Treatment of juvenile chronic arthritis

Indications for consultation of other specialists

• Consultation ophthalmologist is shown to all patients with joint damage, reduced visual acuity.
• Consultation of the endocrinologist is indicated for Cushing's syndrome, growth impairment.
• Consultation of the otolaryngologist is indicated in the presence of foci of chronic infection in the nasopharynx.
• Consultation of the dentist, orthodontist is indicated for caries, dysplasia of the jaws, teeth and bite.
• Consultation phthisiatric is indicated with a positive reaction Mantoux, lymphadenopathy.
• Consultation of a hematologist, oncologist is indicated for ossalgii, stubborn artralgia, severe general condition in the presence of oligoarthritis, severe systemic manifestations with hematological disorders.
• Consultation of the orthopedist is indicated with functional insufficiency of joints, bone growth in length, subluxations, for the development of rehabilitation measures.
• Genetic consultation is indicated for multiple small developmental anomalies, connective tissue dysplasia syndrome.

Indications for hospitalization

Indications for hospitalization are listed below:

• development of systemic manifestations (fever, defeat of the heart, lungs);
• marked exacerbation of the joint syndrome;
• selection of immunosuppressive drugs;
• absence of effect in outpatient treatment of exacerbation;
• intercurrent infection;
• the presence of doubt in the correctness of the established diagnosis;
• carrying out rehabilitation measures during periods of exacerbation of the joint syndrome (especially when hip joints are affected).

Confirmation of the diagnosis and choice of tactics of treatment is carried out in a specialized children's rheumatology department.

Objectives of treatment of juvenile rheumatoid arthritis

• Suppression of inflammatory and immunological activity of the process.
• Kupirovanie systemic manifestations and articular syndrome.
• Preservation of the functional capacity of joints.
• Prevention or slowing down the destruction of joints, disability of patients.
• Achieving remission.
• Improving the quality of life of patients.
• Minimizing the side effects of therapy.

Non-drug treatment of juvenile rheumatoid arthritis

During periods of exacerbation of juvenile rheumatoid arthritis, the infant's movement should be limited. Complete immobilization of joints with overlapping of langets is contraindicated, it contributes to the development of contractures, muscle tissue atrophy, aggravation of osteoporosis, rapid development of ankylosis. Physical exercises contribute to the preservation of the functional activity of the joints. Useful cycling, swimming, walking. Running, jumping, active games are undesirable. Recommend to maintain a straight posture when walking and sitting, sleep on a hard mattress and a thin cushion. To exclude psychoemotional stresses, stay in the sun.

In patients with Cushing's syndrome, it is advisable to limit the intake of carbohydrates and fats, a protein diet is preferred. It is recommended to eat foods with high calcium and vitamin D for the prevention of osteoporosis.

Physiotherapy is the most important component of the treatment of juvenile arthritis. Daily exercises are needed to increase the amount of movement in the joints, eliminate flexion contractures, restore muscle mass. When hip joints are affected, traction procedures are recommended for the affected limb after preliminary consultation of the orthopedist, walking on crutches. During the development of coxite and aseptic necrosis of hip joints, the movement of a patient without crutches is contraindicated. Physiotherapy exercises should be carried out in accordance with the individual capabilities of the patient.

Apply static orthoses (tires, longes, insoles) and dynamic sections (light removable devices). For static orthoses, discontinuity of immobilization is necessary: they should be worn or put on during their free time and during the day must be removed to stimulate the muscular system during physical exercises, occupations, occupational therapy, and toilets. With severe osteoporosis in the thoracic and lumbar spine, it is recommended to wear a corset or a reclining system; with the defeat of the joints of the cervical spine - the head (soft or hard).

Drug treatment of juvenile rheumatoid arthritis

For the treatment of juvenile arthritis, several groups of drugs are used: NSAIDs, corticosteroids, immunosuppressants and biological agents obtained by genetic engineering. The use of NSAIDs and glucocorticosteroids contributes to the rapid reduction of pain and inflammation in the joints, improving function, but does not prevent the progression of joint destruction. Immunosuppressive and biological therapy halts the development of destruction and disability.

[1], [2], [3], [4], [5]

Treatment of systemic juvenile rheumatoid arthritis

With the development of life-threatening systemic manifestations, pulse-therapy with methylprednisolone in a dose of 10-15 mg / kg, and if necessary 20-30 mg / kg for 3 consecutive days.

Pulse therapy with methylprednisolone is combined with the appointment of immunosuppressive therapy. In early adolescent arthritis with a systemic onset (duration of less than 2 years), pulse-therapy with methotrexate at a dose of 50 mg / m ^{2 of} the body surface once a week in the form of intravenous infusions for 8 weeks. Subsequently, methotrexate is administered subcutaneously or intramuscularly at a dose of 20-25 mg / m ² body surface per week. As a rule, severe systemic manifestations are stopped within 4 weeks after the onset of combined use of methotrexate with methylprednisolone, and therefore, most patients do not need to prescribe prednisolone. In case of persistence of systemic manifestations, high laboratory indicators of disease activity after a 4-week course of treatment, cyclosporine can be added to the therapy at a dose of 4.5-5.0 mg / kg per day for ingestion.

To reduce the side effects of methotrexate, folic acid should be given at a dose of 1-5 mg on days that are free from taking the drug.

With a continuous continuously recurring course of the disease, generalized joint syndrome, high activity, hormone dependence after the 8-week course of pulse therapy, methotrexate is immediately prescribed combined therapy with methotrexate at a dose of 20-25 mg / m ² body surface per week (subcutaneously or intramuscularly) and cyclosporine in a dose of 4.5-5 mg / kg per day.

With co-enzyme with or without aseptic necrosis, combined therapy is used: methotrexate at a dose of 20-25 mg / m ² body surface per week (subcutaneously or intramuscularly) and cyclosporine at a dose of 4.5-5.0 mg / kg per day.

If methotrexate is ineffective at a dose of 20-25 mg / m ² body surface per week (subcutaneously or intramuscularly) for 3 months, combination therapy with methotrexate and cyclosporine is advisable. Methotrexate is prescribed at a dose of 20-25 mg / m ² body surface per week (subcutaneously or intramuscularly), cyclosporine 4.5-5.0 mg / kg per day.

If the standard therapy is not effective with immunosuppressants and corticosteroids, therapy with a biological agent called rituximab is indicated, which should be performed in a specialized rheumatology department. A single dose of the drug is 375 mg / m ^{2 of} the body surface. Rituximab is administered intravenously once a week for 4 weeks. For 30-60 minutes before each infusion, premedication with corticosteroids (methylprednisolone at a dose of 100 mg intravenously), analgesics and antihistamines (for example, paracetamol and diphenhydramine) is recommended. To reduce the risk of side effects, infusion of rituximab is carried out through the infusomat.

When immunosuppressive therapy is ineffective, parenteral administration of corticosteroids, biological agents, corticosteroids are administered orally at a dose of 0.2-0.5 mg / kg per day in combination with the above treatment methods.

The indication for the use of normal human immunoglobulin is the presence of an intercurrent infection. Preferably the use of an immunoglobulin containing antibodies of classes IgG, IgA and IgM. Doses and mode of administration: 0.3-0.5 g / kg per course. The drug is administered intravenously intravenously no more than 5 g per infusion. In the presence of indications, normal human immunoglobulin can be used in parallel with pulse therapy with methylprednisolone and methotrexate or immediately after it.

Indications for the appointment of antibacterial therapy: bacterial infection, sepsis, general inflammatory systemic reaction (fever, leukocytosis with neutrophil shift in the leukocyte formula to the left, multiple organ dysfunction), accompanied by a doubtful (0.5-2 ng / ml) or positive (> 2 ng / ml ) the value of the procalcitoid test, even without a foci of infection, confirmed by bacteriological and / or serological methods.

It is necessary to prescribe drugs with a wide range of action (aminoglycosides III and IV generation, cephalosporins III and IV generation, carbapenems, etc.). With obvious signs of sepsis, the combined use of 2-3 antibiotics of different groups is shown to suppress the activity of gram-positive, gram-negative, anaerobic and fungal flora.

Drugs are administered intravenously or intramuscularly. The duration of treatment is 7-14 days. If necessary, antibiotics replace and prolong the course of treatment.

Indications for the appointment of antiplatelet agents, anticoagulants, fibrinolysis activators - changes in the coagulogram, indicating a tendency to thrombus formation or coagulopathy of consumption.

The purpose of therapy is correction of the parameters of the vascular-platelet unit of hemostasis.

A combination of anticoagulants (heparin sodium or supraparin calcium), disaggregants (pentoxifylline, dipyridamole) and fibrinolysis activators (nicotinic acid) should be given.

Sodium heparin is administered intravenously or subcutaneously (4 times per day) from the calculation of 100-150 U / kg under the control of the APTT values. Nadroparin calcium is administered subcutaneously once a day from the calculation of 80-150 anti-Xa ED / kg. The duration of treatment with direct anticoagulants is 21-24 days with the subsequent appointment of anticoagulants of indirect action (warfarin).

Pentoxifylline is administered intravenously from the calculation of 20 mg / kg 2 times a day for 21-30 days.

Dipiridamole is prescribed internally at a dose of 5-7 mg / kg per day, divided into 4 receptions. Duration of admission is at least 3 months.

Nicotinic acid is administered intravenously in a daily dose of 5-10 mg, divided into 2 injections.

The sequence of administration of drugs for infusion therapy:

• methylprednisolone is dissolved in 200 ml of 5% glucose solution or 0.9% sodium chloride solution (duration of administration 30-40 min);
• antibiotics are administered according to generally accepted rules for each drug;
• symptomatic therapy (detoxification, cardiotropic) according to indications;
• pentoxifylline is dissolved in 0.9% sodium chloride solution (daily dose is divided into 2 injections);
• Immunoglobulin normal human is administered intravenously in accordance with the instructions for use;
• heparin sodium is administered intravenously (round the clock) or subcutaneously 4 times a day, subcutaneous injections of calcium supraparin are performed once a day;
• nicotinic acid in a daily dose of 5-10 mg is dissolved in 0.9% sodium chloride solution and administered intravenously twice a day.

In the presence of pronounced effusion in the joints, intraarticular injections of corticosteroids (methylprednisolone, betamethasone, triamcinolone) are performed.

Doses of glucocorticoids for intraarticular administration

Joints	The drug and its dose
Large (knee brachial, ankle)	Metiprednisolone (1.0 ml - 40 mg); betamethasone (1.0 ml - 7 mg)
Medium (elbow, wrist)	Methylprednisolone (0.5-0.7 ml - 20-28 mg); betamethasone (0.5-0.7 ml - 3.5-4.9 mg)
Small (interphalangeal, metacarpophalangeal)	Methylprednisolone (0.1-0.2 ml - 4-8 mg); betamethasone (0.1-0.2 ml - 0.7-1.4 mg)

Indications for the appointment of local therapy with glucocorticoids in juvenile rheumatoid arthritis

Indications and conditions of use	Conditions for prescribing methylprednisolone	Conditions for prescribing betamethasone
Synovitis with predominance of exudation	Small, medium, large joints	Arthritis of large, medium joints; tenosynovitis; bursitis
Synovitis and systemic manifestations	Lymphadenopathy, hepatosplenomegaly, subfebrile fever, rash	Febrile, hectic fever, rash, carditis, polyserositis
Synovitis, Cushing's syndrome with concurrent treatment with prednisolone	It is shown (does not strengthen adrenal insufficiency)	Undesirable (increases adrenal insufficiency)
Type of constitution	It is shown for all types of constitution	Undesirable in lymphatic-hypoplastic constitution
Pain syndrome in joints with predominance of proliferation	Indicated (does not cause soft tissue atrophy)	Undesirable (causes atrophy of soft tissues)

Of NSAIDs, diclofenac is usually used at a dose of 2-3 mg / kg per day. In severe systemic manifestations from the appointment of NSAIDs, one should abstain, since they can provoke the development of the macrophage activation syndrome.

Doses of non-steroidal anti-inflammatory drugs used in pediatric rheumatology practice

A drug	Dose, mg / kg per day	The maximum dose, mg / day	Number of receptions
Diclofenac	2-3	100	2-3
Indomethacin	1-2	100	2-3
Naproxen	15-20	750	2
Piroxicam	0.3-0.6	20	2
Acetylsalicylic acid	75-90	4000	3-4
Ibuprofen	35-40	800-1200	2-4
Nimesulide	5	250	2-3
Meloksikam	0.3-0.5	15	1
Sulindak	4-6	300	2-3
Tolmetin	25-30	1200	2-3
Surgham	-	450	1-4
Flugalin	4	200	2-4

Symptomatic therapy includes drugs that normalize the function of the cardiovascular, respiratory systems, antihypertensives, etc.

Treatment of juvenile rheumatoid arthritis (seropositive and seronegative)

Among NSAIDs, it is preferable to use diclofenac at a dose of 2-3 mg / kg, selective inhibitors of cyclooxygenase-2 - nimesulide at a dose of 5-10 mg / kg per day, meloxicam in children older than 12 years at a dose of 7.5-15 mg per day.

Intra-articular injection of PS is carried out in the presence of pronounced effusion in the joints.

Immunosuppressive therapy: the early administration (during the first 3 months of the disease) of methotrexate at a dose of 12-15 mg / m ² of body surface per week, subcutaneously or intramuscularly, is indicated.

If the effectiveness of methotrexate is insufficient at this dose for 3-6 months, it is advisable to increase its dose to 20-25 mg / m ² body surface per week with good tolerability.

If the high dose of methotrexate is ineffective for 3-6 months and / or the development of side effects, combined immunosuppressive therapy with leflunomide is performed. Leflunomide is prescribed according to the following scheme:

• in children with a body weight> 30 kg - 100 mg once a day for 3 days, then in a dose of 20 mg once a day;
• in children with a body weight <30 kg - 50 mg per day for 3 days, then not more than 10 mg per day.

Leflunomide can be treated without the use of a 3-day dose of saturation at a dose of 0.6 mg / kg per day, as well as leflunomide monotherapy with methotrexate intolerance and the development of side effects.

If the combined therapy is ineffective for 3-6 months, the use of a biological agent, infliximab, is advisable. The drug is administered intravenously according to the following scheme: 0-I, 2-nd, 6-th week and then every 8 weeks at a dose of 3-20 mg / kg per administration. The average effective dose of infliximab is 6 mg / kg. In case of insufficient effectiveness, it is possible to continue the administration of infliximab according to the above scheme, but to increase the dose of the drug and / or to shorten the interval between infusions up to 4-5 weeks. Treatment with infliximab is carried out in combination with methotrexate in a dose of 7.5-15 mg / m ² body surface per week.

With ineffectiveness of immunosuppressive and biological therapy, parenteral administration of corticosteroids, corticosteroids may be administered orally at a dose of not more than 0.25 mg / kg per day in combination with the above-listed treatment methods.

Treatment of oligoarticular (pausiarticular) juvenile rheumatoid arthritis

Among NSAIDs, it is preferable to use diclofenac at a dose of 2-3 mg / kg, selective inhibitors of yujuoxygenase-2 - nimesulide at a dose of 5-10 mg / kg per day, meloxicam in children older than 12 years at a dose of 7.5-15 mg per day.

In the presence of pronounced effusion in the joints, intraarticular injections of corticosteroids are carried out: methylprednisolone, betamethasone, triamcinolone.

Immunosuppressive therapy depends on the subtype of oligoarticular juvenile rheumatoid arthritis.

In a subtype with early onset, it is recommended that early administration (within the first 3 months of the disease) of methotrexate at a dose of 7.5-10 mg / m ² of body surface per week.

If the standard dose of methotrexate is ineffective, it is possible to increase its dose to 15 mg / m ^{2 of} the body surface per week or the administration of infliximab in combination with methotrexate according to the scheme described above.

In the case of development of uveitis, it is advisable to use cyclosporine in a dose of 3.5-5 mg / kg per day.

In the case of the preservation of articular syndrome and the development of remission of uveitis on the background of treatment with cyclosporin, it is advisable to use combined immunosuppressive therapy with methotrexate and cyclosporine. Methotrexate is prescribed at a dose of 10-15 mg / m ² body surface per week (subcutaneously or intramuscularly), cyclosporine 4.5-5.0 mg / kg per day.

If combined therapy is ineffective and uveitis is highly active, treatment with infliximab in combination with methotrexate or cyclosporine is indicated. Infliximab is administered intravenously according to the following schedule: at 0, 2, 6, and then every 8 weeks at a dose of 3-20 mg / kg per administration. The average effective dose of infliximab is 6 mg / kg. In case of insufficient effectiveness, it is possible to continue the administration of infliximab according to the above scheme, but to increase the dose of the drug and / or to shorten the interval between infusions up to 4-5 weeks. Treatment with infliximab is performed in combination with methotrexate in a dose of 7.5-15 mg / m ² body surface in weeks or cyclosporine at a dose of 4.5 mg / kg.

With a late-onset subtype, early administration (within the first 3 months of the disease) of sulfasalazine at a dose of 30-40 mg / kg per day is indicated. Treatment should begin with a dose of 125-250 mg per day (depending on the weight of the child). The increase in the dose of sulfasalazine to the calculated dose is 125 mg once every 5-7 days under the control of clinical and laboratory indicators (clinical blood test, urea levels, creatinine, transaminase activity and total serum bilirubin concentration).

If sulfasalazine is ineffective for 3-6 months, a biological agent, infliximab, is administered.

With uveitis, topically apply dexamethasone, betamethasone in drops, subconjunctivally, retrobulbarno, and also use drops with anti-inflammatory drugs and mydriatica (treatment of uveitis should be performed by an ophthalmologist).

Surgical treatment of juvenile rheumatoid arthritis

The main types of surgical treatment - prosthetics of joints, tenotomy, capsulotomy.

Indications for surgical treatment of juvenile rheumatoid arthritis:

• severe joint deformities, significant limitation of joint movements;
• ankylosis of the joints (joint prosthetics are performed);
• development of aseptic necrosis of femoral head heads (endoprosthetics of hip joints are performed);
• expressed contractures of the joints, not amenable to drug and conservative orthopedic treatment (carry out tenotomy, capsulotomy).