Eye damage in Bechterew's disease

Bechterew's disease

Bechterew's disease ( international name - ankylosing spondylitis).Inflammatory changes in intervertebral joints cause their fusion( ankylosis).The volume of movements in the joints is gradually limited, the spine becomes immovable. The first manifestations of the disease in the form of pain and stiffness arise first in the lumbar spine, and then spread up the vertebral column. Over time, a pathological thoracic kyphosis typical for Bekhterev's disease is formed. In Russia Bekhterev's disease is detected in 0.3% of the population. The disease often affects men aged 15 to 30 years. Women are sick 9 times less often than men.

Bechterew's disease

Bechterew's disease ( international name - ankylosing spondylitis).Inflammatory changes in intervertebral joints cause their fusion( ankylosis).The volume of movements in the joints is gradually limited, the spine becomes immovable. In Russia Bekhterev's disease is detected in 0.3% of the population. The disease often affects men aged 15 to 30 years. Women are sick 9 times less often than men.

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Causes of Bechterew's disease

The causes of the disease development are not fully understood. According to many researchers, the main cause of the disease is an increased aggression of immune cells in relation to the tissues of their own ligaments and joints. The disease develops in people with hereditary predisposition. People with Bechterew's disease are carriers of a certain antigen( HLA-B27), which causes a change in the immune system.

The starting point in the development of the disease may be a change in the immune status due to hypothermia, acute or chronic infectious disease. Bechterew's disease can be caused by a trauma to the spine or pelvis. Risk factors in the development of the disease are hormonal disorders, infectious-allergic diseases, chronic inflammation of the intestine and urogenital organs.

Mechanism of development of ankylosing spondylitis

Elastic intervertebral disks are located between the vertebrae, providing mobility of the spine. On the posterior, anterior and lateral surfaces of the spine are long, dense ligaments that make the spinal column more stable. Each vertebra has four processes - two upper and two lower. The processes of the adjacent vertebrae are interconnected by moving joints.

With Bechterew's disease, as a result of the constant aggression of immune cells, a chronic inflammation occurs in the tissues of the joints, ligaments, and intervertebral discs. Gradually, the elastic connective tissue structures are replaced by a solid bone tissue. The spine loses mobility.

Immune cells in Bechterew's disease attack not only the spine. Large joints can suffer. More often the disease affects the joints of the lower extremities. In a number of cases, the inflammatory process develops in the heart, lungs, kidneys and urinary tract.

Classification of Bechterew's disease

Depending on the primary lesion of organs and systems, the following forms of Bechterew's disease are distinguished:

  • Central form. Only the spine is affected. There are two types of the central form of the disease: kyphoid( accompanied by kyphosis of the thoracic and hyperlordosis of the cervical spine) and rigid( thoracic and lumbar spinal bends are smoothed, the back becomes straight as a board).
  • Risomelic form. The defeat of the spine is accompanied by changes in the so-called root joints( hip and shoulder).
  • Peripheral shape. The disease affects the spine and peripheral joints( ankle, knee, elbow).
  • Scandinavian form. On clinical manifestations resembles the initial stages of rheumatoid arthritis. Deformation and destruction of joints does not occur. Affected small joints of the hand.

Some investigators further distinguish the visceral form of Bechterew's disease, in which the damage to the joints and the spine is accompanied by changes in the internal organs( heart, kidneys, eyes, aorta, urinary tract, etc.).

Symptoms of Bechterew's Disease

The disease begins gradually, gradually. Some patients note that for several months or even years before the onset of the disease, they experienced constant weakness, drowsiness, irritability, weak volatile pain in the joints and muscles. As a rule, during this period the symptoms are so weak that the patients do not consult a doctor. Sometimes, precursors of Bekhterev's disease are persistent, poorly treatable eye lesions( episcleritis, irites, iridocyclitis).

  • Symptoms of spine injury in Bechterew's disease
A characteristic early symptom of Bechterew's disease is pain and a feeling of stiffness in the lumbar spine. Symptoms occur at night, increase by morning, decrease after a hot shower and exercise. During the day, pain and stiffness occurs in a state of rest, disappears or decreases with movement.

Gradually the pain spreads up the spine. Physiological curves of the spine are smoothed out. Pathological kyphosis( pronounced stoop) of the thoracic region is formed. As a result of inflammation in the intervertebral joints and ligaments of the spine there is a constant tension of the muscles of the back.

In the late stages of Bekhterev's disease joints of the vertebrae fuse, intervertebral disks ossify. Intervertebral bony "bridges" that are clearly visible on the roentgenograms of the spine are formed.

Changes in the spine develop slowly, for several years. The periods of exacerbations alternate with more or less prolonged remissions.

  • Symptoms of joint damage in Bechterew's disease

Often one of the first clinically significant symptoms of Bechterew's disease becomes sacroiliitis( inflammation of the joints of the sacrum).The patient is concerned about the pain in the depth of the buttocks, sometimes extending to the groin and upper thighs. Often this pain is considered a sign of inflammation of the sciatic nerve, a hernia of the intervertebral disc or radiculitis.

Pain in large joints occurs in about half of patients. Feeling of stiffness and pain in the joints are more pronounced in the mornings and in the first half of the day. Small joints are less likely to be affected.

  • Extra-articular symptoms of

Approximately thirty percent of cases of Bechterew's disease are accompanied by changes in the eyes and internal organs. Possible damage to the heart tissue( myocarditis, sometimes as a result of inflammation formed valvular heart disease), aorta, lungs, kidneys and urinary tract. When Bechterew's disease is often affected by eye tissue, develops iritis, iridocyclitis or uveitis.

Diagnosis of ankylosing spondylitis

Diagnosis is made on the basis of examination, medical history and additional research data. A patient with a suspicion of Bekhterev's disease needs consultation of an orthopedist and a neurologist. X-ray examination, MRI and CT of the spine are performed. The results of a general blood test revealed an increase in ESR.In case of doubt, a special analysis is performed to identify the antigen HLA-B27.

Differential diagnosis

Bechterew's disease must be differentiated from degenerative spine diseases( sprain) - spondylosis and osteochondrosis. Bechterew's disease affects young men more often, while CWD usually develops at an older age. Pain in the case of Bekhterev's disease intensifies in the morning and at rest. For DZP is characterized by increased pain in the evenings and after physical exertion. ESR with DZP does not increase, specific changes on the roentgenogram of the spine are not detected.

Scandinavian form of Bechterew's disease( primary lesion of small joints) should be differentiated from rheumatoid arthritis. Unlike Bekhterev's disease, rheumatoid arthritis, as a rule, affects women. With Bekhterev's disease, a symmetrical lesion of the joints is practically not found. In patients, there are no subcutaneous rheumatoid nodules, in the study of blood rheumatoid factor is detected in 3-15% of cases( in patients with rheumatoid arthritis - in 80% of cases).

Treatment of Bechterew's disease

Therapy for Bechterew's disease is complex, prolonged. It is necessary to maintain continuity at all stages of treatment: inpatient( department of traumatology) - polyclinic - sanatorium. Glucocorticoids and non-steroidal anti-inflammatory drugs are used. In severe treatment, immunosuppressants are prescribed.

A large role in the treatment of Bekhterev's disease is played by lifestyle and special physical exercises. The curative gymnastics program is made individually. Exercises should be performed daily. To prevent the development of vicious postures( the pose of the petitioner, the pose of the proud), the patient is recommended to sleep on a hard bed without a pillow and regularly engage in sports that strengthen the muscles of the back( swimming, skiing).To maintain the mobility of the chest, it is necessary to perform breathing exercises.

In the treatment of massage, magnetotherapy, reflexotherapy. Patients with Bechterew's disease are shown radon, hydrogen sulfide, nitrogen medicinal baths.

It is impossible to completely recover from Bechterew's disease, however, following the recommendations and properly selected treatment, the development of the disease can be slowed down. Patients with Bechterew's disease should be constantly observed by a doctor, and during an exacerbation they undergo treatment in a hospital.


Ankylosing spondylitis> Diseases> DoctorPiter.ru

With Bechterew's disease, immune cells attack intervertebral discs, tendons and ligaments of joints. Inflammation develops in the affected tissues, as a result of which the elastic tissues are replaced by a solid bone tissue, as a result of which the mobility of the spine and of the compounds is impaired.

There are several types of Bechterew's disease. With , the central form of affects only the spine. There are two kinds of this form - the kyphoid form, in which the spine straightens in the lower back, but strongly flexes in the chest area, and a rigid view, in which both the lumbar and thoracic bends of the spine are smoothed, resulting in the back becoming completely straight and flat.

With , the rhizome-shaped affects not only the spine, but also large joints - hip and shoulder joints.

With peripheral form of Bekhterev's disease, the spine and peripheral joints - elbows, ankles, knees, are affected.

The manifestations of the Scandinavian form of disease are similar to the initial symptoms of rheumatoid arthritis. In this case, small joints are affected, but their deformation and destruction does not occur.

With , the visceral form of affects not only the spine and joints, but also other organs - the eyes, kidneys, heart, blood vessels.


Often, the diagnosis of "ankylosing spondylitis" is made when the disease has passed into a neglected stage. This is due to the fact that the disease is still poorly understood, the beginning of it is implicit, and the symptoms are similar to other diseases, for example, to osteochondrosis.

Diagnosis of Bechterew's disease is a lengthy process, since the doctor must observe the patient for at least three months.

One of the most reliable ways to diagnose this disease is x-ray. In the picture of the pelvis, the changes are visible at rather early stages, however, the radiographs of the joints of the hands and feet in the early stages are not informative. Changes in them can be detected using magnetic resonance imaging( MRI).

If suspected, the disease is tested for antigen HLA-B27.

Be sure to do a general blood test.

Treatment of

Treatment of Bechterew's disease is complex, long-term, consists of several stages. First, the patient is treated in a trauma hospital, after being treated in a polyclinic, and then sent to a sanatorium.

Non-steroidal anti-inflammatory drugs and intra-articular injections of corticosteroids are used to treat this disease.

Very often for the treatment of Bekhterev's disease, physiotherapy is used. Most often this is magnetotherapy. This method almost always brings relief to patients. True, relief is temporary. In some cases, heat treatment helps, for this use warmers or paraffin applications. But in some patients such treatment causes, on the contrary, an exacerbation.

Used for treatment and balneotherapy. Basically this treatment is spent in sanatoria. Often patients are prescribed chloride sodium, hydrogen sulphide, radon and bischofite baths.

The suffering illness of Bekhterev is shown by therapeutic physical training. Exercises are chosen by the doctor individually for each patient. The only thing they have in common is that they need to do gymnastics twice a day for 30 minutes.


The suffering illness of Bekhterev shows swimming, regular gymnastics, stretching, systematic hardening. Showing and massage, but in the phase of exacerbation of the disease can not do it.

In no case should not engage in traumatic sports. Also, hypothermia, nervous and physical overwork are contraindicated. Treatment with immunostimulants can lead to an exacerbation of the disease, as they activate the immune system.

Bekhterev's disease sufferers must follow the weight to prevent an increase in the load on the joints. To do this, you must follow a diet and exercise.

Bechterew's disease worsens on the background of various infectious diseases. Suffering ankylosing spondylitis should be protected from infections, timely and correctly treat infectious diseases, if they could not be avoided.

A bedding patient suffering from this disease should be firm, and in some cases it is not recommended to use a pillow. This is done to prevent deformation of the spine.


For the prevention of Bechterew's disease, it is necessary to protect against infections, including intestinal infections, and sexually transmitted infections. You can not overcool, you need to avoid heavy physical and mental overload. It is necessary to play sports, these exercises strengthen muscles, improve coordination, thereby protecting from injuries.


Bechterew's disease: symptoms, treatment, causes |The ABD of

's health is the primary localization of processes in the spine of all the departments, which leads to ankylosis of the entire spine, loss of physiological and pathological distortions of , mainly sacral and lumbar;(after 50-60 years),
lesions of the vessels, aorta, lungs, heart, kidneys and liver do not lead to marked changes with the development of hepatic and renal insufficiency. is characterized by

. Forms of the disease

. Depending on the predominant localization of the lesions, the following forms of the diseaseBechterew:

  1. Root, or rhizomelic( 17 - 18%), in which the spine is predominantly affected and the largest joints are humeral and hip joints.
  2. Peripheral( 20 - 75%) - localization also in the spine, but in combination with smaller joints( knee, ankle and small joints of the foot).
  3. Central( 46,6%) - only the spine( all or some of its departments).
  4. Scandinavian - a rare form in which the spine and small joints of the hands and feet are affected. This form is very similar to rheumatoid arthritis.

The first symptoms suggesting the initial stages of the disease:

  • Feeling of stiffness and pain in the lumbosacral spine, which gives to the legs and buttocks and is strengthened by the morning.
  • Pain in young people in the heel.
  • Sensation of lack of mobility and stiffness in the thoracic spine.
  • In the study of a clinical blood test - ESR up to 30 - 60 mm / h.

Preservation of these clinical symptoms for 3 months should be an occasion for immediate treatment of the patient to a rheumatologist.

For the purpose of diagnosing the Institute of Rheumatology of the Russian Academy of Medical Sciences, it was recommended( 1997) to consider the following main signs:

  • Soreness for more than 3 months in the lumbar region, which does not pass in a calm state, but its intensity decreases with movement.
  • Limited mobility of the spine in the anterior, posterior and lateral directions.
  • Reduction of the volume of inspiration and expiration in comparison with the age and sexual norms.
  • Two-sided( II-IV stages) sacroileitis.

Authentic diagnosis of Bechterew's disease is considered if the last symptom is combined with at least one of the three previous ones. For greater reliability and refinement stage and disease activity in clinical blood and urine tests, biochemical tests, chest X-ray and magnetic resonance( MRI) and computer tomography( CT) of the spine imaging and joints( allow in the first months to identify the disease), studyaimed at determining the presence of antigen HLA B27 and t. d.

treatment of ankylosing spondylitis

main treatment of ankylosing spondylitis is directed to reducing and slowing down processes ankilozirovaniya joints. Recommended:

  • complexes of physiotherapy and gymnastics is aggravation periods
  • swimming, walking on
  • skiing balneotherapy
  • physiotherapy( phonophoresis with hormonal therapy, ultrasound, paraffin on the area of ​​the joints)
  • observance of correct posture and body position in bed - the bed should be flat, solid with a small pillow
  • in the period of the unfolded course of the disease are contraindicated loads on the spine of a static nature, running, some sports and heavyx gymnastic exercises

These drugs are a major component of the treatment of ankylosing spondylitis, prescribers long courses from one continuous reception to 5 years. In case of exacerbation, the reception is carried out at the maximum dosage, then the patient is transferred to the supporting regimen( 1/4 or 1/3 of the maximum dose).

Of the NSAIDS are considered most preferred Ketoprofen( Ketonal, Flamaks, flexo), Diclofenac( Voltaren, Altrofen) Butodion, indole derivatives( indomethacin, indomethacin) and meloxicam( Movalis, Artrozan, Amelotex) cm. Comprehensive list of NSAID articlenyxes from pain in the lower back, back.

The action of these drugs for the treatment of Bechterew's disease is so great that if the effect of their reception does not occur, this makes one doubt the correctness of the established diagnosis. If the patient does have Bechterew's disease, prolonged use of NSAIDs can significantly slow the progression of the disease.

Other drugs
  • Salazosulfapyridine( sulfasalazine) as a basic therapy is used as in rheumatoid arthritis, it has a bactericidal and anti-inflammatory effect. The therapeutic effect does not come immediately, but after 2-3 months, 60-70% of patients benefit.
  • With a marked increase in muscle tone, central action relaxants( Midokalm, Tolperisone) are prescribed.
  • anti-inflammatory effects have a glucocorticosteroid hormone series, prolonged use of which has its own disadvantages as the emergence of hormone dependence, education digestive tract steroid ulcers of diabetes and osteoporosis.
  • patients with fever, vistseritami in severe disease using cytostatic( antitumor drugs, immunosuppressants - azathioprine, leykeran), corticosteroids( prednisolone).
  • Basic preparations - Delagil, Plakvenil, Immard, gold salts, Kuprenil with Bechterew's disease are often not very effective and rarely used.
Local therapy
  • For local treatment of an inflamed joint, injections of corticosteroids into the joint cavity and compresses with dimexide are prescribed.
  • A good effect is provided by cryotherapy with liquid nitrogen in the spine, which in 90% of cases leads to a relief of the patient's condition. It is also possible to use X-ray therapy, which has a direct anti-inflammatory effect on the affected tissues.
  • Hirudotherapy is an ancient method of treating all diseases, and the use of medical leeches as an auxiliary therapy in ankylosing spondylitis is possible, they increase the immunity and have an anti-inflammatory effect.
  • Back massage is useful both for the treatment of the spine with Bechterew's disease, and for the whole organism. But it should be remembered that any massage, heating, therapeutic mud can be used only with relative remission of the disease, when blood tests are normal, there are no inflammatory processes in the body, otherwise the effect will be opposite with involving new joints in inflammation.
Selective immunosuppressants

Of drugs recently effective drugs that stop the inflammatory process are drugs that block the tumor necrosis factor, which stimulates the formation of substances( cytokines) that lead to inflammatory processes in the joints.

In the world pharmaceutical market, there are three drugs of this group: Adalimumab( Humira), Infliximab( Remicade), Etanercept( Enbrel).They have a positive effect even in cases when conventional therapy is ineffective. However, they are very expensive and their use is associated with a high risk of tuberculosis activation, development of septic conditions and severe infections, as immunity is significantly reduced.


Therapeutic gymnastics is important in the fight against ossification and progressive stiffness of the joints and spine. A distinctive feature of gymnastics in the case of Bekhterev's disease is that unlike exercises with arthrosis( sparing joint development), here exercises should be energetic, amplitude, perform gymnastics should be active. This is due to the fact that such movements with a wide amplitude( rotation of the joints, slopes, turns) prevent the ossification and fusion of the ligaments of the spine. It is very important to produce therapeutic exercise every day without a gap of at least half an hour a day( without exacerbation).

A good way that combines gymnastics with muscle relaxation is exercise in the pool. And also in the "dry pool" on the apparatus "ugul" - when the patient performs gymnastics in a sitting or lying position, suspended in special suspensions. The uniqueness and effectiveness of such gymnastics is that the movements are performed with complete relaxation of the muscles. This significantly increases the activity of the joints and reduces the pain syndrome.


Protein diets are recommended by rheumatologists for all patients with ankylosing spondylitis - that is, a decrease in the diet of bakery, pasta, potatoes, flour confectionery and other products with a high content of starch. Increase the consumption of fish( not fried, but steam or baked), eggs, cottage cheese, cheese, boiled meat, among vegetables - to introduce into the diet more carrots, beets, peppers, cabbage, greens, onions, and also all fruits and berries.

Sanatorium treatment

Undoubtedly, rest and treatment in the resort area always has a beneficial effect on the general state of health, on the mood. Patients with Bekhterev's disease during the remission are shown sanatorium treatment in Evpatoria, Sochi, Pyatigorsk, Tskhaltubo, Odessa and other resorts. Radon, sulfide baths, physiotherapy - ultrasound, ultraviolet radiation, DDT currents, phonophoresis with hydrocortisone, ozocerite and mud treatment have a particularly good effect, as mentioned above, may exacerbate, so they are prescribed only in the calm period of the course of the disease.

In conclusion

Complete cure for Bechterew's disease is impossible. Prosthesis is performed in the late stages of the disease with ankylosis of the hip joints. However, early diagnosis and proper treatment can significantly slow down the development of pathological processes, reduce the frequency and severity of exacerbations and long-term maintain an active full-fledged lifestyle. Patients, who every day struggling with the disease, engaged in therapeutic gymnastics, retain sufficient mobility of the joints and spine, suspending the development of the disease.


Symptoms of ankylosing spondylitis

  • backache, worsening at rest( more often in the second half of the night and in the early morning hours), weakening during movements and reception of non-steroidal anti-inflammatory drugs;
  • morning stiffness in the back;
  • restriction of movements in the spine( it is difficult to tilt forward, turns to the sides, patients can not touch the chin to the sternum with the head tilted forward);
  • spinal deformity( smoothing of the physiological bending forward in the lumbar region, strengthening of the spinal column bending back in the thoracic region);
  • restriction of chest mobility during inspiration( arises due to damage to the attachment of ribs to the spine and sternum with the development of immobility in these departments);
  • is typical of the ascending character of the lesion of the spine( from the bottom up - from the lumbar region to the cervical spine).
Kestzno-iliac articulation:
  • pain in the buttocks, giving back to the thigh;
  • pain intensifies at rest and weakens during movements;
  • morning stiffness in the lumbar spine.
  • mainly affects the large and medium joints of the limbs( for example: hip, knee, ankle, shoulder), involvement of the elbows, wrists and small joints of the hands and feet is rare;
  • develops unstable inflammation of the joint with pain, an increase in the joint volume, difficulty in movement. However, a prolonged course of the inflammatory process is possible with the outcome in the immobility of the joint( most characteristic of the hip, shoulder joints);
  • lesion, usually asymmetric and not plural( usually 1-3 joints).
Bundles and tendons:
  • develops an inflammatory process in the places of attachment of ligaments and tendons to the bones( most often found in the spine and heels - in places of Achilles tendon fixation);
  • is characterized by pain at rest and during movements, swelling;
  • over time, ligaments and tendons become hard up to bone density, movements in the corresponding joints are disrupted.
  • there is an inflammatory process in various eye structures. Typical symptoms are decreased vision, pain in the eyes, a foreign body sensation in the eye, lacrimation;
  • process is usually one-sided;
  • eye damage can be the first symptom of Bechterew's disease and precede the remaining symptoms for several years.
Cardiovascular system:
  • inflammation of the heart valves with the development of defects( most often aortic insufficiency);
  • inflammation of the heart muscle with arrhythmias;
  • inflammation of the aorta followed by thickening of its walls.
Nervous system - the lesion is caused by pathological changes of the spine, which leads to compression of the nerve trunks:
  • subluxation in the joint connecting the skull with the first cervical vertebra, compressing the nerves and vessels, causes attacks of headaches and dizziness accompanied by nausea;
  • compression of the nerves in the lumbar and lower parts leads to impaired function of the pelvic organs - impotence, urinary incontinence.
  • possible development of glomerulonephritis( inflammatory kidney disease), urolithiasis;
  • amyloidosis is a complication of a long-term current disease, characterized by the deposition of a special protein( amyloid) in the kidneys with impaired renal function and an outcome in renal failure.
  • lung injury is a rare manifestation of Bekhretev's disease;
  • because of the limitation of the mobility of the thoracic spine, the ability of the lungs to maximal stretch during inspiration and, therefore, normal gas exchange is limited, which facilitates the attachment of infections;
  • a fibrous process is possible-pulmonary tissue tightening with impaired lung function.


Depending on the primary involvement in the process of those or other joints, there are four forms of Bechterew's disease:
  • central - lesion of only the spine( all or some departments);
  • rhizome ( rhiso- root) - affection of the spine and root joints( humeral and hip);
  • peripheral - affection of the spine and peripheral joints( knee joints, foot joints);
  • Scandinavian - defeat of the spine and small joints of hands and feet.

Causes of

  • The causes of the development of Bechterew's disease are unknown.
  • The most common theory of its occurrence is the presence of a genetic predisposition, which under the influence of environmental factors gives rise to the disease.
  • Among the environmental factors, the greatest value is given to infectious infection( for example: Shigella, Salmonella, Klebsiella).
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  • Collection of complaints( pain in the back, especially in the lower part, in the joints, restriction of the spine and joint movements, morning stiffness).
  • Collecting an anamnesis( development history) of the disease - an inquiry about how the disease began and proceeded.
  • General examination( examination and feeling of the spine and joints, determination of the volume of movements in the spine and joints).
  • Laboratory indicators. There is no specific laboratory indicator, the detected changes allow only to judge the activity of the inflammatory process:
  • an increase in ESR( erythrocyte sedimentation rate) indicates the presence of an inflammatory process in the body;
  • presence of C-reactive protein in the blood;
  • anemia( decrease in the level of erythrocytes and hemoglobin in the blood);
  • no rheumatoid factor in the blood( important in the differential diagnosis of Bechterew's disease and rheumatoid arthritis).
  • Radiographic examination of the iliac articulation and spine allows the doctor to detect signs characteristic of Bekhterev's disease and important for diagnosis.
The physician establishes the diagnosis for a combination of clinical manifestations, radiologic changes and laboratory data. It is also possible to consult a rheumatologist. Treatment of Bechterew's disease is considered imperfect, as it is ineffective and unable to slow the progression of the disease.
  • Non-steroidal anti-inflammatory drugs are used to eliminate pain and stiffness.
To try to slow down the progression, it is possible to use such drugs as:
  • sulfasalazine;
  • cytostatics;
  • glucocorticosteroid hormones - intraarticular with prolonged persistent inflammation of the joints;
  • is a new class of genetically engineered drugs that can influence the impaired processes of immunity in the body. Indications for their prescription are:
  • rapid disease progression;


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