Pavel Novikov rheumatologist making an appointment. Philosophical, theological and deontological problems of palliative medicine

Pavel Novikov on the preservation of traditions and the latest advances in modern rheumatology

Position: rheumatologist, head of the rheumatology department of the Clinic of Nephrology, Internal and Occupational Diseases named after E. M. Tareev, University Clinical Hospital No. 3 of the First Moscow State Medical University named after I. M. Sechenov, assistant of the Department of Internal, Occupational Diseases and Pulmonology of Medical and Preventive Medicine Faculty of the First Moscow State Medical University named after I. M. Sechenov

Hobbies: science, board games

Marital status: married, two sons

In the life of every person there comes a moment when significant efforts are required to maintain an active quality life. Pavel Igorevich Novikov often says these words to his patients, trying to set them up for treatment. Despite his youth, the doctor looks like a great scientist. Arriving to study in Moscow from a small Belarusian town, he is an example of a real intellectual, an educated person and focused on his work.

KS: Pavel Igorevich, when did you move from Belarus to Moscow?

Pavel: I started my studies at the Gomel Medical Institute, and after the second year I applied to the faculty of training scientific and pedagogical personnel of the I.M. Sechenov Moscow Medical Academy. He passed the selection tests successfully, and from the third year he continued his studies in Moscow. In the same place, at the First Moscow State Medical University, he completed residency in internal medicine and received a certificate in the specialty of rheumatology.

KS: When did you decide to specialize in rheumatology?

Pavel: In the third year, classes in propaedeutics began at the Department of Internal and Occupational Diseases at the E. M. Tareev Clinic. Since the main area of interest of my teacher, Oleg Gennadyevich Krivosheev, was in the field of rheumatic diseases, I also continued to deal with the problems of systemic vasculitis, having received a specialization in rheumatology. Over time, these observations and analysis of the experience of the Clinic formed the basis of my PhD thesis.

KS: Could you please tell us more about what your thesis is about?

Pavel: My thesis is about granulomatosis with polyangiitis (Wegener's granulomatosis). Our Clinic has been dealing with the problem of systemic vasculitis for more than 50 years. I analyzed the change in the clinical picture, course, therapy and outcomes in patients who came to the clinic over the past ten years, and those patients who were observed in previous years.

Thanks to increased physician awareness, improved diagnostics, and perhaps also due to an increase in the incidence, the number of patients over the past few years is comparable to and even exceeds that of the previous four decades. Therefore, the comparison of these data was, it seems to me, important and worthy of interest. I hope that this systematized experience will result in improved patient management in the future.

KS: Has the prognosis for this category of patients changed over 50 years?

Pavel: We can say with confidence that the effectiveness of therapy has grown. The life prognosis for patients has improved significantly, and now, with the correct use and individual selection of immunosuppressive therapy, we expect that their life expectancy will differ little from that of healthy people comparable in sex and age. This question is, in fact, the most common among patients. Especially when they read online that life expectancy can be as little as 8-16 months after diagnosis.

Of course, the quality of life of a patient with a severe chronic disease always suffers to some extent. A patient with a systemic rheumatic disease needs to regularly monitor tests, be observed by specialists depending on the affected organs, and adjust treatment with a rheumatologist. However, now a person can maintain both labor activity and an acceptable quality of life.

CS: What should the primary care physician do if an autoimmune process is suspected in a patient with articular syndrome?

Pavel: It depends on the specific clinical situation and the qualifications of the doctor. There are a lot of tests for rheumatic diseases, and each of them answers certain questions. However, there is no general screening for systemic rheumatic diseases, including systemic vasculitis, lupus, and scleroderma. The main question is what specific clinical symptoms led the doctor to suspect the autoimmune nature of the pathological process.

For example, if rheumatoid arthritis is suspected, it would be logical to evaluate the ESR, check the level of C-reactive protein, rheumatoid factor, and antibodies to cyclic citrullinated peptides. And the rest of the examination in the presence of clinical and laboratory signs of an active process, it is advisable for the patient to continue with a rheumatologist.

KS: How is the flow of patients to the E. M. Tareev Clinic formed?

Pavel: We have a federal medical institution, which is directly part of the structure of the Ministry of Health of the Russian Federation. The clinic can examine patients from all over the country who have a compulsory medical insurance policy. If the patient has a referral from the polyclinic, then he can apply for an appointment with the clinic's general practitioner or rheumatologist for an initial consultation.

If there is no referral, the patient can make an appointment for a paid appointment with the same specialists. If indications for hospitalization are revealed at a paid appointment, then hospitalization is carried out free of charge under the CHI policy.

KS: What is the indication for hospitalization specifically in your department?

Pavel: Indications for hospitalization are quite standard. Most importantly, we must be sure that we can help the patient. If I understand that the patient is a non-core patient, that doctors of another specialty can help him better, then I will explain this. It must be understood that rheumatic diseases are chronic. The vast majority of problems can and should be dealt with on an outpatient basis. But the beginning and selection of therapy, when the risk of undesirable effects is high, is best done in a hospital setting.

KS: What diseases are the most relevant for your department?

Pavel: We have accumulated the greatest experience in systemic vasculitis in Russia, significant even on the scale of world medicine. This is about a third of the department's patients. The second third are patients with diffuse connective tissue diseases such as systemic lupus erythematosus, systemic scleroderma, dermatopolymyositis, and Sjögren's disease. And another third of patients from the category of so-called articular rheumatology (rheumatoid arthritis, ankylosing spondylitis - Bechterew's disease, etc.). We have relatively few patients with degenerative joint diseases. We practically do not deal with osteoarthritis.

KS: How well are the causes of autoimmune diseases now studied?

Pavel: Understanding of the causes is increasing, but, unfortunately, for most of these diseases, we cannot yet establish the cause. There are predisposing genetic factors. However, we must clearly understand that autoimmune diseases are not inherited. And if the child of our patient has no complaints, then no additional studies are needed in addition to the standard observation by a pediatrician. Moreover, there are no specific ways to prevent inflammatory rheumatic diseases. Here, as in medicine in general, maintaining a generally accepted healthy lifestyle is important.

KS: Are there screening studies for aggravated heredity?

Pavel: We cannot prescribe specific tests for everyone, because the same antinuclear factor, depending on the titer, occurs in 3-6% of people in the general population. And if we get a positive result without clinical manifestations, then it will not have any practical application. On the contrary, it will be harmful, because in this case we will completely unreasonably "scroll" the patient through various specialists and examinations. And the patient will receive useless significant stress and an unreasonable risk of complications during medical manipulations. Therefore, asymptomatic screening for rheumatological diseases is not currently developed, applied or recommended.

KS: What has changed in recent years in the approach to the treatment of these serious diseases?

Pavel: Significant progress. First of all, this is an individualization of approaches to therapy. In the past, for example, very high doses of cyclophosphamide and glucocorticoids were used to treat systemic vasculitis, at a very significant cost in terms of side effects. Now, scientific and practical data have been obtained that justify the appointment of "weaker", respectively, safer regimens of therapy for patients without severe lesions of internal organs, especially upon reaching remission.

Over the past fifteen to twenty years, genetically engineered biological preparations have become quite widespread. These drugs specifically neutralize inflammatory cytokines, helping patients who do not respond well to conventional antirheumatic drugs.

Pavel: In the direction of targeted (targeted) therapy, the mechanism of which is briefly as follows. A key molecule or group of molecules is established in various diseases, and then we try to influence them with antibodies. There is a neutralization of the molecules involved in pathogenesis. The main focus in rheumatology is now on clarifying the specific mechanisms of disease and creating antibodies that act on them. The same approach to treatment is widely used in oncology, cardiology, and hematology. In general, now the topic of monoclonal antibodies is a hot spot in all areas of medicine.

Pavel: We must understand that the use of these drugs has raised its own layer of problems. First, they have their undesirable effects. Secondly, genetically engineered biological preparations, like traditional approaches to therapy, affect the mechanism of the disease, often at the later stages of pathogenesis, so they provide only temporary control of activity, and the disease may return when therapy is discontinued. Finally, they are expensive, although they can be obtained free of charge in most regions with a disability and a strict indication. These drugs are only needed for patients who do not respond to traditional medicines or who have unacceptable side effects of traditional medicines.

In most patients, proven standard treatment regimens, when used correctly, successfully control rheumatic diseases.

KS: How is the rheumatology service going through the era of reorganization of Russian medicine?

Pavel: I believe that almost everything that is in world medicine is available in Russia. The vast majority of drugs are available, there is complete information on treatment regimens. Of course, there are objective difficulties. The cost of monthly treatment with "biological" preparations is from 50 thousand rubles, but if there are indications, appropriately executed documents, the patient can receive these drugs free of charge. It is very important to use the available resources efficiently.

State mechanisms to meet the patient's needs for such treatment exist, although the availability of treatment varies from region to region. Our task, as a federal center, is to give recommendations and rationale so that the patient receives therapy for all the necessary time. Then the patient is observed by doctors at the place of residence, and comes to us to decide on a strategic change in therapy.

KS: Does busy work interfere with family relationships?

Pavel: No, it doesn't. My wife Olga is an ophthalmologist and is now continuing her postgraduate studies. But we do not like to discuss medical issues at home and find other interesting topics for communication. First of all, they concern our children. We have two sons, Fedor and Stepan, they are nine and four years old respectively. We try to get out with the whole family to performances in theaters, to movie screenings, at home we often play board games. Fedor is additionally studying English, Stepan likes choreography classes. I want them to grow up, first of all, as good responsible people and find an exciting profession for themselves. And I try to be a good example for them.

KS: What are your goals for the next decade?

Pavel: First of all, I am a practitioner, so the first goal is to continue to lead the rheumatology department. As an independent department, it was established in 2013, so the task is to further improve rheumatological care in our multidisciplinary hospital.

My separate concern is to increase the awareness of patients through the main specialists about our work, about modern approaches to treatment.

Another challenge is to expand international cooperation. Since the clinic has been dealing with rare diseases for many years, a lot of experience has been accumulated, which needs to be updated and demonstrated in Russia and in the world. There are also plans to grow a galaxy of young rheumatologists, so we now have a lot of graduate students. With the whole team, I hope we will continue the glorious traditions of the therapeutic and rheumatological school of Evgeny Mikhailovich Tareev.

12/27/2018 I underwent surgery to release the ulnar nerve on my left arm. The operation was performed with the golden hands of a very cool neurosurgeon Alipbekov Nasip Nuripashaevich. This doctor knows how to find an approach to each patient, easily makes contact in discussing treatment methods, takes into account the wishes of the patient. Moreover, he is excellent at endoscopes! In another hospital, they insisted on a strip operation with a 10 cm suture. Sechenov in the Clinic of Nervous Diseases. A. Ya. Kozhevnikova Alipbekov Nasip Nuripashaevich performed the operation with an endoscope, leaving a suture, only 2 cm. After the operation, sensitivity immediately appeared in the 5th and 4th fingers and numbness practically disappeared. The postoperative period went smoothly.
Nasip Nuripashaevich, thank you very much!

In the summer of 2018, I faced severe pain in my left leg and back. At first I thought that I had a cold in the sciatic nerve, but after an MRI it turned out that it was a herniated disc L4-L5. Conservative treatment generally helped to relieve severe pain, but after the treatment, the pain still remained, albeit in a subdued form, until the next acute attack. After the 3rd such attack, and there were three of them in 2 months, it became clear that it was necessary to turn to a neurosurgeon for help.
On the recommendation of a friend who had an operation here in the Department of Neurosurgery several years ago and was very pleased with the treatment, I signed up for a consultation with the head of the department, Rosen Andrey Igorevich (my wife traveled, since I practically did not move myself). After the consultation, Andrey Igorevich suggested that I go to the department for an examination, which I did on September 12, 2018, having previously done all the medical tests and tests necessary for hospitalization. I was sent to the attending doctor Alipbekov Nasip Nuripashaevich in ward 415. After studying my medical examinations and conducting additional, as well as repeatedly discussing my situation at consultations, the doctors diagnosed me with lateral stenosis of the spinal canal at the level of L4-L5 and decided on surgical treatment. On September 17, 2018, I was operated on by N. N. Alipbekov, who performed decompression of the spinal canal at the level of L4-L5 on the left, i.e., removed the herniated disc L4-L5, which was compressing the nerve root, which made my left leg. The operation went well and on the second day I was on my feet. On October 4, 2018, I was discharged from the department and now I am undergoing a postoperative rehabilitation period. Those wild pains in my left leg that tormented me before the operation are NO, and this fact is very pleasing! I express my HUGE gratitude to the entire team of the neurosurgical department for the highest professionalism and knowledge of their business, for attentiveness and care, for empathy and an individual approach to each patient!
Special thanks to the neurosurgeon who treated and operated on me - Alipbekov N.N.! Nasip Nuripashaevich is the most talented, extremely able-bodied, sensitive, patient and very attentive doctor! A true professional in his field!
I am very grateful to the head of the department, Rosen A.I., for giving me the opportunity to be examined and treated in the department of the NCT of the Clinic for Nervous Diseases named after. A. Ya. Kozhevnikova! Andrei Igorevich is a kind, sympathetic, high-class doctor and, moreover, an excellent manager who has created an excellent team and professionally manages it! The atmosphere reigning in the department is wonderful and conducive to a successful cure and a quick return to a full life!
Many thanks to the neurosurgeon Mikhail Grigorievich Zonov for the high-quality and fast preparation for the operation, the anesthesiologist Lyudmila Anatolyevna Kenzhekulova for the excellent preparation for the operation and her professional support, the instructor of the exercise therapy Kameneva Lyudmila Genrikhovna for the high quality and extremely necessary instructions on postoperative rehabilitation, as well as everything to medical staff and employees of NHO and resuscitation!
May God grant good health to all employees of the neurosurgical department, success in your difficult and so necessary profession, happiness and good luck in life!

We know firsthand about Korsakov's clinic in Mytishchi, it was here that our son recovered from alcohol addiction and became a real person! Before that, they turned to other clinics and it was just money down the drain (I won’t say the names of the clinics, let it remain on their conscience). But they skillfully blew dust in the eyes! We arrived at Korsakov's clinic, the head doctor Kazantsev received us there and calmly explained what and how. We talked about the treatment program. We complained to him about previous clinics and told him everything, we no longer trusted anyone. Kazantsev listened and said that it really was not a treatment, but just to rip off money. And in the Korsakov clinic, the methods are completely different and they treat their patients. We still had a few doubts, but when the son returned to us healthy and for six months he had not even drunk a bottle of beer, then what doubts could there be! Only gratitude!

The problem of invasive mycoses in rheumatology (part I)

B.S. Belov, O.N. Egorova, G.M. Tarasova, M.V. Polyanskaya, R.M. Balabanova

Research Institute of Rheumatology RAMS, Moscow

In modern rheumatology, the problem of invasive mycoses is becoming increasingly important. Doctors are noted to be slightly wary of fungal infections in patients with systemic rheumatic diseases, the complexity of life-time diagnosis, and the difficulty of therapy. The significance of this problem increases significantly due to the active introduction of biological agents into clinical practice, primarily inhibitors of tumor necrosis factor a (infliximab, adalimumab, etanercept), which is accompanied by an increase in the risk of developing opportunistic infections. The first part of the review provides information on various aspects of systemic aspergillosis, including the tactics of its diagnosis and rational therapy.

Key words: rheumatic diseases, aspergillosis, diagnosis, treatment.

Contacts: Boris Sergeyevich Belov [email protected]

THE PROBLEM OF INVASIVE MYCOSES IN RHEUMATOLOGY

B.S. Belov, O.N. Egorova, G.M. Tarasova, M.V. Polyanskaya, R.M. Balabanova

Research Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow

The problem of invasive mycoses is becoming ever more urgent in modern rheumatology. The fact that physicians are unalert to mycoses in patients with systemic rheumatic diseases and that there are difficulties in their lifetime diagnosis and treatment is noteworthy. The significance of this problem substantially increases with the active clinical introduction of biologicals, primarily tumor necrosis factor a inhibitors (infliximab, adalimumab, etanercept), which goes on concurrently with the increasing risk for opportunistic infections. Part I presents information on different aspects of systemic aspergillosis, including the tactics of its diagnosis and rational therapy.

Key words: rheumatic diseases, aspergillosis, diagnosis, treatment.

Contact: Boris Sergeyevich Belov [email protected]

Infectious pathology still remains one of the most urgent problems in medicine, requiring the attention of physicians of various specialties, including rheumatologists. Infectious diseases often complicate the course of many rheumatic diseases (RD) and occupy the 2nd-3rd place among the causes of death in these patients.

In recent years, there has been a clear upward trend in the number of mycotic infections. Yeasts and molds are among the 10 most frequently detected pathogens in clinics, and they are ranked 5th (17.1%) in intensive care units. Approximately 7% of fevers of unknown origin are caused by fungi, and in oncohematology, the frequency of invasive fungal infections reaches 50%.

Mortality in invasive mycoses remains high. Even with timely systemic antifungal therapy, approximately 40% of patients die from an infection caused by fungi of the genus Candida. With aspergillosis, mortality is about 70%, and in patients with persistent neutropenia - 100%.

The problem of invasive mycoses in rheumatology in modern conditions is very acute. In recent years, individual reports have appeared more and more often.

studies and a series of observations of patients suffering from systemic connective tissue diseases, primarily systemic lupus erythematosus (SLE), with the development of comorbid invasive mycoses (aspergillosis, candidiasis, etc.). At the same time, the main risk factors for the occurrence of invasive fungal infections in SLE include a high degree of disease activity, granulocytopenia, the presence of a bacterial infection and the use of antibiotics, as well as treatment with glucocorticoids (GCs) and immunosuppressants. There is a slight alertness of doctors regarding mycoses in these patients, the complexity of life-time diagnosis, the difficulties of therapy, which may be due to the multi-organism of fungal infection.

The active introduction of biological agents into clinical practice, primarily inhibitors of tumor necrosis factor a - TNF a (infliximab, adalimumab, etanercept), and the associated increase in the risk of developing opportunistic infections significantly increase the importance of the problem of invasive mycoses in rheumatology. Therefore, it is so important that rheumatologists have up-to-date information about systemic mycoses, in particular, about their diagnosis and rational therapy.

Aspergillosis

It is most commonly caused by the fungus Aspergillus fumigatus. In recent years, there has been an increase in the frequency of isolation of other representatives - A. flavus, A. niger, A. ferrens, etc. The spores of these fungi are ubiquitous, their number increases significantly in hot and humid weather. In most cases, infection occurs through the upper respiratory tract, the infection can also penetrate through damaged skin and intestines.

Aspergillus causes lesions traditionally classified as invasive, saprophytic, and allergic. Invasive forms include damage to the lower respiratory tract, sinusitis, as well as infections of the skin and soft tissues, which may represent the entry gate for the etiotropic agent. Damage to the central nervous system, cardiovascular system, other organs and tissues may be observed due to hematogenous dissemination or direct spread from closely located foci. Saprophytic lesions include otomycosis and pulmonary aspergilloma. Allergic forms are represented by allergic aspergillus sinusitis and allergic bronchopulmonary aspergillosis.

Lung involvement occurs in aspergillosis in about 90% of cases. At the onset of the disease in 1/3 of patients, invasive pulmonary aspergillosis (IPA) may be asymptomatic, and the first signs appear only with the progression of mycosis. The earliest symptoms are cough (initially dry) and fever resistant to broad-spectrum antibiotics. In the future, shortness of breath joins, “pleural” pains in the chest appear (due to fungal invasion into the vessels, leading to multiple pulmonary infarctions) and hemoptysis, usually moderate, although in some cases massive is possible. It should be borne in mind that during GC therapy, body temperature may be sub-febrile or normal, and pain syndrome is minimally pronounced. Perhaps the development of spontaneous pulmonary bleeding due to the formation of decay cavities in the lungs.

Chest x-rays in the early stages of IPA are nonspecific. Usually, focal rounded seals, infiltrates presenting to the pleura, resembling pulmonary infarcts, cavity formation, and rarely pleural effusion are detected. Computed tomography (CT), especially high resolution, is much more informative. A typical CT picture of IPA is multiple nodes and a “corolla” or “halo” symptom, which is a rarefaction zone around a focal lung tissue defect. A little later, a symptom of a “sickle” or “crescent” appears, which is represented by a crescent-shaped enlightenment in the area

sti node due to compression of necrotic tissue. It must be borne in mind that the halo symptom may occur with bronchoalveolar carcinoma, bronchiolitis obliterans, eosinophilic pneumonia, or other mycoses.

How to interpret the allocation of Aspergillus from sputum depends on the immune status of the body. In patients with a normally functioning immune system, the isolation of Aspergillus spp. from sputum in the vast majority of cases indicates colonization, and antifungal therapy, as a rule, is not indicated for them, but additional studies should be carried out to rule out IPA. In immunocompromised patients, the isolation of Aspergillus spp. from sputum is an important indicator of an invasive process. At the same time, a negative sputum test is observed in 70% of patients with confirmed IPA.

The “gold standard” for diagnosing IPA remains histological examination of lung tissue biopsy obtained by thoracoscopy or open biopsy. However, histological confirmation is not always possible in critically ill patients with immunosuppression, granulocytopenia, or other contraindications for biopsy. In such patients, in the presence of clinical symptoms or new infiltrates in the lungs, the isolation of Aspergillus from bronchoalveolar lavage is sufficient to initiate therapy.

An important role in the diagnosis of IAL is played by the determination of the galactomannan antigen. Galactomannan is a polysaccharide component of the cell wall and is released during the growth of Aspergillus. Serum galactomannan can be detected on average 5-8 days before the onset of the first clinical symptoms, changes on chest x-rays, or positive cultures of the fungus.

According to a meta-analysis of studies evaluating the effectiveness of the galactomannan test for the diagnosis of IPA, its sensitivity and specificity were 71 and 89%, respectively. The negative predictive value ranged from 92-98%, positive - 25-62%. The authors conclude that the test for galactomannan is more informative in patients with malignant hemoblastoses or hematological transplant recipients than in patients who have undergone solid organ transplantation or patients without neutropenia. The sensitivity and specificity of the galactomannan test may change with certain drugs. False-positive reactions have been demonstrated in patients treated with piperacillin/tazobactam and amoxicillin/clavulanate due to the presence of galactomannan in these antibiotics. The same reactions were observed within 5 days after discontinuation of β-lactam therapy. Feelings

the validity of the test is also reduced during antifungal therapy.

When determining Aregn-ish-DNA during the polymerase chain reaction (PCR) in patients with IAL, ambiguous results were obtained - sensitivity 67-100 and 100%, specificity - 55-95 and 65-92% for samples of bronchoalveolar fluid and blood serum, respectively. This method does not distinguish between colonization and active infection. Moreover, PCR is performed only in specialized laboratories and cannot be considered as a routine study.

Determination of another component of the fungal wall - 1,3-beta-D-glucan - is a highly sensitive and specific test for the detection of deep invasive mycoses, including candidiasis, fusarium and aspergillosis, but its diagnostic value in patients without neutropenia and in recipients of allogeneic stem cells, included in the high-risk IAL categories is unclear.

The Mycosis Research Group of the European Organization for Research and Treatment of Cancer has proposed criteria for the diagnosis of invasive mycosis. Diagnostic criteria for IAL are presented in Table. 1. It is emphasized that the category of "proven" diagnosis can be applied to any patient. "Probable" and "possible" diagnoses of IPA are valid only in patients with immunodeficiency.

Table 1. Diagnostic criteria for IAL

responsibly), as well as a higher 12-week survival (71 and 58%, respectively).

In neutropenic patients, voriconazole is given intravenously at 6 mg/kg twice daily for 1 day, then 4 mg/kg twice daily. With the improvement of the clinical condition of the patient after 7 days of therapy, they switch to oral administration of the drug 200 mg 2 times a day. In the absence of neutropenia (the number of neutrophils> 0.5 10 9), it is recommended to start treatment with an oral form.

The main contraindication for the appointment of voriconazole is hepatic porphyria. It should also be borne in mind that voriconazole is a substrate and inhibitor of the cytochrome P2C19, P2C9 and P3A4 systems, therefore, the development of undesirable drug interactions with drugs such as cyclosporine, warfarin, carbamazepine, terfenadine, rifampicin, statins, etc.

If there are contraindications to the use of voriconazole, caspofungin is used as the drug of choice for IAL. Amphotericin B is used as a first-line drug for IAL is extremely rare due to its lack of efficacy and high toxicity, primarily nephrotoxicity, the likelihood of which is associated with the total dose of the drug.

If after 7 days of treatment in a patient with IPA, CT shows negative dynamics in the lungs (an increase in the primary focus or the appearance of new

Diagnosis of IAL Criteria

Proven Detection of mycelium in histological and cytological examination of lung tissue obtained by

needle biopsy, or the presence of relevant tissue changes in the biopsy, or the seeding of Mreg & Ft-culture from samples taken during a sterile procedure from unchanged parts of the lungs and sites clinically and radiologically consistent with infection (excluding bronchoalveolar lavage)

Probable Presence of host factors* + clinical criteria** + plus microbiological criteria***

Possible Presence of macroorganism factors* + clinical criteria**

*Macroorganism factors: neutropenia, transplantation of hematopoietic stem cells and solid organs, oncological diseases, long-term and high-dose GC therapy (> 0.3 mg / kg / day in terms of prednisone for > 3 weeks), treatment with other T-cell- other immunosuppressive agents, including cyclosporine, TNF-a inhibitors, specific monoclonal antibodies (eg, alemtuzu-mab) or nucleoside analogues within the previous 90 days, chronic granulomatous disease, severe combined immunodeficiency states.

**Clinical criteria - one of the three signs identified on CT: a) a dense, well-defined lesion (foci) with or without a "corolla" symptom, b) a "half-moon" symptom, c) cavity formation.

***Microbiological criteria: a) Aspergillus-positive results of cytological, microscopic or cultural studies of sputum, bronchoalveolar fluid, brush biopsy specimens, b) positive test for galactomannan in serum or bronchoalveolar fluid.

IAL treatment is prescribed immediately if invasive aspergillosis is suspected, i.e. until culture results are obtained. Voriconazole is the drug of choice for all cases of IPA. Large prospective randomized trials have shown that patients with IPA who received voriconazole as initial therapy had a significantly better response over 12 weeks of treatment than those treated with amphotericin B (53% vs.

foci) and at the same time fever persists, caspofungin is added to voriconazole or, in its absence, amphotericin B. When the process stabilizes (a decrease in the number of foci by 50%), voriconazole therapy is continued.

The criteria for discontinuation of antimycotics in IPA are the absence of clinical manifestations of infection and the regression of foci on CT scan of the lungs. The duration of the course of treatment is 1-3 months.

Immunomodulatory therapy (colony stimulating factor, interferon y) may be prescribed to reduce the degree of immunosuppression and as an adjunct to antifungal treatment of IAL.

With the development of IAL in patients with SLE, rheumatoid arthritis (RA) and other systemic RD, modification of the therapy of the underlying disease is required. It is advisable to temporarily cancel cytostatics and TNF-a inhibitors, and reduce the dose of GC (if it is impossible to cancel them) to the minimum, which allows controlling the activity of the inflammatory process. Unfortunately, the lack of studies on the prevention and treatment of IPA in these patients does not allow specific recommendations to be made.

Chronic necrotizing pulmonary aspergillosis (CNAL) is a special form of pulmonary aspergillosis, characterized by a slowly progressive course, low frequency of invasion and dissemination of the pathogen to other organs. CNAL usually develops in mature and elderly people with background chronic lung diseases (chronic obstructive diseases, previous tuberculosis, consequences of operations, etc.), as well as in patients with moderate immunodeficiency due to diabetes mellitus, alcoholism, rheumatic diseases (RA, ankylosing spondylitis ), as well as with long-term HA therapy at low doses.

The main complaints in patients with CNAL are fever, weight loss, malaise, fatigue, prolonged productive cough and hemoptysis, which vary from mild to moderate severity. Occasionally there is an asymptomatic course.

Chest x-rays and CT scans usually show pleural induration and thickening, with cavities forming in the upper lobes of the lungs, up to and including a bronchopleural fistula.

Diagnostic value of bronchial or percutaneous puncture biopsy in relation to Table 2. Diagnostic criteria for CVD

Diagnostic criteria

Clinical:

prolonged (> 1 month) pulmonary or systemic symptoms, including at least one of the following: weight loss, productive cough, hemoptysis

X-ray:

cavity pulmonary lesions with the presence of paracavitary infiltrates; the formation of new cavities and their increase in size over time

Laboratory:

elevated levels of inflammatory markers (ESR, CRV). Isolation of Aspergillus spp. from the lung or pleural cavity or a positive precipitation test for Aspergillus. Exclusion of other pulmonary pathogens (using microbiological and serological testing), including mycobacteria and endemic fungi, which may cause similar symptoms

low, so they are rarely carried out. Patients with CNAL often have late diagnosis, which leads to increased morbidity and mortality. In this regard, a high “alertness index” of the doctor is extremely important for early diagnosis, especially in the presence of characteristic clinical and radiological manifestations.

In table. Table 2 presents diagnostic criteria for CNAL, which may be useful for early recognition of the disease and improving the prognosis in these patients.

In accordance with the recommendations of the Infectious Diseases Society of America (IDSA), the most reasonable approach to the treatment of CNAL is the appointment of oral forms of itraconazole at a dose of 400 mg / day. Voriconazole is also effective, but publications on its use in this form of aspergillosis are much less. Oral forms of the drug are preferable because of the need for long courses of treatment (up to 24 weeks).

Aspergilloma (mushroom lump) is the most common and most recognizable form of lung lesions caused by Aspergillus fungi. It consists of fungal mycelium, inflammatory cells, fibrin, mucus and tissue detritus. Usually develops in an already formed cavity in the lung. The formation of aspergilloma has been described in patients with tuberculosis (most often), sarcoidosis, bronchiectasis, ankylosing spondylitis, neoplasms, and pulmonary infections.

In some cases, aspergilloma is asymptomatic. In the presence of clinical symptoms leading is hemoptysis. Perhaps the development of life-threatening bleeding from the bronchial vessels. Cough, shortness of breath and fever are less common, which may be more associated with underlying pulmonary pathology or bacterial superinfection in the lung cavity. On radiography, pulmonary aspergilloma is a round, sometimes mobile formation with a round or oval cavity and an air meniscus along the periphery. Similar radiological manifestations can be observed in other diseases, such as hematoma, tumors, abscess, echinococcosis and Wegener's granulomatosis, and aspergilloma can be combined with them. Isolation of Aspergillus culture from sputum is possible only in 50% of cases. Serum IgG antibodies to Aspergillus may be negative in GC treatment. Antifungal therapy using itraconazole, voriconazole, and possibly posaconazole may be beneficial with relatively minimal risk. In selected patients with solitary aspergilloma, surgical resection or intracavitary antifungal therapy may be indicated.

One of the most serious complications of IAL is CNS damage, the lethality of which exceeds 90%.

In the literature, there are descriptions of cases of the development of aspergillus pathology of the central nervous system in patients with SLE. Unlike candidiasis and CNS cryptococcosis, aspergillosis is more characterized by focal neurological lesions and convulsive syndrome. With dissemination of infection from the paranasal sinuses, especially from the ethmoid bone, the frontal and temporal lobes of the brain, the cavernous sinus, and even the internal carotid artery may be involved in the process. The detection of the galactomannan antigen in the cerebrospinal fluid improves the reliability of the diagnosis and helps to avoid invasive procedures for histological verification of the diagnosis. For the treatment of this form of aspergillosis, voriconazole is the most preferred, the effectiveness of which has been demonstrated in a number of studies. The high mortality rate in this pathology, in addition to antimycotic therapy, necessitates surgical resection of the affected areas. Other therapies have been proposed, including higher doses of a single antimycotic, combinations of antifungals, and immunomodulators. However, there are no data from prospective controlled clinical trials proving the advantages of these methods over standard monotherapy.

Focal extrapulmonary invasive aspergillosis can occur as an infectious lesion of a specific organ or be a manifestation of a disseminated infection. Based on the results of randomized trials, GOBA experts recommend using voriconazole for initial therapy of extrapulmonary forms of IA. When appointing al-

alternative drugs can be guided by the principles of treatment of IPA.

Primary prevention involves the administration of antifungal drugs to patients who do not have symptoms of a fungal infection, but the epidemiological profile indicates a high likelihood of invasive aspergillosis. However, the allocation of risk groups to prevent the development of this infection is still one of the problems. In relation to rheumatology, this may include patients receiving high-dose GC therapy (1 mg/kg prednisolone per day for at least 2-3 weeks), cytotoxic drugs and TNF-α inhibitors, but recommendations regarding specific doses and regimens are on absent today. In patients with hematological diseases accompanied by neutropenia, itraconazole administered intravenously and per os in the form of a solution had a certain effect on reducing the incidence of invasive aspergillosis, but the use of this drug is limited due to its dose-dependent toxicity. Prophylactic clinical studies are currently underway with voriconazole, but the final results have not yet been published.

In conclusion, we note that the emergence of new antifungal drugs with greater activity and better tolerance has significantly improved the outcomes of treatment of patients at risk of severe Aspergillus infection. However, there are still many issues that need to be addressed, in particular, the development of methods for the early detection of an infectious process, the assessment of disease outcomes, the treatment of progressive or refractory Aspergillus infection, and the identification of groups of patients in whom aspergillosis prophylaxis would be most effective.

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et al. Voriconasole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002;347:408-15.

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Rheumatoid hand (part I)

Yu.A. Olyunin, A.V. Smirnov

Research Institute of Rheumatology RAMS, Moscow

At an early stage, the symptoms of rheumatoid arthritis (RA) are mainly represented by signs of inflammation of the synovial membrane of the joints. On examination, there is a change in the configuration of the joints, local pain on palpation, as well as impaired function. One of the earliest and most characteristic radiological manifestations of polyarthritis is periarticular osteoporosis (OP). Narrowing of the joint spaces is one of the most important radiological symptoms. It reflects the destruction of the articular cartilage and is taken into account when assessing the progression of the pathological process. The most typical sign of RA - bone erosion - is relatively rare at the onset of the disease and is an unfavorable prognostic sign. The progression of RA over time leads to the destruction of articular cartilage and bones, damage to ligaments and tendons. The failure of the ligamentous apparatus can cause the occurrence of dorsal subluxation of the radius. At the late stage of RA, bone erosions are detected in almost all patients. This is the most characteristic x-ray symptom of polyarthritis. Extensive and multiple destructive changes in the joints are accompanied by the formation of multiple subluxations, dislocations and contractures of the joints typical of RA. In addition to destructive changes in the joints, most deformities are associated with tendon and ligament looseness and ruptures in them, as well as a restructuring of the normal muscle tension around one or more joints. In the later stages of RA, ankylosing of the joints also occurs.

Key words: rheumatoid arthritis, hand, tendovaginitis, periarticular osteoporosis, narrowing of joint spaces, ulnar deviation, bone erosion, joint ankylosis, carpal tunnel syndrome.

Contacts: Yuri Alexandrovich Olyunin [email protected]

THE RHEUMATOID HAND (Part I)

Yu.A. Olyunin, A.V. Smirnov

Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow

Early rheumatoid arthritis (RA) is mainly presented as the signs of articular synovial membrane inflammation. Examination reveals the changed outline of joints, their dysfunction, and local palpatory tenderness. Juxta-articular osteoporosis is one of the earliest and characteristic X-ray manifestations of polyarthritis. Its most important X-ray symptoms should include joint space narrowing. It reflects articular cartilage destruction and it is taken into account in evaluating the progression of a pathological process. The most typical sign of RA is bone erosions that comparatively rarely occur at the onset of the disease and are a poor predictor.

Progression of RA leads to articular cartilage and bone destruction and ligament and tendon damage over time. Incompetence of the ligamentous apparatus may cause dorsal subluxation of the radius. In late RA, bone erosions are detectable in almost all patients. This is the most characteristic X-ray symptom of polyarthritis. Extensive and multiple destructive changes in the joints are accompanied by the development of their multiple subluxations, dislocations, and contractures. In addition to destructive changes in the joints, most deformities are associated with their tendinous and ligamentous looseness and ruptures and with the rearrangement of normal muscle tension around one joint or more. Articular ankylosis occurs in late RA. Key words: rheumatoid arthritis, hand, tendovaginitis, juxta-articular osteoporosis, joint space narrowing, ulnar deviation, bone erosions, articular ankyloses, carpal tunnel syndrome.

Contact: Yuri Aleksandrovich Olyunin [email protected]

early arthritis

The defeat of the hand occupies a special place in the clinical picture of chronic diseases of the joints. On the one hand, the originality of its changes is of great importance for diagnosis, on the other hand, they are associated with

Mi violations can lead to severe functional insufficiency and a significant decrease in the quality of life of patients. Inflammation of the joints of the hands is a typical manifestation of systemic rheumatic diseases, primarily rheumatoid arthritis (RA).

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Pavel Novikov on the preservation of traditions and the latest advances in modern rheumatology

Pavel Novikov

Hobbies: science, board games

Marital status: married, two sons

KS: Pavel Igorevich, when did you move from Belarus to Moscow?

KS: When did you decide to specialize in rheumatology?

KS: Could you please tell us more about what your thesis is about?

KS: Has the prognosis for this category of patients changed over 50 years?

CS: What should the primary care physician do if an autoimmune process is suspected in a patient with articular syndrome?

KS: How is the flow of patients to the E. M. Tareev Clinic formed?

KS: What is the indication for hospitalization specifically in your department?

KS: What diseases are the most relevant for your department?

KS: How well are the causes of autoimmune diseases now studied?

KS: Are there screening studies for aggravated heredity?

KS: What has changed in recent years in the approach to the treatment of these serious diseases?

In most patients, proven standard treatment regimens, when used correctly, successfully control rheumatic diseases.

KS: How is the rheumatology service going through the era of reorganization of Russian medicine?

KS: Does busy work interfere with family relationships?

KS: What are your goals for the next decade?

My separate concern is to increase the awareness of patients through the main specialists about our work, about modern approaches to treatment.

Source: www.katrenstyle.ru