Chemo-radiation methods of treatment in palliative care.

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 relevant. There is a weak alertness of doctors regarding mycoses in patients with systemic rheumatic diseases, the complexity of intravital diagnosis, and difficulties in therapy. The importance of this problem increases significantly due to the active implementation in clinical practice biological agents, primarily tumor necrosis factor a inhibitors (infliximab, adalimumab, etaner-cept), which is accompanied by an increased 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 Sergeevich 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 diagnosis and treatment is noteworthy lifetime. 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 actual problems medicine, requiring the attention of doctors of various specialties, including rheumatologists. Infectious diseases often complicate the course of many rheumatic diseases (RDs) and occupy 2-3rd place among the causes of death in these patients.

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

Mortality in invasive mycoses remains high. Even with timely systemic antifungal therapy, approximately 40% of patients die from infection caused by Candida fungi. 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 increasingly appeared

research 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 mycoses 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 weak alertness of doctors regarding mycoses in these patients, the complexity of intravital diagnosis, and difficulties in therapy, which may be due to the multi-organ nature of the fungal infection.

The active introduction into clinical practice of biological agents, primarily inhibitors of tumor necrosis factor α - TNF α (infliximab, adalimumab, etanercept), and the resulting 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 often 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. Spores of these fungi are widespread, 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 divided into invasive, saprophytic and allergic. Invasive forms include lesions of the lower respiratory tract, sinusitis, as well as infections of the skin and soft tissues, which may represent an entry point for an etiotropic agent. Damage to the central nervous system, cardiovascular system, and other organs and tissues may occur due to hematogenous dissemination or direct spread from nearby foci. Saprophytic lesions include otomycosis and pulmonary aspergilloma. Allergic forms are represented by allergic aspergillus sinusitis and allergic bronchopulmonary aspergillosis.

Lung damage is observed with aspergillosis in approximately 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. Most early symptoms- cough (initially dry) and fever resistant to broad-spectrum antibiotics. Subsequently, shortness of breath develops, “pleural” pain in the chest appears (due to fungal invasion of the vessels, leading to multiple lung infarctions) and hemoptysis, usually moderate, although in some cases it can be massive. It should be borne in mind that during GC therapy the body temperature can be subfebrile or normal, and the pain syndrome can be minimally pronounced. The development of spontaneous pulmonary hemorrhages due to the formation of decay cavities in the lungs is possible.

Chest radiography in the early stages of IPA is nonspecific. Usually, focal rounded compactions are detected, infiltrates adjacent to the pleura are reminiscent of pulmonary infarctions, the formation of cavities, and rarely - pleural effusion. Computed tomography (CT) is much more informative, especially high resolution. A typical CT picture of IPA is multiple nodes and a “crown” or “halo” symptom, which is a rarefaction zone around a focal defect in the lung tissue. Somewhat later, the “sickle” or “crescent” symptom appears, which is represented by a crescent-shaped clearing in the area

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

How to interpret the isolation 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 is usually not indicated for them, but additional studies should be carried out to exclude IPA. In patients with immunodeficiency, 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 a biopsy of lung tissue obtained during thoracoscopy or open biopsy. However, histological confirmation is not always possible in severely ill patients with immunosuppression, granulocytopenia, or other contraindications to biopsy. In such patients, in the presence of clinical symptoms or new pulmonary infiltrates, isolation of Aspergillus from bronchoalveolar lavage is sufficient to initiate therapy.

The determination of galactomannan antigen plays an important role in the diagnosis of IPA. Galactomannan is a polysaccharide component of the cell wall and is released during Aspergillus growth. Serum galactomannan can be detected on average 5-8 days before the onset of clinical symptoms, changes in chest radiographs, 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 galactomannan test is more informative in patients with malignant hematological malignancies or recipients of hematological transplants than in individuals who have undergone solid organ transplantation or patients without neutropenia. The sensitivity and specificity of the galactomannan test may change with certain medications. False-positive reactions have been demonstrated in patients receiving piperacillin/tazobactam and amoxicillin/clavulanate due to the presence of galactomann in these antibiotics. The same reactions were observed within 5 days after stopping β-lactam therapy. Feelings

The test's effectiveness also decreases with antifungal therapy.

When determining Alregion-DNA during polymerase chain reaction (PCR) in patients with IPA, 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 differentiate between colonization and active infection. Moreover, PCR is performed only in specialized laboratories and cannot be considered as a routine test.

Determination of another component of the fungal wall - 1,3-beta-B-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 categories of IPA is unclear.

The Mycoses Study Group of the European Organization for Research and Treatment of Cancer has proposed criteria for the diagnosis of invasive mycoses. Diagnostic criteria for IPA 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 IPA

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

For patients with neutropenia, voriconazole is prescribed intravenously at 6 mg/kg 2 times a day for the 1st day, then 4 mg/kg 2 times a day. If the patient's clinical condition improves after 7 days of therapy, they switch to oral administration of the drug 200 mg 2 times a day. In the absence of neutropenia (neutrophil count > 0.5 10 9), treatment is recommended to begin with the oral form.

The main contraindication for the use 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. is possible.

If there are contraindications to the use of voriconazole, caspofungin is used as the drug of choice for IPA. Amphotericin B is used as a first-line drug for IPA extremely rarely due to its lack of effectiveness 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, a CT scan shows negative dynamics in the lungs (an increase in the primary lesion or the appearance of new

Diagnosis IPA Criteria

Proven Identification of mycelium during histological and cytological examination of lung tissue obtained from

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

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

Possible Presence of microorganism factors* + clinical criteria**

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

**Clinical criteria - one of three signs identified on CT: a) dense, clearly defined lesion(s) with or without the “crown” symptom, b) “crescent” symptom, c) cavity formation.

***Microbiological criteria: a) positive for Aspergillus results of cytological, microscopic or cultural examination of sputum, bronchoalveolar fluid, samples obtained by brush biopsy, b) positive test to galactomannan in serum or bronchoalveolar fluid.

IPA treatment is prescribed immediately if invasive aspergillosis is suspected, i.e. until culture results are available. The drug of choice is voriconazole, prescribed in all cases of IPA. Large prospective randomized trials have shown that patients with IPA treated with voriconazole as initial therapy have a significantly better response within 12 weeks of treatment than those treated with amphotericin B (53% vs. 32% of patients).

foci) and fever persists, caspofungin is added to voriconazole or, in its absence, amphotericin B. When the process stabilizes (reduction 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 regression of lesions on CT scan of the lungs. Duration of treatment is 1-3 months.

Immunomodulatory therapy (colony-stimulating factor, interferon γ) can be prescribed to reduce the degree of immunosuppression and as an addition to antifungal treatment of IPA.

With the development of IPA in patients with SLE, rheumatoid arthritis (RA) and other systemic RDs, modification of the therapy of the underlying disease is required. It is advisable to temporarily discontinue cytostatics and TNF inhibitors, and reduce the dose of GC (if it is impossible to cancel them) to the minimum that allows you to control the activity inflammatory process. Unfortunately, the lack of studies on the prevention and treatment of IPA in such patients does not allow us to make specific recommendations.

Chronic necrotizing pulmonary aspergillosis (CNPA) 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 underlying 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 therapy with GCs in 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. Rarely, an asymptomatic course is observed.

X-rays and CT scans of the chest usually reveal compaction and thickening of the pleura with the formation of cavities in the upper lobes of the lungs, up to the formation of a bronchopleural fistula.

The diagnostic value of bronchial or percutaneous puncture biopsy is relative to Table 2. Diagnostic criteria for PRAISE

Diagnostic criteria

Clinical:

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

X-ray:

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

Laboratory:

increased level inflammatory markers (ESR, SRV). Isolation of Aspergillus spp. from the pulmonary or pleural cavity or a positive precipitation reaction for Aspergillus. Rule out other pulmonary pathogens (via microbiology and serology), including mycobacteria and endemic fungi that may cause similar symptoms

low, so they are rarely performed. In patients with CNAL, there is often 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 2 presents diagnostic criteria for CNAL, which may be useful for early recognition of the disease and improvement of the prognosis in these patients.

According to the recommendations of experts from the American Society for infectious diseases(Infectious Diseases Society of America - IDSA), the most reasonable approach to the treatment of CNAL is the administration of oral forms of itraconazole at a dose of 400 mg/day. Voriconazole is also effective, but there are significantly fewer publications on its use in this form of aspergillosis. Oral forms of the drug are preferable due to the need for long courses of treatment (up to 24 weeks).

Aspergilloma (mushroom ball) is the most common and most recognized form of pulmonary 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 aspergillomas 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, hemoptysis is the leading symptom. The development of life-threatening bleeding from the bronchial vessels is possible. 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 appears as 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, for example with 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. Test results for serum IgG antibodies to Aspergillus may be negative during GC treatment. Antifungal therapy with itraconazole, voriconazole, and possibly posaconazole may provide beneficial results with relatively minimal risk. Surgical resection or intracavitary antifungal therapy may be indicated in selected patients with a single aspergilloma.

One of the most severe complications of IPA is damage to the central nervous system, the mortality rate 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. In contrast to candidiasis and cryptococcosis of the central nervous system, aspergillosis is more characterized by focal neurological lesions and convulsive syndrome. When infection disseminates from the paranasal sinuses, especially from the ethmoid bone, the process may involve the frontal and temporal lobes of the brain, the cavernous sinus, and even the internal carotid artery. Detection of galactomannan antigen in the cerebrospinal fluid improves the reliability of diagnosis and helps to avoid invasive procedures for histological verification of the diagnosis. For the treatment of this form of aspergillosis, the most preferred is voriconazole, the effectiveness of which has been demonstrated in a number of studies. High level mortality in this pathology, in addition to antimycotic therapy, necessitates surgical resection of the affected areas. Other methods of therapy have also been proposed, including higher doses of a single antimycotic, combinations of antifungal drugs, and immunomodulators. However, there is no data from prospective controlled clinical studies 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 studies, GOBA experts recommend using voriconazole for initial treatment of extrapulmonary forms of IA. When prescribing al-

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

Primary prevention involves prescribing antifungal drugs to patients who do not have symptoms of fungal infection, but the epidemiological profile suggests a high likelihood of invasive aspergillosis. However, identifying risk groups to prevent the development of this infection still remains a problem. In relation to rheumatology, this may include patients receiving GC therapy in high doses (1 mg/kg prednisolone per day for at least 2-3 weeks), cytotoxics and TNF-a inhibitors, but recommendations regarding specific doses and regimens missing today. In patients with hematological diseases accompanied by neutropenia, itraconazole administered intravenously and orally as 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. Clinical trials examining the use of voriconazole for prophylactic purposes are currently underway, but definitive results have not yet been published.

In conclusion, we note that the emergence of new antifungal drugs with greater activity and better tolerability has significantly improved treatment outcomes for 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 early detection of the infectious process, assessment of disease outcomes, treatment of progressive or refractory aspergillus infection, and identification of groups of patients in whom prevention of aspergillosis would be most effective.

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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, changes in the configuration of the joints, local pain on palpation, and dysfunction are noted. One of the earliest and most characteristic radiological manifestations of polyarthritis is periarticular osteoporosis (OP). The most important radiological symptoms include narrowing of the joint spaces. It reflects the destruction of articular cartilage and is taken into account when assessing the progression of the pathological process. The most typical sign of RA - bone erosions - occurs relatively rarely 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. Ligamentous failure can cause dorsal subluxation of the radius. At the late stage of RA, bone erosions are detected in almost all patients. This is the most characteristic radiological symptom of polyarthritis. Extensive and multiple destructive changes in the joints are accompanied by the formation of multiple subluxations, dislocations and joint contractures typical of RA. In addition to destructive changes in the joints, most deformities are associated with tendon and ligament laxity and tears in them, as well as a change in the normal muscle tension around one or more joints. In the later stages of RA, joint ankylosis also occurs.

Key words: rheumatoid arthritis, hand, tenosynovitis, 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

Damage to the hand occupies a special place in the clinical picture of chronic joint diseases. On the one hand, the originality of its changes has great importance for diagnostics, on the other hand - related to

These disorders can lead to severe functional impairment 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 about preserving traditions and latest successes in modern rheumatology

Pavel Novikov

Position: rheumatologist, head rheumatology department 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 at the Department of Internal, Occupational Diseases and Pulmonology, Faculty of Preventive Medicine, First Moscow State Medical University named after I. M. M. Sechenova

Hobbies: science, board games

Marital status: married, two sons

There comes a time in every person’s life when significant effort is required to maintain an active, high-quality life. Pavel Igorevich Novikov often says these words to his patients, trying to motivate them for treatment. Despite his youth, the doctor looks like a great scientist. Having come to study in Moscow from a small Belarusian town, he is an example of a true intellectual, an educated person who is 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 of Scientific and Pedagogical Personnel of the I.M. Sechenov Moscow Medical Academy. He passed the qualifying tests successfully, and from the third year he continued his studies in Moscow. There, in the First Moscow State medical university, completed his residency in internal medicine and received a certificate in rheumatology.

CS: 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 Gennadievich Krivosheev, was in the field of rheumatic diseases, I continued to work on the problems of systemic vasculitis, receiving a specialization in rheumatology. Over time, these observations and analysis of the Clinic’s experience formed the basis of my Ph.D. thesis.

KS: Please tell us in more detail what your dissertation is about?

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

Thanks to increased awareness among doctors, improved diagnosis, and perhaps also due to an increase in incidence, the number of patients over the past few years is comparable to or even higher than that of the previous four decades. Therefore, the comparison of these data was, it seems to me, important and worthy of interest. I hope this systematic 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 increased. The life prognosis for patients has improved significantly, and now, with proper use and individual selection of immunosuppressive therapy, we expect that their life expectancy will differ little from that of healthy people comparable in gender and age. This question is actually the most common among those who are sick. 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 systemic rheumatic disease needs to regularly monitor tests, be observed by specialists depending on the affected organs, and have treatment adjusted by a rheumatologist. However, now a person can maintain both work activity and an acceptable quality of life.

KS: What should a 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 in the presence of clinical and laboratory signs of an active process, it is advisable for the patient to continue the rest of the examination 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 included in the structure of the Ministry of Health Russian Federation. The clinic can examine patients from all over the country who have compulsory medical insurance policy. If the patient has a referral from the clinic, he can see a therapist or rheumatologist at the clinic for an initial consultation.

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

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

Pavel: Indications for hospitalization are quite standard. Most importantly, we must be confident that we can help the patient. If I understand that the patient is not specialized, that doctors of another specialty can help him better, then I will explain this. We must understand that rheumatic diseases are chronic. The vast majority of problems can and should be treated on an outpatient basis. But the initiation 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 approximately 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 Sjogren's disease. And another third of patients from the category of so-called articular rheumatology (rheumatoid arthritis, ankylosing spondylitis - ankylosing spondylitis, etc.). We hospitalize relatively few patients with degenerative joint diseases. We practically do not deal with osteoarthritis.

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

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 our patient’s child has no complaints, then no additional studies beyond standard observation by a pediatrician are needed. Moreover, there are no specific ways to prevent inflammatory rheumatic diseases. Here, as in medicine generally, it is important to maintain generally accepted healthy image life.

KS: Are there screening tests for a family history?

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 no practical application he won't have it. On the contrary, it will be harmful, since in this case we will completely unreasonably “scroll” the patient through different specialists and examinations. And the patient will receive unnecessary significant stress and an unreasonable risk of complications during medical procedures. Therefore, asymptomatic screening for rheumatological diseases is not currently developed, used or recommended.

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

Pavel: Significant progress. First of all, this is the individualization of approaches to therapy. Previously, for example, very high doses of cyclophosphamide and glucocorticoids were used to treat systemic vasculitis, for which they had to pay a very significant price in the form of side effects. Now scientific and practical data have been obtained that justify the prescription of “weaker”, and therefore safer, treatment regimens for patients without severe lesions internal organs, especially after achieving remission.

Over the past fifteen to twenty years, genetically engineered biological drugs have become quite widespread. These drugs target inflammatory cytokines, allowing them to help patients for whom traditional disease-modifying antirheumatic drugs do not work.

Pavel: Towards targeted therapy, the mechanism of which is briefly as follows. A key molecule or group of molecules is established when various diseases, and then we try to influence them using antibodies. Neutralization of molecules involved in pathogenesis occurs. The main focus in rheumatology is now on identifying specific disease mechanisms and creating antibodies that target them. The same treatment approach is widely used in oncology, cardiology, and hematology. In general, the topic of monoclonal antibodies is now 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. Firstly, they have their own unwanted effects. Secondly, genetically engineered biological drugs, like traditional approaches to therapy, affect the mechanism of the disease, often at late stages of pathogenesis, so they provide only temporary control of activity, and if therapy is discontinued, the disease may return. Finally, they are expensive, although they can be obtained free of charge in most regions if you have a disability and strict indications. These drugs are only needed for patients for whom traditional medications do not work or for whom traditional medications cause unacceptable side effects.

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

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

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

Government mechanisms exist to meet patient needs for such treatment, although access to treatment varies from region to region. Our task, as a federal center, is to provide recommendations and justification so that the patient receives therapy for as long as necessary. Then the patient is observed by doctors at his place of residence, and then comes to us to decide on a strategic change in therapy.

KS: Does busy work interfere with family relationships?

Pavel: No, it doesn’t interfere. My wife Olga is an ophthalmologist and is currently continuing her graduate studies. But we don’t 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. The whole family tries to go to plays in theaters, to movies, and we often play board games at home. Fedor studies further English language, Stepan likes choreography classes. I would like them to grow up, first of all, to be good, responsible people and find an exciting profession for themselves. And I try to be a worthy example for them.

KS: What are your goals for the next decade?

Pavel: I am primarily a practitioner, so my first goal is to continue to lead the rheumatology department. It was created as an independent department in 2013, so the task is urgent to further improve rheumatological care in our multidisciplinary hospital.

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

Another challenge is to expand international cooperation. Since the clinic has been dealing with rare diseases for many years, it has accumulated a lot of experience that needs to be updated and demonstrated in Russia and in the world. We also plan to raise a galaxy of young rheumatologists, so we now have quite a lot of graduate students. As a whole team, I hope we will continue the glorious traditions of the therapeutic and rheumatological school of Evgeniy Mikhailovich Tareev.

Source: www.katrenstyle.ru

Pavel Novikov about preserving 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 Preventive Medicine Faculty of the First Moscow State Medical University named after I. M. Sechenov

Hobbies: science, board games

Marital status: married, two sons

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 of Scientific and Pedagogical Personnel of the I.M. Sechenov Moscow Medical Academy. He passed the qualifying tests successfully, and from the third year he continued his studies in Moscow. There, at the First Moscow State Medical University, he completed his residency in internal medicine and received a certificate in the specialty of rheumatologist.

CS: When did you decide to specialize in rheumatology?

KS: Please tell us in more detail what your dissertation is about?

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

KS: What should a 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?

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 clinic, he can see a therapist or rheumatologist at the clinic for an initial consultation.

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 studied now?

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 our patient’s child has no complaints, then no additional studies beyond standard observation by a pediatrician are needed. Moreover, there are no specific ways to prevent inflammatory rheumatic diseases. Here, as in medicine in general, it is important to maintain a generally accepted healthy lifestyle.

KS: Are there screening tests for a family history?

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, since in this case we will completely unreasonably “scroll” the patient through different specialists and examinations. And the patient will receive unnecessary significant stress and an unreasonable risk of complications during medical procedures. Therefore, asymptomatic screening for rheumatological diseases is not currently developed, used or recommended.

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

Pavel: Significant progress. First of all, this is the individualization of approaches to therapy. Previously, for example, very high doses of cyclophosphamide and glucocorticoids were used to treat systemic vasculitis, at a significant cost in terms of side effects. Now scientific and practical data have been obtained that justify the prescription of “weaker”, and therefore safer, treatment regimens for patients without severe damage to internal organs, especially after achieving remission.

Pavel: Towards targeted therapy, the mechanism of which is briefly as follows. A key molecule or group of molecules for different diseases is identified, and then we try to influence them with the help of antibodies. Neutralization of molecules involved in pathogenesis occurs. The main focus in rheumatology is now on identifying specific disease mechanisms and creating antibodies that target them. The same treatment approach is widely used in oncology, cardiology, and hematology. In general, the topic of monoclonal antibodies is now a hot spot in all areas of medicine.

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

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

KS: Does busy work interfere with family relationships?

Pavel: No, it doesn’t interfere. My wife Olga is an ophthalmologist and is currently continuing her graduate studies. But we don’t 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. The whole family tries to go to plays in theaters, to movies, and we often play board games at home. Fedor is additionally studying English, Stepan enjoys choreography classes. I would like them to grow up, first of all, to be good, responsible people and find an exciting profession for themselves. And I try to be a worthy example for them.

KS: What are your goals for the next decade?

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

Good day!

My name is Novikov Sergey Valentinovich, all the information about meYou can find outfrom the section "About the consultant"

Correspondence Consultation is possible by correspondence to the following address: [email protected]

Face-to-face I am conducting a consultation on weekdays in 8.15 by prior arrangement!

(call or write whatsapp, viber, sms, e-mail the day before to confirm because I can operate in another clinic, provide urgent consultations on the road, be on a business trip, vacation, etc...)

In the morning of the consultation day, do not drink or eat!

Write:[email protected]

Call/write - phone, SMS, Viber, whatsapp : 8(985) 195-27-91

Address :

Research Institute of Emergency Medicine named after N.V. Sklifosovsky, Bolshaya Sukharevskaya Square, building 3, building 21

go from metro station Prospekt Mira or metro station Sukharevskaya, entrance from Grokholsky lane to 15-storey building(on the 1st floor there are shoe covers and a wardrobe).

If you have problems getting through the guard, call me and hand the phone to the guard.

If I'm not in the office, call me, I can be in the ward, dressing room, operating room!

On the 10th floor is the office of senior researcher. Novikova S.V.(from any elevator to the right to the end of the corridor, the third door on the right from the balcony) First come, first served!

Have with you:

1. sheet or towel

2. results of previous examinations and photographs

Scheme maps

CONSULTATIONS are carried out in the following areas:

1. Ultrasound diagnosis of organ diseases abdominal cavity, retroperitoneal space, superficial organs ( thyroid, mammary gland, salivary glands, lymph nodes), soft tissues.

2. Biopsy under ultrasound control of diseases of the abdominal organs, retroperitoneal space, superficial organs (thyroid gland, mammary gland, salivary glands, lymph nodes), soft tissues.

3. Minimally invasive treatment under ultrasound control of diseases of the abdominal cavity, retroperitoneal space, superficial organs, soft tissues.

4. Radiofrequency ablation and sclerotherapy of neoplasms and cysts of the abdominal cavity, retroperitoneal space, and superficial organs.

5. Ultrasound diagnosis and minimally invasive treatment under ultrasound control of liver echinococcosis.

6. Ultrasound diagnosis and minimally invasive treatment under ultrasound guidance of acute pancreatitis/pancreatic necrosis.

7. Ultrasound diagnosis and minimally invasive treatment under ultrasound control of obstructive jaundice.

8. Ultrasound diagnosis and minimally invasive treatment under ultrasound guidance of chronic complicated pancreatitis.

9. Ultrasound diagnostics and minimally invasive treatment under ultrasound control of postoperative complications (abdominal cavity, retroperitoneal space, superficial organs, soft tissues).

Endoscopic, X-ray, laparoscopic and open operations for diseases of the abdominal cavity and retroperitoneal space:

1. Tumors of the pancreas and periampullary zone.

2. Stomach tumors.

3. Tumors of the small intestine.

4. Colon tumors.

5. Rectal tumors.

6. O liver tumors.

7. Tumors of the bile ducts.

8. Chronic complicated pancreatitis.

9. Bile duct strictures.

10. Mechanical jaundice.

11. Complicated peptic ulcer of the stomach and duodenum.

12. Hernia of the anterior abdominal wall.

13. Housing and communal services Chronic calculous cholecystitis.

14. Haemorrhoids.

15. Anal fissure.

16. Intestinal fistulas.

17. Chronic appendicitis.

Consultations on other issues can only be advisory in nature with referral to appropriate specialists, assistance in choosing a specialist and in specialized hospitalization!