Sarcoidosis (syn. Besnier-Beck-Schaumann pathology). A systemic disease that occurs with damage to the intrathoracic and peripheral lymph nodes, lungs, bones, skin, mucous respiratory tract, parotid glands, spleen, liver, eyes and other organs. Young and middle-aged people are more likely to get sick, and older people and children who get sick at the age of 9-12 years are more rare.

Etiology and pathogenesis. Unknown. The main morphological element of sarcoidosis is epithelioid cell granuloma, in which giant cells are occasionally found, but there is no necrosis, which distinguishes it from tuberculosis.

Clinical picture. Damage to the lungs and bronchial lymph nodes is most common. There are 3 stages of pulmonary sarcoidosis:
- Stage I: mediastinal, in which the bronchial lymph nodes are affected;
- Stage II: mediastinal-pulmonary, in which, along with damage to the intrathoracic lymph nodes, there are interstitial and focal changes in the lungs;
- Stage III: characterized by the formation of focal conglomerates and the development of widespread pulmonary fibrosis.

Clinical manifestations in stage I capcoidosis are scant; malaise, cough, asthenia, chest pain, and low-grade fever are noted. Sometimes there is an asymptomatic course. X-ray reveals sharply enlarged bronchial lymph nodes (some or all groups may be affected), having clear, often polycyclic outlines. The defeat is two-sided. Clinical manifestations of stage II sarcoidosis are more pronounced; shortness of breath, cough, sometimes with sputum, and low-grade fever are noted. Dry and wet rales are sometimes heard in the lungs.

X-ray, along with enlarged bronchial lymph nodes, reveals focal shadows located symmetrically; on both sides, more in the middle pulmonary lobes and hilar areas, and linear shadows of compacted interstitial tissue. At stage III of sarcoidosis, the clinical manifestations of the disease are most pronounced. There is a cough, often with sputum, shortness of breath, febrile outbreaks, and dry and wet wheezing is almost always heard in the lungs. X-ray examination reveals the fusion of foci, the formation of infiltrates, the development of widespread pulmonary fibrosis, emphysema, and bullous changes. In some situations, the formation of large focal changes in the lungs, “sarcoids,” resemble metastases of malignant tumors. Severe adenopathy is usually absent at this stage. Progression of the disease can lead to the development of air exchange insufficiency and the formation of cor pulmonale.

In sarcoidosis, the bronchial mucosa is often affected. Granulomas in the submucosal layer in some situations can be detected during bronchoscopy in the form of nodules or plaques. Much more often they are detected by biopsy of the bronchial mucosa. Changes in the morphological composition of blood do not have any special features. Patients may experience monocytosis, neutrophilia with band shift, and increased ESR. In some patients, an increase in calcium and gamma fractions in the proteinogram are detected in the blood serum and daily urine. Tuberculin sensitivity is sharply reduced. About 30% of patients have generalized forms. Damage to peripheral lymph nodes has no characteristic differences. Their increase does not reach large sizes, they are painless, mobile, and are not welded together by themselves and adjacent tissues. More often the cervical, supraclavicular, ulnar and axillary lymph nodes are enlarged. Skin lesions in sarcoidosis in the form of single or multiple nodular elements, dense to the touch, the size of a pinhead to a pea, reddish, with a cyanotic tint, are usually localized on the face, upper and lower extremities, and more rarely on the torso. Nonspecific skin elements appear in some cases in the form of erythema nodosum. Bone lesions are usually localized in the epiphyses of small bones of the hand or foot and are not clinically manifested. Radiologically they are determined in the form of multiple or single rounded clearings.

When the eyes are affected, iritis or hirodocyclitis most often appears. Sarcoidosis parotitis occurs without a temperature reaction.

Forecast. In stages I and II, it is usually favorable; in stage III, it is serious; the process is likely to progress, leading to disability.

Diagnosis. At stage I, sarcoidosis must be differentiated from tuberculous bronchoadenitis and lymphogranulomatosis. Tuberculous bronchoadenitis is often unilateral, has a difficult course, and tuberculin tests are positive. With lymphogranulomatosis, the clinical manifestations are more severe. At stages II and III, they differentiate from reticulohistiocytosis, Hammen-Rich symptom complex, and cystic fibrosis. In unclear situations, you need to resort to a biopsy of the bronchial mucosa. The intradermal Kveim reaction (a specific response to the administration of a suspension prepared from tissue of the spleen affected by sarcoidosis) has a certain diagnostic value.

Treatment. The main treatment for sarcoidosis is corticosteroid therapy. The best drug is prednisolone in an initial daily dose of 1 mg/kg. The duration of treatment is about 6 months.

Sarcoidosis is a disease about which ordinary people know little, and most know nothing at all. Not even all medical workers are aware of it. What is this mysterious disease that can lead to a forced lung transplant, and in some cases goes away spontaneously? What details are known about this disease, its causes and symptoms, what place does sarcoidosis occupy in the ICD, what are its most common forms? In what cases do doctors take a wait-and-see approach, when are medications needed, and is alternative treatment for sarcoidosis possible?

Sarcoidosis in adults

Sarcoidosis is a disease that usually develops in adulthood. People between 20 and 40 years of age are most vulnerable to it.

Men develop sarcoidosis much less frequently than women. However, the presence of occupational hazards associated with contact with small particles of dust, gas, various suspensions in the air, and prolonged smoking significantly increase the likelihood of the onset of the pulmonary form of the disease.

Sarcoidosis in women

Female gender is an additional risk factor in the development of any autoimmune disease. Since Beck's sarcoidosis can be classified in this group, it turns out that it most often develops in girls and young women aged 20 to 40 years. However, in identifying this disease, an additional role is played by the fact that representatives of the fairer sex more often undergo fluorographic examination, since they are more attentive to their health.

Sarcoidosis disease in children

Sarcoidosis in children is a very rare occurrence. It is usually associated with other autoimmune diseases. Clinical manifestations do not differ from those in adults, but cases of spontaneous recovery occur more often.

Sarcoidosis disease: what is it?

The disease sarcoidosis still raises many questions among practicing doctors and is a difficult mystery for them. The reasons are that, despite the development of medical science, little is still known about it. Synonyms for the disease sarcoidosis are Besnier-Beck-Schaumann disease. The essence of this disease is the appearance of granulomas (dense nodules) in various tissues of the human body, which are its main criterion in diagnosis. Most often they occur in the intrathoracic and peripheral lymph nodes, lung tissue, liver, eyes, spleen and less often in other organs: bones, skin.

Typically, the disease sarcoidosis debuts in both sexes between the ages of 20 and 40, but women still suffer from it more often than men. In childhood, this disease practically does not occur. It is not a contagious disease, but symptoms of sarcoidosis are often observed in several members of the same family, that is, there is a version about the hereditary nature of its transmission. Considering the difficult nature of the diagnostic search, the number of patients with this disease in different countries is not reliably known: the situation is more or less clear with the assessment of incidence in European countries, the USA, Japan, and Australia. However, how many patients with sarcoidosis there are in African or Asian countries remains a mystery due to the lack of accurate statistics.

A feature of the disease sarcoidosis is the completely unexpected nature of its course: some people, after a certain time, recover on their own without any treatment. Doctors still cannot answer the question: why does this depend and how to give the patient an accurate prognosis. For the same reason, they cannot reliably say how long people with sarcoidosis live, since the disease sometimes behaves completely unpredictably.

The prevalence of Beck's sarcoidosis in Russia ranges from 22 to 47 people per 100 thousand population, which allows us to classify this disease as rare.

Causes of sarcoidosis

Beck's sarcoidosis is an autoimmune disease, for most of which the exact cause is unknown to science. This disease is not infectious and is not transmitted from one person to another, but there are frequent cases of familial onset of the disease. However, there is also no evidence that the disease sarcoidosis is genetically determined. And, nevertheless, there are works that confirm the influence of nationality and race on the course of this disease. For example, in dark-skinned people it occurs more often, in the Japanese a complication in the form of myocarditis is quite common, and in people of the Caucasian race - erythema nodosum.

There are several theories about the possible origin of the disease sarcoidosis. Among them are infectious-mediated (the influence of fungi, protozoa, bacteria), hereditary and associated with the fact that the disease is directly associated with the presence of occupational hazards and appears in people working in specific industries (workers in agriculture, the chemical industry, post offices, millers and firefighters). The prevalence of pulmonary sarcoidosis is also slightly higher among smokers.

Beck's sarcoidosis is one of the names for this disease. In addition, it has several synonyms: Beignet and Schauman. However, the first name is the most common.

Place of sarcoidosis in ICD 10 revision

This disease has its place in the International Classification of Diseases, 10th revision. However, sarcoidosis in ICD (D86) is represented by several subtypes of the disease, which depends on the location of the lesion. Here are the most common:

• D86.0 – pulmonary sarcoidosis,
• D86.1 – sarcoidosis of the lymph nodes,
• D86.2 – pulmonary sarcoidosis with damage to the lymph nodes,
• D86.3 – cutaneous sarcoidosis,
• D86.8 – sarcoidosis of other specified and combined localizations,
• D86.9 – sarcoidosis, unspecified.

This disease belongs to the group: individual disorders involving the immune mechanism. Thus, the very location of the disease sarcoidosis in the ICD 10 revision does not allow it to be classified as a specific group, since there is no specific localization of the process, as, for example, happens with pneumonia, tonsillitis or pyelonephritis.

Forms of sarcoidosis

Doctors distinguish various forms of sarcoidosis, and they are primarily due to the different localization of the appearance of granulomas. The disease behaves so unpredictably that it is difficult to predict exactly where in the patient they will appear.

The most common of all existing forms of this disease is pulmonary sarcoidosis. It is no coincidence that pulmonologists see such patients more often than others, because it is to them that internists or general practitioners refer them.

This form of sarcoidosis develops due to the fact that peculiar neoplasms specific to it appear in the lung tissue - granulomas of epithelioid cells with giant nuclei. They gradually increase in size and merge with each other. In appearance, they are very reminiscent of similar lesions in the tuberculosis process; it is for this reason that these diseases are often differentiated from each other. However, unlike the latter, there are no foci of caseous necrosis and mycobacteria inside these formations, they do not disintegrate, so the prognosis for pulmonary sarcoidosis is completely different. These lesions may suddenly disappear spontaneously, or sometimes they resolve with the formation of areas of fibrosis (scar tissue).

Thus, the clinical manifestations of pulmonary sarcoidosis directly depend on the number of lesions and their effect on respiratory function, that is, how much lung tissue is lost from the gas exchange process. This is one of the few chronic diseases in which complete self-healing is possible, which is what patients and their doctors hope for.

Clinical manifestations are very dependent on the stage of sarcoidosis, of which there are only 3. At each of them, the volume of the pathological process is different, so medical tactics are also different. Moreover, the damage begins not from the lungs, but from the fact that the patient develops sarcoidosis of the intrathoracic lymph nodes. After this, as it progresses, when doctors diagnose stage 2 sarcoidosis, the parenchyma of the lungs themselves is also involved in the process. However, at each stage, spontaneous remission or complete recovery may occur, which distinguishes this disease from most others.

Identifying the stage of sarcoidosis in the diagnosis is very important for understanding the advanced stage of the process and determining treatment tactics.

Stage 1 sarcoidosis or sarcoidosis of the intrathoracic lymph nodes

If a patient is diagnosed with sarcoidosis of the intrathoracic lymph nodes or stage 1 of the disease, then granulomas usually appear in the bronchopulmonary, tracheobronchial, bifurcation or paratracheal lymph nodes. In most cases, these changes are an incidental finding during routine fluorography or x-ray examination of the chest organs for a completely different reason. If there is sarcoidosis at this stage, there are usually no symptoms. Only in rare cases may a patient complain of a feeling of heaviness in the chest, which intensifies with breathing, but almost no one makes such complaints. In some cases, there are nonspecific symptoms such as weakness, malaise, sweating, weight loss, prolonged low fever, etc. However, they may indicate a large number of other ailments, among which sarcoidosis of the intrathoracic lymph nodes is far from the first place. Some patients experience spontaneous recovery, but sometimes the initial stage of the disease smoothly turns into stage 2 sarcoidosis.

Pulmonary sarcoidosis stage 2

Sarcoidosis grade 2 is characterized by combined damage to the lymph nodes and lung tissue. This stage of the disease is usually a natural development of sarcoidosis of the intrathoracic lymph nodes, in which miliary (smallest) or focal (larger) formations appear in the lungs. In terms of their radiological signs, they are very similar to disseminated pulmonary tuberculosis, however, these are two completely different diseases and the tactics for them are not the same. In the second case, the patient definitely requires treatment, because he is contagious to those who live next to him. A patient with stage 2 sarcoidosis does not pose any danger to others and doctors choose individual tactics, which may include watchful waiting, that is, without the use of medications.

In some cases, even at this stage of the disease, the patient may not experience any negative sensations and these changes will be only an accidental finding during an x-ray or fluorography. However, usually patients are still bothered by shortness of breath, cough, chest pain; during auscultation, dry or moist rales are sometimes heard in the lungs. This is usually accompanied by nonspecific symptoms, such as weakness, low-grade fever, chills, sweating, and fatigue. If a patient has combined sarcoidosis, the symptoms may indicate the appearance of extrapulmonary symptoms, as complications develop in the liver, spleen, bones, joints, and eyes.

Stage 2 sarcoidosis can progress to stage 3 of the process, and spontaneous recovery can occur.

At stage 3 of sarcoidosis, granulomas in the lungs and lymph nodes transform into areas of fibrosis, or scar tissue. This is an alternative to spontaneous recovery and is the final stage of the process. These foci of fibrosis fall out of gas exchange, since the lung tissue in them is no longer actually such and is a regular scar. At the same time, an increased load is placed on other parts of the lung (healthy ones), since the need for oxygen does not decrease, they grow and emphysema forms. Unfortunately, this process is irreversible and no medications can completely help the patient.

As a rule, this stage of the process is not asymptomatic. The patient is worried about shortness of breath, cough with scanty sputum, weakness, weight loss, dizziness, decreased tolerance to physical activity, frequent colds, respiratory diseases, etc.

During the course of the disease at any stage, periods of exacerbation, remission, and spontaneous recovery are distinguished. According to the rate of growth of pathological changes, the process can be slow, abortive, chronic or progressive.

Sarcoidosis of peripheral lymph nodes

Sarcoidosis of lymph nodes located outside the chest is a fairly common complication of this disease. It occurs in 25% of patients with this disease. In this form of sarcoidosis, the following lymph nodes are affected:

• back and front cervical,
• elbows,
• supraclavicular,
• inguinal

With sarcoidosis, the lymph nodes become larger in size and have a densely elastic consistency, but fistulas do not form. They are painless and do not cause suffering to the patient if they do not increase to such an extent that they compress the surrounding tissues, organs and blood vessels.

Sarcoidosis of the lymph nodes is a prognostically unfavorable sign of this disease, as it usually indicates the malignant, transient nature of the process. Often the course of the disease becomes persistently relapsing. If a person is suspected of having sarcoidosis, a biopsy of the lymph node is very important for the doctor, because it can reveal the presence of epithelioid cell granulomas specific to this disease.

Sarcoidosis of the skin occurs in about a third of patients with this disease, that is, only these people have specific skin lesions that allow a specialist to easily make a diagnosis. Often they are the first signs of the disease, which appear long before complications from the respiratory system, and they are more obvious than all the others. However, not every doctor, seeing such bright and specific areas of damage, will be able to determine that it is sarcoidosis of the skin, since it occurs very rarely.

The most common symptoms of this disease are the following:

• Erythema nodosum.

This skin manifestation of the disease is the result of secondary vascular damage - vasculitis. That is, visually the doctor sees round, dark, fairly dense nodes on the skin that are painful on palpation. They cause discomfort to the patient and sometimes cause serious suffering. The most common localization of the process is on the lower extremities. A biopsy for this form of sarcoidosis is not diagnostically informative, since the nodes are a consequence of vasculitis and do not contain epithelioid cells with giant nuclei characteristic of this disease. Considering the painfulness of the process, erythema nodosum must be subject to adequate treatment, and the sooner it is started, the more likely a favorable outcome.

• Sarcoid plaques.

They are painless convex skin lumps, burgundy in color with a clearing in the center. They do not itch, itch or cause any discomfort. They are usually located symmetrically on the buttocks, lateral surfaces of the body, face and limbs. They are usually part of the structure of the disease sarcoidosis, the symptoms of which affect several organs and systems at once and are complemented by the involvement of the lungs, lymph nodes, spleen, and liver in the process. These skin lesions persist for quite a long time, usually do not go away on their own, cause mental suffering to the patient, as they are a significant cosmetic defect, and therefore require mandatory treatment. If a patient has cutaneous sarcoidosis, plaque biopsy followed by histological analysis is an excellent method for accurately verifying the diagnosis.

• Lupus chills.

Cutaneous sarcoidosis, which occurs in this form, visually resembles the rashes that appear with systemic lupus erythematosus. They are represented by bright symmetrical purple rashes on the sides of the nose, cheeks, fingers and ears. They are painless, do not itch or cause discomfort. However, given the fact that they are in a visible place, these skin lesions represent a major cosmetic defect and cause mental suffering to the patient. As well as sarcoid plaques, lupus pernio is usually combined with other localizations of damage in this disease.

The prognosis for the cutaneous form of sarcoidosis depends primarily on the nature of the process. If the rash appears suddenly, sharply, spontaneously, then the likelihood of self-healing or a quick response to adequate therapy is more likely than with a chronic, sluggish process.

In addition to the most common localizations, there are rarer forms of sarcoidosis. They are often extremely difficult to recognize, since the changes are nonspecific, that is, they outwardly resemble many other diseases. Here are the most common localizations of this disease:

• Sarcoidosis of the spleen.

Occurs in 10-40% of patients. It manifests itself as an increase in the size of this organ (splenomegaly), or an increase in its work to destroy blood cells (hypersplenism). In some cases, this organ has to be removed, since the massive spleen interferes with normal movement and causes pain in the left hypochondrium.

• Sarcoidosis of the organ of vision.

This form occurs in 25% of all patients with this disease and is the most dangerous, because without timely treatment, sarcoidosis can lead to blindness. It is represented by anterior, posterior uveitis, uveoretinitis. With this type of complication, in 80% it is possible to detect simultaneous damage to nearby lymph nodes and lymph nodes of the roots of the lungs, changes in the bones, spleen and liver.

• Sarcoidosis of the hematopoietic organs.

Occurs infrequently. However, complications from the operation of this system are not uncommon, because many drugs used as basic therapy inhibit it and lead to erythro- and neutropenia.

• Sarcoidosis of the kidneys.

Occurs in 10% of patients with this disease. It may cause the appearance of granulomas that interfere with the normal process of urine formation, as well as secondary deposition of calcium salts, which also negatively affects the functioning of these organs.

• Sarcoidosis of the musculoskeletal system.

Presented with complications from joints, bones, muscles. The most dangerous is the appearance of cysts in the bones of the skull and spine.

• Sarcoidosis of the heart.

It is one of the most serious forms of this disease, because in this case granulomas form in the heart muscle and prevent its full contraction.

• Neurosarcoidosis.

It also belongs to the most severe forms, but the prognosis depends primarily on which nerves are involved in the pathological process.

• Sarcoidosis of the digestive organs.

It is represented mainly by the diffuse formation of granulomas in the liver parenchyma. Most often, patients are bothered by heaviness in the right hypochondrium caused by the enlargement of this organ (hepatomegaly).

If a patient has sarcoidosis, the symptoms of the disease can be completely varied. Starting with the fact that they may not exist at all. At the first stage of the disease, when there is only damage to the intrathoracic lymph nodes, patients do not complain of anything. Sometimes they may only be bothered by nonspecific symptoms, such as weakness, fatigue, weight loss, loss of appetite, prolonged low-grade fever, chest pain without a specific localization.

When foci appear in the lung tissue, shortness of breath, coughing, sometimes sputum appears, episodes of respiratory infectious diseases become more frequent, and dry or moist rales can be heard in the lungs. This is often accompanied by skin complications (erythema nodosum), eye damage (uveitis), and enlarged liver and/or spleen.

At the third stage of the disease, the patient experiences respiratory failure, which is caused by the exclusion of part of the lung tissue from gas exchange and emphysematous growth of the rest. A person has a hard time with physical activity, during which he experiences shortness of breath (typically difficulty breathing), and periodically he has bouts of coughing with phlegm. At the same time, such patients already have one or more combined lesions of other organs.

Sarcoidosis: diagnosis of the disease

Sarcoidosis is a complex and rare disease. It occurs infrequently and each patient has different clinical manifestations. For this reason, if a patient has developed sarcoidosis, diagnosis can take a lot of time and the result will depend primarily on the competence of doctors: not every one of them has encountered a similar disease.

The first and very important step in verifying the diagnosis is the examination of such a patient. If only the intrathoracic lymph nodes are affected, it may be completely uninformative. However, starting from stage 2 and in the presence of damage to other organs, the diagnosis of sarcoidosis will certainly reveal important facts already at the examination stage, especially if there is damage to the eyes, joints, liver, spleen and peripheral lymph nodes.

The doctor carefully talks with the patient, asks if he has lost weight recently, how he tolerates the usual physical activity, if there is shortness of breath or cough, if there is a low fever without signs of a cold. Patients with sarcoidosis often describe their condition vaguely, because there are no specific symptoms for this disease, and patients themselves do not attach much importance to many of them for several years.

If a patient is suspected of having sarcoidosis, a biopsy is one of the most important methods in the diagnostic search. Indeed, with this disease, granulomas (small focal formations) appear in various organs, consisting of macrophages and epithelioid cells (giant multinucleated ones). It is on the basis of their detection that doctors can make this diagnosis, which in its clinical manifestations is similar to a whole list of others, among which tuberculosis and systemic connective tissue diseases take the first place.

Biopsies are most often taken from intrathoracic or peripheral lymph nodes, but the initial diagnosis of sarcoidosis may require an invasive procedure on the lungs. Previously, it was always performed using the open thoracotomy method, but it is extremely traumatic and requires general anesthesia, which is not always possible. Today, doctors have access to methods such as transbronchial biopsy or using thoracoscopic instruments. With these methods, pain relief is less deep, and mechanical damage is not as serious as with classic thoracotomy.

Skin lesions with erythema nodosum are not suitable for puncture, since the cause of their appearance is vasculitis (vascular pathology). However, a biopsy of sarcoid plaques or formations in lupus pernio turns out to be informative, because cells characteristic of this disease are present in them.

Laboratory and instrumental research methods

If a patient is suspected of having sarcoidosis, the diagnosis of the disease is carried out through a large list of various measures. Among them there are both laboratory and instrumental methods.

Laboratory diagnosis of sarcoidosis includes the following mandatory points:

• general clinical analysis of blood, urine,
• biochemical analysis of liver and kidney function indicators, the presence of acute phase proteins and rheumatic tests,
• tuberculin test, which will always be negative, which makes it possible to differentiate this disease from tuberculosis,
• blood gas composition is examined in patients in serious condition.

Instrumental methods for diagnosing sarcoidosis are as follows:

• X-ray examination of the chest organs,
• magnetic resonance, positron emission or computed tomography,
• spirometry (assessment of external respiration),
• endoscopic ultrasound examination of intrathoracic lymph nodes,
• electrocardiographic examination and echocardiography of the heart,
• additional diagnostic methods are carried out depending on the presence of a specific form or complications of the disease.

How to treat sarcoidosis

After the diagnosis is made, all patients are interested in the answer to one question - how to treat sarcoidosis. However, not all of them can accept the fact that doctors are in no hurry to immediately prescribe them active therapy. The fact is that with this disease there is a high probability of spontaneous recovery without taking any pills. Therefore, if a patient is diagnosed with initial sarcoidosis, treatment consists of active observation: the patient comes to the doctor once or twice a year and undergoes the required amount of examinations. If no deterioration is detected, there are no signs of respiratory failure and the person calmly tolerates all normal physical activity, he is simply sent home. However, not all patients go so well; in some cases, sarcoidosis is treated with more active methods.

The most common form of sarcoidosis affects the intrathoracic lymph nodes and lungs. Therefore, most often such patients are seen by a pulmonologist and are under constant supervision. If, as a result of the examination, it is revealed that all granulomas have spontaneously disappeared, then such a patient will be removed from the register after several months or years, which is rare for any chronic disease.

If, according to the results of the examination, it was revealed that the patient’s condition is deteriorating, the pathological process is gradually progressing, respiratory failure is increasing, erythema nodosum has appeared, damage to the eyes, bones, joints, the liver and spleen are greatly enlarged, then the question of how to treat sarcoidosis becomes relevant. In this case, the patient is managed jointly by a pulmonologist and a rheumatologist.

Today, if a patient has sarcoidosis, treatment is carried out with the following drug groups:

• Glucocorticosteroids (prednisolone) are the first-line drug. Initially, high doses are prescribed and gradually reduced after 4-6 months,
• cytostatics (azathioprine, methotrexate) are an alternative to corticosteroids, or are prescribed in cases of intolerance to them, the presence of steroid diabetes,
• bisphosphonates are prescribed to prevent osteoporosis during hormonal therapy,
• other drugs for treatment (pentoxifylline, alpha-tocopherol, chloroquine, inhaled bronchodilators, etc.)

However, there is no specific method of therapy for this disease, that is, all treatment is aimed at relieving symptoms and reducing the activity of the immune system against its own body.

If all possible methods of therapy have been exhausted, the patient is in a terminal condition due to progressive severe respiratory failure, then the only answer to the question of how to treat sarcoidosis in this case is one - donor lung transplantation. In our country, transplantation is not developed, so such patients often do not live to see the moment when they are invited for surgical treatment.

Is traditional treatment for sarcoidosis acceptable?

The answer to the question of whether alternative treatment for sarcoidosis is acceptable is not as simple as it seems at first glance. The fact is that until the patient feels well, doctors do not try to prescribe him medications, since a large percentage of people experience spontaneous remission or get better altogether. However, not everyone is willing to sit and wait to see what his fate will be. Some patients choose traditional treatment for sarcoidosis, which is usually represented by various herbs, breathing exercises and other alternative options. But none of them is able to influence the prognosis, and if the patient does recover, it will certainly not be from such treatment, although he will be more confident of a favorable outcome.

Thus, if we consider the alternative treatment of early stage sarcoidosis as a possible “placebo effect”, which is known to work in 30-60% of patients, then it will not make you worse. However, if the patient’s condition quickly deteriorates and there is a need to prescribe basic therapy, then abandoning it in favor of alternative therapy is very risky.

Patients often ask doctors how long people with sarcoidosis live. However, there is no answer to this question. Most live long lives, as the disease rarely causes life-threatening conditions. The prognosis depends on many parameters: the nature of the course, the extent of the pathological process, the initial state of health. In each case, the outcome will be individual.

Sarcoidosis is a disease that is most often diagnosed in adults between the ages of 20 and 40. Unfortunately, sarcoidosis in children has also been reported in clinical practice. The pathology is characterized by the formation of clusters of immune cells, called granulomas, in various tissues and organs throughout the body.

Childhood sarcoidosis is extremely rare and its true prevalence is unknown. According to Danish study, the incidence rate is 0.22-0.27 cases per 100,000 children, and the pathology often manifests itself in early adolescence.

Types of sarcoidosis in children

Pediatric sarcoidosis is a systemic disease with an undulating course, when periods of exacerbation are systematically replaced by remission. The frequency of exacerbations depends on the age of onset of sarcoidosis.

• Early sarcoidosis develops in children under 4 years of age, and manifests itself in the form of a triad: rash, arthritis and uveitis ().
• Late sarcoidosis is observed in children 13-15 years old; the disease is multisystemic and symptoms are predominantly similar to those in adult patients. Pathology most often in this case affects the respiratory system.

Symptoms of sarcoidosis in children

Late childhood sarcoidosis is more common than early childhood sarcoidosis. Regardless of the fact that the disease manifests itself primarily in the lungs, pathological processes can also be observed in other organs of the child.

Children often experience enlarged intrathoracic lymph nodes (in the late form), skin rashes and eye damage like uveitis (more often in the early form of sarcoidosis).

Early-onset sarcoidosis is often mistaken for juvenile rheumatoid arthritis because both diseases are associated with nonspecific symptoms: loss of weight, loss of appetite, fever, and fatigue. Paying close attention to the skin rash can help doctors differentiate between the two conditions.

In addition, arthritis in these pathologies is also different: with sarcoidosis, inflammation of the joints in a child does not lead to limitation of movements and is not painful, while with rheumatoid arthritis, exactly the opposite happens.

Diagnosis of childhood sarcoidosis

Making a diagnosis of sarcoidosis in children is extremely difficult because the disease is variable at this age and often manifests itself as other pathological conditions. The correct diagnosis depends on the assessment of clinical symptoms and confirmation of the presence of granulomas using imaging or analysis of biopsy material, similar to tests.

Treatment of sarcoidosis in children

Corticosteroids are the main form of treatment for children with sarcoidosis. Dosage and timing of treatment should be tailored to each patient. Treatment is continued until significant improvement occurs, then the dose is gradually reduced.

Some children may experience worsening after a period of successful treatment. When this happens, children may need to start taking steroid medications again. In some cases, immunosuppressants, which suppress the activity of the immune system, may be used instead of or in combination with steroids.

The influence of heredity on sarcoidosis in children

The exact cause of sarcoidosis, including the childhood type, is unknown. Familial cases of sarcoidosis exist and hint at a genetic component as a possible cause of the disease.

For example, mutations in a gene called NOD2 have been associated with children. However, there is only limited evidence to support a potential link between childhood sarcoidosis and genetics, as many children with the disease do not have the NOD2 gene mutation.

Sarcoidosis is a chronic disease of unknown origin, which is based on granulomatous inflammation of many organs. It is most common among young people, but sometimes develops in children.

Granulomas with sarcoidosis resemble those that form during mycobacterial and fungal infections or hypersensitivity to organic chemicals. These similarities have led to speculation about the role of microbes or organic pollutants as causes of sarcoidosis, but despite extensive research this has not been proven.

It is found throughout the world and among all ethnic groups. In the southeastern United States, the disease is found more often among African Americans than among whites. Familial cases suggest a role for genetic factors, but the mode of inheritance remains unknown.

Granulomas can appear in almost any organ. In typical granulomas there is no caseous necrosis; they consist of epithelioid cells, macrophages and giant cells surrounded by monocytes, lymphocytes and fibroblasts. Activated lymphocytes and macrophages in granulomas release various inflammatory mediators, including IL-1, IL-2, IFN, and other cytokines that support inflammation.

In the active stage diseases Granulomas contain predominantly T helper cells (CD4). Healing usually occurs without damage to the organ parenchyma, but in approximately 20% of cases, fibroblasts at the periphery of the granuloma proliferate and fibrous scars form in the tissue. Macrophages in granulomas secrete 1,25-(OH)2-D3, the active form of vitamin D, which is normally produced in the kidneys. Excess vitamin D leads to hypercalcemia and hypercalciuria.

Initial clinical manifestations are extremely varied and depend on the damage to certain organs, but in children the disease usually begins with weight loss, cough, fatigue, pain in bones and joints, and anemia. As in adults, the lungs are most often affected, but the extent and nature of the damage varies greatly. X-rays reveal infiltrates in the parenchyma of the organ, multiple small nodules, and enlargement of the hilar and paratracheal lymph nodes.

At research Pulmonary function reveals mainly restrictive changes. Peripheral lymphadenopathy, eye lesions (uveitis or iritis), skin and liver lesions are common. Children under 4 years of age sometimes develop a special form of sarcoidosis, characterized by a large patchy erythematous rash, uveitis and arthritis without lesions of the lung tissue. The joint disease (which can be mistaken for juvenile rheumatoid arthritis) is accompanied by pain and effusion in the tendon sheaths and some limitation of movement.

Any specific diagnostic indicators does not exist. Common findings include increased ESR, hyperproteinemia, hypercalcemia, hypercalciuria, eosinophilia, and elevated ACE levels. The Kveim test - intradermal injection of material from sarcoidosis granulomas with examination of a skin biopsy several weeks later - is not sensitive and specific enough; in addition, it is difficult to obtain standardized material for administration. Therefore it is rarely used. Definitive diagnosis requires detection of characteristic noncaseating granulomas in biopsies of affected tissues.
All patients sarcoidosis It is necessary to regularly check the condition of the eyes and kidneys, since changes in these tissues are not always accompanied by clinical symptoms.

Due to the variety of manifestations sarcoidosis in the differential diagnosis, it is necessary to exclude many diseases, including tuberculosis, pneumomycosis (histoplasmosis, blastomycosis, coccidioidomycosis), lymphoma, Crohn's disease and inflammatory eye diseases (phlyctenular conjunctivitis).

Treatment of sarcoidosis symptomatic. Because the prognosis and natural history of sarcoidosis in children are uncertain, it is often difficult to decide to use potentially dangerous therapies. Spontaneous recovery may occur over several months or years; in other cases, the disease becomes chronic and lung damage progresses. Corticosteroids weaken acute inflammatory changes in eye tissue, slow down the progression of processes in the lungs and reduce hypercalcemia and hypercalciuria.

In severe cases that cannot be treated corticosteroid therapy, methotrexate can be used. Eye damage can lead to blindness. Therefore, local use of corticosteroids is justified, although it requires careful monitoring of patients.
Periodic study external respiration function allows you to assess the dynamics of the process in the lungs. The level of ACE can indicate the activity of the disease.

Sarcoidosis (D86), Pulmonary Sarcoidosis (D86.0)

Pulmonology

General information

Brief description

Ministry of Health of the Russian Federation
Russian Respiratory Society

Diagnosis and treatment of sarcoidosis(Federal Consensus Clinical Guidelines)

DEFINITION

Sarcoidosis is a systemic inflammatory disease of unknown origin, characterized by the formation of non-caseating granulomas, multisystem involvement with a certain frequency of involvement of various organs, and activation of T cells at the site of granulomatous inflammation with the release of various chemokines and cytokines, including tumor necrosis factor (TNF-alpha). The clinical signs of sarcoidosis are varied, and the lack of specific diagnostic tests makes non-invasive diagnosis difficult. Variations in the presentation of this disease suggest that sarcoidosis has more than one cause, which may contribute to different clinical course (phenotypes) of the disease.

Classification

Phenotypes (special variants of the course) of sarcoidosis
1. By localization
a. Classic, with a predominance of intrathoracic (pulmonary) lesions
b. With a predominance of extrapulmonary lesions
c. Generalized
2. According to the characteristics of the flow
a. With an acute onset of the disease (Löfgren's, Heerfordt-Waldenström syndromes, etc.)
b. With an initially chronic course.
c. Relapse.
d. Sarcoidosis in children under 6 years of age.
e. Sarcoidosis refractory to treatment.

Currently, sarcoidosis of the chest is divided into 5 stages (from 0 to IV). This classification is used in most foreign and some domestic works and is included in the international agreement.

Stage	X-ray picture	Frequency occurrence
STAGE 0	There are no changes on the chest x-ray.	5%
STAGE I	Lymphadenopathy of the intrathoracic lymph nodes; the lung parenchyma is not changed.	50%
STAGE II	Lymphadenopathy of the intrathoracic lymph nodes; pathological changes in the lung parenchyma.	30%
STAGE III	Pathology of the pulmonary parenchyma without lymphadenopathy of the hilar lymph nodes.	15%
STAGE IV	Irreversible pulmonary fibrosis.	20%

The concept of stages in respiratory sarcoidosis is quite arbitrary; the transition of the disease sequentially from stage to stage is rarely observed. Stage 0 indicates only the absence of damage to the lungs and intrathoracic lymph nodes, but does not exclude sarcoidosis of another location. In this regard, clinical and radiological forms of sarcoidosis should be distinguished: sarcoidosis of the upper lymph nodes, sarcoidosis of the upper lymph nodes and lungs, pulmonary sarcoidosis, as well as sarcoidosis of the respiratory system, combined with a single lesion of other organs and generalized sarcoidosis. To describe the course of the disease, the concepts of active phase (progression), regression phase (spontaneous or under the influence of treatment) and stabilization phase (stationary phase) are used. Complications include bronchial stenosis, atelectasis, pulmonary and pulmonary-heart failure. Pneumosclerosis, pulmonary emphysema, incl. bullous, fibrous changes in the roots.

To characterize the course of the disease, the concept of progressive, stationary (stable) and recurrent sarcoidosis is used. Left to its natural course, sarcoidosis can regress, remain stationary, progress within the initial stage (form) or with transition to the next stage or with generalization, and proceed in waves.

In the International Classification of Diseases, 10th revision, sarcoidosis is classified as a disease of the blood, hematopoietic organs and immunological disorders:

ICD-10:

D50- DCLASS 89III. Diseases of the blood, hematopoietic organs and certain disorders involving the immune mechanism

D86 Sarcoidosis
D86.0 Pulmonary sarcoidosis
D86.1 Sarcoidosis of the lymph nodes.
D86.2 Sarcoidosis of the lungs with sarcoidosis of the lymph nodes
D86.3 Sarcoidosis of the skin
D86.8 Sarcoidosis of other specified and combined locations
Iridocyclitis in sarcoidosis +(H22.1*)
Multiple cranial nerve palsies in sarcoidosis +(G53.2*)

Sarcoidosis:
athropathy +(M14.8*)
myocarditis +(I41.8*)
myositis +(M63.3*)

D86.9 Sarcoidosis, unspecified.

Etiology and pathogenesis

MORPHOLOGY OF SARCOIDOSIS

The morphological substrate of sarcoidosis is epithelioid cell granuloma - a compact accumulation of mononuclear phagocytes - macrophages and epithelioid cells, with or without the presence of giant multinucleated cells, lymphocytes and granulocytes. The processes of cell transformation and differentiation are regulated by cytokines - low molecular weight proteins produced by cells of the immune system.

More often than other organs, sarcoidosis affects the lungs and intrathoracic lymph nodes (up to 90% of cases). Each granuloma in sarcoidosis goes through several stages of development: 1) early - an accumulation of macrophages, sometimes with an admixture of histiocytes, lymphocytes, neutrophils, 2) a granuloma with an accumulation of epithelioid cells in the center and macrophages along the periphery, 3) epithelioid-lymphocytic granuloma 4) the appearance of giant multinucleated cells (first “foreign body” cells, and subsequently Pirogov-Lanhhans cells), 5) early cellular necrosis in the center of the granuloma due to pyknosis of nuclei, the appearance of apoptotic bodies, necrosis of epithelial cells, 6) central fibrinoid, granular, coagulation necrosis, 7) granuloma with partial fibrosis, sometimes reminiscent of amyloid; when stained with silver, reticulin fibers are revealed, 8) hyalinizing granuloma. However, biopsy specimens almost always reveal granulomas at various stages of development, and there is no correspondence between the clinical, radiological and morphological stages of the process in sarcoidosis.

The process of organizing granulomas begins from the periphery, which gives them a clearly defined, “stamped” appearance. Domestic authors distinguish three stages of granuloma formation - proliferative, granulomatous and fibrous-hyalinous. Granulomas in sarcoidosis are usually smaller in size than in tuberculosis and are not characterized by fusion. With sarcoidosis, central necrosis may develop in 35% of cases, however, it is usually point-like and poorly visualized. In this case, in the center of the granuloma there may be an accumulation of cellular detritus and necrotic giant cells. Small necrobiotic foci or single apoptotic cells should not be regarded as fibrosis. In the initial stage of necrosis formation, neutrophils can be detected. Sarcoid granulomas heal either by characteristic concentric fibrosis or as homogeneous hyaline bodies. Unlike sarcoidosis, tuberculous granulomas heal in the form of linear or stellate scars, or lymphohistiocytic accumulations remain in their place.

Monocytes, tissue macrophages and epithelioid cells have a common origin and belong to the mononuclear phagocytic system. Epithelioid cells are larger than macrophages, their size is 25-40 µm, they have a centrally or eccentrically located nucleus with nucleoli and heterochromatin. A significant number of lymphocytes in lung tissue in sarcoidosis are represented predominantly by T cells. Lymphocytes are usually numerous and clearly visible in histological sections along the periphery of granulomas.

Giant cells are formed by the fusion of mononuclear phagocytes, however, their phagocytic activity is low. At first, giant cells contain randomly located nuclei - cells of the “foreign body” type; subsequently, the nuclei shift to the periphery, which is characteristic of Pirogov-Lanhhans cells. Sometimes giant cells may contain inclusions in the cytoplasm, such as asteroid bodies, Schaumann bodies, or crystalloid structures.

Asteroid inclusions are also found in the cytoplasm of giant cells in various granulomatoses. In sarcoid granulomas they are detected in 2-9% of patients. Hamazaki-Wesenberg bodies are also found in sarcoidosis. These bodies are found in granulomas, in the areas of peripheral sinuses of lymph nodes inside giant cells and extracellularly. They are also called yellow or spiral bodies. These are oval, round or elongated structures measuring 0.5-0.8 microns, containing lipofuscin. Slit-like (needle-like) crystalloid structures, which are cholesterol crystals, occur in more than 17% of patients with sarcoidosis. Also in sarcoidosis, the presence of centrospheres is described - defined clusters of vacuoles in the cytoplasm of giant cells. When stained with hematoxylin and eosin, these structures may resemble mushrooms.

When examining biopsy specimens of the bronchi and lungs in granulomatous diseases, as a rule, a disseminated lesion with vasculitis, perivasculitis, and peribronchitis is detected; granulomas are most often localized in the interalveolar septa; sometimes diagnosis is complicated by developing fibrosis. Granulomatous lesions of the bronchi and bronchioles in sarcoidosis are common and are described in 15-55% of patients. In this case, the mucous membrane of the bronchi may not be changed; in a number of observations, it thickens, edema, and hyperemia occurs. A study of bronchobiopsies confirms the presence of granulomas in the bronchial wall in 44% with unchanged mucous membrane and in 82% with endoscopically visible changes. Granulomatous lesions of the bronchi can lead to bronchoconstriction with subsequent development of atelectasis. Bronchoconstriction may also be associated with the development of fibrosis and, extremely rarely, with compression of the bronchi by enlarged lymph nodes.

Vascular involvement in the pulmonary circulation is a common finding; the incidence of granulomatous angiitis can reach 69%. In some observations, the appearance of granulomas in the vessel wall is due to the growth of granulomas from perivascular pulmonary tissue, but in most cases, granulomas initially form in the vessel wall. In rare cases, sarcoid granulomas are found in the intima of the vessel.
It is believed that the development of alveolitis precedes the formation of granulomas. Alveolitis in sarcoidosis is characterized by the presence of inflammatory infiltration in the interstitium of the lung, with 90% of the cellular composition represented by lymphocytes.

ETIOLOGY OF SARCOIDOSIS
No guidelines currently provide precise information about the etiology of this disease, limiting them to a number of hypotheses.

Hypotheses related to infectious factors. The infection factor in sarcoidosis is considered a trigger: constant antigenic stimulation can lead to dysregulation of cytokine production in a genetically predisposed individual. Based on the results of studies published around the world, triggers of sarcoidosis may include:
- myocobacteria (classical and filterable forms)
- Chlamydophila pneumoniae ;
- Borrelia burgdorferi- causative agent of Lyme disease;
- Propionibacterium acnes commensal bacteria of the skin and intestines of a healthy person;
- certain types of viruses: hepatitis C virus, herpes virus, JC virus (John Cunningham).
The significance of the trigger theory is confirmed by the possibility of transmission of sarcoidosis from animal to animal in experiments, during organ transplantation in humans

Environmental hypotheses. Inhalation of metal dust or smoke can cause granulomatous changes in the lungs, similar to sarcoidosis. Dusts of aluminum, barium, beryllium, cobalt, copper, gold, rare earth metals (lanthanides), titanium and zirconium have the ability to stimulate the formation of granulomas. The international ACCESS study found an increased risk of sarcoidosis among people employed in industries exposed to organic dust, especially those with white skin. An increased risk of sarcoidosis was noted among workers who worked with construction and gardening materials, as well as among teachers. The risk of sarcoidosis was also higher among people who worked in contact with children. There have been isolated studies linking sarcoidosis to inhalation of toner powder. American researchers noted that there are quite convincing studies indicating that agricultural dust, mold, work in fires and military service associated with contact with mixed dust and smoke are risk factors for the development of sarcoidosis.

Smoking in sarcoidosis has two different effects. In general, sarcoidosis was significantly less common among smokers, however, smokers suffering from sarcoidosis had lower values ​​of pulmonary function, interstitial changes were more common, and the level of neutrophils in the BAL fluid was higher. In heavy smokers, the diagnosis is made late because sarcoidosis is hidden by other symptoms.

Hypotheses related to heredity. Prerequisites for possible inherited susceptibility to sarcoidosis include familial cases of this disease, the first of which was described in Germany in two sisters in 1923. Family members of people with sarcoidosis are several times more likely to develop sarcoidosis than other people in the same population. The multicenter study ACCESS (A Case-Control Etiology Study of Sarcoidosis) showed that among first- and second-level relatives of a patient with sarcoidosis, the risk of the disease is significantly higher than in the general population. In the United States, familial sarcoidosis occurs in 17% of cases among African-Americans and 6% among whites. The phenomenon of familial sarcoidosis admits the presence of specific genetic causes.

The most likely hereditary factors are:
- chromosome loci responsible for leukocyte antigens of the human major histocompatibility complex (HLA);
- polymorphism of tumor necrosis factor genes - TNF-alpha;
- polymorphism of the antiotensin-converting enzyme (ACE) gene;
- polymorphism of the vitamin D receptor gene (VDR);
- other genes (there are still separate publications).

The role of macrophages and lymphocytes, key cytokines. The basis of the immunopathogenesis of pulmonary sarcoidosis is a delayed-type hypersensitivity reaction (DTH). This type of immune inflammation represents the effector phase of a specific cellular response. The classic HRT reaction includes the following processes of immunoreactivity: activation of the vascular endothelium by cytokines, recruitment of monocytes and lymphocytes from the bloodstream and tissues to the site of HRT, activation of the functions of alveolar macrophages by lymphokines, elimination of the causative antigen and tissue damage by secretion products of activated macrophages and lymphocytes. The most common effector organ of inflammation in sarcoidosis is the lungs; lesions of the skin, heart, liver, eyes and other internal organs can also be observed.

In the acute phase of development of HRT, an antigen that persists in the body and is difficult to destroy stimulates the secretion of IL-12 by macrophages. Activation of T lymphocytes by this cytokine leads to suppression of the cytokine-secreting function of Th2 lymphocytes and to increased secretion of IFN-γ, TNF-α, IL-3, GM-CSF by Th1 lymphocytes, which activate macrophages/monocytes, contributing not only to the stimulation of their production, but also their migration from the bloodstream to the site of inflammation. Failure to eliminate the antigenic stimulus causes macrophages to differentiate into epithelioid cells that secrete TNF-α. Subsequently, some epithelioid cells fuse to form multinucleated giant cells.
The granulomatous type of inflammation, which is based on the HRT reaction, is characterized by the activation of type 1 T helper cells. One of the key cytokines for inducing a cellular immune response in the lungs is IL-12. The interaction of IL-12 with specific receptors on the surface membrane of lymphocytes leads to the activation of g-INF synthesis and the development of a Th1 cell clone.

The progressive course of sarcoidosis is characterized by the following indicators:

1. High levels of chemokines in BALF and in the supernatants of BALF cells - CXC chemokines (MIP-1, MCP-1, RANTES), as well as CC chemokine - IL-8. It is these chemokines that are responsible for the recruitment of inflammatory effector cells into the lung tissue.
2. Increased levels of expression of IL-2 and INF-g, as well as CXCR3, CCR5, IL-12R, IL-18R by CD4+ lymphocytes of BALF.
3. The level of TNF-a synthesis by alveolar macrophages has the greatest prognostic value. Using this criterion, it is possible to identify a group of patients in whom the disease will progress in the near future and may enter the stage of formation of pneumofibrosis.

Epidemiology

EPIDEMIOLOGY OF SARCOIDOSIS

The detection of sarcoidosis is closely related to the level of knowledge of doctors about the signs of this disease, since sarcoidosis is considered to be the “great imitator”. Intrathoracic forms of the disease are most often detected during fluorographic and radiographic examination, after which the patient is immediately sent to a phthisiatrician (to rule out tuberculosis) and/or to a pulmonologist for further examination and observation. When presenting with complaints, articular, skin, ocular, neurological (other localizations - less often) manifestations of sarcoidosis are most often detected. The process of diagnosing sarcoidosis is far from perfect, and until 2003, when all patients with sarcoidosis were under the supervision of phthisiatricians, every third patient underwent trial anti-tuberculosis therapy and almost everyone received preventive therapy with isoniazid. Currently, this practice is recognized as irrational.

Morbidity sarcoidosis in Russia has not been sufficiently studied; according to available publications, it ranges from 2 to 7 per 100 thousand of the adult population.

Prevalence sarcoidosis in Russia varies from 22 to 47 per 100 thousand adult population and depends on the availability of centers and specialists. In Kazan in 2002, the first active screening of these patients was carried out, the prevalence was 64.4 per 100 thousand. The prevalence of sarcoidosis among African-Americans reaches 100 per 100 thousand, in Scandinavian countries - 40-70 per 100 thousand population, and in Korea, China, African countries, Australia - sarcoidosis is rare. There are ethnic characteristics of the manifestation of the disease - frequent skin lesions among black patients, a high prevalence of cardiac sarcoidosis and neurosarcoidosis - in Japan. The prevalence of familial sarcoidosis was 1.7% in the UK, 9.6% in Ireland and up to 14% in other countries, 3.6% in Finland and 4.3% in Japan. The greatest risk of developing sarcoidosis was found in siblings, followed by uncles, then grandparents, then parents. In Tatarstan, cases of familial sarcoidosis were 3%.

Fatal outcomes from sarcoidosis in Russia are relatively rare - from 0.3% of all observed and up to 7.4% of chronically ill patients. Their cause is mainly pulmonary heart failure, neurosarcoidosis, cardiac sarcoidosis, and during immunosuppressive therapy - as a consequence of the addition of a nonspecific infection and tuberculosis. Mortality from sarcoidosis is no more than 5-8%. In the USA, the mortality rate from sarcoidosis is 0.16-0.25 per 100 thousand adults. Mortality from sarcoidosis in reference samples reaches 4.8%, which is more than 10 times than in the population sample (0.5%). In the reference sample, corticosteroids were prescribed 7 times more often than in the population, and this factor was highly correlated with mortality. This led to the conclusion that excessive use of steroids in sarcoidosis may adversely affect the prognosis of this disease.

Diagnostics

CLINICAL DIAGNOSIS

History (exposure to environmental and occupational factors, symptoms)
Physical examination
Plain X-ray of the chest organs in frontal and lateral projections
RCT of the chest organs
Respiratory function testing: spirometry and DLco
Clinical blood test: white blood, red blood, platelets
Blood serum content: calcium, liver enzymes (ALAT, AST, ALP), creatinine, blood urea nitrogen
General urine test
ECG (Holter monitoring if indicated)
Examination by an ophthalmologist
Tuberculin skin tests

Anamnesis collection, complaints. Patients with acute sarcoidosis describe their condition most vividly: Löfgren's syndrome, which is easily recognized on the basis of acute fever, erythema nodosum, acute arthritis of the ankles and bilateral hilar lymphadenopathy, clearly visible on a direct and lateral plain chest radiograph.

Weakness. The frequency of fatigue and fatigue varies from 30% to 80% depending on age, gender, race and may not have a direct correlation with damage to certain organs involved in the granulomatous process.

Pain and discomfort in the chest are common and unexplained symptoms. Chest pain in sarcoidosis does not have a direct connection with the nature and extent of changes detected even on RCT. Patients often note discomfort in the back, burning in the interscapular area, and heaviness in the chest throughout the entire active period of the disease. The pain can be localized in the bones, muscles, joints and does not have any characteristic signs.

Dyspnea may have various causes - pulmonary, central, metabolic and cardiac origin. Most often, it is a sign of increasing restrictive disorders and a decrease in the diffusion capacity of the lungs. When detailing the complaint, the patient usually characterizes shortness of breath as a feeling of lack of air, and the doctor specifies whether it is inspiratory, expiratory, or mixed.

Cough with sarcoidosis it is usually dry. When the intrathoracic lymph nodes are enlarged, it may be caused by compartment syndrome. At the same time, in the later stages, cough is a consequence of extensive interstitial changes in the lungs, and relatively rarely - a consequence of damage to the pleura.

Fever- characteristic of the acute course of Löfgren's syndrome or Heerfordt-Waldenström syndrome - “uveoparotid fever”, when the patient, along with fever, has enlarged parotid lymph nodes, anterior uveitis and paralysis of the facial nerve (Bell's palsy). The incidence of fever in sarcoidosis varies from 21% to 56%.

Joint syndrome most pronounced in Löfgren's syndrome, but can occur as an independent symptom. Pain and swelling may occur in the ankles, fingers and toes, and less commonly in other joints, including the spine. Joint syndrome is divided into acute, which can pass without consequences, and chronic, which leads to deformation of the joints.

Decreased visual acuity and/or blurred vision- may be important signs of sarcoidous uveitis, which requires mandatory ophthalmological examination and active treatment.

Unpleasant sensations from the heart, palpitations or bradycardia, a feeling of irregularities - may be a sign of heart damage from sarcoidosis, which is one of the most serious manifestations of this disease, leading to sudden cardiac death. According to the clinical manifestations of sarcoidosis of the cardiovascular system, three main syndromes are distinguished: pain (cardiac), arrhythmic (manifestations of rhythm and conduction disturbances) and circulatory failure syndrome. Infarction-like and myocardial variants of the course of cardiac sarcoidosis have also been described. The diagnosis of cardiac sarcoidosis is based on the results of instrumental examinations and, if possible, a biopsy.

Neurological complaints varied. Bell's palsy, a unilateral paralysis of the facial nerve, is considered pathognomonic for sarcoidosis, which is considered to be a sign of a favorable prognosis. Cerebral disorders manifest themselves in advanced stages of sarcoidosis, since neurosarcoidosis can be asymptomatic for quite a long time. The complaints are nonspecific: a feeling of heaviness in the occipital region, decreased memory for current events, headaches that increase over time, meningeal symptoms without fever, moderate paresis of the limbs. In sarcoidosis with “volumetric” brain damage, epileptiform seizures and mental changes develop. There have been cases of stroke-like onset followed by severe neurological deficits. The volume of neurological damage is determined by the death of nerve cells and the destruction of interneuron connections between surviving neurons.

Inspection is a critical aspect of the diagnosis of sarcoidosis, since the skin is affected quite often and can be biopsied. Erythema nodosum is an important but nonspecific sign, its biopsy has no diagnostic value. Nodules, plaques, maculopapular changes, lupus pernio, cicatricial sarcoidosis are specific for sarcoidosis. Manifestations of cutaneous sarcoidosis are likely to occur in areas of the skin where foreign bodies may have entered (scars, scars, tattoos, etc.). Detection of skin changes and histological examination of them can sometimes avoid endoscopic or open diagnostic operations. Detection of enlarged salivary glands (mumps) is of great clinical importance in sarcoidosis of younger children.

Physical examination may not detect pulmonary pathology even with pronounced changes on chest x-rays. Palpation can reveal painless, mobile, enlarged peripheral lymph nodes (usually cervical and inguinal), as well as subcutaneous lumps - Darier-Roussy sarcoids. Steto-acoustic changes occur in approximately 20% of patients with sarcoidosis. It is important to assess the size of the liver and spleen. Obvious clinical signs of respiratory failure are detected in sarcoidosis of the respiratory organs relatively rarely, as a rule, in the case of the development of pronounced pneumosclerotic changes and stage IV.

Damage to organs and systems in sarcoidosis

Lung damage in sarcoidosis is the most common, its manifestations form the basis of these recommendations.

Skin changes in sarcoidosis occur with a frequency of 25% to 56%. Skin changes in sarcoidosis can be divided into reactive ones - erythema nodosum, which occurs during the acute and subacute course of the disease, and skin sarcoidosis itself - specific polymorphic disorders that are difficult to visually recognize and require a biopsy.
Erythema nodosum ( Erythema nodosum ) is a vasculitis with primary destructive-proliferative damage to arterioles, capillaries, and venules. Perivascular histiocytic infiltration is observed in the dermis. Signs of septal panniculitis are observed. The subcutaneous fat septa are thickened and infiltrated by inflammatory cells, which extend to the periseptal areas of the fat lobules. Thickening of the septa is caused by edema, hemorrhage and neutrophil infiltration. The histopathological marker of erythema nodosum is the presence of so-called Miescher radial granulomas - a type of necrobiosis lipoidica - which consist of well-defined nodular clusters of small histiocytes arranged radially around a central cleft. Erythema nodosum does not contain sarcoid granulomas; a biopsy of its elements has no diagnostic significance.. In sarcoidosis, erythema nodosum often manifests itself as part of Löfgren's syndrome, which makes it advisable conducting direct plain radiography in frontal and lateral projections to identify or exclude hilar lymphadenopathy.
Typically, erythema nodosum nodes regress spontaneously within a few weeks, and simply rest and bed rest are often sufficient treatment. Aspirin, NSAIDs, and potassium iodide help relieve pain and resolve the syndrome. Systemic corticosteroids can quickly eliminate the manifestations of erythema nodosum. We should not forget about the high probability of spontaneous remission of sarcoidosis, and erythema nodosum itself is not an indication for prescribing SCS for sarcoidosis.

Sarcoidosis of the skin occurs with a frequency of 10-30% or almost every 3rd patient with systemic sarcoidosis, which makes a thorough examination of the skin of a patient with sarcoidosis highly important. Skin lesions may be the first noticeable manifestation of the disease. Nodules, plaques, maculopapular changes, lupus pernio, cicatricial sarcoidosis are specific for sarcoidosis. Rare manifestations include lichenoid, psoriasiform, ulcers, angiolupoid, ichthyosis, alopecia, hypopigmented macules, nail lesions, and subcutaneous sarcoidosis. Sarcoidosis can also manifest as annular, indurative plaques - granuloma annulare. The following forms of cutaneous sarcoidosis are distinguished: clinically typical - Beck's cutaneous sarcoid - large-nodular, small-nodular and diffuse-infiltrative; lupus pernio of Besnier-Thenesson, Broca-Pautrier angiolupoid; subcutaneous Darrieus-Roussy sarcoids and atypical forms - spotted, lichenoid, psoriasis-like sarcoids, as well as mixed forms - small nodular and large nodular, small nodular and subcutaneous, small nodular and angiolupoid, diffuse-infiltrating and subcutaneous.
Sarcoidosis plaques usually localized symmetrically on the skin of the torso, buttocks, limbs and face, they are painless, clearly defined, raised areas of skin compaction with a purplish-bluish color along the periphery and atrophic, paler ones in the center. Plaques are one of the systemic manifestations of chronic sarcoidosis, combined with splenomegaly, damage to the lungs and peripheral lymph nodes, persist for a long time and require treatment. Histological examination of the plaque has a high diagnostic value.
The histological picture of skin sarcoidosis is most often characterized by the presence of a “naked” epithelioid cell granuloma, that is, without an inflammatory reaction around and inside the granuloma, without caseation (fibrinoid necrosis may occur); the presence of a different number of giant cells of the Pirogov-Langhans type and the type of foreign bodies; unchanged or atrophic epidermis. All these signs are used in the differential diagnosis of cutaneous sarcoidosis and tuberculous lupus.
Lupus pernio (Lupus pernio) - chronic lesions of the skin of the nose, cheeks, ears and fingers. The most common changes are in the skin of the nose, cheeks and ears, and less commonly in the forehead, limbs and buttocks; they cause serious cosmetic defects and thereby cause significant psychological suffering to patients. The affected areas of the skin are thickened, colored red, purple or violet due to the large number of blood vessels in the area of ​​​​changes. The disease is chronic, usually with relapses in winter. Lupus pernio, as a rule, is one of the components of chronic systemic sarcoidosis with damage to the lungs, bones, and eyes; it does not go away spontaneously, is often resistant to therapeutic and surgical interventions, and can be used as a marker of the effectiveness of treatment of systemic sarcoidosis.
Acute cutaneous sarcoidosis usually resolves spontaneously, whereas chronic cutaneous sarcoidosis causes aesthetic damage and requires treatment. Local application of GCS in the form of ointments, creams and intradermal injections of triamsinolone acetonide (3-10 mg/ml) is effective for limited skin lesions without pronounced systemic manifestations, when systemic GCS are not used or their dose must be reduced. Severe skin lesions and generalized sarcoidosis involving the skin are indications for systemic therapy, including systemic steroids, methotrexate, and antimalarial drugs.

Damage to the organ of vision in sarcoidosis are considered the most dangerous, requiring the attention of doctors and treatment, since inadequate assessment of the condition and untimely prescribed therapy can lead to a significant decrease and even loss of vision. The eyes are affected in sarcoidosis in approximately 25-36% of cases. 75% of them have anterior uveitis, 25-35% have posterior uveitis. There are lesions of the conjunctiva, sclera and iris. Eye damage requires active therapy, local and systemic. Untreated eye lesions can lead to blindness. Sarcoidosis is a possible cause of long-term inflammatory processes in the vascular tract of the eyes. 1.3-7.6% of patients with chronic uveitis and uveoretinitis have a sarcoid etiology. 13.8% of chronic granulomatous uveitis are sarcoid. With ocular sarcoidosis, 80% have systemic disorders (parotid and submandibular glands, lymph nodes of the roots of the lungs, pathology of the skeletal system, liver, spleen, skin and mucous membranes). Uveitis is a component of Heerfordt-Waldenström syndrome or “uveoparotid fever”, characteristic of sarcoidosis, when the patient, along with fever, has enlarged parotid lymph nodes, anterior uveitis and facial paralysis (Bell's palsy).
When uveitis of any nature is detected, long-term monitoring of the patient is necessary, since systemic sarcoidosis can be detected over the next 11 years. In addition, if uveitis preceded the diagnosis of sarcoidosis by 1 year or more, sarcoidosis should be regarded as chronic. Patients with sarcoidosis are advised to undergo an annual examination by an ophthalmologist with determination of visual acuity and examination with a slit lamp. Children under 5 years of age are characterized by a clinical triad of uveitis, skin lesions and arthritis. Involvement of the optic nerve by sarcoidosis is uncommon but is an indication for long-term treatment with corticosteroids.

Sarcoidosis of peripheral lymph nodes (LN), accessible palpation occurs in every fourth patient. More often, the process involves the posterior and anterior cervical lymph nodes, supraclavicular, ulnar, axillary and inguinal. The lymph nodes are densely elastic, do not soften and do not form fistulas. The appearance of sarcoidosis in peripheral lymph nodes or their involvement in the process is a poor prognostic sign. The course of the disease in this case can be recurrent. Histological examination of the removed lymph node and the detection of epithelial cell granulomas in it requires comparison with the clinic and damage to other organs for the differential diagnosis of sarcoidosis and sarcoid reaction.

Damage to the spleen in sarcoidosis. In sarcoidosis, splenomegaly occurs - an enlargement of the spleen, and hypersplenism - an enlargement of the spleen with an increase in the number of cellular elements in the bone marrow and a decrease in formed elements in the peripheral blood (red blood cells, leukocytes or platelets). The incidence of splenic involvement varies from 10% to 40%. Changes are detected by ultrasound, MRI and CT studies and are the basis for differential diagnosis with neoplastic and infectious diseases. Changes in the spleen have the character of foci or foci, the size of the organ increases (homogeneous splenomegaly).
Splenomegaly may present clinically with abdominal discomfort and pain. Systemic effects may include thrombocytopenia with purpura and agranulocytosis. Sarcoidosis may affect the spleen and skull bones without intrathoracic pathology; cases of splenomegaly and hypersplenism have been described in patients with multiple organ sarcoidosis.
Needle biopsy of the spleen (informativeness reaches 83%) under the control of computed tomography or ultrasound imaging is difficult if the size of the changed areas is small. It can be dangerous if the lesion is located close to the hilum or is localized on the periphery. In case of massive splenomegaly with pronounced systemic manifestations, splenectomy is performed. Sometimes splenectomy has a beneficial effect on the course of sarcoidosis. Splenic lesions in sarcoidosis are most often sensitive to SCS treatment.

Sarcoidosis of the hematopoietic system. Granulomas are an uncommon finding on bone marrow biopsy and can be associated with a wide range of infectious and non-infectious disorders. In this context, sarcoidosis is the most likely cause of granulomas in the bone marrow. Granulomas can also occur secondary, caused by taking medications (toxic myelopathy), as well as with myelopathy caused by HIV infection. In these cases, granulomas are small, associated with the underlying disease and difficult to recognize. To identify microorganisms, special staining is necessary. Fibrin annular granulomas (ring-like granulomas) are typical of Q fever, but can occur in reactive conditions, after drug therapy, and during other infectious diseases such as Lyme disease. One of the manifestations of non-caseating bone marrow granulomas may be fever of unknown origin in combination with lymphopenia. Most often, damage to the hematopoietic system is detected in multiple organ sarcoidosis.

Kidney damage with sarcoidosis it occurs in 15-30% of patients. The spectrum of clinical signs associated with renal involvement in sarcoidosis is quite wide, from subclinical proteinuria to severe nephrotic syndrome, tubulointerstitial disorders and renal failure. Kidney damage in sarcoidosis is caused by changes due to the formation of granulomas and nonspecific sarcoid-like reactions, including electrolyte imbalances and, above all, calcium metabolism disorders. Granulomas in the kidneys are most often localized in the cortex.
An important contribution to the development of nephropathy in sarcoidosis is made by calcium metabolism disorders, hypercalcemia and hypercalciuria. Calcium nephrolithiasis is detected in 10-15% of patients with sarcoidosis; in some patients, calcifications disappear when calcium metabolism is normalized.
It should be borne in mind that the detection of epithelioid cell granulomas in the kidneys in itself does not definitively confirm the diagnosis of sarcoidosis, since it can also occur in other diseases, for example, infections, drug-induced nephropathy, and rheumatic diseases.

Damage to the musculoskeletal system in sarcoidosis it often occurs, primarily in the form of articular syndrome, while lesions of bones and muscles are diagnosed much less frequently.
Joint damage in sarcoidosis it is included in the symptom complex of Löfgren's syndrome. The incidence of articular syndrome in acute sarcoidosis reaches 88%. Most often, arthritis is localized in the ankles, knees and elbows, and arthritis is often accompanied by erythema nodosum. Clinical manifestations disappear within a few weeks, chronic or erosive changes have been extremely rare and are always accompanied by systemic manifestations of sarcoidosis. Rheumatic manifestations of sarcoidosis, along with arthritis, may be accompanied by swelling of the soft tissues adjacent to the joint, tenosynovitis, dactylitis, bone damage and myopathy. There are 2 types of arthritis, differing in clinical course and prognosis. Acute arthritis in sarcoidosis often resolves spontaneously and without sequelae. Chronic arthritis, although less common, can progress and cause joint deformities. In this case, proliferative and inflammatory changes occur in the synovium, and noncaseating granulomas occur in half of the patients. Differential diagnosis is most often carried out with rheumatoid arthritis.
Sarcoidosis of bones occurs with varying frequency in different countries - from 1% to 39%. The most common is asymptomatic cystoid osteitis of the small bones of the hands and feet. Lytic lesions were rare, localized to the vertebral bodies, long bones, pelvis, and scapula, and were usually accompanied by visceral lesions. In the diagnosis, radiography, X-ray CT, MRI, PET, radioisotope scanning are informative, but only a bone biopsy allows us to confidently speak about the presence of granulomatosis. Damage to the bones of the fingers is manifested by bone cysts of the terminal phalanges and nail dystrophy; most often, this combination is a sign of chronic sarcoidosis. The scintigraphic picture is similar to multiple bone metastases.
Damage to the skull bones It is rare and manifests itself as cyst-like formations of the lower jaw, extremely rarely - in the form of destruction of the bones of the skull.
Spinal lesions manifested by back pain, lytic and destructive changes in the vertebrae, and may be similar to ankylosing spondylitis.
Muscle sarcoidosis manifested by the formation of nodes, granulomatous myositis and myopathy. The diagnosis is confirmed by electromyography. Muscle biopsy reveals the presence of mononuclear cell infiltration with the formation of noncaseating granulomas.

Sarcoidosis of ENT organs and oral cavity accounts for 10-15% of sarcoidosis cases.
Sinonasal sarcoidosis occurs more often than other localizations of sarcoidosis in the ENT organs. Damage to the nose and paranasal sinuses in sarcoidosis occurs in 1-4% of cases. Sarcoidosis of the nose is manifested by nonspecific symptoms: nasal congestion, rhinorrhea, crusting on the mucous membrane, nosebleeds, nasal pain, and impaired sense of smell. Endoscopic examination of the nasal mucosa most often reveals a picture of chronic rhinosinusitis with nodes on the septum and/or in the nasal turbinates, with the formation of crusts; small sarcoid nodules can be detected. The most typical localization of changes in the mucous membrane is the nasal septum and superior turbinate. In rare cases, with sarcoidosis, destruction of the nasal septum, sinuses, and palate is observed, which creates serious differential diagnostic problems and requires mandatory histological verification of the diagnosis.
Sarcoidosis of the tonsils occurs as a manifestation of generalized sarcoidosis, much less often as an independent pathology. It can manifest as asymptomatic unilateral or bilateral enlargement of the palatine tonsils, in the tissue of which, after tonsillectomy, non-caseating granulomas characteristic of sarcoidosis were detected.
Sarcoidosis of the larynx(0.56-8.3%) is often a manifestation of multi-organ, systemic sarcoidosis and can lead to symptoms such as dysphonia, dysphagia, cough, and sometimes increased breathing due to obstruction of the upper respiratory tract. Sarcoidosis of the larynx can be detected by direct or indirect laryngoscopy: the tissues of the upper part of the larynx are symmetrically changed, the tissue is pale, swollen and similar to the tissue of the epiglottis. You can detect swelling and erythema of the mucous membrane, granulomas and nodes. The final diagnosis is confirmed by biopsy. Sarcoidosis of the larynx can lead to life-threatening airway obstruction. Inhaled and/or systemic steroids may be prescribed initially, but if symptoms persist and/or upper airway problems occur, corticosteroids may be injected into the affected area. In severe cases, tracheotomy, low-dose radiation therapy, and surgical excision are used.
Sarcoidosis of the ear refers to rare localizations of the disease and is usually combined with other localizations of the disease. Sarcoidosis of the ear is manifested by hearing loss, ringing in the ears, deafness, and vestibular disorders. Damage to the ear can be combined with damage to the salivary glands, often accompanied by paresis and paralysis of the facial nerve. Sarcoidosis can cause sensorineural hearing loss of varying severity. Cases with damage to the middle ear and conductive hearing loss have been reported. Granulomas are identified in the middle ear during diagnostic tympanotomy. The granulomatous process causes necrosis of the incus of the inner ear and surrounds the chorda tympani nerve. Ear involvement in sarcoidosis can be similar to many other ear diseases. Sarcoidosis is not suspected, and intrathoracic manifestations of the disease may be absent or go unnoticed. A combination of damage to several organs helps to suspect ear sarcoidosis.
Sarcoidosis of the mouth and tongue It is not common and can manifest itself as swelling and ulceration of the mucous membrane of the mouth, tongue, lips, and gums. Oropharyngeal sarcoidosis can cause obstructive sleep apnea as the only manifestation of the disease. Just as with sarcoidosis of other localizations, damage to the oral cavity and tongue can be either isolated or a manifestation of a systemic disease. Sarcoidosis of the oral cavity and tongue creates differential diagnostic problems. In case of histological confirmation of sarcoidosis of the oral cavity and tongue, further examination of the patient is necessary, aimed at searching for other localizations of sarcoidosis or the source of a sarcoid-like reaction. In cases of severe multiple organ damage, as a rule, the administration of systemic corticosteroids is required; in case of isolated damage, local use of anti-inflammatory drugs may be sufficient.

Sarcoidosis of the heart is one of the life-threatening manifestations of the disease, occurring in 2-18% of patients with sarcoidosis. The course of cardiac sarcoidosis is characterized by a certain autonomy, not coinciding with the phases of the process in the lungs and intrathoracic lymph nodes. There are fulminant (sudden cardiac death, infarction-like variant, cardiogenic shock), rapidly progressive (with an increase in the severity of manifestations to a critical level within a maximum of 1-2 years) and slowly progressive (chronic, with relapses and improvements) variants of cardiac sarcoidosis. Independent predictors of mortality are the functional class of circulatory failure (NC, according to the New York classification), end-diastolic size of the left ventricle (LV), and the presence of sustained ventricular tachycardia. Laboratory markers There are currently no drugs specific for cardiac sarcoidosis. The role of increased natriuretic peptides type A and B in patients with normal ejection fraction is discussed. The level of cardiac-specific enzymes and troponins increases extremely rarely. In patients with cardiac sarcoidosis, an increase in the titer of antibodies to the myocardium has been described without specifying the quantitative range. Frequency of detection of ECG pathology significantly depends on the nature of granulomatosis in the heart: 42% for the microscopic type and 77% for extensive granulomatous infiltration. To clarify the diagnosis, carry out myocardial scintigraphy with perfusion radiopharmaceuticals, cardiac MRI with delayed contrast enhancement with gadolinium diethyl pentaacetate, PET.

Neurosarcoidosis
Lesions of the nervous system occur in 5-10% of cases. The following clinical manifestations of neurosarcoidosis are distinguished:
1. Damage to the cranial nerves.
2. Damage to the membranes of the brain.
3. Hypothalamic dysfunction.
4. Lesions of the brain.
5. Lesions of spinal cord tissue.
6. Convulsive syndrome.
7. Peripheral neuropathy.
8. Myopathy.
The granulomatous process in sarcoidosis involves any parts of the central and peripheral nervous system, individually or in various combinations. Patients complain of chronic headaches of a dull, much less acute, and sometimes migraine nature; moderate, rarely intense, dizziness, usually in an upright position; swaying when walking, sometimes for several years; constant daytime sleepiness. The dominant place in objective neurological symptoms is occupied by dysfunction of the analyzers: vestibular, gustatory, auditory, visual, olfactory. In examining patients, CT and MRI studies are of leading importance. Sarcoidosis of the pituitary gland can manifest as dysfunction and impotence. Many nonspecific symptoms in sarcoidosis may indicate damage to small nerve fibers (small fiber neuropathy), the manifestation of which in 33% of cases is impotence. Clinical data, quantitative sensitivity testing, and skin biopsies suggest that small fiber neuropathy is a common finding in sarcoidosis. As a rule, patients with neurosarcoidosis require active treatment with SCS and immunosuppressants.

Sarcoidosis in gynecology

Sarcoidosis of the urinary tract. Sarcoidosis of the urethra in women occurred in isolated cases and was manifested by a decrease in the strength of the urine stream.

Sarcoidosis of the external genitalia is a very rare condition that manifests as nodular changes in the vulva and skin of the perianal area

Sarcoidosis of the ovaries and uterus. The most dangerous manifestation of sarcoidosis of the uterus is bleeding in postmenopause. The diagnosis is usually made accidentally after histological examination of material obtained during curettage or removal of the uterus.

Fallopian tube damage in sarcoidosis it was extremely rare in women with multiple organ damage.

Sarcoidosis of the breast often detected during examination for suspected breast cancer. It is diagnosed by biopsy of a dense, painless formation in the mammary gland based on the identification of multiple non-caseating granulomas.
Thus, sarcoidosis should not be considered as a condition that frequently and seriously impairs a woman’s reproductive function. In most cases, pregnancy can be saved, but in each case the issue must be resolved individually, and patronage of the pregnant woman should be carried out by both antenatal clinic doctors and sarcoidosis specialists.

Sarcoidosis in urology.
Sarcoidosis of the testis and appendages can occur both with intrathoracic lesions, with other extrathoracic manifestations, and without them. Sarcoidosis of the testis and appendages can be combined with oncopathology of the same location, or a granulomatous reaction can accompany the tumor process without being a sign of sarcoidosis.
Sarcoidosis of the prostate creates difficulties in differential diagnosis with prostate cancer, since it may be accompanied by elevated PSA levels.
Opinion about the active treatment of urogenital sarcoidosis in men is ambiguous: from the early use of glucocorticosteroids to prevent the development of male infertility to many years of observation without treatment and serious consequences; impotence in patients with sarcoidosis is very likely a consequence of damage to the pituitary gland and small fiber neuropathy.

Damage to the digestive system in sarcoidosis

Sarcoidosis of the salivary glands(6%) should be differentiated from changes in chronic sialadenitis, tuberculosis, cat scratch disease, actinomycosis and Sjogren's syndrome. It manifests itself as bilateral swelling of the parotid salivary glands, which is usually accompanied by damage to other organs. Occurs as part of a characteristic syndrome - Heerfordt-Waldenström) , when the patient has fever, enlarged parotid glands, anterior uveitis and facial paralysis (Bell's palsy).

Sarcoidosis of the esophagus extremely rare and difficult to diagnose localization. Traction diverticula are more common with granulomatous inflammation of the mediastinal lymph nodes; secondary achalasia due to sarcoidosis of the esophagus is described.
Sarcoidosisstomach occurs more often as granulomatous gastritis, can cause the formation of ulcers and gastric bleeding, formations similar to polyps during gastroscopy. In all patients, histological examination of biopsy specimens reveals noncaseating epithelioid cell granulomas.
Sarcoidosis of the intestine both thin and thick are presented in the literature by descriptions of individual cases confirmed by histological studies of biopsy specimens. May be combined with limited and massive abdominal lymphadenopathy.
Sarcoidosis of the liver referred to as a frequent (66-80% of cases) localization of the disease, often occurring latently. Multiple focal changes of reduced density have been described in the liver and spleen on RCT of the abdominal organs, even with a normal chest x-ray. Hepatopulmonary syndrome (HPS), characterized by a triad of severe liver pathology, arterial hypoxemia and intrapulmonary vascular dilatation, was rare in sarcoidosis. Liver sarcoidosis leads to cirrhosis and portal hypertension in only 1% of cases.
Pancreas It is rarely affected and changes may resemble cancer. Abdominal pain occurs in 2/3 of patients with sarcoidosis of the pancreas, and hilar lymphadenopathy occurs in 3/4 of cases. Chronically elevated lipase levels may be one of the primary signs to rule out sarcoidosis. In some cases, diabetes mellitus may develop as a result of sarcoidosis infiltration of the pancreas.

FUNCTIONAL STUDIES
A mandatory and quite informative method is spirometry. From the entire complex of spirometric examinations, forced expiratory spirometry should be used with determination of volumes (FVC, FEV 1 and their ratio FEV 1 / FVC%) and volumetric velocities - peak (POV), and instantaneous at the level of 25%, 50% and 75% from the beginning forced expiration (MOE 25, MOE 50 and MOE 75). In addition, it is advisable to determine the average volumetric velocity in the area from 25% to 75% FVC (SOS 25-75). Spirometry should be performed at least once every 3 months during the active phase of the process and annually during follow-up.

The second important method is to measure diffusion capacity of the lungs single breath method to assess the degree of carbon monoxide absorption ( DLco). This technique is usually available in pulmonary or diagnostic centers.
Assessment of lung compliance, based on measurement of intraesophageal and transdiaphragmatic pressure, is not recommended for widespread use, but can be used in centers involved in the diagnosis of sarcoidosis to assess the dynamics of the condition of patients with a pronounced interstitial process in the lungs.

Results of pulmonary respiratory function (RPF) studies in sarcoidosis very heterogeneous. In stage I, the state of the respiratory apparatus remains intact for a long time. As sarcoidosis progresses, changes occur that are characteristic of both interstitial lung lesions and hilar lymphadenopathy. Most patients with progressive sarcoidosis develop restrictive disorders, but endobronchially located granulomas can lead to the development of irreversible bronchial obstruction. The type of impairment does not strictly correlate with the stage of sarcoidosis (with the exception of stage IV). Thus, in patients with stage III sarcoidosis, both types of dysfunction of external respiration are described - with a predominance of obstruction and with a predominance of restriction.

Restrictive changes with progressive intrathoracic sarcoidosis, they are primarily due to increasing fibrosis of the lung tissue and the formation of a “honeycomb lung”. A decrease in VC (FVC) during a dynamic study indicates the need for active therapy or correction of treatment. To accurately diagnose restrictive syndrome, it is necessary to perform body plethysmography with assessment of total lung capacity (TLC) and residual volume (RR).

Obstructive syndrome in the early stages it is manifested by a decrease only in MOS 75 . Approximately half of the patients have reduced MOC 50 and MOC 75 in combination with a decrease in DLco. The classic test with a short-acting bronchodilator in patients with sarcoidosis is negative; the use of SCS does not improve the response to the bronchodilator. Some patients may experience improvement in obstruction after treatment with SCS or methotrexate. Bronchial hyperreactivity, proven by a methacholine test, often accompanies endobronchial sarcoidosis.
To assess the safety and reversibility of the functional state of the lungs during observation and treatment, FVC (VC) and DLco are the most informative

Diffusion capacity of the lungs (DLco) - an indicator that is included in the standard of mandatory examination for interstitial (diffuse, disseminated) lung diseases. In sarcoidosis, DLco is a highly informative and dynamic parameter. Cellular infiltration can deform the capillary bed and lead to reversible disturbances in gas exchange. More often, disorders of diffusion capacity in patients occur in stages II, III and IV of the disease, with dissemination of sarcoid foci and the development of pneumofibrosis.

Gas exchange disorders in sarcoidosis can be detected by measuring blood oxygen saturation (saturation, Sa0 2) during the 6-minute walk test (6MWT). In patients with stage II or higher sarcoidosis, 6MWD may be reduced. Factors limiting this distance were FVC, saturation during exercise, and self-assessed respiratory health status.

Violations of central respiratory function and muscle disorders. The lungs are affected in most cases of sarcoidosis, but respiratory failure is not necessarily a consequence of damage to the lungs themselves. Impaired respiratory regulation with hypoxemia requiring ventilatory support may be due to neurosarcoidosis (this should be taken into account when saturation is reduced in patients with sarcoidosis). A decrease in spirometry parameters may also be a consequence of muscle damage by sarcoidosis. Maximum oral pressure during inspiration (PImax) and during expiration (PEmax) are reduced in every third patient with sarcoidosis.

Cardiopulmonary stress tests are more sensitive indicators of early detection of lung disease than pulmonary function tests in patients with sarcoidosis. Changes in gas exchange during exercise may be the most sensitive method to reflect the prevalence of sarcoidosis in its early stages. In sarcoidosis, there is a decrease in maximum aerobic capacity (VO2max) by 20-30%. This was noted in patients with both normal and impaired respiratory function, which makes the mechanism of this phenomenon unclear. Explanations for hypoventilation could include muscle weakness or decreased stimulus from the central nervous system.

VISUALIZATION METHODS

Due to the difficulties of clinical and laboratory recognition of sarcoidosis in various organs, a decisive role in its diagnosis belongs to medical imaging methods, which include traditional X-ray techniques, computed tomography (CT), magnetic resonance imaging (MRI), radionuclide methods, ultrasound ( Ultrasound), including endoscopic ultrasound with fine-needle biopsy of lymph nodes.

Traditional X-ray techniques important in the primary diagnosis of intrathoracic sarcoidosis are verification fluorography and plain radiography in two projections. Radiography retains its importance in dynamic monitoring and evaluation of treatment effectiveness. Special X-ray techniques, such as linear tomography, contrast techniques, and x-ray functional techniques have now lost their practical significance and are replaced by computed tomography (CT). An X-ray of a patient with intrathoracic sarcoidosis reveals a symmetrical enlargement of the lymph nodes of the roots of the lungs and/or bilateral focal interstitial changes in the lungs. There is a characteristic discrepancy between the relatively satisfactory condition of the patient and the prevalence of the pathological process in the photographs. It should be remembered that an atypical radiological picture of sarcoidosis is possible - unilateral enlargement of the upper mediastinal lymph nodes or lymph nodes, unilateral dissemination, foci, infiltrates, cavities, bullae. In 5-10% of cases of sarcoidosis, there are no changes in the lungs on radiographs at all.
The X-ray method, while maintaining a leading place in the primary detection of pulmonary pathology, is gradually losing its importance in characterizing pulmonary disease. Moreover, the so-called radiological stages that form the basis for the classification of sarcoidosis do not reflect the chronology of the process; they are more accurately called types or variants of the course of the process. This became especially obvious when X-ray computed tomography became widely used in the diagnosis and monitoring of patients with sarcoidosis.

Computed tomography is currently the most accurate and specific method for diagnosing intrathoracic and extrapulmonary sarcoidosis.
Currently, two CT technologies are used in the diagnosis of sarcoidosis. The first of these is a traditional step-by-step study, in which individual thin tomographic slices (1-2 mm) are separated from each other by a distance of 10-15 mm. Such a study can be carried out on any tomograph. It allows you to obtain a detailed image of the smallest anatomical structures of the lung tissue and identify minimal pathological changes in it. The disadvantage of step-by-step technology is the selective image of the pulmonary parenchyma, the impossibility of constructing two and three-dimensional reformations, the difficulty of assessing soft tissue structures and blood vessels of the mediastinum, for which it is necessary to first perform a series of standard tomograms with a thickness of 8-10 mm.

The advent of multi-slice CT (MSCT) has significantly changed the approach to diagnosing pulmonary pathology. Tomographs with a multi-row detector allow one X-ray beam to be divided into several tomographic layers, from 4 to 300 or more. The advantage of MSCT is the ability to obtain a series of adjacent tomographic slices with a thickness of 0.5 - 1 mm. The result of spiral scanning with MSCT is the ability to construct two and three-dimensional reformations, as well as simultaneous HRCT and CT angiography.

Sarcoidosis is characterized by enlargement of the lymph nodes of all groups of the central mediastinum and the roots of the lungs, which is radiographically manifested by a bilateral expansion of the shadow of the mediastinum and the roots of the lungs, and the polycyclic nature of their contours. Lymph nodes have a spherical or ovoid shape, a homogeneous structure, smooth clear contours, without perifocal infiltration and sclerosis. With a significant increase in lymph nodes, causing external compression of the bronchi, changes characteristic of hypoventilation and atelectatic disorders may appear in the lungs. However, such changes are observed much less frequently than with tuberculosis or tumor lesions of the lymph nodes. With a long-term chronic course, calcifications appear in the structure of the lymph nodes in a third of patients. The latter in the CT image appear as multiple, bilateral, monolithic, irregularly shaped calcareous inclusions located away from the bronchi in the center of the lymph nodes.

The most characteristic sign of sarcoidosis is dissemination of a mixed, focal and interstitial nature. Most large ones show polymorphism of focal changes. Multiple small foci are located along the bronchovascular bundles, interlobar fissures, costal pleura, and in the interlobular septa, causing uneven (“bead-shaped”) thickening of the interstitial structures of the lungs. This type of distribution of foci along the pulmonary interstitium is defined in CT as perilymphatic, i.e. lesions arise and are visualized along the course of the lymphatic vessels. Unlike other diseases with a similar distribution of foci, such as lymphogenous carcinomatosis, in sarcoidosis it is focal changes in combination with peribronchial and pervascular couplings that predominate, while thickening of the interlobular and intralobular septa is observed to a much lesser extent. One of the manifestations of active sarcoidosis on HRCT may be a “ground glass” symptom of varying extent and localization. The morphological substrate of the ground glass symptom is a multitude of tiny foci that are indistinguishable on HRCT as independent formations or, in more rare cases, true “ground glass” is observed as a manifestation of diffuse thickening of the interalveolar septa due to alveolitis. Such changes must be differentiated from lymphogenous disseminated tuberculosis, allergic alveolitis and desquamative interstitial pneumonia.

The chronic relapsing course of sarcoidosis is characterized by the appearance of polymorphism of focal changes, in the form of an increase in the size of the lesions, deformation of their contours and merging into small zones of consolidation. Along with this, varying degrees of severity of infiltration and sclerosis of the interstitial structures of the lungs are determined. More or less large soft tissue conglomerates are formed around the upper lobe bronchi, inseparable from the anatomical structures of the root. In the structure of the soft tissue masses, deformed lumens of the bronchi are visible. Peribronchial conglomerates spread deep into the lung tissue along the bronchovascular bundles. In such infiltrates, cavities can form.

The fourth stage of intrathoracic sarcoidosis is characterized by fibrous transformation of the lung tissue of varying degrees with the formation of pleuropneumocirrhosis, degenerative changes, the development of honeycomb lung or emphysema. In most cases, extensive areas of pneumosclerosis form in the lung tissue in the form of zones of compaction of the lung tissue with dilated and deformed air gaps of the bronchi visible in them. Such changes are usually observed in the upper lobes, in the basal region. The volume of the upper lobes decreases. Which leads to swelling of the cortical and supradiaphragmatic parts of the lungs, and in the most severe cases - to the formation of bullous emphysema and honeycomb lung.

Magnetic resonance imaging(MRI) in patients with sarcoidosis has diagnostic capabilities similar to CT in detecting hilar lymphadenopathy. But in assessing the condition of the pulmonary parenchyma, MRI is significantly inferior to CT and therefore has no independent diagnostic value. MRI is informative in neuro- and cardiac sarcoidosis.

From radionuclide methods Studies for respiratory sarcoidosis use perfusion pulmonary scintigraphy with MMA-Tc-99m and positive pulmonary scintigraphy with Ga-67 citrate. Scintigraphic methods have an important diagnostic value for characterizing disturbances in pulmonary microcirculation and the function of lymph nodes, both in the area of ​​localization of the process and in intact parts of the lung, and make it possible to clarify the prevalence and degree of activity of the inflammatory process in patients with various courses of respiratory sarcoidosis.
However, radionuclide testing is not a method of nosological diagnosis and a positive result of pneumoscintigraphy with Ga-67 citrate is not diagnostic for sarcoidosis, since increased accumulation of radiopharmaceuticals in the lungs and VLN is found in tumors, metastatic lesions, various inflammatory and granulomatous diseases, and tuberculosis.

Positron emission tomography(PET) is one of the relatively new methods of radiological diagnostics. The most common indicator is 18-fluoro-2-dioxyglucose (18FDG). In addition, the clinic uses radiopharmaceuticals labeled with 13N and 15O. In sarcoidosis, PET allows one to obtain reliable information about the activity of the process, and in combination with anatomical imaging methods (CT, MRI) to identify the localization of increased metabolic activity, that is, the topography of active sarcoidosis. Treatment with prednisolone suppressed inflammatory activity to such an extent that it was undetectable by PET.

Endoscopic ultrasound examination with transesophageal fine-needle aspiration biopsy of the mediastinal lymph nodes, it is currently becoming the most promising method for the differential diagnosis of lymphadenopathy. The endoscopic echographic picture of the lymph nodes in sarcoidosis has some distinctive features: the lymph nodes are well delimited from each other; the structure of the nodes is isoechoic or hypoechoic with atypical blood flow. However, these features do not allow differentiating lymph node damage in sarcoidosis from tuberculosis or tumor.

Radiation diagnosis of extrapulmonary sarcoidosis. Ultrasound usually reveals multiple hypoechoic nodes, which are localized in both the liver and spleen. In some patients, CT examination will not only confirm hepatolienal changes, but also detect small focal changes and infiltrates in both lungs, with or without hilar lymphadenopathy. Computed tomograms, as a rule, show hepatomegaly with smooth or wavy contours and diffuse heterogeneity of the parenchyma. When contrasting, small foci of low density can be detected in the liver structure. In most cases, splenomegaly and enlarged lymph nodes in the hepatoduodenal ligament, in the hilum of the liver and spleen, and in peripancreatic tissue are also detected. CT changes in granulomatous diseases are nonspecific and require morphological verification.

In cardiac sarcoidosis, ultrasound reveals single lesions in the myocardium, including in the interventricular septum, measuring 3-5 mm. Lesions in the heart can become calcified over time. An ECG may record extrasystoles and conduction disturbances. With MRI, in the affected area of ​​the heart there may be an increase in signal intensity on T-2 weighted images and after contrast on T-1 weighted images. In rare cases, on CT, cardiac sarcoidosis may manifest itself as areas of myocardial thickening that weakly accumulate the contrast agent, but this sign is nonspecific and can only be considered in conjunction with clinical and laboratory data.
In neurosarcoidosis, MRI reveals hydrocephalus, dilatation of the basal cisterns, single or multiple granulomas, isointense on T-1 weighted tomograms and hyperintense on T-2 weighted images with good signal enhancement after contrast. Typical localization of sarcoids is the hypothalamus and the optic chiasm area. Vascular thrombosis with micro-strokes is possible. MRI is especially sensitive for meningeal lesions.

Sarcoidosis of bones and joints appears on radiographs and X-rays as cystic or lytic changes. MRI for musculoskeletal symptoms reveals infiltration of small and large bones, signs of osteonecrosis, arthritis, infiltration of soft tissues, space-occupying formations of various locations, myopathy and nodular formations in the muscles. It is important that of those patients in whom bone lesions were detected on MRI, X-ray examination showed similar changes in only 40% of cases.

INVASIVE DIAGNOSTIC METHODS
Pulmonary sarcoidosis requires differential diagnosis with a number of pulmonary diseases, which is based on morphological verification of the diagnosis. This makes it possible to protect such patients from the most often unreasonably prescribed anti-tuberculosis chemotherapy or chemotherapy with antitumor drugs. Systemic steroid therapy used as indicated for sarcoidosis should also be used only in the presence of a morphologically confirmed diagnosis, so as not to cause a sharp progression of the disease in people with an erroneous diagnosis of sarcoidosis.
Sarcoidosis refers to diseases in which only the study of tissue material allows one to obtain diagnostically significant data, in contrast to tuberculosis and some lung cancers, when it is possible to examine natural secretions (sputum) for the content of the pathogen or tumor cells.

Ideally, the diagnosis of sarcoidosis is established when clinical and radiological data are supported by the identification of non-caseating (without necrosis) epithelioid cell granulomas in a biopsy of lung tissue and/or lymph node and/or bronchial mucosa.
In patients with pulmonary sarcoidosis, morphological verification of the diagnosis should be carried out in all cases immediately after identifying radiological changes in the lymph nodes of the mediastinum and/or pulmonary tissue, regardless of the presence or absence of clinical manifestations. The more acute the process and the shorter its duration, the greater the likelihood of obtaining a biopsy containing structures typical for this disease (non-caseating epithelioid cell granulomas and foreign body cells).
In world practice (including in the Russian Federation), it is considered advisable to use the following biopsy methods for diagnosing pulmonary sarcoidosis:

Bronchoscopic:
· Transbronchial lung biopsy (TBL). It is performed during bronchoscopy with special micronippers, which move into the subpleural space under X-ray control or without it and biopsy the lung tissue there. As a rule, it is carried out in the presence of dissemination in the lung tissue, but in patients with sarcoidosis it is quite effective even with radiologically intact lung tissue.
· Classical transbronchial needle biopsy of intrathoracic lymph nodes - KCHIB VGLU (synonym transbronchial needle aspiration (VHLN), international abbreviation TBNA). It is carried out during bronchoscopy with special needles; the puncture site through the bronchial wall and the penetration depth are selected in advance according to computed tomography data. It is carried out only with a significant increase in the VGLU of certain groups.
· Endoscopic fine-needle puncture of mediastinal lymph nodes under endosonography control. It is carried out during endoscopy with an ultrasound bronchoscope or ultrasound gastroscope with special needles, “targeting” and the puncture itself are controlled by ultrasound scanning [EUSbook 2013]. Use only for enlarged VGLUs. There are the following types of these biopsies used for pulmonary sarcoidosis:

♦ Transbronchial fine-needle aspiration biopsy guided by endobronchial sonography EBUS-TTAB (international abbreviation - EBUS-TBNA) . Performed during bronchoscopy using an ultrasound bronchoscope.
♦ Fine-needle aspiration biopsy under endosonography control EUS-FNA (international abbreviation - EUS-FNA) (transesophageal using an ultrasound gastroscope). It is carried out during esophagoscopy with an ultrasound gastroscope.
♦ Fine-needle aspiration biopsy under endosonography control EUS-b-FNA (international abbreviation - EUS-b-FNA) (transesophageal using an ultrasound bronchoscope). It is carried out during esophagoscopy with an ultrasound bronchoscope.
· Direct biopsy of the bronchial mucosa (direct biopsy). Biting of the mucous membrane is performed during bronchoscopy. It is used only in the presence of changes in the mucosa characteristic of sarcoidosis.
· Brush biopsy of the bronchial mucosa (brush biopsy). Scarification is carried out and the layer of bronchial mucosa is removed with a special brush. It is used only in the presence of mucosal changes characteristic of sarcoidosis.
· Bronchoalveolar lavage (BAL), to obtain bronchoalveolar lavage (synonym - bronchoalveolar lavage fluid), is performed during bronchoscopy by injecting and aspirating saline into the bronchoalveolar space. The ratio of lymphocyte subpopulations has diagnostic value, but the cytogram is mainly used to determine the activity of sarcoidosis.

Surgical methodsbiopsy

Thoracotomy With biopsy lung And intrathoracic lymphatic nodes .
The so-called “open biopsy” is currently used extremely rarely due to its traumatic nature; its more gentle version is more often used - minithoracotomy, which also makes it possible to remove fragments of the lung and lymph nodes of any group.
During the operation, endotracheal anesthesia is used and an anterolateral thoracotomy is used through the 4th or 5th intercostal space, which provides an optimal approach to the elements of the lung root.
Indications For this type of surgical intervention, it is impossible at the preoperative stage to classify the process in the lung tissue and mediastinal lymph nodes as benign. Suspicious cases are isolated asymmetrical round shadows in combination with mediastinal lymphadenopathy, which are often manifestations of a blastomatous process in people over 50 years of age. In such cases, the diagnosis of respiratory sarcoidosis is a histological finding within the walls of oncological institutions.
Relative contraindications As with any abdominal surgery, there are unstable conditions of the cardiovascular and respiratory systems, severe liver and kidney diseases, coagulopathy, decompensated diabetes mellitus, etc.
Thoracotomy is accompanied by a long postoperative recovery period. Patients in most cases complain of pain in the area of ​​the postoperative scar, a feeling of numbness in the dermatome along the damaged intercostal nerve, which persists for up to six months and, in some cases, for life.
Thoracotomy provides the best access to the organs of the chest cavity, but the risks of general anesthesia, surgical trauma, and prolonged hospitalization must always be assessed. Typical complications of thoracotomy are hemothorax, pneumothorax, the formation of bronchopleural fistulas, and pleurothoracic fistulas. The mortality rate from this type of surgical intervention ranges from 0.5 to 1.8%, according to various sources.

Videothoracoscopy/ video- assisted thoracoscopy (VATS).
There are the following types of minimally invasive intrathoracic interventions:
· Videothoracoscopic operations, in which a thoracoscope and instruments combined with a video camera are inserted into the pleural cavity through thoracoports,
· Operations with video-assisted support, when they combine mini-thoracotomy (4-6 cm) and thoracoscopy, which allows for a double view of the operated area and the use of traditional instruments.
These methods of minimally invasive interventions significantly reduced the length of hospitalization of patients and the number of postoperative complications.
Absolute contraindications for videothoracoscopy are obliteration of the pleural cavity - fibrothorax, unstable hemodynamics and the patient's shock state.
Relative contraindications are: the impossibility of separate ventilation of the lungs, previous thoracotomies, a large volume of pleural damage, coagulopathy, previous radiation therapy for lung tumors and plans for lung resection in the future.

Mediastinoscopy

The procedure is low-traumatic, highly informative in the presence of enlarged groups of lymph nodes available for examination, and is significantly lower in cost than thoracotomy and videothoracoscopy.

Absolute contraindications: contraindications for anesthesia, extreme kyphosis of the thoracic spine, the presence of a tracheostomy (after laryngectomy); superior vena cava syndrome, previous sternotomy, mediastinoscopy, aortic aneurysm, tracheal deformities, severe lesions of the cervical spinal cord, radiation therapy of the mediastinum and neck organs.

Algorithm for using biopsies:
· first, endoscopic (bronchoscopic or transesophageal) biopsies are performed, if there are changes in the bronchial mucosa - direct biopsy and brush biopsy of areas of the mucosa. If enlarged VLNs are identified that are available for aspiration biopsy, CCIP VLNs or EBUS-TBNA and/or transesophageal EUS-b-FNA are also performed
· surgical biopsies are performed only in those patients in whom endoscopic methods failed to obtain diagnostically significant material, which is about 10% of patients with sarcoidosis. More often this is VATS resection, as the least traumatic of the operations, less often classic open biopsy, and even less often mediastinoscopy (due to the small number of available VGLU groups).
Positive points use of endoscopic techniques: the ability to perform on an outpatient basis, under local anesthesia or sedation; conducting several types of biopsies from different groups of lymph nodes and different areas of the lung and bronchi in one study; low rate of complications. Significantly lower cost than surgical biopsies.
Negative points: small size of the biopsy sample, which is sufficient for cytological, but not always for histological studies.
Contraindication for all types of endoscopic biopsies there are all contraindications for bronchoscopy and additionally - a violation of the blood coagulation system, the presence of an infectious process in the bronchi, accompanied by purulent discharge
Indicators of the effectiveness of endoscopic biopsies, including comparative ones.

Transbronchial lung biopsy(NBL) is the recommended biopsy for sarcoidosis. Diagnostic yield largely depends on the experience of the procedure performed and the number of biopsies, and also carries the risk of pneumothorax and bleeding.
The overall diagnostic level for sarcoidosis was significantly better by EBUS-TBNA than by PBL (p<0,001). Но анализ с учетом стадии процесса показал, что эта разница за счет пациентов с 1 стадией процесса - у них диагностирован саркоидоз по EBUS-TBNA в 90,3% (обнаружены неказеозные гранулёмы и/или эпителиоидные клетки), при ЧБЛ у 32,3% пациентов (p<0.001). У пациентов со II стадии каждый метод имеет 100% диагностическую эффективность при отсутствии осложнений. Частота ятрогенного пневмоторакса составляет 0,97% (из них 0,55% требующего дренирования плевральной полости) и частота кровотечений 0,58%.

Classic transbronchial needle biopsy intrathoracic lymph nodes - KIB VGLU has a diagnostic value of up to 72% in patients with stage 1 pulmonary sarcoidosis, sensitivity - 63.6%, specificity - 100%, positive predictive value - 100%, negative predictive value - 9.1%.

Transesophageal fine-needle aspiration biopsy under endosonography-guided EUS-FNA (EUS- FNA) AndEUS- b- FNA have a very high diagnostic value and have sharply reduced the number of mediastenoscopies and open biopsies in the diagnosis of pulmonary sarcoidosis. These types of biopsies are used only when the mediastinal lymph nodes adjacent to the esophagus are affected.

Transbronchial fine needle aspiration biopsy guided by endobronchial sonography EBUS-TBNA is a reasonable method for assessing the condition of intrathoracic lymphatics in the absence of severe complications. With its help, it is possible to diagnose sarcoidosis, especially in stage I, when there is adenopathy, but there are no radiological manifestations in the lung tissue. Comparison of the results of modern sonography-guided biopsy - EBUS-TBNA and mediastinoscopy for mediastinal pathology proved a high agreement of methods (91%; Kappa - 0.8, 95% confidence interval 0.7-0.9). The specificity and positive predictive value for both methods were 100%. Sensitivity, negative predictive value, and diagnostic accuracy were 81%, 91%, 93% and 79%, 90%, 93%, respectively. At the same time, there are no complications with EBUS - TBNA, and with mediastinoscopy - 2.6%.

Direct biopsy of the bronchial mucosa (direct biopsy) and brush biopsy of the bronchial mucosa (brush biopsy). Bronchoscopy in 22-34% of patients in the active phase of pulmonary sarcoidosis reveals changes in the bronchial mucosa characteristic of this disease: tortuous vessels (vascular ectasia), single or multiple whitish formations in the form of nodules and plaques, ischemic areas of the mucosa (ischemic spots). With such changes in 50.4% of patients, and with unchanged mucosa - in 20%, it is possible to identify non-caseating granulomas and/or epithelioid cells in the biopsy specimen.

Bronchoalveolar lavage, liquid biopsy is performed in patients with sarcoidosis during diagnosis and during treatment. Thus, the CD4/CD8 ratio > 3.5 is characteristic of sarcoidosis, and occurs in 65.7% of patients with stage 1-2 sarcoidosis. An endopulmonary cytogram of bronchoalveolar lavage obtained as a result of BAL is used to characterize the activity of pulmonary sarcoidosis and the effectiveness of treatment: with an active process, the proportion of lymphocytes reaches 80%, with stabilization it decreases to 20%.

Laboratory diagnostics

Laboratory diagnostics

Interpretation of laboratory results and additional tests
Clinical blood test

may be within normal limits. Nonspecific and at the same time important is the increase in ESR, which is most pronounced in acute variants of sarcoidosis. Wave-like changes in ESR or a moderate increase are possible for a long time with a chronic and asymptomatic course of the disease. An increase in the number of leukocytes in peripheral blood is possible in acute and subacute sarcoidosis. Signs of activity also include lymphopenia. Interpretation of a clinical blood test should be carried out taking into account the therapy being performed. When using systemic steroids, the ESR decreases and the number of peripheral blood leukocytes increases, and lymphopenia disappears. During methotrexate therapy, monitoring the number of leukocytes and lymphocytes is a criterion for the safety of treatment (simultaneously with assessing the values ​​of aminotransferases - ALT and AST). Leuko- and lymphopenia in combination with an increase in ALT and AST are indications for discontinuation of methotrexate.

Thrombocytopenia in sarcoidosis it occurs with damage to the liver, spleen and bone marrow, which requires appropriate additional examinations and differential diagnosis with autoimmune thrombocytopenic purpura.

Renal function assessment includes a general urine test, determination of creatinine, blood urea nitrogen.

Angiotensin converting enzyme (ACE). In granulomatous diseases, local stimulation of macrophages leads to abnormal ACE secretion. Determining ACE activity in the blood takes 5-10 minutes. When taking blood from a vein for this study, you should not apply a tourniquet for too long a time (more than 1 minute), as this will distort the results. 12 hours before taking blood, the patient should not drink or eat. The basis for determining ACE is the radioimmune method. For persons over 20 years of age, values ​​from 18 to 67 units per liter (u/l) are considered normal. In younger people, ACE levels fluctuate significantly and this test is not usually used. With a sufficient degree of certainty, a pulmonary process can be defined as sarcoidosis only when serum ACE activity reaches more than 150% of normal. An increase in ACE activity in the blood serum should be interpreted as a marker of the activity of sarcoidosis, and not a significant diagnostic criterion.

C-reactive protein- a protein of the acute phase of inflammation, a sensitive indicator of tissue damage during inflammation, necrosis, and injury. Normally less than 5 mg/l. Its increase is characteristic of Löfgren's syndrome and other variants of the acute course of sarcoidosis of any localization.

Calcium levels in blood and urine. Normal serum calcium levels are as follows: general 2.0—2.5 mmol/l, ionized 1.05-1.30 mmol/l; in urine - 2.5 -- 7.5 mmol/day; in the cerebrospinal fluid - 1.05 - 1.35 mmol/l; in saliva - 1.15 - 2.75 mmol/l. Hypercalcemia in sarcoidosis is considered to be a manifestation of active sarcoidosis, caused by overproduction of the active form of vitamin D (1,25-dihydroxyvitamin D3 or 1,25(OH)2D3) by macrophages at the site of the granulomatous reaction. Hypercalciuria is much more common. Hypercalcemia and hypercalciuria with established sarcoidosis are a reason to start treatment. In this regard, you should be careful with nutritional supplements and vitamin complexes containing high doses of vitamin D.

Kveim-Silzbach test. Kveim Breakdown is called intradermal injection of tissue from a lymph node affected by sarcoidosis, in response to which in patients with sarcoidosis a papule is formed, upon biopsy of which characteristic granulomas are found. Louis Silzbach improved this test using a spleen suspension. Currently, the test is not recommended for widespread use and can be used in well-equipped centers specifically involved in the diagnosis of sarcoidosis. This procedure may introduce an infectious agent if the antigen is poorly prepared or poorly controlled.

Tuberculin test is included in the list of mandatory primary research in both international and domestic recommendations. The Mantoux test with 2 TE PPD-L in active sarcoidosis gives a negative result. When treating SCS in patients with sarcoidosis who were previously infected with tuberculosis, the test may become positive. A negative Mantoux test has high sensitivity for diagnosing sarcoidosis. BCG vaccination carried out in childhood has no correlation with tuberculin reaction in adults. Tuberculin anergy in sarcoidosis is not associated with tuberculin sensitivity in the general population. A positive Mantoux test (papule 5 mm or more) in a suspected case of sarcoidosis requires a very careful differential diagnosis and exclusion of concomitant tuberculosis. The significance of Diaskintest (intradermal injection of recombinant tuberculosis allergen - CPF10-ESAT6 protein) in sarcoidosis has not been definitively established, but in most cases its result is negative.

Treatment

TREATMENT OF SARCOIDOSIS

USE OF MEDICINES
The goals of treatment for sarcoidosis are to prevent or control organ damage, relieve symptoms, and improve patients' quality of life. There is no etiotropic therapy for sarcoidosis. In all cases, the doctor’s main tactic is to compare the need to prescribe treatment with the severity of the consequences of the use of modern corticosteroid, cytostatic and biological (“targeted”) therapy. Currently, no drugs are approved by health regulators (eg the FDA in the USA) for the treatment of patients with sarcoidosis. All existing schemes are advisory and in each case the attending physician takes responsibility, based on knowledge, for the prescribed treatment.
If a diagnosis of sarcoidosis has been established, there is no life-threatening condition, a decrease in the functions of organs and systems, and there is obvious evidence of rapid progression of the disease, active observation is preferable.

List of drugs used in the treatment of sarcoidosis

Preparation	Dosage	Main adverse reactions	Monitoring
Prednisolone (or analogues in doses equivalent to prednisolone)	3-40 mg per day at least 9 months Pulse therapy 1 g per day for 3 days (or 3 days every other day)	Diabetes mellitus, arterial hypertension, weight gain, cataracts, glaucoma, osteoporosis	Blood pressure, body weight, blood glucose, bone density, ophthalmologist examination
Hydroxychloroquine	200-400 mg per day	Visual impairment, liver and skin changes
Chloroquine	0.5—0.75 mg/kg/day	Visual impairment, liver and skin changes (more common than hydroxychloroquine)	Every 6-12 months, examination by an ophthalmologist
Methotrexate	5-20 mg once a week, up to 2 years	Blood changes, hepatotoxicity, pulmonary fibrosis	General clinical blood test, liver and kidney function tests every 1-3 months, radiation examination of the lungs. Once a week, 24 hours after taking methotrexate, 5 mg of folic acid orally.
Azathioprine	50-200 mg per day
Leflunomide	10-20 mg per day	From the blood system and hepatotoxicity	General clinical blood test, liver and kidney function tests every 1-3 months.
Mycophenolate	500-1500 mg 2 times a day	From the blood system and gastrointestinal tract	General clinical blood test, liver and kidney function tests every 1-3 months.
Pentoxifylline	0.6-1.2 g per day for 3 doses, 6-12 months.	Nausea, weakness, sleep disturbances	No specific indications
Indomethacin (other non-steroidal anti-inflammatory drugs may be available)	0.075-0.1 g per day per os	Reactions from the gastrointestinal tract, from the blood, with “aspirin” asthma	General clinical blood test monthly.
Alpha tocopherol	200-400 mg day, unlimited time	Allergic reactions	No specific indications

TNF-alpha inhibitors, tetracyclines, macrolides, thalidomide, sartans are under study in the treatment of sarcoidosis; experts have not reached agreement on their use, although in the recommendations of a number of countries they are included in the list of drugs of choice.

Statements in the treatment of sarcoidosis that have levels of evidence
1. Because the spontaneous remission rate is high, treatment is not indicated for asymptomatic patients with stage 1 sarcoidosis [Evidence Level B].
2. Because the remission rate is high, treatment is not indicated in asymptomatic patients with stage II and III sarcoidosis with mild pulmonary dysfunction and stable condition [D].
3. Oral corticosteroids are first-line treatment in patients with progressive disease based on radiographic and respiratory function tests, severe symptoms or extrapulmonary manifestations requiring treatment [B].
4. Treatment with prednisolone (or an equivalent dose of another corticosteroid) is prescribed at a dose of 0.5 mg/kg/day for 4 weeks, then the dose is reduced to a maintenance dose to control symptoms and disease progression over 6-24 months [D].
5. Bisphosphonates should be used to reduce steroid-induced osteoporosis [D].
6. Inhaled corticosteroids have no value in either initial or maintenance therapy [B]. They may be used in selected subgroups of patients with severe cough and bronchial hyperresponsiveness [D].
7. Other immunosuppressive and anti-inflammatory drugs have limited value in the treatment of sarcoidosis, but they should be considered as an alternative treatment when SCS do not control the course of the disease, there are serious severe concomitant diseases (diabetes mellitus, obesity, arterial hypertension, osteoporosis, glaucoma, cataracts , peptic ulcer) or severe adverse reactions of intolerance develop. The drug of choice currently is methotrexate [C].
8. Lung transplantation should be considered in end-stage hilar sarcoidosis [D].

Possible drug treatment regimens for sarcoidosis

№№	Medicines	Route of administration and frequency of administration	Dosage	Duration of the course, weeks.
1.	Glucocorticosteroids	per os daily		36-40
2.	Glucocorticosteroids	per os every other day	Initial dose 0.5 mg/kg/day with a reduction of 5 mg at 6-8 weeks	36-40
3.	Glucocorticosteroids Chloroquine	per os daily	0.1 mg/kg/day continuously 0.5—0.75 mg/kg/day continuously	32-36
4.	Glucocorticosteroids Alpha tocopherol	per os daily	0.5—0.75 mg/kg/day continuously	32-36
5.	Methotrexate	per os once a week	up to 25 mg constantly 1 time per week, every other day 5 mg of folic acid	32-40
6.	Pentoxifylline	per os daily	0.6-1.2 g per day for 3 doses	24-40
7.	Pentoxifylline Alpha tocopherol	per os daily per os daily	0.6-1.2 g per day for 3 doses 0.3-0.5 mg/kg/day continuously	24-40
8.	Alpha tocopherol	per os daily	0.3-0.5 mg/kg/day continuously	32-40

Note *—doses of glucocorticosteroids are indicated in terms of prednisolone

EFFERENT METHODS OF THERAPY
The simplest and most frequently used extracorporeal method is plasmapheresis. In addition to the removal of immune complexes and pro-inflammatory interleukins, during plasmapheresis there is an improvement in microcirculation, unblocking of cellular receptors and stabilization of cell membranes, which leads to an increase in the sensitivity of “target cells” to the effects of pharmacological agents. The operation involves removing 500-1000 ml of plasma from the bloodstream in one session. The cycle consists of 3-4 plasmapheresis with a week break between each procedure.
Methodology for extracorporeal modification of blood lymphocytes(immunopharmacotherapy): blood collected in a plastic container of the “Gemakon” type is centrifuged for 15 minutes in a laboratory centrifuge at 2700 vol. per minute to a clear separation of plasma and red blood cells. Next, the plasma is almost completely removed. The lower part of the plasma and the upper part of the red blood cell mass (approximately 1 cm each) are evacuated into a clean plastic container. The procedure is repeated 3-4 times until a sufficient amount of centrifugate is obtained. Lymphocyte counting is carried out in the Goryaev chamber. After receiving lymphocyte concentrate in the amount of 0.5-2.0 ppm. cells, prednisolone 30-60 mg (at the rate of 200 μg/ml) or cyclosporine “A” (at the rate of 10 μg/ml) is added to it and it is placed in a thermostat at a temperature of 37 C for 2 hours. The course includes at least 2 procedures of extracorporeal modification of blood lymphocytes with a 10-day break between them.

PULMONARY HYPERTENSION IN SARCOIDOSIS

Definition and classification
Pulmonary hypertension (PH) is defined as an increase in mean pulmonary artery pressure (mPAP) at rest >25 mm Hg. (with normal pressure in the left atrium). PH can be a consequence of chronic cardiac and pulmonary diseases that cause systemic and/or regional hypoxia, pulmonary embolism, or pulmonary microcirculation disorders (PH in the latter case is called pulmonary arterial hypertension - PAH). According to the current classification, PH in sarcoidosis belongs to class 5 PH (group with various causes of PH) and is usually considered separately from PH in respiratory diseases, such as interstitial or obstructive pulmonary diseases (group 3). The basis for such stratification is the relatively frequent development of severe PH in patients with sarcoidosis, even in the absence of pronounced parenchymal changes in the lungs; the cause of such PH may be the direct involvement of the pulmonary vessels in the inflammatory process.

Diagnosis of PH
Clinical manifestations and objective symptoms of PH usually appear in the later stages of sarcoidosis and are often masked by manifestations of the underlying disease. The development of PH in patients with sarcoidosis is associated with persistent dyspnea, decreased exercise tolerance, and increased oxygen consumption. The “gold standard” in assessing sPAP and, therefore, diagnosing PH is right heart catheterization. However, this invasive technique is associated with a small but stable risk for a patient with PH, so non-invasive methods for assessing PH are most often used in clinical practice.

Transthoracic Doppler echocardiography
Transthoracic Doppler echocardiography (ECHO-CG) is widely used to calculate right ventricular systolic pressure (RVSP), which, in the absence of pulmonary outflow tract obstruction, is equivalent to systolic PAP (RPP). SPV can only be calculated in the presence of systolic flow from tricuspid regurgitation. Even experienced specialists can detect tricuspid regurgitation only in 70-80% of cases. The absence of tricuspid regurgitation sufficient for measurement does not exclude the presence of severe PH. PPV assessed by echocardiography correlates well with systolic PAP measured by right ventricular catheterization and has high sensitivity in diagnosing PH (>85%). In patients with ILD, the specificity and positive predictive value of MPAP, correctly measured by ECHO-CG, is 97% and 98%, respectively, when using a threshold MPAP of ³45 mm Hg.

Brain natriuretic peptide ( brain natriuretic peptide - BNP )
BNP is mainly secreted in the ventricles of the heart during stress and is increased in patients with chronic pulmonary diseases and PH. In a prospective study of patients with lung disease, elevated plasma BNP levels had a sensitivity, specificity, positive and negative predictive value of 0.85, 0.88, 0.73 and 0.92, respectively, in the presence of PH confirmed by right ventricular catheterization.

Pulmonary function test
A decrease in DL CO is of limited value for the diagnosis of PH in patients with ILD. In sarcoidosis, the prevalence of PH is significantly higher in patients with DL CO<40% должного и сатурацией кислорода в покое <88%.

Epidemiology of PH in sarcoidosis. The prevalence of PH in patients with sarcoidosis, according to various studies, varies from 1 to 28%. A review of the INOS registry found that 75% of 363 patients with sarcoidosis awaiting lung transplantation had a meanPAP >25 mmHg, and a third of these had severe PH (mPAP ³40 mmHg). .). PH is more likely to develop in stages III and IV of sarcoidosis, but cases of PH have been described at stages 0 and I and even with cardiac lesions, granulomatous infiltration of the pulmonary vessels, including capillaries and veins (leading to the development of occlusive venopathy) or with increased sensitivity to vasoactive drugs and compression of the pulmonary artery by enlarged mediastinal lymph nodes. When conducting morphological studies, granulomatous vascular changes are often detected.

The influence of PH on the prognosis of sarcoidosis. PH in sarcoidosis is an independent predictor of mortality. Descriptions of individual cases show that such PH in sarcoidosis is resistant to steroid therapy, in addition, PH increases the risk of death in patients awaiting lung transplantation.

PH therapy for sarcoidosis. Therapy with corticosteroids and cytostatics usually does not lead to a decrease in pulmonary artery pressure in stage IV sarcoidosis (fibrosis, “honeycomb lung”).

Oxygen therapy. The administration of oxygen to patients with PH due to sarcoidosis is indicated for chronic hypoxemia (PaO 2< 55 мм рт.ст.), при этом дозу титруют до достижения SpO 2 >90% when breathing through an oxygen concentrator.

Anticoagulants. Prospective cohort studies have shown that long-term warfarin therapy improves survival in idiopathic PAH and PH due to chronic thromboembolic disease. However, there are no data that evaluate the risk-benefit ratio of warfarin therapy for PH in the setting of sarcoidosis. Warfarin should be prescribed when there is clear clinical, radiological or histological confirmation of thromboembolism. Extrapolation from observational studies in idiopathic PAH (in the absence of direct evidence) suggests that warfarin therapy may be used in patients with sarcoidosis with severe PH.

Specific therapy for PH in sarcoidosis. Currently, there are effective drugs for the treatment of pulmonary arterial hypertension (PAH), such forms as idiopathic (primary) PAH, PAH in systemic scleroderma, etc. It is possible that these same drugs are also the most effective therapy for PH associated with sarcoidosis. Small retrospective and prospective non-randomized studies have demonstrated good treatment options for PH in sarcoidosis with drugs such as epoprostenol, iloprost, bosentan and sildenafil (level D). These drugs should be administered with caution to patients with proven or suspected occlusive venopathy.

Forecast

QUALITY OF LIFE, PROGNOSIS AND LEGAL FRAMEWORK IN THE MANAGEMENT OF PATIENTS WITH SARCOIDOSIS

Quality of life (QOL) in sarcoidosis.
Health related quality of life (HRQL) is determined by the patient’s level of satisfaction with those aspects of life that are affected by illnesses, accidents or their treatment. It depends on the ability to perform basic physiological functions, including sexual ones, the presence of pain symptoms, and a subjective sense of well-being, health or ill health. Medical aspects of QoL include the impact of the disease itself, its symptoms and signs and the resulting limitations in functional ability, as well as treatment, on the patient’s daily activities. WHO defines health-related quality of life as " the value ascribed to the continuation of life and altered by social opportunities, beliefs, functional status and various impairments influenced by disease, injury, treatment and policy in the field".
QoL in sarcoidosis is assessed using different tools - questionnaires. These include the Medical Outcomes Study Short Form (SF-36), the WHO Quality of Life Questionnaire-100 (WHOQOL-100), the St George's Hospital Respiratory Questionnaire (SGRQ) and the Specialized Patient Health Questionnaire. sarcoidosis (Sarcoidosis Health Questionnaire, SHQ) is a tool for assessing health-related quality of life. Factors that reduce quality of life in sarcoidosis are severe fatigue syndrome, damage to specific organs with impaired function, conflicting information received from doctors of different specialties at the diagnostic stage, stay in anti-tuberculosis institutions, and adverse reactions to treatment.

Predicting the course of sarcoidosis
In its course, sarcoidosis can have the following options:
· spontaneous regression;
regression during treatment;
stabilization of the condition (spontaneous, during or after therapy);
· progression;
· wavy current;
· relapse.

Exacerbation this is the reactivation of the process within a year after the end of the main course of treatment, which ended with the complete disappearance of signs of activity and regression of the process;
Relapse This is the resumption of the active process 1 year after the end of the main course of treatment or after spontaneous regression.
Spontaneous remission rate- an indicator that varies very widely - 12% to 80%, which requires a particularly careful and careful attitude to the term “spontaneous involution”. Spontaneous involution should be understood as a slow but steady reverse development of the pathological process, documented by objective research methods and presented to the natural course without the use of therapeutic measures.
Recurrent course of sarcoidosis noted in 15-68% of cases. Such a significant spread in indicators is associated with many factors: the form and stage of the process, the regimen and method of treatment, concomitant and background diseases, etc. The duration of observation plays an important role: the longer the observation, the more often it is possible to register a relapse.

Favorable prognostic factors for sarcoidosis include:
Clinical signs: asymptomatic disease, acute or subacute onset with high body temperature, Löfgren's syndrome, young age, absence of extrapulmonary lesions, spontaneous remission after initial detection, effectiveness of an initial course of low doses of SCS, a full (at least 9 months) course of SCS and remission for more than three years (spontaneous or after treatment).
Laboratory signs: preservation of tuberculin sensitivity, high activity of leukocyte acid phosphatase, normal iodine absorption function of the thyroid gland, high lymphocytosis of BAL fluid, the absolute number of polymorphonuclear neutrophils is not more than 0.2x10 4 cells per 1 ml, a higher level of production of IL-6 and TNF-alpha by macrophages BAL fluid, BAL fluid phospholipids above 30 mmol/l.
X-ray signs: X-ray stage I, less often - II.
Extrapulmonary manifestations Erythema nodosum, anterior uveitis, Bell's palsy without other neurological signs.
Genetics: ACE genotype II, human lymphocyte antigen (HLA) type DR17.

Unfavorable prognostic factors for sarcoidosis include:
Clinical signs: the presence of cough and shortness of breath when detected, the presence of damage to several organs and systems with clinical signs, prolonged low-grade fever.
Anamnestic data: older age at identification, African American or Scandinavian; environmental factors (dust and chemical exposure), hyperinsolation, stressful situations. Initially chronic course of the disease. The fact of using SCS in the past, the insufficiently effective result of the first course of SCS therapy in life, relapse after treatment with steroids. A course of anti-tuberculosis therapy without confirmed tuberculosis.
Laboratory signs: lymphopenia (absolute lymphopenia), band shift, increased fibrinogen and blood calcium, hypoalbuminemia, increased g-globulins above 25%, deep depression of T-cell immunity, detection of granular forms of MBT in sputum, BALF or blood; a higher content of neutrophils and eosinophils in the BALF, a decrease in the diffusion capacity of the lungs, a decrease in FEV 1 and vital capacity at the time of detection.
X-ray signs: X-ray stages III or IV, pulmonary sarcoidosis without involvement of the lymph nodes, significant increase in VLN upon detection, severe deformation of the pulmonary pattern, the presence of progressive mesh fibrosis, pleural changes.
Bronchoscopic signs: stenosis and deformation of the bronchial lumens, sarcoidosis lesions of the bronchial mucosa, rash of granulomas and plaques in the bronchial wall
Extrapulmonary manifestations: Lupus pernio, posterior uveitis, arm bone cysts, cardiac sarcoidosis, Cor pulmonale, long-term tachycardia, sinus lesions, neurological signs without Bell's palsy, nephrolithiasis.
Genetics: ACE genotype DD.

The likelihood of relapse increases in cases of absence of spontaneous remission after initial detection, use of SCS in the past, relapse after completion of primary treatment, initial course of treatment with SCS for up to 4 months, low sensitivity to SCS, as well as such signs as neuro-emotional stress, female gender, age over 40 years, concomitant background diseases, presence of crepitus, wheezing, peripheral blood eosinophilia, low (less than 200 nmol/l) blood cortisol level, hypothyroidism, FEV 1/FVC<65%, изначально большой распространённости поражения лёгких, наличия ультрамелких форм микобактерий туберкулёза в мокроте, крови или лаважной жидкости, выраженное угнетение Т-клеточного иммунитета, пневмонический и интерстициальный варианты внутригрудного саркоидоза.
Most exacerbations of sarcoidosis (2/3 of cases) occurred in the next 4-6 months after the end of the main course of treatment. During this period, careful regular clinical, radiological, laboratory and functional monitoring is necessary in order not to miss the initial manifestations of sarcoidosis reactivations. Timely detection allows for a quick decision on treatment and/or monitoring of these patients.

Medical legal basis for the management of patients with sarcoidosis and examination of work capacity
In accordance with the Federal Law of the Russian Federation “On preventing the spread of tuberculosis in the Russian Federation” dated June 18, 2001. N 77-FZ, Decree of the Government of the Russian Federation of December 25, 2001. N 892 “On the implementation of the Federal Law “On preventing the spread of tuberculosis in the Russian Federation”, by order of the Ministry of Health of the Russian Federation No. 109 of March 21, 2003, by order of the Ministry of Health of the Russian Federation No. 312 of July 14, 2003. “On the recognition as invalid of the orders of the Ministry of Health and Medical Industry of Russia and the Ministry of Health of Russia dated November 22, 1995 No. 324 and dated February 2, 1998 No. 33” in the Russian Federation - the VIII group of dispensary registration of patients with sarcoidosis in anti-tuberculosis institutions was abolished.
The management of patients with sarcoidosis is currently recommended to be carried out by general practitioners with the advice of a pulmonologist, phthisiatrician and doctors of other specialties, in accordance with the prevailing localizations of the disease.

Approximate criteria for assessing the working capacity of patients with sarcoidosis.
The criteria for determining disability group III are :
· moderate clinical and radiological changes in the respiratory organs in the form of pneumosclerosis and fibrosis;
· respiratory failure of I and II degrees, if the work of these patients in their main profession contains contraindicated factors, and the recommended employment is accompanied by a significant reduction in qualifications and a decrease in the volume of production activities;
· limiting the employment opportunities of low-skilled persons.

Criteria for determining disability group II :
· significant clinical and radiological changes in the respiratory organs;
formation of the pulmonary heart;
Respiratory failure II degree;
generalization of sarcoidosis involving the heart, eyes, and nervous system, which is difficult to effectively treat;
· loss of profession and qualifications as a result of a long course of the disease.

Criteria for determining disability group I:
· significant irreversible clinical and radiological changes in the respiratory organs (stage IV of the disease with pronounced morphological and significant functional changes in the respiratory organs);
· pulmonary heart in the decompensation phase;
· respiratory and cardiovascular failure of the third degree;
· generalized process involving the heart, eyes, nervous system, kidneys that cannot be effectively treated;
· chronic or progressive relapsing course of sarcoidosis with corticosteroid dependence.

The presented criteria can serve as a guideline when referring patients for medical and social examination.

Information

Sources and literature

1. Clinical recommendations of the Russian Respiratory Society

Information

Chuchalin Alexander Grigorievich (scientific editor)	Director of the Federal State Budgetary Institution "Research Institute of Pulmonology" FMBA of Russia, Chairman of the Russian Respiratory Society, chief freelance specialist pulmonologist of the Ministry of Health of the Russian Federation, academician of the Russian Academy of Medical Sciences, professor, doctor of medical sciences.
Avdeev Sergey Nikolaevich	Deputy Director for Scientific Work of the Federal State Budgetary Institution "Research Institute of Pulmonology" FMBA of Russia, Professor, Doctor of Medical Sciences.
Baranova Olga Petrovna	Senior researcher at the laboratory of ISL, Research Institute of Pulmonology, State Budgetary Educational Institution of Higher Professional Education, PSPbSMU named after. acad. I.P. Pavlova, Ministry of Health of Russia, Ph.D.
Borisov Sergey Evgenievich	Deputy Director for Scientific and Clinical Work of the Moscow City Scientific and Practical Center for the Fight against Tuberculosis of the Moscow Department of Health, Professor, Doctor of Medical Sciences.
Vizel Alexander Andreevich (coordinator)	Head of the Department of Phthisiopulmonology of the State Budgetary Educational Institution of Higher Professional Education "Kazan State Medical University" of the Ministry of Health of Russia, chief freelance specialist pulmonologist of the Ministry of Health of Tatarstan, professor, doctor of medical sciences.
Vizel Irina Yurievna	Assistant at the Department of Therapy and Family Medicine, Kazan State Medical Academy, Ministry of Health of Russia, Ph.D.
Ilkovich Mikhail Mikhailovich (coordinator)	Head of the Department of Pulmonology of the Faculty of Professional Education with the clinic of the State Budgetary Educational Institution of Higher Professional Education, PSPbSMU named after. I.P. Pavlova of the Ministry of Health of Russia, chief freelance specialist pulmonologist of St. Petersburg, professor, doctor of medical sciences.
Lovacheva Olga Viktorovna	Head of the endoscopic department of the Central Research Institute of Tuberculosis of the Russian Academy of Medical Sciences, Professor of the Department of Phthisiology of the Russian Medical Academy of Postgraduate Education, Professor, Doctor of Medical Sciences.
Ovsyannikov Nikolay Viktorovich	Head of the Pulmonology Department of the Omsk Region City Clinical Hospital No. 1 named after. Kabanova", Ph.D.
Petrov Dmitry Vladimirovich	Pulmonologist of the pulmonology office of the polyclinic of the Omsk Region City Clinical Hospital No. 1 named after. Kabanova"
Romanov Vladimir Viktorovich
Samsonova Maria Viktorovna	Head of the Laboratory of Pathological Anatomy and Immunology, Federal State Budgetary Institution "Research Institute of Pulmonology" FMBA of Russia, Doctor of Medical Sciences.
Solovyova Irina Pavlovna	Head of the laboratory of pathological anatomy of the First Moscow State Medical University named after. I.M.Sechenova, professor, doctor of medical sciences
Stepanyan Igor Emilievich	Leading researcher at the Department of Differential Diagnosis of Pulmonary Tuberculosis and Extracorporeal Treatment Methods of the Federal State Budgetary Institution "Central Research Institute of Infectious Diseases" of the Russian Academy of Medical Sciences, Professor, Doctor of Medical Sciences.
Tyurin Igor Evgenievich	Head of the Department of Radiation Diagnostics, Radiation Therapy and Medical Physics, GBOU DPO RMAPO, Chief Freelance Specialist in Radiation Diagnostics of the Ministry of Health of the Russian Federation, Professor, Doctor of Medical Sciences.
Chernyaev Andrey Lvovich	Head of the Department of Pathology, Federal State Budgetary Institution "Research Institute of Pulmonology" FMBA of Russia, Professor, Doctor of Medical Sciences.
Shmelev Evgeniy Ivanovich	Head of the Department of Differential Diagnosis of Pulmonary Tuberculosis and Extracorporeal Treatment Methods of the Federal State Budgetary Institution "Central Research Institute of Infectious Diseases" of the Russian Academy of Medical Sciences, Professor, Doctor of Medical Sciences.
Shmeleva Natalya Mikhailovna	District pulmonologist of the Northern Administrative District of Moscow, Ph.D.

METHODOLOGY

Description of methods used to collect/select evidence: The evidence base for the recommendations is publications included in the Cochrane Library, EMBASE and MEDLINE databases. The search depth was 25 years. The analysis included meta-analyses, systematic reviews, recommendations and consensuses of medical societies from different countries. In selecting publications as potential sources of evidence, the methodology used in each study was examined to ensure its validity.

The main method for creating consensus recommendations was achieving expert agreement by creating a basis for recommendations and adjusting each section by each expert, followed by revision and re-correction. Any differences in ratings were re-discussed by all group members via email. If it was impossible to reach consensus, an independent expert was involved.

Consent tables were filled in by all members of the working group, the final distribution of opinions of 16 experts is presented below:

CHAPTER	I AGREE COMPLETELY	I AGREE IN PRINCIPLE	I DO NOT AGREE
Methodology	93,8%	6,2%	0
Definition, classification	93,8%	6,2%	0
Morphology of sarcoidosis	75,0%	25,0%	0
Epidemiology, etiology and pathogenesis	81,3%	18,7%	0
Clinical diagnosis of sarcoidosis	93,8%	6,2%	0
Laboratory and functional diagnostics	68,8%	31,2%	0
Visualization methods	100%	0	0
Invasive diagnostic methods	43,8%	56,2	0
Treatment of sarcoidosis	75%	25%	0
Quality of life, prognosis and legal framework for the management of patients with sarcoidosis	81,3%	18,7%	0

Methods used to formulate recommendations:
Expert consensus.

Indicators of good practice (Good Practice Points - GPPs):
Recommended good practice was based on the clinical experience of the guideline working group members.

Economic analysis:
No cost analysis was performed and pharmacoeconomics publications were not reviewed.

Description of the method for validating recommendations:
These draft recommendations were reviewed by independent experts who were asked to comment primarily on the extent to which the interpretation of the evidence underlying the recommendations is understandable.
Comments were received from primary care physicians and local therapists regarding the clarity of the recommendations and their assessment of the importance of the recommendations as a working tool in daily practice.
A preliminary version was also sent to a non-medical reviewer for comments from patient perspectives.