Rheumatoid arthritis national guidelines. Rheumatoid arthritis clinical guidelines. We speak in detail. Basic principles of diagnostics

Rheumatoid arthritis of the hand

Rheumatoid arthritis according to clinical guidelines is a rheumatic autoimmune pathology of unknown etiology, which is manifested by chronic inflammation of the bone joints and systemic lesions of systems and organs. Most often, the disease begins with damage to one or more joints. It is characterized by the predominance of pain syndrome of varying intensity, stiffness, general symptoms of intoxication.

Basic principles of diagnostics

According to clinical guidelines, the diagnosis of arthritis should be carried out in a complex manner. Before making a diagnosis, it is necessary to analyze the general condition of the patient. Collect anamnesis, conduct laboratory and instrumental tests, refer the patient to a consultation of narrow specialists (if necessary). To make a diagnosis of rheumatoid arthritis, the following criteria must be met:

• Presence of at least one joint with signs of inflammation on physical examination.
• Exclusion of other pathologies of bone joints (based on analyzes and other signs).
• According to clinical recommendations based on a special classification, score at least 6 points (points are based on the clinical picture, the severity of the process and the subjective feelings of the patient).

1. Physical examination: collection of anamnesis of fluid, anamnesis of the disease, examination of the skin and mucous membranes. Examination of the cardiovascular, respiratory, digestive systems.
2. Laboratory data (OAC: increase in the number of leukocytes, ESR during an exacerbation of the disease, b / x analysis: the presence of rheumatoid factor, CRP, an increase in sialic acids, seromucoid). With an advanced stage of rheumatoid arthritis, an increase in other indicators is possible: CPK, ALT, AST, urea, creatinine, etc.
3. Instrumental studies include X-ray of the joints, ultrasound diagnostics. An additional method is magnetic resonance imaging of the required joint.

The doctor performs an ultrasound of the hand.

How else to detect the disease in time

The obligatory diagnostics of the pathological process, according to clinical recommendations, includes survey radiographs of the feet and hands. This method is carried out both at the initial stage of the disease, and for chronic patients annually. As a dynamic observation of the course of the pathological process. Typical signs of the development of rheumatoid lesions are: narrowing of the joint space, signs of osteoporosis, bone thinning, etc. MRI is the most sensitive and revealing method in rheumatology. On the basis of it, one can say about the stage, neglect of the process, the presence of erosions, contractures, etc. Most often, ultrasound of the hands or feet and ultrasound of large joints are performed. This method provides information about the presence of fluid and inflammation in the joint bag. The state of the joints and the presence of additional formations on them.

The use of the above diagnostic methods, according to clinical recommendations, provides valuable information about the degree and stage, as well as the exacerbation of the process. Thanks to additional methods, even the most initial signs of the disease can be determined. Based on the data obtained, the rheumatologist makes a diagnosis of the disease and prescribes a specific treatment. Here is an example of the correct formulation of the diagnosis (data from clinical recommendations):

Rheumatoid arthritis seropositive (M05.8), early stage, activity II, non-erosive (X-ray stage I), without systemic manifestations, ACCP (+), FC II.

According to the latest clinical recommendations, the appointment of a treatment for the disease - rheumatoid arthritis is possible only if you undergo an examination by a rheumatologist, all diagnostic procedures and an accurate diagnosis. In no case should you take medications for arthritis on your own, only a general practitioner or a rheumatologist can prescribe competent therapy.

Differential diagnosis of rheumatoid pathology based on clinical guidelines.

Modern trends in the treatment of rheumatoid arthritis

A rheumatologist examines a patient's hand.

According to clinical guidelines, the main goal of drug treatment of rheumatoid arthritis is to reduce the activity of the inflammatory process. As well as achieving remission of the disease. A rheumatologist should conduct and prescribe treatment. He, in turn, can refer the patient for consultations to other narrow specialists: orthopedic traumatologists, neurologists, psychologists, cardiologists, etc.

Also, a rheumatologist should conduct a conversation with each patient about the timing of prolonging the remission of the disease. The prevention of relapses includes: giving up bad habits, normalizing body weight, constant physical activity of low intensity, warm clothes in winter, caution when engaging in traumatic sports.

• Non-steroidal anti-inflammatory drugs (nimesulide, ketorol) are used to relieve all signs of the inflammatory process. They are used both parenterally and in the form of tablets.
• Analgesics (analgin, baralgin) should be used for pain in the acute phase of the disease.
• Hormonal preparations of the glucocorticoid series (methylprednisolone, dexamethasone) are used due to side effects with a pronounced clinical picture of the disease. And also in the advanced stage. Used in the form of tablets, intravenously, intramuscularly, as well as intra-articular injections.
• Basic anti-inflammatory drugs (methotrexate, leflunomide), according to clinical recommendations, affect the prognosis and course of the pathological process. They suppress the destruction of bone and cartilage tissue. They are most often used parenterally.
• Genetically engineered biological drugs (infliximab, rituximab, tocilizumab)

According to clinical recommendations, the appointment of additional therapy: multivitamins, muscle relaxants, proton pump blockers, antihistamines, can significantly reduce the risk of side effects from basic therapy medications. And also improve the general condition of the patient and the prognosis of the disease.

The role of the disease in modern society

Rheumatoid arthritis is a serious pathological condition that occurs with periods of exacerbation and remission. The acute phase, according to clinical recommendations, is always accompanied by severe pain and inflammation. These symptoms significantly impair the performance and general condition of patients. Periods of subsiding exacerbation are characterized by the absence or slight severity of symptoms of inflammation. The prevalence of rheumatoid arthritis disease, according to the latest clinical guidelines, among the general population of people is about 1-2%. The disease often begins in middle age (after 40 years), but all age groups can be affected (eg, juvenile rheumatoid arthritis). Women are 1.5-2 times more likely to get sick than men.

When contacting a specialist at the initial stage of the disease, competent diagnosis and timely treatment, as well as following all the doctor's recommendations, it is possible to maintain remission of the disease for several years and delay the loss of working capacity and physical activity for many years.

A very important role in predicting rheumatoid arthritis is played by the timing of the treatment started. The earlier the diagnosis and medications are taken, the easier the disease proceeds, and the more often there are long periods of remission. With late diagnosis of the disease, there is a high probability of early disability and rapid destruction of the joints.

Conclusion

Despite the development of medicine and rheumatology, in particular, in the modern scientific community there are still disputes about the origin, development and treatment of rheumatoid arthritis. This ailment has no specific prevention, and it is almost impossible to predict its onset. However, there are measures that will help reduce the risk of developing this disease. These measures include: strengthening one's own immunity, timely treatment of infectious diseases, rehabilitation of foci of inflammation, giving up bad habits, observing the basics of proper nutrition, controlling body weight, and sufficient consumption of vegetables and fruits. Read about these important foundations of personal development on the ZhitVkayf portal. It will also be correct to undergo preventive examinations by a general practitioner and a pediatrician (in the case of juvenile rheumatoid arthritis). When it comes to children, all the necessary information is collected on the website of the Sharkun Education University.

As mentioned above, poor ecology and malnutrition disrupt the water-salt balance in the body. This can be seen in the morning swelling, when it is difficult to remove the ring from the finger. A healthy person wakes up in a light condition, and going to the toilet after a glass of water occurs after a short time. If everything is the opposite for you, then your water-salt balance is not in order.

What leads to such violations:

• abuse of fatty and smoked foods;
• bad habits in the form of smoking and alcohol;
• low physical mobility;
• violation of the kidneys;
• heredity;
• hypothermia;
• excessive consumption of coffee and tea;
• inadequate drinking of clean water.

Symptoms

Although the joints are already affected by salts, a person may not be aware of this because the diseases associated with them develop gradually. The first symptoms begin to appear in the form of a crunch with sudden movements, for example, when squatting, when knee joints are affected by salts.

Over time, pain appears, even when the joint is stationary. An inflammatory process begins, which later covers the nerve endings, tendons and muscles. After some time, the patient may notice a subsidence of pain.

What provokes the deposition of salts and how to recognize?

Common Causes

People who are attentive to their health do not self-medicate, and in the presence of malaise and pain, they go to the doctor. Joints can hurt for a variety of reasons. It’s not very smart to diagnose yourself and try to heal yourself for some unknown reason.

Suppose a shoulder hurts, and a person, having decided that this is a deposit of salts in the shoulder joint, begins to follow a special diet, uses various folk recipes, lotions and poultices, and in the meantime the condition is getting worse.

What diagnostics can be carried out in the clinic? Well, firstly, to do an ultrasound of the joints or an X-ray, and secondly, blood and urine tests. According to the indicators obtained, the issue of making a diagnosis and prescribing treatment will already be decided;

if necessary, the examination will be continued. In the case of arthrosis, the doctor can prescribe good modern preparations for joints and cartilage, which will quickly relieve pain and relieve inflammation, and possibly prescribe physiotherapy exercises or physiotherapy.

You will need to consult with the doctor regarding the appropriateness of certain folk remedies for removing excess salts from the body. Perhaps physiotherapy exercises with an instructor will be recommended; in severe, advanced cases, hospital treatment may be necessary.

Possible Complications

If the accumulated salts are not removed in a timely manner, the following complications may appear:

• Osteoporosis. Excessive salt content in the body negatively affects the bone tissue and joints. Their condition worsens, which is observed against the background of a decrease in calcium levels.
• The appearance of kidney stones. Associated with the accumulation of salt in the body. It settles in the kidneys, which leads to the formation of stones.
• Stomach cancer. It develops due to constant irritation of the mucosa with excessively salty foods.

Cure gout at home

After the diet is adjusted, it is possible, on the recommendation of the attending physician, to introduce drugs into the diet according to the recipes of traditional healers.

Method number 1

This method of liberation from accumulations of salts came from oriental medicine. Quite an interesting recipe.

1. Count as many tablespoons of dry rice grains as your age.
2. Rinse it, pour it into a glass bowl, pour warm boiled water to the edge of the rice.
3. Cover tightly and leave overnight in a cold place.
4. Drain off the rest of the water in the morning.
5. cook porridge

Cooking rice porridge for breakfast: take 1 tbsp. l. soaked cereals, cook for 2-3 minutes without adding salt.

Pour the remaining rice with fresh boiled water, leave in a cold place. So daily cook yourself for breakfast for 1st spoon of rice.

Don't forget to change the water in the remaining cereal. Starch is released from rice into the water, and rice absorbs excess salt in the intestines. As a result, the joints get relief, pain symptoms disappear.

Method number 2

Rice is used in another method. Cooking technology: take 70-100 g of rice, wash it, soak in water for 2-3 hours. Then change the water, boil, cook for 2 minutes.

Drain the water, rinse the rice with boiled water, add fresh water, boil for another 2 minutes, change the water again, boil the rice again for 2 minutes. After the 4th boiling, the resulting porridge should be eaten, it is possible with honey and butter.

This will be breakfast, after which it is not recommended to eat more until lunch. You can drink regular filtered drinking water. For lunch, dinner, ordinary dishes are prepared, preferably with a minimum of salt.

If the joints tend to accumulate salts, the risk of inflammation increases, blood and lymph circulation is disturbed. When the hands are affected, patients complain that their fingers tingle. Traditional healers will tell you how to treat arthritis in small articular joints.

It is not necessary to drink drugs, you can make baths with soda, rub sore joints with ointments, put medical horseradish compresses. If the reasons are known, lotions of sulfur can be made.

Ingredients: mustard powder, honey and vegetable oil are taken in equal parts. The components should be mixed until a homogeneous mass. An ointment is ready for rubbing diseased joints and for compresses at night.

During rubbing, a light massage is used, which relieves pain, relieves inflammation.

Method of preparation: mix equal parts of boiled potatoes and rye flour. Form a cake from the resulting mass. Lubricate the skin with vegetable oil before applying the compress.

Lubricate one side of the cake with turpentine, put it with this side on the sore joint and wrap it up, as a compress usually hides. Such a compress should be kept until the turpentine begins to burn.

If there is no burning sensation, the compress can be left overnight. Then wipe the place of the compress with fresh vegetable oil or nourishing cream.

Ingredients: honey and salt in equal proportions. Method of preparation: mix the components of the mixture thoroughly, apply the resulting mass to the sore joint. Wrap the compress warmly, hold for 2 hours.

Unpleasant sensations should not appear. Then wash off the place of the compress with wet wipes with warm water, and smear the joint with a nourishing cream.

As established by the Japanese scientist K. Nishi, oxalic salts, which include salts of uric acid, dissolve only with oxalic acid. This acid is formed during the digestion of raw vegetables and fruits.

Therefore, to cure gout at home, you need to use a raw food diet. This is a separate large and serious topic will be covered in another article. And here I would like to talk about the treatment of joints with bay leaves.

To do this, 15 g of chopped bay leaf should be poured with one and a half glasses of boiling water and continue to boil this water for 5 minutes. Then the decoction, together with the leaves, insist in a thermos for 2 hours.

Strain the resulting solution and drink in small sips evenly throughout the day. Caution: Drinking the entire amount of liquid at a time may cause bleeding.

Repeat a similar procedure for the treatment of joints with bay leaf on the second and third days. Then give the body a rest for a week. After that, repeat the three-day course of taking the decoction.

Such annual procedures will allow you to consolidate a positive result and cure gout at home. For successful treatment, it is necessary to create appropriate conditions inside the body that will ensure the normalization of metabolism.

These include: adherence to a salt-free alkaline diet with a daily fluid intake of 2.0 - 2.5 liters and the rejection of alcohol. About this - in the articles "What you can eat with gout" and "What you can not eat with gout."

In the first year, you can conduct 3 similar courses for the treatment of joints with bay leaves, focusing on periods of exacerbation of gout. For example, in spring, early autumn and closer to winter. With a positive dynamics of the course of the disease for the next year and in the future, courses can be made seasonal: spring - summer.

In winter, skiing can be a good preventive measure, which must be practiced regularly so as not to overload the joints with one-time unusual loads and constantly to help the body regularly remove excess uric acid with sweat.

In addition, you need to pay due attention to the feet themselves. Wearing tight shoes is one of the risk factors for gout. But, as a rule, such shoes are more attractive in appearance. And I want to wear it. How to be?

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You can wear narrow shoes for a short time, for example, on the street, and where possible, use looser models. At the same time, constantly monitor the condition of the feet. Regularly do their massage or self-massage, and then exercises to develop the muscles of the feet.

Such a cooling muscle of the foot and lower leg by a procedure carried out several times a day, it is possible to carry out not only the prevention of the disease. But also the gradual removal of inflammation during the onset of an attack.

At the same time, by increasing the tone of arteries and veins, blood circulation improves, which means nutrition in the affected joint and drainage of toxins from it. In this way, you can even stop the onset of a gout attack.

At the same time, by switching to a low-protein diet, we reduce the production of uric acid in the body. And with the help of alkaline teas, the recipe of which is described at the beginning of this article, we increase its evacuation.

Health to you!

Traditional medicine has a lot of excellent effective recipes for salt deposits in the joints.

Recipe 1. Treatment with pine nuts shell

To prepare the drug, you will need 300 or 400 gr. pine nuts. They need to be split and shells poured into a jar or bottle, then pour alcohol (medical) or vodka into it. Top the vessel with a lid and wrap in black paper.

For three weeks, the drug is kept in a warm and dark place, then filtered and stored in the refrigerator. For treatment in the morning, 2 drops of tincture are dissolved in two tablespoons of water and taken before breakfast on an empty stomach.

Recipe 2. Epsom salt treatment

In the pharmacy you need to buy Glauber's salt. 25 g of "medicine" is divided into 25 parts and every day take 1 g. Salt is diluted in half a glass of water and drunk on an empty stomach. After 25 days, a break is made for 5 days, then the course is repeated.

Recipe 3. Treatment with horseradish leaves

On a sore joint, you need to put a sheet of horseradish, previously scalded with boiling water. Parchment or cellophane is applied on top and everything is wrapped in a woolen cloth. You need to do this before going to bed. When the compress is removed in the morning, you can see a coating of salt on the sheet, which the horseradish pulled out of the joint overnight.

Cleansing the body of excess salt can be carried out by medication. But it is forbidden to prescribe any drugs on your own. The choice of drugs is carried out by the doctor on the basis of existing pathologies. You can treat excess salt in the body with the following drugs:

Folk remedies or how to get rid of at home?

One of the ways to treat folk remedies at home is to drink fluids throughout the day. The consumption of at least 2-3 liters of water per day is implied. Salt deposits are very well exposed to dissolution in the aquatic environment.

To remove salts, in addition to pure water, you can use herbal teas, juices (citrus fruits are recommended), fruit drinks. This method of therapy will not only have a positive effect on improving health, but also help to lose weight.

Treatment of excess salt in the human body should be comprehensive. To achieve a positive effect, it is necessary to change the lifestyle to a more correct one and adjust the diet.

Nutrition principles

You can expel excess salt from the body if you change your usual diet. First of all, it is necessary to increase the volume of water consumed - from 1.5 to 3 liters. Volume depends on sex, weight and physical activity.

Throughout the day, you need to eat small portions, give preference to healthy food, refuse the following:

• fatty and fried foods seasoned with lots of spices;
• fast food
• canned and pickled foods;
• semi-finished products;
• carbonated drinks;
• coffee, tea.

One of the conditions for excellent health is regular physical activity. Intensive sweating helps to remove salts from the body. With regular moderate physical activity, the first positive results will be visible within 1-2 months.

For the average person, it will be enough to conduct daily workouts lasting 30 minutes. It is recommended to perform moderate exercises. Dancing, cycling, swimming in the pool are also useful.

Products with a slight diuretic effect will help to cleanse the body of accumulated salt and excess fluid. These include any green vegetables, beets, onions, citrus fruits. They are especially useful in their raw form. Vegetables and fruits can be eaten whole or juiced.

Now we will tell you how to remove salt from the joints using ordinary rice. We will be treated with rice breakfasts. Every morning in water without salt, you need to boil a small amount of rice and eat one tablespoon.

After that, you do not need to eat or drink for about three hours. The main secret is that before cooking, rice is soaked in clean water for a day. The course of treatment is from one month to two.

The reasons

With gouty arthritis, the joints (one or several at once) become swollen, the skin in this area is reddened and inflamed, and there is sharp pain when moving. The joint becomes hot to the touch and sensitive to any mechanical influences, even to very light touches.

Aggravation (attack of gout) usually occurs at night. Uric acid salts are often deposited on the joints of the big toes, but the ankle, knee, and hands may also be involved.

The main cause of the disease is an imbalance in metabolic processes, namely, disturbances in salt metabolism in the body. With this disease, uric acid derivatives - sodium urate crystals - are deposited in the joints.

A healthy body is able to independently remove salts and all harmful substances that disrupt its functioning. Sometimes this process goes wrong. This leads to the accumulation of salt.

The following conditions are called the reasons that provoke failures in the excretion of harmful substances:

• pathology of the kidneys, liver;
• intoxication of the body, which happens with poisoning or with any infectious disease;
• frequent use of alcohol;
• malnutrition;
• age-related changes;
• sedentary lifestyle.

The accumulation of salt occurs evenly throughout the body, which negatively affects the functioning of many organs and systems.

Contraindications for cleansing

Removal of salts from the body is a complex process. The mineral substance tends to linger in the muscles, joints, tissues. If a person is healthy, the cleansing method can harm and cause a water-salt imbalance.

• inflamed bladder;
• diseases of the cardiovascular system;
• pregnancy and lactation;
• if the kidney is clogged with stones;
• constipation;
• haemorrhoids;
• allergic reactions;
• kidney failure;
• arterial hypertension;
• arrhythmia and other malfunctions of the heart.

Discuss treatment tactics strictly with your doctor.

When a person is diagnosed with a severe disease of the locomotor system, he begins to look for the cause in external factors - bad shoes, a house away from the bus stop, vinegar, sugar in food, an incorrectly performed exercise in the gym, bad doctors, etc.

Any doctor, Malyshev, Malakhov, Ivanov will say that the problem is inside. Often diseases provoke an excess of salt in the body. A person does not notice the first, second symptom, as a result he gets an unpleasant consequence - inflammation of the joints, bones, muscles, pressure, heart disease, swelling.

An overdose of the mineral is dangerous. It is important to get rid of it and prevent new accumulation. Review your diet, increase physical activity, natural drinks and juices will come to the rescue. Remember, these are not evil forces and not damage, but your way of life.

The article has been approved

editorial

Cleansing Recipes

Traditional healers offer a lot of recipes based on different parts of medicinal plants. Each of the recipes has its own effect on the body, and the healers talk in detail about the properties of each plant.

Signs of disease enable healers to choose the most effective recipes. They know what to do in each case of illness, how salt deposits manifest themselves, how to remove salts.

Method of preparation: wash the greens, soak for ½ hour in a strong salt solution. Then wash the leaves, pour over with boiling water, chop finely.

Then squeeze the crushed leaves through a cloth, add water 1: 1 to the liquid, and boil for a couple of minutes. Decoction is recommended to drink 2 r. 50 ml per day, ½ hour before meals.

Method of preparation: dry the lilac flowers, put them in a glass bowl, pour in good quality vodka 1:10. Close the container tightly, put in a dark place for 10 days. During this time, shake the mixture a couple of times. Ready tincture is recommended to drink 1 r. per day, 30 drops.

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With the same remedy, you should rub the joints of the arms and legs, put compresses on sore spots. It relieves pain well, even old ones, if the knee, hip, elbow joints hurt.

How to make: scald 5 bay leaves with ½ liter of boiling water, then cook for another 5 minutes. Drain the cooled broth, add 1 tbsp. l. honey, juice of half a lemon, mix thoroughly.

Drink for 1 day. A fresh decoction is prepared every day. Course - 2 weeks. After a 2-week break, repeat the treatment.

Method of preparation: grind the dried leaves to a powder form. ½ tsp powder pour 200 ml of boiling water, let it brew in a warm place for ½ hour.

Strain the infusion and drink freely, like tea, during the day. It is useful to eat fresh lingonberries, the practice of treatment confirms their effective action for removing salts.

bark decoction

Ingredients: birch, aspen, oak bark in a ratio of 10:10:1, in a crushed state. Method of preparation: both fresh and dried tree bark is used. Pour the mixture with 10 parts of boiling water, cook for ½ hour.

Then the dishes must be covered, wrapped warmly, allowed to cool naturally. After that, drain the broth, store in the cold. Drink 50 ml 2-3 r. per day, regardless of food.

Ingredients: finely chopped roots of burdock, couch grass, violet grass - in equal proportions. Cooking method: 2 tbsp. l. mixed raw materials pour 1 liter of boiling water, boil for another 15 minutes.

Cover the dishes, cool naturally. Strain the broth, take 50 ml 2-3 r. per day, between meals.

Potato decoction

Cooking method: cut 1 kg of washed unpeeled potatoes into large pieces, pour 3 liters of boiling water, cook for 1.5 hours. Cover the dishes warmly, after natural cooling, drain the broth, drink 100 ml 3 r. per day for 1.5 months. After a break of 1 month, the course is repeated.

Method of preparation: peel the root from small shoots, chop. Take 200 g of chopped rhizome, pour 3 liters of boiling water, cook for 2 minutes. Strain the broth, drink for 3 days. After 3 days of break, you need to cook a fresh broth, and also drink it in 3 days.

At the time of using a decoction of sunflower rhizomes, it is necessary to remove dishes that irritate digestion from the menu - spicy, salty. The result will be noticeable in 2-3 weeks, when the color of the urine changes, rust flakes appear in it. This will be the outgoing salts.

Before starting to take measures to cleanse the joints, it is necessary to pay attention to a balanced diet and an increase in physical activity on the body so that the removal of salts occurs without hindrance.

Here are recipes from traditional medicine:

• Cleansing the joints with bay leaf. 5 g of dry bay leaf is poured into 1.5 cups of boiling water and insisted in a thermos for 12 hours. Drink ready-made broth 2-3 tablespoons during the day between meals. It is necessary to drink the infusion for 4 days, then take a break for 2 days, and so alternate until the pain stops.
• Infusion of parsley roots. 400 g of fresh parsley roots and 3 lemons scroll through a meat grinder. The resulting mixture is thoroughly mixed with 300 g of honey. Take one teaspoon before meals several times a day until the mixture runs out. As traditional healers advise, such a course is held 4 times a year.
• Infusion of sunflower roots. This recipe is suitable for those who grow sunflowers in their garden, because these roots are hard to find in the general market. For 3 liters of water, take 1 cup of dry roots and boil for literally 1-2 minutes. The infusion is drunk abundantly, several glasses a day. Sunflower roots can be reused, just boil now for 5 minutes. The treatment is continued until the urine becomes light, in other words, until the salts come out of the joints.
• Infusion of dill seeds. One glass of seeds is poured with 500 ml of alcohol and sent to infuse for a week in a dark place. Take the tincture in a teaspoon, after diluting it with water. The course of cleansing - 2 weeks.
• Cleansing with black radish. Pass 10 kg of radish through a juicer. The resulting juice is taken 1 tablespoon before meals. Leftovers are stored in the refrigerator. Black radish can be used as a compress on a sore joint.
• Oatmeal compress. For 2 cups of water, take 3 tablespoons of cereal, boil and strain. Soak the bandage with the resulting broth and apply to the joint, wrapping it with polyethylene. Hold the compress until a feeling of cold appears.
• Infusion of walnut leaves. Take one tablespoon of dry walnut leaves for one glass of boiling water and insist for an hour. Infusion drink 4 tbsp. spoons several times a day.
• Infusion of horseradish roots. Pass 1 kg of fresh washed horseradish roots through a meat grinder, pour 4 liters of water and boil for 5 minutes. Add honey for taste. Drink this infusion in a glass a day until it runs out.

These herbs include coltsfoot, horsetail, marsh cinquefoil, sunflower and rosehip roots, and many others. For the treatment of gout, according to the method of Academician Bolotov Boris Vasilyevich, alkaline tea is prepared on the basis of one of these herbs, which is drunk in large doses for at least a month.

The recipe for making this tea is simple: 1 tbsp. a spoonful of vegetable raw materials is brewed for 15 - 20 minutes in 1 cup of boiling water. On the day you need to drink up to 10 - 12 glasses of this drink.

A list, description and methods of using plants and herbs that allow you to remove excess salts from the body can be found in the collection of articles “Arthritis - Herbal Treatment”.

During the first four weeks, an alkaline and predominantly plant-based diet is followed. You can read more about diet in the article "Diet - the path to health." What's next?

During the second month of treatment, the organism is oxidized with the help of enzymes of bearberry, lingonberry, coniferous buds. Such an alternation of multidirectional influences - alkalization, and then oxidation of the body, according to Boris Vasilyevich, gives a positive result and makes the disease recede.

The whole treatment scheme is described in detail in the book of the authors B. Bolotov, G. Pogozhev “Healing and rejuvenating bath according to Bolotov”. Publishing house "Piter" - 2011.

Health to you!

Balanced diet

With an increased content of urea in the blood, crystals form. Small hard stones with sharp edges accumulate in the kidneys and articular bag. Salts constantly injure soft tissues, causing chronic inflammation and pain.

The level of urea rises when eating preservatives, smoked meats, marinades and strong meat or fish broths. To cleanse the joints of salts, you need to give up sausages, sugar, black tea and coffee, and also reduce salt intake to 5–8 g per day. No desserts, semi-finished products, fried foods and too spicy.

The concentration of uric acid in the body is reduced due to natural and dietary products that speed up metabolic processes. With a crunch and pain in the joints, it is recommended to use:

1. Vegetarian soups made from vegetables, cereals, milk or fruits. Once a week, weak fish or meat broths are allowed.
2. Vinaigrette with olive or linseed oil. Vegetable salads and stews of cabbage, tomatoes, eggplant, zucchini and carrots. The ban includes beans, peas and other legumes.
3. Mucus porridge. Useful buckwheat, oatmeal, millet, pearl barley and corn grits. White rice is contraindicated. The product clogs the intestines, leads to constipation and intoxication of the body. Brown rice can be consumed, but 1-2 times a week.
4. During the period of remission, when the pain subsides, low-fat chicken or turkey is introduced into the menu. Beef and rabbit are allowed. Meat dishes are cooked in a double boiler or oven.
5. Sour fruits and berries reduce the concentration of salts in the body. Fresh salads from apples, pears or citruses activate metabolic processes, stimulate the production of collagen, which is part of cartilage. Only grapes and freshly squeezed juice from this product are contraindicated.
6. Steamed, stewed and baked fish saturates the body with amino acids. Sea and river varieties are useful. You can not only dried and smoked fish.
7. Peppermint tea and rosehip decoction wash out salt crystals from the joints and internal organs. Herbal drinks are supplemented with alkaline mineral water and ordinary distilled water. A patient with healthy kidneys should drink 2.5 liters of fluid per day.

Over the past decade, the tactics of managing patients with rheumatoid arthritis (RA) has changed dramatically, which is due, on the one hand, to the emergence of new highly effective drugs, and on the other hand, the development of standardized algorithms that determine the choice of therapeutic tactics in each case. The basis of these recommendations is the strategy of treatment to achieve the goal. It was developed by experts taking into account the results of scientific research of the last decades and includes the basic principles of RA treatment. Experts believe that the goal of RA treatment should be remission or low disease activity. The treatment-to-target strategy provides that, until the treatment goal (remission or low inflammatory activity) is achieved, the level of activity should be assessed monthly using one of the summary indices. The ongoing therapy, taking into account these results, must be adjusted at least once every 3 months. If the patient persistently maintains low activity or remission, then the status can be assessed less frequently - about 1 time in 6 months. Achieved goal of treatment should be constantly maintained in the future.

Keywords: rheumatoid arthritis, treatment, glucocorticoids, basic anti-inflammatory drugs, genetically engineered biological drugs, non-steroidal anti-inflammatory drugs, activity, remission, methotrexate, nimesulide, tumor necrosis factor inhibitors, tofacitinib.

For citation: Olyunin Yu.A., Nikishina N.Yu. Rheumatoid arthritis. Modern treatment algorithms // RMJ. Medical review. 2016. No. 26. S. 1765-1771

Modern treatment algorithms of rheumatoid arthritis
Olyunin Yu.A., Nikishina N.Yu.

V.A. Nasonova Research Institute of Rheumatology, Moscow

Treatment approach to rheumatoid arthritis (RA) has undergone dramatic changes in the last decade as a result of the development of novel effective medications and standard algorithms which determine treatment choice in individual cases. These recommendations are based on the “treat-to-target” strategy which was developed on the basis of recent findings and includes major principles of RA treatment. According to the experts, RA treatment goal is the remission or low disease activity. “Treat-to-target” strategy means that disease activity should be measured monthly using one of the RA activity indices until treatment goal (i.e., remission or low inflam-matory activity) is achieved. The prescribed treatment should be corrected at least every 3 months (or every 6 months in stable low disease activity or remission). The achieved treatment goal should be maintained permanently.

key words: rheumatoid arthritis, treatment, glucocorticoids, disease-modifying anti-rheumatic drugs, engineered biological agents, non-steroidal anti-inflammatory drugs, activity, remission, methotrexate, nimesulide, tumor necrosis factor inhibitors, tofacitinib.

For quote: Olyunin Yu.A., Nikishina N.Yu. Modern treatment algorithms of rheumatoid arthritis // RMJ. 2016. No. 26. P. 1765–1771.

The article presents modern algorithms for the treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease. The functional insufficiency associated with it can lead to a significant disability and social activity, reducing the quality of life of patients. The chronic inflammatory process characteristic of RA can also induce the development of cardiovascular pathology, thereby creating a threat of shortening the patient's life expectancy. Over the past decade, the tactics of managing RA patients have changed dramatically, which is due, on the one hand, to the emergence of new highly effective drugs, and on the other hand, to the development of standardized algorithms that determine the choice of therapeutic tactics in each specific case.
The basis of these recommendations is the strategy of treatment to achieve the goal. It was developed by experts taking into account the results of scientific research of the last decades and includes the basic principles of RA treatment. The fundamental provision of this strategy is the postulate of the need for a coordinated decision between the doctor and the patient in determining the tactics of treatment, which should ensure the highest possible quality of life for the patient. Experts believe that the goal of RA treatment should be remission or low disease activity. However, when choosing the goal of therapy, the presence of comorbid diseases and other individual characteristics of the patient, including the degree of risk associated with the appointment of certain medications, should be taken into account. Experts emphasize that one of the quantitative assessment methods must be used to determine the level of disease activity.
Currently, in routine practice and in clinical trials, three total indices of inflammatory activity are widely used - DAS28, SDAI and CDAI. All of them have their advantages and disadvantages, and none of them is considered the gold standard. The DAS was the first summary index to gain wide popularity. It was developed in the early 1990s. based on the management of patients with RA in routine clinical practice. Its simplified version, DAS28, was actively used in scientific research and then was recommended for practical healthcare. DAS28 is calculated according to 4 initial indicators, these are: 1) the number of painful joints (PJS) out of 28 (proximal interphalangeal, metacarpophalangeal, radiocarpal, shoulder, elbow, knee); 2) number of swollen joints (SPJ) out of 28; 3) overall health assessment for patients (OHZB) in mm on a 100 mm visual analogue scale (VAS); 4) erythrocyte sedimentation rate (ESR) according to Westergren in mm/h. The value of each of these indicators in the composition of DAS28 reflects its real clinical significance. A significant drawback of this index is a rather complicated mathematical data processing.

DAS 28=0.56√NBS+0.28√NPV+0.70lnESR+0.014OOZB

SDAI=OOAB+OOAB+NPV+NBS+SRP,

CDAI=OOAB+OOAB+NPV+PBS.

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Clinical and anatomical forms: rheumatoid mono-, oligo- and polyarthritis, RA with systemic lesions, individual syndromes (Felty, Stilla).

Seropositive, seronegative.

Degrees of activity (0 to 3).

Flow: rapidly progressive, slowly progressive, without noticeable progression.

X-ray stage:I - periarticular osteoporosis; II- stage I + narrowing of the joint spaces and single uzura; III – stage III + multiple uzuras; IV – stage III+ bone ankylosis.

Functional classes:I – full preservation of the performance of a normal daily load without restriction, II- restriction or impossibility of performing professional activities; III- Loss of ability to self-care.

Clinical and diagnostic criteria for rheumatoid arthritis

1. Possible antecedent factors: acute respiratory infections, mental trauma, hypothermia.

2. 70-75% of cases of rheumatoid arthritis are women, the average age of onset is 35-45 years.

3. progressive nature of the disease.

4. Polyarticular type of lesion in 70-80% of cases. In 20-30% of patients, rheumatoid arthritis begins with oligo-monoarthritis, which evolves into polyarthritis in 1-2 years.

5. Symmetrical lesions of the small joints of the hands and feet:

II-III metacarpophalangeal, proximal interphalangeal, II-V metatarsophalangeal, later - knee, wrist and others.

6. The presence of "joints of exclusion of rheumatoid arthritis" (which almost always remain unaffected): distal interphalangeal, I metacarpophalangeal, proximal interphalangeal joint of the little finger.

7. Subacute onset with a gradual increase in symptoms of inflammation within 1-2 weeks.

8. Severe morning stiffness of the joints of varying duration (at least 30-60 minutes) depending on the activity of the process (“tight gloves symptom” with lesions of the hands).

9. Constant pain with intensification in the second half of the night (“inflammatory rhythm”), an increase in the volume of the joint (defiguration) due to synovitis and swelling of the periarticular soft tissues, an increase in local temperature, slight skin hyperemia, impaired joint function. The exudative period lasts on average about a year.

10. In the proliferative phase, a decrease in the inflammatory response with the development of joint deformity due to muscle atrophy, ligament tension, flexion contractures, fibrous, and then bone ankylosing. With the defeat of the brushes develops " rheumatoid hand"-" visiting card of the disease ":

- ulnar deviation fingers - “walrus flippers”

Flexion contracture of proximal interphalangeal and extensor contracture distal interphalangeal joints - " buttonhole»;

Proximal interphalangeal extensor contracture and flexion contracture distal interphalangeal joints - " neckswan"- deformity of the hand due to wrinkling of the skin over the phalanges of the fingers shortened due to the osteolytic process with their pronounced contracture -" hand withlorgnette»;

- interosseous atrophymuscles with retraction of interosseous spaces.

11. Reducing the intensity of pain and morning stiffness while taking glucocorticoids and NSAIDs.

12. With systemic manifestations of rheumatoid arthritis (10-15% of cases) - the presence of extra-articular lesions, which occur more often subclinically and asymptomatically.

Rheumatoid nodules: in 7-25% of cases - a few (2-3), dense, rounded, painless, mobile fibrous formations with a diameter of 2-3 mm to 2-3 cm or more, located on the extensor surface of the forearm near the elbow, on the back surface of the small joints of the hand, in the region of the Achilles tendons.

Lung injury: diffuse fibrosing alveolitis, interstitial pulmonary fibrosis, pulmonary vasculitis. Alveolitis is characterized by the presence of shortness of breath, cyanosis, diffuse crepitus, symmetrical enhancement of the lung pattern (radiologically). Pneumonitis is diagnosed on the basis of cough, shortness of breath, subfebrile body temperature, crepitus and fine bubbling rales over the lungs, infiltrative shadows on x-ray.

Heart failure: rheumatoid carditis, myocardial dystrophy, heart defects (mitral and aortic valve insufficiency, much less often aortic stenosis) with little or no hemodynamic disturbances.

Defeatserous membranes with the development of adhesive (detected radiographically), less often exudative pleurisy with a small amount of effusion and / or pericarditis. The peculiarity of the course is positive dynamics under the influence of glucocorticoids.

Kidney damage manifested by amyloidosis, which is characterized by persistent proteinuria, cylindruria, a gradual violation of the concentration and nitrogen excretion functions of the kidneys. Much less often, glomerulonephritis is detected, manifested by an isolated urinary syndrome.

Vasculitis(less than 1%), more often develops in men with severe seropositive rheumatoid arthritis - " digital vasculitis(gangrene of the fingertips), livedo reticularis, cerebral syndrome, abdominal syndrome, epistaxis, uterine bleeding, painless leg ulcers.

Damage to the nervoussystems: peripheral ischemic neuropathy due to vasculitis with the development of parasthesia, weakness, decreased sensitivity in the distal extremities. Polyneuritis. Encephalopathy due to cerebral vasculitis.

Eye damage manifested by episcleritis, scleritis with the development of pain and hyperemia of the sclera, iritis, iridocyclitis. With a combination of rheumatoid arthritis with Sjögren's syndrome, dry keratoconjunctivitis is observed,

Felty syndrome- a combination of splenomegaly, hepatomegaly, lymphadenopathy (enlarged dense, painless, mobile cervical, submandibular, axillary, elbow lymph nodes), neutropenia, thrombocytopenia, anemia. Patients in this group have a 12-fold increased risk of developing non-Hodgkin's lymphoma, there is a predisposition to severe, recurrent infectious diseases and chronic leg ulcers.

Still's syndrome characterized by hectic, remitting or intermittent fever (with chills, sweating, erythematous-papular multiform rash without itching, localized on the trunk and extremities, most pronounced at the height of the fever), weight loss, sore throat, lymphadenopathy, anemia, leukocytosis, increased ESR . Arthritis is intermittent in nature with exudative phenomena within 5-7 days, damage to several large and small joints (wrist, carpometacarpal, tarsal, shoulder, hip). In a third of patients, arthritis takes a chronic course with the development of destruction and ankylosis.

13. Laboratory data:

In the general blood test - an increase in ESR, normochromic or hypochromic anemia (often of an iron redistribution nature).

In the general analysis of urine - hematuria, leukocyturia, moderate proteinuria, cylindruria, a decrease in relative density.

Acute phase markers of inflammation: increased levels of α- and γ-globulins, C-reactive protein, seromucoid, sialic acids, fibrinogen.

The presence of rheumatoid factor in 80% of patients. When rheumatoid factor is detected, arthritis is considered seropositive, in cases of its absence - seronegative. To determine the rheumatoid factor, latex agglutination reactions (a positive test with a titer of 1:20 and above) and Vaaler-Rose (a positive test with a titer of 1:32 and above) are used. The latex test is more sensitive but less specific and is used for screening.

Normal uric acid levels.

Normal titers of antistreptolysin-0, antistreptokinase, antistreptohyaluronidase, antistreptodeoxyribonuclease-B.

Absence of LE cells in the blood.

Lack of HLA 27.

14. Radiography of the joints - periarticular epiphyseal osteoporosis, narrowing of the joint space, significant destruction of cartilage, marginal bone usuration, subluxations, bone cysts, ankylosis Computed tomography, magnetic resonance imaging are used to detect changes in the periarticular tissues.

Treatment

Includes a fast-acting (" up-to-date"") and slow-acting ("b basic”) therapy, as well as agents that improve microcirculation, methods of gravitational blood surgery, physiotherapy, and prevention of the development of gastropathy.

1. fast acting(symptomatic, up-to-date”), therapy is aimed at the speedy reduction of local inflammatory and exudative phenomena and suppression of disease activity. The main therapeutic agents are non-steroidal anti-inflammatory drugs and glucocorticoids.

- Nonsteroidal anti-inflammatory drugs are the first line drug. They are used continuously, during the entire period of activity of the process, depending on individual tolerance. If after 7-10 days the drug does not have a sufficient anti-inflammatory effect, it is replaced with another one. The main mechanism of action of NSAIDs is the inhibition of the synthesis of cyclooxygenases, key enzymes in the metabolism of arachidonic acid, a precursor of prostaglandins. Cyulooxygenase-1 exhibits the activity of a structural enzyme that regulates the production of prostaglandins. With inhibition of cyclooxygenase-1, the development of gastropathy, impaired renal function (sodium and water retention) and platelets (decrease in aggregation) are observed. These side effects are pronounced in non-selective NSAIDs and are much less common in selective and specific inhibitors of cyclooxygenase-2. Cyclooxygenase-2 is normally found in trace amounts in most tissues, its expression significantly increases against the background of the development of inflammation. Selective NSAIDs:

- Sulfonamides: nimesulide (nise, nimesil) is used 100 mg 2 times a day. In terms of anti-inflammatory action, nise is comparable to traditional NSAIDs.

- Coxibs: celecoxib (celebrex) is used at 100-400 mg 1-2 times a day; rofecoxib.

- Meloxicam(melox, movalis) is used at 7.5-15 mg 1-2 times a day. Non-selectiveNSAIDs:

Derivatives salicylic acid: acetylsalicylic acid. It is rarely used due to the ulcerogenic effect, the development of bronchospastic syndrome. Daily dose 4-6 g.

- Pyrazolone derivatives: butadione (phenylbutazone). The strength of the anti-inflammatory action is comparable to that of indomethacin. They promote water and sodium retention, inhibit hematopoiesis, cause dermatitis, dyspepsia. Not suitable for long term use. The daily dose is 450-600 mg.

Derivatives propionic acids. Well tolerated, have analgesic and weak anti-inflammatory action. Discomfort in the epigastric region is detected in 18% of patients. Used: ibuprofen (brufen) - 800-1200 mg / day, naproxen 250 mg 2 times a day, surgam (thiaprofenic acid) 300 mg 2 times a day. Surgam practically does not inhibit the formation of protective gastric prostaglandins.

Derivatives enolacids(oxicams): piroxicam. It is well tolerated, but side effects are possible, the same as those of other NSAIDs. The advantage is a single dose in the morning after breakfast at a dose of 20 mg,

Derivatives indoacetic acid: metindol (indo-methacin), daily dose 75-150 mg. Causes gastropathy, dizziness, headache, tinnitus, arterial hypertension, leukopenia, may reduce kidney function. Sulindac (clinoril) has a satisfactory tolerance, less than other NSAIDs, affects kidney function. Applied 200 mg 2 times a day.

Derivatives phenylacetic acid: voltaren (diclofenac, ortofen). It is well tolerated, surpassing other NSAIDs in this respect. Combines pronounced anti-inflammatory and analgesic effects. It is used at 100-150 mg per day. Recently, rapten rapid has proven itself well - a fast-acting drug, the potassium salt of diclofenac, prescribed 50 mg 2-3 times a day. In addition to a pronounced anti-inflammatory effect, it has a pronounced analgesic effect, which is based on the central opioid-like effect due to the hyperproduction of endorphins.

Derivatives atranilic acids: mefenamic acid. It has a weak anti-inflammatory and predominantly analgesic effects, so it is rarely used in rheumatoid arthritis. Daily dose 1.5 g,

Glucocorticoids. They suppress the transcription and translation of genes for pro-inflammatory cytokines, genes for metalloproteinases involved in the final stages of cartilage destruction, reduce the permeability of capillaries and lysosomal membranes, suppress phagocytosis and migration of neutrophils to the site of inflammation, have an immunosuppressive effect and inhibit the activity of fibroblasts, inhibiting the processes of fibrosis. They have side effects in the form of damage to the gastrointestinal tract, the development of arterial hypertension, steroid diabetes, osteoporosis, muscle atrophy, Cushing's syndrome, adrenal insufficiency. Contribute to the retention of sodium and water, excretion of potassium and calcium from the body, exacerbation of chronic infections. Applied in the form bridge "-therapy, pulse therapy and locally.

"Bridge" therapy low doses of glucocorticoids (prednisolone 10-15 mg / day, methylprednisolone 4-6 mg / day), Most of the dose of glucocorticoids is prescribed in the morning, although there is an opinion that taking prednisolone (5-7.5 mg) in patients with rheumatoid arthritis at night time is preferable from the point of view of clinical effectiveness than in the morning. This is due to the peculiarities of circadian fluctuations in interleukin-6, ACTH and cortisol in patients with rheumatoid arthritis.

Pulse therapy glucocorticoids (up to 1000 mg of methylgtrednisolone per day intravenously). It is carried out in the presence of visceritis, high fever. Allows you to achieve a quick (within 24 hours), but rather short-term (3-12 weeks) suppression of the activity of the inflammatory process. The positive effect of pulse therapy on radiographic progression of joint damage has not been established.

local glucocorticoid therapy (injection into the joint cavity) aims to suppress active synovitis in a limited number of joints. Prolonged drugs are used:

middle duration of action (kenalog-40) and for a long time acting (diprospan).

2. slow acting(pathogenetic, disease-modifying, "basic") therapy. Includes the use of cytostatics, gold preparations, D-penicillamine, sulfonamides, quinoline derivatives, Arava, Remicade. It is aimed at correcting the immune mechanisms of the disease and modifying the evolution of active rheumatoid arthritis. It is used from the II stage of the disease. The effect begins no earlier than 4-8 weeks from the start of treatment. Previously, slow-acting therapy was prescribed only after several years of treatment with anti-inflammatory drugs, but now the paradigm for the treatment of rheumatoid arthritis involves the early start of "basic" therapy. In recent years, the effectiveness of combined treatment regimens has been studied: methotrexate with cyclosporine A, methotrexate with sulfasalazine, methotrexate with azathioprine and plaquenil, gold preparations with plaquenil, etc. The combination of drugs can increase the effectiveness of treatment and reduce the frequency of adverse reactions.

Cytostatics. They inhibit humoral and cellular immunity, inhibit the production of autoantibodies and immune complexes, and stabilize lysosomal membranes. Methotrexate as a folic acid antagonist, it blocks the DNA synthesis reaction at the stage of methylation of uridine to thymidine. It is prescribed at 7.5 mg per week according to the scheme (2.5 mg 3 times a week with an interval of 12 hours). The dose may be increased to 15 mg per week. The duration of treatment is from 2-3 to 5 years or more. To reduce the likelihood of side effects of methotrexate, it is recommended to prescribe folic acid. Azathioprine applied at 100-150 mg / day, followed by a dose reduction to 75-50-25 mg / day, for a long time. Side effects; stomatitis, inhibition of hematopoiesis, damage to the gastrointestinal tract, liver, alopecia, dermatological reactions, development of infectious complications. When using cytostatics, it is necessary to control the general blood test, liver function tests.

Preparationsgold inhibit the function of macrophages, neutrophils, the presentation of antigen by macrophages to T-helpers, the synthesis of pro-inflammatory prostaglandins, the release of lysosomal enzymes. The main mechanisms of action are the effect on the molecules that are located on the surface of macrophages, and the violation of antigen presentation to T-lymphocytes. Crizanol(Aurotioprol) is used in the first week in the amount of 0.5-1 ml of 5% oil suspension IM, then 1-2 ml of 5% oil suspension IM once a week for a long time, at least a year, then in the same dose 1 time in 2-3 weeks. tauredon(sodium aurothiomalate) is used in the first to third weeks 10-20 mg / m, then 50-100 mg / m 1 time per week. In case of obtaining a clinical effect, maintenance therapy is carried out at a dose of 100 mg per month. Auranofin(gold preparation for oral administration) is prescribed 3 mg 2 times a day. When complete clinical and laboratory remission is achieved, the dose is reduced to 3 mg / day. Side effects of this group of drugs: allergic lesions of the skin and mucous membranes, inhibition of hemopoiesis, kidney damage, diarrhea (especially when treated with aurofin). It is necessary to monitor blood, urine, kidney and liver function.

D-penicillamine(Kuprenil) has an immunosuppressive effect (inhibits the function of B-lymphocytes, T-helpers), inhibits collagen synthesis, reduces the level of pathological macroglobulins. It is prescribed at an initial dose of 125-250 mg / day with a gradual increase to 450-600 mg / day in two divided doses, after meals. With a positive result, treatment continues up to 3-5 years with the transition to a maintenance dose of 100-250 mg / day. Side effects: allergic skin lesions, inhibition of hematopoiesis, nephropathy, liver damage, pneumonitis, vitamin B6 deficiency.

Sulfonamides: sulfasalazine 1.0 g 2 times a day after meals. The effect is achieved due to a moderate immunosuppressive effect, inhibition of the synthesis of prostaglandins, leukotrienes, rheumatoid factor. Side effects; allergic skin lesions, dyspeptic syndrome, anemia, leukopenia, thrombocytopenia, arterial hypotension, headaches, dizziness, ulcerative stomatitis. Monitoring of blood and urine parameters, liver function is carried out.

Quinoline derivatives: use delagil 250 mg 2 times a day for 2-4 weeks, then 250 mg / day or plaquenil 200 mg 2 times a day for 2-4 weeks, then 200 mg / day after dinner (tolerance to plaque -nila is better). The drugs have a weak immunosuppressive effect, stabilize lysosomal membranes, inhibit the synthesis of pro-inflammatory prostaglandins, inhibit neutrophil phagocytosis and chemotaxis, and bind free radicals. Side effects - retinopathy, skin rashes, itching, dyspepsia, rarely leuko- and thrombocytopenia. They are the weakest of the basic remedies and therefore are used in mild forms of the disease.

Antibodiesmonoclonal to tumor necrosis factor-alpha: infliximab (Remicade). It is used in the form of intravenous injections at a dose of 3 mg / kg, the duration of the infusion is 2 hours. After 2 and 6 weeks after the first injection, additional infusions of 3 mg / kg each are prescribed, then the administration is repeated every 8 weeks. The use of monoclonal antibodies to cytokines is a promising treatment for rheumatoid arthritis.

Le Leflunomide(arava): has anti-proliferative, immunomodulatory/immunosuppressive and anti-inflammatory properties. Treatment begins with a loading dose of 100 mg for 3 days, followed by a transition to maintenance therapy at 10-20 mg per day, regardless of food intake. Side effects - leukopenia, mild allergic reactions, hair loss, hepatitis, diarrhea, nausea, vomiting, anorexia, aphthous stomatitis, a slight increase in blood pressure.

3. Funds, improving microcirculation: pentoxifylline, nicotinic acid, chimes.

4. Gravity Surgery Methods: hemosorption, plasmapheresis, lymphocytopheresis. The use of these methods is based on the possibility of removing pro-inflammatory cytokines, circulating immune complexes, autoantibodies from the circulation, which leads to unloading of the cells of the mononuclear phagocyte system, and improvement of the rheological properties of blood.

5. Physiotherapy: With high activity of the disease, dimexide electrophoresis, NSAIDs, magnetotherapy, erythemal ultraviolet irradiation of the joints are used. With moderate activity of rheumatoid arthritis, along with the above methods, hydrocortisone phonophoresis, laser therapy, electromagnetic fields of ultrahigh frequencies are used. With minimal activity of the process, in addition, balneotherapy, ozocerite and paraffin applications on the joints, acupuncture are indicated.

6. Prevention the development of gastropathy caused by the use of NSAIDs or glucocorticoids - blockers of H2-histamine receptors: famotidine (kvamatel) 40 mg / day; misoprostol or proton pump inhibitors (omeprazole - omez 20 mg 2 times a day).

Annex 2. Test tasks:

1 .Which of the following indicates inflammatory pain? a) deformity of the joint; b) crunch in the joint; c) joint swelling; d) skin hyperthermia over the joint; e) pain occurs when the joint is loaded. Choose the correct combination of answers:

2. Rheumatic polyarthritis is characterized by: a) persistent deformity of the joints; b) unstable deformation of the joints; c) damage to large and medium joints; d) volatility of pain; e) the disappearance of pain after taking NSAIDs. Choose the correct combination of answers:

3. What joint disease is rheumatoid arthritis?

1) inflammatory

2) degenerative

3) metabolic

4) reactive

5) associated with spondyloarthritis

4. Which joints are most commonly affected in rheumatoid arthritis?

1) distal interphalangeal joints

2) proximal interphalangeal joints

3) first metacarpophalangeal joint

4) joints of the cervical spine

5) joints of the lumbar spine

5. What symptoms are important for early diagnosis of rheumatoid arthritis? a) lateral deviation of the joints of the hands; b) pain on palpation of the Achilles tendon; c) morning stiffness; d) subcutaneous nodules; e) swelling of the proximal interphalangeal joints. Choose the correct combination of answers:

6. The activity of rheumatoid arthritis is evidenced by: a) ESR acceleration; b) morning stiffness for more than 1 hour; c) increase in ALT; d) Heberden's nodules; e) high titer of ASL-0. Choose the correct combination of answers:

7. When examining a patient with rheumatoid arthritis, the following are found: a) redness in the joints; b) Bouchard's nodules; c) fingers in the form of a “swan neck”; d) ulnar deviation of fingers; e) crunch in the joints. Choose the correct combination of answers:

8. Rheumatoid arthritis is characterized by: a) morning stiffness; b) symmetry of joint damage; c) damage to the distal interphalangeal joints; d) severe hyperemia in the joints; e) pain in the joints in the first half of the night. Choose the correct combination of answers:

9. Laboratory signs of rheumatoid arthritis activity are: a) the presence of CRP; b) ESR acceleration; c) increase in LDH; d) leukocytosis; e) ASL‑0 titer. Choose the correct combination of answers:

10. Radiological signs of rheumatoid arthritis are: a) osteoporosis; b) erosion; c) osteophytosis; d) intervertebral ossifications; e) unilateral sacroiliitis. Choose the correct combination of answers:

11. Means of basic therapy for rheumatoid arthritis are: a) tauredone (krizanol); b) methotrexate; c) aspirin; d) prednisolone; e) ibuprofen. Choose the correct combination of answers:

12. Specify the indications for the use of corticosteroids in rheumatoid arthritis: a) ineffectiveness of previous NSAID therapy; b) a high degree of activity of the process; c) visceritis; d) young age; e) lymphadenopathy. Choose the correct combination of answers:

13. For rheumatic polyarthritis, the following joints are most commonly affected: a) hip; b) ankle; c) elbow; d) small joints of the hands; e) intervertebral; e) knee. Choose the correct combination of answers:

14. Specify the characteristic localization of the articular syndrome in rheumatoid arthritis:

1) II and III metacarpophalangeal and proximal interphalangeal joints;

2) I metatarsophalangeal joint

3) knee joints

5) joints of the spine

15. Specify the drug that is not used to treat rheumatoid arthritis:

1) methotrexate

2) metipred

3) movalis

4) pentoxifylline

5) allopurinol

16. In the clinical picture of rheumatoid arthritis, all signs are observed except:

1) atrophy of the interosseous muscles

2) damage to the proximal interphalangeal, wrist and metacarpophalangeal joints

3) rheumatoid nodules

4) morning stiffness

17. What factors are involved in the pathogenesis of rheumatoid arthritis:

1) rheumatoid factor

3) immune-based inflammation of the synovial membrane

4) genetic predisposition

5) all answers are correct

18. Which drug is not classified as a selective NSAID:

1) movalis

3)celebrex

4) nimesil

5) ortofen

19. Which of the visceral lesions is not typical for rheumatoid arthritis:

1) kidney amyloidosis

2) fibrosing alveolitis

3) peripheral neuropathy

4) mitral stenosis

20. Which drug does not belong to the "basic" in the treatment of rheumatoid arthritis:

1) methotrexate

2) remicade

4) sulfasalazine

5) diprospan

Answers to test tasks: 1 – 3; 2 – 5; 3 – 1; 4 – 2; 5 – 3; 6 – 1; 7 – 3; 8 – 1; 9 – 1; 10 – 1; 11 – 1; 12 – 4; 13 – 5; 14 – 1; 15 – 5; 16 – 5; 17 – 5; 18 – 5; 19 – 4; 20 – 5.

Annex 3. Situational tasks:

Task 1.

The patient is 45 years old. Complaints of pain and stiffness in the joints, morning stiffness. Sick for 2 years. I took Brufen with no visible effect. Treatment with delagil was interrupted due to dizziness and blurred vision.

Objectively: slight swelling, soreness and limitation of movements in the joints of the hands, wrists and knees. The rest without features.

X-ray of the joints: narrowing interarticular fissures, adhesions and single uzura, osteoporosis of the articular ends of the bones. ESR - 45 mm/h, Waaler-Rose reaction - 1/64, latex test 1/160.

1) Formulate a complete diagnosis.

2) Given the ineffectiveness of previous treatment, the duration of the disease without remissions, the activity of the process, there are indications for changing the basic therapy. What diseases should be excluded before their appointment?

3) What is the method of treatment?

4) What are the methods of treatment tolerance control?

5) When can we expect a positive effect from basic therapy?

What should be prescribed before its full appearance?

Task 2.

A 29-year-old patient complains of constant pain in the joints of the arms and legs at rest and during movement, a significant limitation of the range of motion in the limbs, especially before noon. Sick for 11 years. Since then, gradually increasing pain in the joints, limitation of movement in them. Repeatedly treated in hospitals and sanatoriums. Present worsening a week before admission. The condition is satisfactory. From the side of internal organs: no pathology. Severe deformity and defiguration of the joints. Ankylosis of the elbow joints. Brushes in the form of "walrus fins", atrophy of the interosseous muscles. The range of motion in the joints is sharply reduced, stiffness persists throughout the day.

Blood analysis: Hb - 90 g/l, ESR - 41 mm/hour. The reaction of Waaler - Rose -1:32.

Radiography - osteoporosis, narrowing of the joint spaces, ankylosis of the elbow joints, subluxations of the joints of the hands.

1) Set the form, stage and phase of the disease?

2) What is expected on a joint x-ray?

3) What does the Waaler-Rose reaction mean?

4) What treatment is indicated?

Task 3.

The patient is 63 years old. Complaints of pain in the joints of the hands, shortness of breath when walking, weakness, nausea, poor appetite, constipation. Within 15 years - rheumatoid arthritis without disability. Receives ibuprofen 0.2x3 times, iron preparations inside. Deterioration of health 3 months. Objectively: pallor of the skin and mucous membranes. Ulnar deviation of the hands and swelling of the metacarpal and proximal interphalangeal joints, subcutaneous nodules over the elbow joints. Pulse - 80 per minute. BP - 180/100 mm Hg. Art. Spleen at 4 cm edge of the costal arch. Analysis of urine: protein traces.

Blood analysis: Hb - 78 g/l, leuk. - 1.8x10 9 / l, eos. - 1%, base. - 1%, neutral. -19%, lymph. - 77%, mine. - 2%, reticulum. - 7%, thrombus. - 120x10 9 /l, aniso-poikilocytosis, ESR - 80 mm/hour.

1) What is the form, stage and activity of the disease?

2) How to explain changes in peripheral blood?

3) How to explain the symptoms of the gastrointestinal tract?

4) How to explain anemia? What research needs to be done

Task 4.

A 40-year-old patient has been suffering from rheumatoid arthritis for 5 years. He notes a limited range of motion in the joints of the hands, feet, knee and shoulder joints, their periodic swelling, morning stiffness for about an hour. About three months ago I noticed the appearance of nosebleeds, bleeding gums in the morning, recurrent stomatitis. Takes metrotrexate, folic acid, prednisolone, omez, nise

On examination - pale skin . Ulnar deviation of the hands, atrophy of the interosseous muscles, defiguration due to edema of the wrist and knee joints. Pulse 66 per minute of satisfactory tension and filling, blood pressure 120/80 mm Hg. The liver and spleen are not enlarged.

1) How to explain the appearance of nosebleeds, bleeding gums and stomatitis?

2) What kind of examination should be carried out?

3) Tactics of further treatment of rheumatoid arthritis, methods of tolerance control.

Task 5.

Compile in the form of a table the main differential diagnostic differences between rheumatic and rheumatoid arthritis, taking into account the localization of the process, clinical features, radiological data, the effect of taking medications, and the prognosis for quality of life.

Annex 1. Abstract (current state of the issue):

Gout - a chronic metabolic disease associated with a violation of purine metabolism, an increase in the content of uric acid in the blood (hyperuricemia) and the subsequent deposition of microcrystals of its sodium salt in the tissues of the body, which has a relapsing course with characteristic articular manifestations.

Gout occurs only in humans, since uric acid in the human body is the end product of a complex chain of transformations in the metabolism of purine compounds. All mammals, except humans and great apes, have the enzyme uricase, under the action of which uric acid undergoes further breakdown, turning into soluble allantoin, which is easily excreted from the body by the kidneys. According to the etiopathogenetic feature, they are distinguished primary(idiopathic) and secondary gout (caused by another disease or medication). At primary In gout, which is an independent disease, genetic defects in the enzymes involved in purine metabolism are detected: a decrease in the activity of hypoxanthine-guanine phosphoribosyltransferase and an increase in the activity of phosphoribosyl pyrophosphate synthetase (5-phosphoribosyl-1-synthetase), which leads to an increase in the synthesis of uric acid. The activity of these enzymes is controlled by genes associated with the X chromosome, so the development of the disease is observed almost exclusively in men. With hyperuricemia, the secretion of uric acid in the distal tubules of the nephron increases inadequately to the excess level of the metabolite, as a result of which urates are deposited in the tissues. The deposition of urates in the parenchyma, interstitial tissue and tubules of the kidneys causes the development of gouty nephropathy with a predominance of disorders of tubular functions over glomerular ones. Uric acid microcrystals in the joint cavity are precipitated and “covered” with a protein shell, acquiring the ability to initiate inflammatory processes, adsorbed on crystals, reacts with Pc receptors of inflammatory cells. The production of chemotaxis factors, cytokines, eicosanoids and oxygen radicals by neutrophils, monocytes and synovial cells is stimulated. The complement system and the release of lysosomal enzymes by neutrophils are activated. Secondary Gout is a syndrome of another disease in which the metabolism of uric acid is disturbed due to increased production or reduced excretion.

Factors that aggravate the course of gout include excess nutrition, meat food, a sedentary lifestyle, the use of alcoholic beverages, especially dry wines, beer, cognac. Alcohol intake leads to an increase in the content of lactic acid, which reduces the excretion of urate by the kidneys and promotes the formation of urate, increasing the rate of ATP breakdown. Finally, beer contains large amounts of guanosine, a purine base that is a precursor to uric acid.

Clinical diagnostic criteria for gouty arthritis

1. The development of an attack of gout (arthritis) under the influence of provoking factors: the use of a large amount of meat or fat, alcoholic beverages (cognac, wine, beer), mushrooms; hypothermia (reduces the already poor solubility of urates), long walking with microtrauma of the joints when wearing tight shoes, nervous stress, sauna, diuretics.

2. The development of an advanced form of the disease in persons aged 35-55 years, in the vast majority of men (up to 90%). Women before menopause rarely get gout due to the stimulating effect of estrogens on the tubular secretion of uric acid.

3. Sudden onset of an attack, most often at night, towards the morning ("with cockcrow"), in the midst of full health.

4. The rapid increase in local symptoms of inflammation, reaching a maximum after a few hours.

5. Monoarticular type of lesion: 65-70% of patients develop monoarthritis of the I metatarsophalangeal joint, in 15-20% of cases gout debuts with damage to other joints (II-IV metatarsophalangeal, ankle, knee, wrist, hand, elbow). Only in 5% there is a polyarticular onset of the disease, and the shoulder, hip joints, joints of the spine with gout are practically not affected.

6 . The presence of extremely severe pain, aggravated at night and with the slightest movement, which leads to a sharp limitation of movements (even the contact of the affected joint with a blanket is painful), a pronounced increase in the volume of the joint (defiguration) due to synovitis and swelling of the periarticular soft tissues, hyperthermia and bright hyperemia of the skin to a bluish-purple color over the affected joint, followed by peeling. The differential diagnosis is carried out with phlegmon, erysipelas, infectious septic arthritis.

7. Complete resolution of the first attacks of the disease after 3-7-10 days, even without the use of anti-inflammatory drugs. This is due to a local increase in temperature that accompanies inflammation processes, which increases the solubility of urates. In addition, apolipoprotein B, which is part of the protein coat of sodium urate crystal precipitates, inhibits phagocytosis and cellular immune response, and an increase in ACTH production helps to suppress inflammation.

8. Presence of general signs of inflammation: fever, chills, etc.

9. Alternating acute attacks and remissions.

10. Shortening of the attack period under the influence of anti-inflammatory therapy and colchicine.

11. Development after 6-7 years from the onset of the disease of chronic gouty arthritis (arthritis with deformity) with constant pain in the joints, persistent swelling, limitation of mobility due to destruction and secondary osteoarthritis, deformity of the joint as a result of accumulation of exudate, deposition of uric acid compounds, subluxations, contractures and bone formations. Ankylosis is extremely rare.

12. The presence of extra-articular lesions.

Tophi. Painless nodules (urate deposits) ranging in size from a pinhead to a walnut, firm. Appear on average after 5-6 years from the onset of the disease. They are located periarticularly, on the extensor surface of the limbs, in the area of ​​the interphalangeal, elbow joints, and also along the edge of the auricles in the area of ​​the Achilles tendon. The skin over the tophi becomes thinner, whitish-yellowish masses of urates are visible through it, which can be released outward through fistulas in the form of chalky, cheesy contents. Fistulas rarely become infected.

Gouty nephropathy. It develops due to predominantly renal (more than 70%) excretion of urates. It is a collective concept and includes urolithiasis, chronic secondary pyelonephritis, tubulointerstitial nephritis, glomerulosclerosis, nephrosclerosis, nephrogenic arterial hypertension and chronic renal failure. Nephrolithiasis is clinically manifested by renal colic, with ultrasound, X-ray negative stones in the pelvicalyceal system, usually small in size, are determined. Kidney damage determines the prognosis of the course of gout. The development of chronic renal failure in gout is the main cause of mortality.

Defeathearts. In 60-80% of patients, the relationship between gout and arterial hypertension, coronary heart disease is determined. Hyperuricemia is a risk factor for coronary artery disease. Cases of severe damage to the valvular apparatus of the heart due to the deposition of urates on the valve leaflets are described. Pericarditis.

13. At secondary(symptomatic) gout reveals the symptoms of the main - "background" disease. Diseases that contribute to hyperuricemia and the development of gouty arthritis include polycythemia, myeloma, leukemia, hemolytic anemia, congenital heart defects of the blue type, diabetes mellitus with ketoacidosis, hyperparathyroidism, hypothyroidism, psoriasis, tumors, kidney disease, lead intoxication. Some medications can contribute to the development of similar symptoms: glucose, glucocorticoids, cytostatics, cyclosporine, vitamin B 12 (activate the breakdown of purines), thiazide diuretics, furosemide, small doses of acetylsalicylic acid, large doses of nicotinic acid, pyrazinamide (inhibit the secretion of purines in the distal tubules of the kidneys ), as well as pancreatin, liver preparations - sirepara, vitohepat (sources of exogenous purines), riboxin (the main participant in purine metabolism), vitamin C, diphenhydramine, aminophylline, caffeine.

14. Laboratory data:

In the general analysis of blood during exacerbation of gout, an increase in ESR, neutrophilic leukocytosis are determined.

In the general analysis of urine, microhematuria, leukocyturia, moderate proteinuria, cylindruria, and a decrease in relative density are detected.

Acute phase indicators of inflammation: increased levels of α 2 - and y-globulins, C-reactive protein, seromucoid, sialic acids, fibrinogen.

Increase in the content of urea and creatinine with the development of renal failure.

An increase in the level of uric acid in the blood: in men, more than 0.42 mmol / l, in women, more than 0.36 mmol / l.

Negative test for rheumatoid factor.

Normal titers of antistreptolysin-0, antistreptokinase, antistreptohyaluronidase, antistreptodeoxyribonuclease-B.

Lack of HLA 27 .

15. Joint x-ray data. Swelling of soft tissues in the area of ​​the affected joints, the development of focal lysis of the subchondral bone, racemose formations with clear contours or a sclerotic border - a "punch symptom". Perhaps the complete destruction of the epiphyses and their replacement with urate masses. Signs such as epiphyseal osteoporosis and ankylosis are not characteristic of gouty arthritis. Classic radiological symptoms appear when the duration of the disease is at least 5 years.

Treatment

1. Diet petty-vegetable with the restriction of foods containing purines: meat broths, beef, lamb, poultry, liver, brains, sardines, herring, mackerel, mushrooms, peas, beans, beans, cauliflower, spinach, radishes, fats, chocolate. Refusal of alcoholic beverages. Normalization of body weight.

2. Abundant alkaline drink- up to 2-2.5 liters per day in the absence of heart and kidney failure.

Author data 1Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria 22nd Department of Medicine, Hietzing Hospital, Vienna, Austria 3Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands 4Zuyderland Medical Center, Heerlen, The Netherlands 5Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands 6Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Free University and Humboldt University Berlin, Berlin, Germany 7Rheumatology Department, Karolinska Institute, Stockholm, Sweden 8Rhumatologie B, Hopital Cochin, Paris, France 9NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK 10Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands 11Department of Psychology , Health and Technology ology, University of Twente, Enschede, The Netherlands 12Division of Rheumatology, Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany 13Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands 14Birmingham NIHR Wellcome Trust Clinical Research Facility, Rheumatology Research Group, Institute of Inflammation and Aging (IIA), University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK 15Department of Rheumatology, Hospital for Special Surgery, Weill Cornell Medical College, New York, New York, USA 16Rebecca McDonald Center for Arthritis & Autoimmune Disease, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada and Division of Clinical Rheumatology, Unive rsity of Genoa, Genoa, Italy 20Department of Patient & Care and Department of Rheumatology, University of Maastricht, Maastricht, The Netherlands 21Division of Rheumatology, University Hospitals of Geneva, Geneva, Switzerland 22Fundación Ramón Dominguez, Hospital Clinico Universitario, Santiago, Spain 23Department of Rheumatology, Sorbonne Universités, Pitié Salpêtrière Hospital, Paris, France 24Institut de Biologie Moléculaire et Cellulaire, Immunopathologie, et Chimie Thérapeutique, Strasbourg University Hospital and University of Strasbourg, CNRS, Strasbourg, France 25Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands 26Arthritis Research UK Center for Epidemiology, Center for Musculoskeletal Research, University of Manchester, Manchester, UK 27 V.A. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation 28European League Against Rheumatism, Zurich, Switzerland 29Cyprus League against Rheumatism, Nicosia, Cyprus 30Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway 31Department of Rheumatology and Immunology, Beijing University People's Hospital, Beijing, China 32Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris -Sud, Université Paris-Sud, INSERM U1184, Center for Immunology of viral Infections and Autoimmune Diseases (IMVA), Le Kremlin Bicêtre, France 33Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK 34Organización Médica de Investigación, Buenos Aires, Argentina 35Department of Medicine, University of Queensland, Queensland, Australia 36Institute of Rheumatology and Clinic of Rheumatology, Charles University, Prague, Czech Republic 37National Institute of Rheumatology and Physiotherapy, Semmelweis University, Budapest, Hungary 38Rheumatology Department, FHU ACRONIM, Pellegrin Hospital and UMR CNRS 5164, Bordeaux University, Bordeaux, France 39Department of Rheumatology, Bernhoven, Uden, The Netherlands 40University of Cologne, Cologne, Germany 41Division of Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA 42Serviço de Reumatologia, Centro Hospitalar e Universitário de Coimbra Praceta Mota Pinto, Coimbra, Portugal 43Section for Outcomes Research, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria 44Keio University School of Medicine, Keio University Hospital, Tokyo, Japan 45Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium 46Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium 47Department Medical Humanities, VU Medical Centre, Amsterdam, The Netherlands Professor Josef Smolen, Department Rheumatology, Department of Medicine 3, Medical University B Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; [email protected] , [email protected] annotation Recent knowledge on rheumatoid arthritis (RA) has necessitated an update of the European League Against Rheumatism (EULAR) RA Management Guidelines. A large international task force based evidence-based decisions made 3 systematic reviews of the literature, developed 4 overarching principles, and 12 recommendations (vs. 3 and 14, respectively, in 2013). These recommendations cover conventional synthetic conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumor necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and synthetic targeted synthetic ( ts) DMARDs (Janus kinase Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and goals of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR logical or index criteria) or low disease activity are discussed. Cost aspects have been taken into account. As a first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC aiming for >50% improvement within 3 and target within 6 months. If this fails stratification is recommended. Without adverse prognostic markers, switching to - or adding - other csDMARDs (plus short-term GCs) is suggested. In the presence of adverse prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs) any bDMARD (current practice) or JAC inhibitor should be added to csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If the patient is in stable remission, bDMARDs may be tapered (tapered, flattened). For each recommendation, levels of evidence and target agreement are provided, both mostly very high. These recommendations are intended to inform rheumatologists, patients, rheumatology National Societies, hospital officials, social security agencies and EULAR regulators in the latest consensus on the management of RA aimed at achieving better outcomes. The treatment of rheumatoid arthritis (RA) has changed dramatically over the last 30 years. Back then, only a few therapeutic agents existed that were minimally or not effective, due to toxicity and the fact that optimal dosage and onset of action were not yet clear for some agents. Available therapies were applied late rather than early in the course of the disease. The notion of an early arthritis clinic has emerged, and these advances have fueled a reevaluation of the classification criteria, which are relevant as they focus primarily on disease duration. Therapeutic goals have not yet been defined because symptom relief appears to be the most important goal and the concept of remission or low disease activity has been desirable at best. To date, we have numerous effective agents. Among conventional synthetic (cs) disease modifying antirheumatic drugs (DMARDs), we have adopted methotrexate (MTX) for its optimal use as an anchor drug; in addition, a number of biological (b)DMARDs have been approved, most recently the first targeted synthetic (ts)DMARDs have been approved, and new ones are being developed (in many countries). Today, new classification criteria for RA facilitate the identification of patients at an earlier stage in their disease course than before and recommendations have been developed to treat patients with RA through strategic algorithms for optimal outcome, regardless of the types of treatments available. A limited number of measures to assess response in clinical trials and to investigate disease activity in clinical practice are widely used and the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) have jointly developed new definitions for remission that provide optimal clinical outcomes and can be achieved to a large extent. part of patients in research and practice. Achieving remission against these criteria, based on an index or Boolean, will prevent joint destruction or at least the progression of joint damage regardless of the residual subclinical form of the change, optimize physical functions, improve quality of life and work productivity, and reduce the risks of comorbidities. Due to the recent evolution of evidence-based control of treatment outcomes, interest in purely symptomatic drugs has declined significantly today, and disease modification has become a key attribute of all modern drugs and treatments. Nevertheless, symptomatic remedies as well as measures of physical, psychological support and surgery can and do have a place in the general treatment of RA. However, disease modification is the mainstay of RA treatment and is a mixture of characteristics: relief of signs and symptoms; normalization - or at least significant improvement - of impaired physical function, quality of life, and social and work opportunities; and - as the main distinguishing feature of DMARDs compared to symptomatic agents - inhibition of structural damage to cartilage and bone. Thus recording inhibition of damage progression on radiography remains a key outcome for classifying a drug as a DMARD, as radiographs can show bone and cartilage damage and have proven sensitive to detect changes even at short intervals and at very low levels of overall progression in the population. Rapid achievement of the target endpoint is now critical, and to achieve the goal of treatment of remission or least disease activity by 6 months, at least 50% clinical improvement within 3 months is desirable. With increasing demand for care and outcomes, RA treatment has become increasingly complex over the last decade. Despite the availability of many effective agents, the treatment strategies that have been developed and the results of evaluations that allow effective follow-up, the high cost of therapy has limited the widespread use of these therapeutic approaches, creating a large degree of disparity. Therefore, management's recommendations for approach in the treatment of patients with RA have become increasingly useful in providing physicians, patients, insurers, regulators, and other providers of medical evidence-based advice, supporting expert opinions involved in many of these new developments. Indeed, EULAR recently updated standardized operating procedures for developing recommendations that include cost considerations beyond accounting for the assessment of evidence and expert opinion. EULAR developed the first set of guidelines for the management of RA with DMARDs in 2010 and updated them in 2013. They were originally based on evidence presented by five (2010) and 3 (2013) systematic literature reviews (SLRs). EULAR recommendations have been widely used. They have been referred by national rheumatology societies and regional leagues to report in the development of their own recommendations (eg, Canadian, French, German, Mexican, Asia-Pacific League of Associations of Rheumatology (APLAR), Pan American League of Associations of Rheumatologists (PANLAR)), as well as regulatory bodies. In line with our approach to provide recommendations based on recent evidence, we continued to evaluate the literature on clinical trials of new agents, new information on established drugs, new policy studies, new insights into evaluation results, and new insights related to the recent research agenda. 3 years. The abundance of new information has prompted us to now further update the EULAR recommendations for the management of RA with DMARDs. Methods Following approval by the EULAR Executive Committee, the supervisor (JSS) and facilitator (RL) invited the Steering Committee and task force to work on this update of the EULAR recommendations for RA management. The 2010 recommendations and their 2013 update of the original EULAR standardized the operating procedures for further development of the recommendation; The 2016 update, following the recently revised version, complied with these standards, which also require adherence to the Appraisal of Guidelines for Research & Evaluation (AGREE) contained in its updated version (AGREE II). Steering Committee The steering committee included seven rheumatologists, one patient representative and three fellows. This group initially developed research questions for three SLRs. These SLRs focus on (i) the effectiveness of synthetic (s)DMARDs (as monotherapy or in combination therapy, including csDMARDs and ts DMARDs) and glucocorticoids (GCs); (ii) efficacy of bDMARDs (as monotherapy or in combination with csDMARDs) and (iii) safety aspects of sDMARDs and biological (b) DMARDs. To this end, the original SLRs obtained in 2013 served as a starting point and an update on the literature published between 2013 and 2016 was performed. New information on treatment strategy was also evaluated in the present SLRs. no formal economic analyzes have been performed, but cost aspects have been considered throughout the process, given the current state of the approaches to guideline development, in previous EULAR SLRs on cost aspects in the context of DMARD therapy and the advent of biosimilars. Three rheumatology fellows (KC, JN, SR) performed by SLRs (and reviewed each other's work) analyzed existing database publications of randomized controlled trials for efficacy and registry data for safety, as well as evaluations of recent EULAR and ACR abstracts. Summary-of-findings (SoF) tables were created and levels of evidence (LoE) levels of evidence were determined using the standards of the Oxford Center for Evidence-Based Medicine. The three SLRs briefed the Task Force and detailed descriptions of their methods are published separately. The SoFs SLRs were presented to the Steering Committee, which made a proposal to update the recommendations based on this information. The SLR data and Steering Committee proposals were subsequently presented to the entire task force for further discussion and eventually development of updated recommendations. Target group The Task Force consisted of 50 people, including members of the Steering Committee. The target group included three patients, two healthcare professionals and two delegates of young rheumatologists from the EULAR New Eular Network (EMEUNET). The rheumatologists were all experienced in the treatment of RA and most often participated in clinical trials; In addition, some of them had experience in maintaining patient registries in their countries or in various aspects of research results. Clinicians and health care managers have all had experience in consensus interventions, as have most rheumatologists. Since we also wished for the work of the Task Force to be informed by rheumatologists from other regions of the world, in addition to a broad representation from 14 European countries, 2 colleagues from Asia, 1 from Australia, 2 from Latin America and 2 from North America were invited to participate. Some of them actively participated in the development of documents of their regional leagues and/or National Societies. All members of the Task Force declared their potential conflicts of interest before starting the process. The Task Force agreed on several key considerations upfront. First, all recommendations that need to be discussed in the context of the new evidence; where there was no new evidence, then the former evidence base. Second, any of the previous recommendations (general principles 4 and recommendations 14) can be retained as they were in the 2013 version, amended, shifted in sequence, or deleted. Third, drugs that are not (yet) approved in Europe but are used elsewhere in the world, or drugs that have not yet passed regulatory evaluations but for which evidence from clinical trials has been available, may be considered in recommendations for some expected effect in clinical practice, with all relevant reservations. Finally, it was agreed that all 2013 recommendations that were either supported by new evidence or for which information was lacking should be included as previously formulated if certain components are now considered inappropriate. Following the presentation of the results of the SLR and the Steering Committee proposals for amendments to the recommendations, the Task Force was divided into four contact groups. One group reviewed bDMARDs, a second group of csDMARDs, a third tsDMARDs, and a fourth GC; all groups proposed draft language for the entire target group of the relevant recommendations. Security aspects were considered in each of these contact groups. Seeking consensus Representatives of each breakthrough group reported on the results of their respective discussions and provided suggestions for formulating individual recommendations for the entire target group. After that, the voting process took place. The general policy principle or recommendation for the final document without further changes requires a majority of 75% of the votes in the first round. If this result was not reached, the respective text was changed and subjected to a second round of voting, for which a majority of 67% was required. If this vote was not successful, additional textual changes were proposed until ≥50% was reached. The recommendations are submitted as finally up for a vote. The results of the relevant last vote are presented as a percentage of voting members. Notes on the content of the discussions and the reasoning behind each decision should be provided in the comments accompanying their individual items. For various reasons, not every member of the Task Force was present in the room throughout the meeting, and therefore there was little variation in the number of votes. However, at each point in time >90% of the members participated in the ballots. After the face-to-face meeting, the recommendations, as agreed by the Working Group, were subjected to an anonymous vote (via email) at the Levels of Agreement (LoA). Each recommendation was scored on a scale of 0-10, with 0 meaning no agreement at all and 10 absolute agreement. During this process, a few weeks after the meeting, one person withdrew from the task force because the inclusion of csDMARD combination therapy in the recommendations did not find a majority during the previous voting process. This colleague was present and voted throughout the face-to-face meetings and the corresponding votes on all recommendations accounted for accordingly, but ultimately the person disclaimed authorship and the vote did not count towards the LoA. The draft manuscript has been circulated to all members of the Task Force for their comments. Following the inclusion of these comments, it was submitted to the EULAR Executive Committee for review and approval; at this time it was again sent to members of the Task Force. Concluding comments were received from members of the Task Force and the Executive Committee and reviewed in the manuscript, which was then submitted with the approval of the EULAR Executive Committee. results General aspects As before, the 2016 update of the EULAR RA management recommendations reflects a balance of clinical, functional, and structural efficacy, safety, cost, and patient perceptions as perceived by the target group. In the general wording of the recommendations, the aspect of drug toxicity was considered, but data are presented only in the safety of SLR, since it is assumed that the prescriber is aware of the safety information provided in the manufacturer's inserts of various agents. In addition, EULAR has developed a series of papers dealing with the safety aspects of RA drugs, and various other publications have addressed these aspects. In particular, as has also been suggested for the safety of SLRs, the main risks of bDMARDs (also tsDMARDs) are associated with infections, and recommendations for vaccination as well as an assessment have recently been developed to allow calculation of the risk of infection in patients susceptible to bDMARDs. For all medicines discussed in this document, the summary of the product specifications document provides valuable information about risks, side effects, and the need for monitoring. The advice given here should in no way be construed as deviating from this information. In any case where toxicity is a serious concern, a specific warning is provided as part of the relevant recommendation or accompanying comments. Note, the three SLRs, as well as the text accompanying each element, should be considered an integral part of this recommendation. Individual key points represent abbreviated conclusions from discussions and, as such, do not cover all aspects related to a particular topic; on the contrary, such aspects are covered in more detail in the relevant explanatory section in the results section. When classifying DMARDs, the Task Force adheres to the previously used nomenclature as shown in . Table 1 also provides a glossary of terms used in the recommendations. The task force did not differentiate between early and established RA with respect to recommending types of drugs, but rather distinguish between steps in the treatment process by differentiating between patients who are "naïve" of any DMARD therapy, patients who had insufficient response (IR) to initial courses of the initial course (s) csDMARDs and those who had IR bDMARDs. There is currently no evidence for differential responses based solely on disease duration, when differences are based on an estimate of damage due to delayed treatment. Valid trials on MTX-naive RA patients selected for a variety of disease durations that ranged from months to years, with no noticeable differences in outcomes for indirect comparisons. However, the Task Force distinguishes between early and established RA in terms of targeted outcomes (see recommendation 2). The task force also took into account prognostic factors (), which have similar predictive power regardless of disease duration. As a note, recommendations for the management of early arthritis, including undifferentiated arthritis, have recently been updated. These recommendations apply to the treatment of patients with RA from the time of diagnosis and unproven RA or undifferentiated arthritis. Table 1 Glossary of terms and definitions (Glossary and definitions)

1. The treatment of patients with RA should be directed towards the best care and should be based on a common decision between the patient and the rheumatologist.. This principle remains unchanged, its textual data and in its place as point A, prominently within the recommendations. Joint decision-making between the patient and the rheumatologist includes all aspects of the disease: information about the disease and its risks, disease assessment methods, decisions on the therapeutic goal and potential means to achieve the goal, development of a treatment plan, and discussion of the benefits and risks of individual therapy. These aspects are also detailed in the guidelines for standards of care. Naturally, "better care" refers to the recommendations presented here and essentially "shared decision" refers to all personal recommendations. For this purpose also qualitative indicators have been developed quite recently.
2. Treatment decisions are based on disease activity and other patient factors such as progression of structural damage, comorbidities, and safety issues.. This is a new principle. This follows from the previous recommendation 14, the last paragraph in the 2013 version, which was considered by the current task force to be presented as a central and self-evident rule of any therapeutic approach, that it should become an overarching principle, rather than a recommendation. Indeed, given these considerations, the level of evidence for this recommendation was rather low in 2013. The removal of this item from the recommendations caused some discussion. Especially in patients who put forward in the final list of recommendations, the preference for moving from elements to patient-related factors to moving to patient-preferences and patient-aspects in the treatment of RA. However, the hope that this point would even benefit more from being a general principle than a recommendation, which is unlikely to ever be studied in all its subtleties, prevailed to such an extent that principle B was unanimously adopted ().
3. Rheumatologists are specialists who should primarily care for patients with RA.. Originally presented as paragraph B, the wording of this principle has not been changed. Interest in 2010 this was even presented as a general policy principle A. However, in recent years, it has been recognized that joint decision-making and consideration of patient factors should gain recognition. Positioned as A, B or C, this element emphasizes the importance of special care for such a complex disease as RA. There is strong evidence that being under the care of a rheumatologist is beneficial to patients in terms of early initiation of therapy, prevention of damage, and reduction in surgical procedures. In addition, rheumatologists have the deepest experience regarding the use of csDMARDs and bDMARDs. This includes the adverse event profiles of these drugs, as well as understanding and experience with comorbidities in RA. Therefore, rheumatologists can provide the best care in accordance with point A, in the sense of a holistic approach. The rationale for the term “mainly” has been discussed at length in previous versions of the guidelines and relates to multidisciplinary care considerations, including nursing specialties and the fact that in some areas of the world rheumatology training is not sufficient and other experts may have experience in the management of RA. In addition, some comorbid diseases, such as chronic hepatitis or interstitial lung disease, may require consultation and treatment by other specialists.
4. RA has high individual, medical and social costs, all of which must be considered in its management by the treating rheumatologist.. Again, this principle is worded exactly as it was last time, except that it was point C, but also the last one. This is meant to remind all stakeholders that effective RA therapy - despite direct costs - will reduce the economic burden on individual patients, their families and society, which includes direct medical costs and indirect costs such as disability and early retirement. . In this context, it should be taken into account that direct medical expenses are charged in addition to those directly attributed to the treatment of overt manifestations of RA and include expenses arising from concomitant diseases associated with the inflammatory process. However, this point is also meant to sound that cost-effective treatment approaches should be preferred, as long as the safety and results are similar to the more expensive ones and they are consistent with the therapeutic paradigm. In some countries, the high cost of treatment is one of the important factors limiting the availability of modern therapy (inequality), and this factor should be taken into account when choosing a treatment strategy. In this regard, the advent of biosimilars provides the potential to reduce the pressure on healthcare budgets. At this point, there must be an understanding that many patients still have not achieved their therapeutic goals despite all of our current treatments and therapeutic strategies. In addition, any of the bDMARDs, if applied after at least one of the csDMARDs and bDMARDs that were ineffective, resulted in only about 10% good results in terms of the ACR70 scale. These aspects impose the need to continue searching for new treatments or strategies.

• The symbols (*, §, #) indicate different levels of evidence, which are respectively provided along with the voting results and levels of agreement in Table 3.
• 1 TNF inhibitors: adalimumab, certolizumab pegol, etanercept, golimumb, infliximab boDMARDs, or appropriate EMA-approved/FDA-approved medicine.
• 2 Abatacept, Rituximab (as the first bDMARD under special circumstances - see text), or tocilizumab or an appropriate EMA-approved/FDA-approved medicine, as well as IL-6 pathway inhibitors, sarilumab or sirukumab, once approved.
• 3 Yak inhibitors (where approved).
• boDMARDs, biologically created (genuine) DMARDs; bsDMARD, biosimilar of DMARDs; csDMARDs, conventional synthetic DMARDs; DMARDs, Disease-modifying antirheumatic drugs; EULAR, European League Against Rheumatism; Jak, Janus kinase; MTX, methotrexate; RA, rheumatoid arthritis; TNF, tumor necrosis factor; tsDMARDs, targeted synthetic DMARDs.

• The symbols (*, §, #) indicate different levels of evidence which are correspondingly provided together with voting results and levels of agreement in table 3.
• 1 TNF-inhibitors: adalimumab, certolizumab pegol, etanercept, golimumb, infliximab boDMARDs or the respective EMA-approved/FDA-approved biosimilars.
• 2 Abatacept, rituximab (as first bDMARD under special circumstances-see text), or tocilizumab or appropriate EMA-approved/FDA-approved biosimilars, as well as other IL-6 pathway inhibitors, sarilumab and/or sirukumab, once approved.
• 3 Jak-inhibitors (where approved).
• boDMARDs, biological originator DMARDs; bsDMARDs, biosimilar DMARDs; csDMARDs, conventional synthetic DMARDs; DMARDs, disease-modifying antirheumatic drugs; EULAR, European League Against Rheumatism; Jak, Janus kinase; MTX, methotrexate; RA, rheumatoid arthritis; TNF, tumor necrosis factor; tsDMARDs, targeted synthetic DMARDs.

1. Therapy withDMARDs should be started as soon as the diagnosis of RA is established. This recommendation remains unchanged from 2013 and is one of the mainstays of any treatment approach to RA. This means (i) the need to establish a diagnosis as early as possible, as was also reflected in the 2010 ACR-EULAR classification criteria, and (ii) the advantage of early initiation of DMARD treatment ('as soon as possible'), which allows prevention of damage in a large proportion of patients. Given the general nature of this key point, the Task Force does not specify the type of DMARD here. Indeed, all DMARDs cannot provide a long-term outcome quickly compared to long-term outcomes, and the following recommendations consider the sequence of types of DMARD therapy. The target group does not deal with pre-RA or undifferentiated arthritis and thus it is assumed that the diagnosis of RA has already been established. However, he should keep in mind that any chronic arthritis, even if undifferentiated, requires appropriate treatment, including consideration of DMARD therapy, because it does not usually subside spontaneously, and an update to the guidelines for the management of early arthritis has just been presented by EULAR. 2016 update of the EULAR recommendations for the management of early arthritis. AnnRheumDis 2016;doi:10.1136/annrheumdis-2016-210602. with LoA 9.9, this recommendation reached high agreement on all counts (). LoA 1a; LoA 9.9.
2. Treatment should be directed towards achieving the goal of sustained remission or low disease activity in each patient.. This recommendation addresses two treatment goals: remission, especially in DMARD-naive patients, and low disease activity, predominantly in patients in whom previous therapy has not been successful. Clinical remission or low disease activity is mentioned as a separate therapeutic target, any disease exacerbation should be considered as inadequate disease control, thus suggesting a change in therapeutic approach, obviously if patient factors do not preclude it. Communication with the patient to clarify and agree on the goals of treatment and the means to achieve this goal is of paramount importance. This allows for alignment of patient and provider considerations and goals and promotes treatment adherence. In 2010, the concept of "as soon as possible" was also part of this clause and during the current discussion it was specifically decided to note that treatment goals should be achieved quickly and not in the distant future. Indeed, there is sufficient evidence that the majority of patients who do not achieve significant improvement within 3 months, or fail to achieve treatment goals within 6 months, will not achieve their desired state subsequently; exceptions apply to those patients whose disease activity has been reduced to a level close to the goal of treatment.

1. Monitoring should be frequent during disease activity (every 1–3 months); If there is no improvement, maximum 3 months after the start of treatment, or if the goal is not reached by 6 months, therapy should be adjusted.. This treat-to-target recommendation remains unchanged in the 2013 development version. The frequencies of follow-up assessments should be adjusted according to the level of disease activity, namely more frequently as monthly when patients have high disease activity and less frequently as every 6 to 12 months when the goal of treatment has been achieved and sustained. EULAR generally recommends the use of a comprehensive disease activity score that includes joint score and ACR-EULAR definitions for remission Felson DT, Smolen JS, Wells G, et al . American college of rheumatology/European league against rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis 2011;70:404–13.

1. MTX should be part of the first treatment strategy. Compared to 2013, when this paragraph read "MTX should be part of the first strategy for the treatment of patients with active RA", the recommendations have been slightly reduced. The Task Force felt that it was not necessary to indicate disease activity as the EULAR recommendations mainly concern patients with active disease. Based on its efficacy, safety (especially in the presence of folic acid), ability to individualize dose and route of administration, and relatively low cost, MTX continues to be the anchor ("first") drug for RA patients as a monotherapy, as well as in combinations with other drugs (“treatment strategy”; see below). In addition, MTX appears to reduce comorbidities and mortality in RA. In clinical trials of bDMARDs in early arthritis patients, MTX monotherapy was associated with 25% ACR70 responses (which put patients in the low disease activity range) at 6 months, even though it was not combined with de novo GC in these trials. . The dose of MTX should be rapidly increased, usually to 25 to 30 mg per week, subcutaneously or orally, with folic acid supplementation, and the maximum dose of MTX, if tolerated, should be maintained for about 8 to 12 weeks to judge MTX treatment response. Indeed, when MTX was rapidly adjusted to 25 mg per week, response rates may be even higher (∼40% low disease activity). Of course, contraindications and the potential for early toxicity must be taken into account; This issue is discussed in point 5. The doses mentioned here do not apply to Asian patients. In China it is not recommended to exceed 20 mg/week and in Japan the maximum recommended dose for MTX is 16 mg/week.

1. In patients with a contraindication toMTX (or early intolerance),leflunomide or sulfasalazine should be considered as part of the (first) treatment strategy. The content of this recommendation has been retained; However, compared to the previous version of item 5, "in cases of MTX contraindications" has been slightly corrected, because these are patients with contraindications, not "cases". The task force was again reminded of the relative safety of MTX and also discussed that patients' frequent concerns after reading the package leaflet should be addressed by providing appropriate information (general policy principle A). However, there are occasional contraindications (such as kidney or liver disease) or intolerances. In these circumstances, leflunomide (dosed at 20 mg/day without a loading dose) or sulfasalazine (increased to 3 g/day) are considered better alternatives. Older studies suggested similar efficacy to both of these drugs as compared to MTX, although MTX was used at much lower doses than recommended today. However, there have been no new studies to refute previous findings. Among all the agents listed above, only sulfasalazine has an acceptable safety profile during pregnancy. In some countries, parenteral gold is still used, and while clinical efficacy is undeniable, there is controversy regarding its safety; in other countries the gold salt is no longer available. On the contrary, the use of antimalarial drugs such as hydroxychloroquine and chloroquine is still significant, especially in combination therapy or as monotherapy in patients with very mild disease, especially in China. Interestingly, antimalarial drugs may have a significant beneficial effect on glucose and lipid metabolism and may reduce cardiovascular risk in RA. However, joint damage is not slowed to a similar extent as is the case with other csDMARDs. This recommendation also uses the term "treatment strategy", implying, as with MTX, that leflunomide and sulfasalazine may be used as monotherapy or in combination with other csDMARDs or biologic agents. Indeed, step-up combination therapies often work, even though comparisons of step combinations with csDMARD switching did not reveal significant differences in outcomes. LoE 1a; LoA 9.0.
2. Short-term GCs should be considered when initiating or changingcsDMARDs, in different dosage regimens and routes of administrationtapered but must declinetapered gradually as quickly as clinically appropriate. The increased efficacy of HA in combination with csDMARDs is well known. Indeed, so far all trials comparing GC plus csDMARD with bDMARDs plus csDMARD have shown similar efficacy. In 2013, GCs were considered in recommendation 7, but the wording is different: "Low-dose GCs should be considered as part of a primary treatment strategy (in combination with one or more csDMARDs) for up to 6 months, but should be tapered as quickly as clinically." it's expedient." The current wording is a compromise, trying to accommodate the larger concerns and suggestions expressed during the debate of the task force.

1. If the treatment goal is not achieved with the first csDMARD strategy, in the absence of adverse prognostic factors, other options should be considered.csDMARDs. This sentence is the first part of previous Recommendation 8. It is essentially worded the same way, except for the last part, "change to a different csDMARD strategy should be considered", has been changed to "other csDMARDs should be considered", taking into account the fact that the combination with GC has now been clearly recommended also for this treatment step of the algorithm (item 6) and combinations of csDMARDs are not specifically recommended as an initial treatment strategy at all anymore. B presents the adverse prognostic factors. The task force also discussed that early csDMARD intolerance should not be considered a treatment failure, which would mean an immediate transition to the next step in the algorithm, but rather would require the restoration of another primary csDMARD (replacement). LoE 5; LoA 8.5.
2. If the goal of treatment is not achieved from the firstcsDMARD therapy, in the presence of adverse prognostic factors, the additionbDMARD ortsDMARD * should be considered; The correct practice would be to start with bDMARD. The division of the second part of previous recommendation 8 (“when adverse prognostic factors are present, the addition of bDMARD should be given”) and the new paragraph 7, reflect the desire of the target group to give stratification of prognostic factors more attention. DMARDs currently include a series of tumor necrosis factor (TNF)-inhibitors (adalimumab, certolizumab, etanercept, golimumab, and infliximab); abatacept (costimulation inhibitor); tocilizumab (an IL-6 receptor blocker, but other IL-6 receptor inhibitors, sarilumab and IL-6 inhibitors such as clazakizumab or sirukumab are also possible in the future); Rituximab (anti B-cell agent); both biological originator (bo)DMARDs are biological originators (bo) and European Medicines Agency EMA-approved or FDA-approved biosimilar (bs) biosimilar DMARDs.

• (Symbols * §, #) refer to the corresponding symbols in the recommendations (Table 2), corresponding LoEs are shown.
• LoE, levels of evidence; n.a., not available; SoR, the power of recommendation.

1. 9. bDMARDs * and tsDMARDs# should be combined with csDMARDs; in patients who cannot use csDMARDs as add-on medication, IL-6 inhibitors and tsDMARDs may have a number of advantages over other bDMARDs. This recommendation replaces former #9 (‘In patients who do not respond adequately to MTX and/or other csDMARD strategies, with or without GCs, bDMARDs (TNF inhibitors, abatacept or tocilizumab and, under certain circumstances, Rituximab) should be started with MTX’). While individual bDMARDs and tsDMARDs have already been discussed above, point 9 now refers to the fact that all bDMARDs have improved efficacy when combined with MTX than as monotherapy. Compared to the 2013 update, more evidence has now accumulated for the combination, even for tocilizumab. Also for baricitinib, combination therapy is more constructive, although not clinically or functionally effective, than monotherapy. However, in terms of signs and symptoms, physical function, and joint damage, there are indications for slightly better efficacy for tocilizumab monotherapy and more potent for JAC inhibitors compared with MTX. Monotherapy with other biological agents has not been found to be clinically superior to MTX monotherapy. MTX can be used at 7.5 - 10mg to provide additional efficacy to TNF inhibitors and intolerance at such low doses that results in discontinuation of therapy is very rare. In addition, biologics can also be effectively combined with other csDMARDs.

1. 10. If bDMARD* or tsDMARD§ are ineffective, treatment with another bDMARD or tsDMARD should be considered; if therapy with one TNF inhibitor is ineffective, patients may receive another TNF inhibitor or a drug with a different mechanism of action. A similar recommendation was presented in 2013: “If the first bDMARD is ineffective, patients should be treated with another bDMARD; If therapy with the first TNF inhibitor is ineffective, patients may receive another TNF inhibitor or a biological agent with a different mechanism of action." Indeed, in studies published since the development of these guidelines, even primary non-responders to a TNF inhibitor have shown a response to another anti-TNF agent, making it difficult to draw conclusions for subsequent therapy on failure with initial versus secondary therapy with TNF blockers. The addition in the first part ("or tsDMARD") is partly necessary because tsDMARDs (Yak inhibition) are currently included in previous recommendations 8 and 9; "First" was removed because the Task Force did not choose to distinguish between ineffectiveness of one or more bDMARDs. However, it should be noted that it is currently not known if a Jak inhibitor is effective the first time and ineffective the next, it has not been established that a second IL-6 receptor inhibitor or IL-6 ligand inhibitors are effective, if tocilizumab is ineffective - this still part of the research agenda. We also lack studies examining if TNF inhibitors are effective and safe after the failure of bDMARDs with other mechanisms of action, and studies on switching between different mechanisms of action. Several members raised the question if the use of csDMARDs should also be considered when bDMARDs are ineffective, but this proposal did not receive a majority.

1. If the patient is in permanent remission after a gradual taper to complete withdrawal of GCs, a gradual reduction of bDMARDs can be started, especially if this treatment is combined with csDMARDs. This point remains unchanged from the 2013 publication. New data have been published that challenge this conclusion. Tapering here means reducing the dose or expanding the interval between injections ("spacing, distancing"). This does not necessarily imply discontinuation of bDMARDs, which can lead to disease recurrence in most patients. However, even if treatment is stopped and the patient flares up, most (>80%) will regain their previous good results when therapy is restarted (but some will not) and patients should be informed accordingly. There are certain prognostic factors in which reduction is likely to be successful, and they relate mainly to early RA, depth of improvement, and duration of remission; prospective research considering these aspects is needed in the future. This point also indirectly reinforces recommendation 9 on combination therapy of bDMARDs with an MTX enhancer or other csDMARD, as it implies that bDMARDs should primarily, if not, be tapered and possibly discontinued when combined with csDMARD, and reduction and discontinuation of bDMARD monotherapy was haven't studied enough yet. LoE 2b; LoA 9.0.
2. If the patient is in permanent remission, a gradual decrease in csDMARD can be performed. The 2013 version corresponding to paragraph 13 states: "In the case of long-term sustained remission, a cautious dose reduction of csDMARD may be considered a common decision between patient and physician." This item has generated considerable controversy as it would mean leaving patients with RA either without or on a low dose of csDMARD. But in general, in recent years no new evidence has been found for or against this view. Controversy arose during the discussion. It has been noted here that tapering primarily means dose reduction and that discontinuation of csDMARDs may only be possible in exceptional cases. Many rheumatologists on the Task Force panel were of the opinion that csDMARDs should never be stopped. Consequently, this item received a low LoA (8.5), although still quite high, on a scale of 0-10. Of note, the part worded "as a shared decision between patient and physician" has now been removed. It is the view of the Task Force that mentioning a common solution for this item among all 12 would mean that no other recommendations need to involve the patient, or highlight this particular recommendation over all others and thus offset Fundamental Principle A. Clearly, removing this phrase does not means that shared decisions with patients are not important, on the contrary: according to principle A it is of the utmost importance for this and for all other recommendations. LoE-4; LoA 8.5.