rare and frequent, this is Punchinel's secret. What tips? It would be nice to change your place of residence, but this is not always possible. If any symptoms begin to appear, fears arise - it is worth consulting a doctor.
Now people are changing their way of life. Have there been any new triggers of orphan diseases in connection with this - for example, the same vaping?
- So I just thought about him. This is a new type of smoking, albeit with a slightly different technology - heating tobacco products and, somewhere, marijuana instead of burning. But in the United States alone, over the past year, there have already been 60 deaths from vaping. Smoking is always dangerous, and new types of smoking are new dangers and new triggers.
Are there any medical interventions or concomitant diseases that affect the likelihood of orphan diseases?
- It is difficult to say specifically about orphan diseases, but, of course, there are many examples of the influence of one disease on another. For example, lung cancer against the background of a previous illness, the result of which was fibrosis.
Can medical interventions somehow, on the contrary, help prevent these diseases? For example, can vaccination, by preventing certain lung diseases, indirectly help prevent orphan lung diseases?
- Regardless of the development of background diseases, vaccinations are an absolute good. They started talking about vaccination again in a positive sense, thanks to the coronavirus, and meanwhile the vaccines that we know today - for influenza, for pneumococcus - are absolutely safe drugs, and the benefits from them are enormous. In recent years, I don't even remember when I saw any side effects after being vaccinated. Therefore, here is just a very good example of a procedure that can prevent many diseases that accompany the main one as complications.
Healthy people do not have a very good idea of life with a rare ailment and are unlikely to go to events organized by professionals for professionals. There is a lot of talk about how this contributes to the isolation of patients
- Should healthy people have an interest in diseases in general is a difficult and debatable question. I believe that in modern society there should be an understanding of this. Here's a simple example: how many ordinary people know about a disease like COPD (chronic obstructive pulmonary disease. - Ed.)? I'm not sure. Here is bronchial asthma - yes, a recognizable example. At the same time, COPD is a more dangerous disease, socially unfavorable, associated with risk factors that can simply be prevented - with smoking. Therefore, there should be information about such diseases, about methods of struggle and prevention in society.
Thank you very much for the interview. What would you, as a doctor, wish our readers in the end?
- I would like to wish your readers not just health, but really be attentive to their health. Fortunately, we have every opportunity to follow it.