Treatment of juvenile chronic arthritis

Indications for consultation with other specialists

• An ophthalmologist consultation is recommended for all patients with joint damage and decreased visual acuity.
• Consultation with an endocrinologist is indicated for Cushing's syndrome and growth disorders.
• Consultation with an otolaryngologist is indicated in the presence of foci of chronic infection in the nasopharynx.
• Consultation with a dentist or orthodontist is recommended in case of caries, growth disorders of the jaws, teeth and bite.
• Consultation with a phthisiatrician is indicated in case of a positive Mantoux reaction and lymphadenopathy.
• Consultation with a hematologist or oncologist is indicated for ossalgia, persistent arthralgia, severe general condition in the presence of oligoarthritis, severe systemic manifestations with hematological disorders.
• Consultation with an orthopedist is indicated in cases of functional insufficiency of joints, impaired bone growth in length, subluxations, and for the development of rehabilitation measures.
• A genetic consultation is indicated for multiple minor developmental anomalies and connective tissue dysplasia syndrome.

Indications for hospitalization

Indications for hospitalization are listed below:

• development of systemic manifestations (fever, heart and lung damage);
• severe exacerbation of articular syndrome;
• selection of immunosuppressive drugs;
• lack of effect in outpatient treatment of exacerbation;
• addition of intercurrent infection;
• the presence of doubts about the correctness of the established diagnosis;
• carrying out rehabilitation measures during periods of exacerbation of joint syndrome (especially in cases of damage to the hip joints).

Confirmation of the diagnosis and choice of treatment tactics are carried out in a specialized pediatric rheumatology department.

Treatment goals for juvenile rheumatoid arthritis

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

Non-drug treatment of juvenile rheumatoid arthritis

During periods of exacerbation of juvenile rheumatoid arthritis, the child's motor regime should be limited. Complete immobilization of joints with the application of splints is contraindicated, as this contributes to the development of contractures, muscle atrophy, worsening of osteoporosis, and rapid development of ankylosis. Physical exercise helps maintain the functional activity of joints. Cycling, swimming, and walking are useful. Running, jumping, and active games are undesirable. It is recommended to maintain a straight posture when walking and sitting, and to sleep on a hard mattress and a thin pillow. Avoid psychoemotional stress and exposure to the sun.

In patients with Cushing's syndrome, it is advisable to limit the consumption of carbohydrates and fats, a protein diet is preferable. It is recommended to eat foods with a high content of calcium and vitamin D to prevent osteoporosis.

Physiotherapy is the most important component of juvenile arthritis treatment. Daily exercises are necessary to increase the range of motion in the joints, eliminate flexion contractures, and restore muscle mass. In case of damage to the hip joints, traction procedures on the affected limb are recommended after a preliminary consultation with an orthopedist, and walking on crutches. During the period of development of coxitis and aseptic necrosis of the hip joints, the patient's movement without crutches is contraindicated. Physiotherapy should be carried out in accordance with the individual capabilities of the patient.

Static orthoses (splints, longuets, insoles) and dynamic sections (lightweight removable devices) are used. Static orthoses require intermittent immobilization: they should be worn or put on during free time and must be removed during the day to stimulate the muscular system during physical exercises, classes, occupational therapy, and toilet. In case of severe osteoporosis in the thoracic and lumbar spine, it is recommended to wear a corset or a reclining system; in case of damage to the joints of the cervical spine - a head support (soft or hard).

Drug treatment of juvenile rheumatoid arthritis

Several groups of drugs are used to treat juvenile arthritis: NSAIDs, corticosteroids, immunosuppressants, and genetically engineered biological agents. The use of NSAIDs and glucocorticosteroids helps to quickly reduce pain and inflammation in the joints, improve function, but does not prevent the progression of joint destruction. Immunosuppressive and biological therapy stops the development of destruction and disability.

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Treatment of systemic juvenile rheumatoid arthritis

In the event of life-threatening systemic manifestations, pulse therapy with methylprednisolone is administered at a dose of 10-15 mg/kg, and if necessary, 20-30 mg/kg per administration for 3 consecutive days.

Pulse therapy with methylprednisolone is combined with the administration of immunosuppressive therapy. In early juvenile arthritis with systemic onset (duration less than 2 years), pulse therapy with methotrexate is administered at a dose of 50 mg / m ² of 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 of body surface per week. As a rule, severe systemic manifestations are relieved within 4 weeks after the start of the combined use of methotrexate with methylprednisolone, and therefore most patients do not require oral prednisolone. If systemic manifestations persist, high laboratory indicators of disease activity after a 4-week course of treatment, cyclosporine at a dose of 4.5-5.0 mg / kg per day for oral administration can be added to the therapy.

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

In case of a long-term continuously recurring course of the disease, generalized joint syndrome, high activity, hormone dependence, after completion of an 8-week course of pulse therapy with methotrexate, combination therapy with methotrexate at a dose of 20-25 mg/m2 of body surface per week (subcutaneously or intramuscularly) and cyclosporine at a dose of 4.5-5 mg/kg per day is immediately ^prescribed.

For coxitis with or without aseptic necrosis, combination therapy is used: methotrexate at a dose of 20-25 mg/m2 ^of body surface per week (subcutaneously or intramuscularly) and cyclosporine at a dose of 4.5-5.0 mg/kg per day.

If methotrexate at a dose of 20-25 mg/m2 of body surface per week (subcutaneously or intramuscularly) for 3 months is ineffective, ^it is advisable to conduct combined therapy with methotrexate and cyclosporine. Methotrexate is prescribed at a dose of 20-25 mg/m2 ^of body surface per week (subcutaneously or intramuscularly), cyclosporine - 4.5-5.0 mg/kg per day.

If standard therapy with immunosuppressants and corticosteroids is ineffective, therapy with a biological agent, rituximab, is indicated and should be performed in a specialized rheumatology department. A single dose of the drug is 375 mg/m2 ^of body surface. Rituximab is administered intravenously once a week for 4 weeks. Premedication with corticosteroids (methylprednisolone at a dose of 100 mg intravenously), analgesics, and antihistamines (e.g., paracetamol and diphenhydramine) is recommended 30-60 minutes before each infusion. To reduce the risk of side effects, rituximab is infused through an infusion pump.

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

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

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

It is necessary to prescribe drugs with a broad spectrum of action (aminoglycosides of the third and fourth generation, cephalosporins of the third and fourth generation, carbapenems, etc.). In case of obvious signs of sepsis, the combined use of 2-3 antibiotics of different groups is indicated in order to suppress the activity of gram-positive, gram-negative, anaerobic and fungal flora.

The drugs are administered intravenously or intramuscularly. The duration of the course of treatment is 7-14 days. If necessary, antibiotics are replaced and the course of treatment is extended.

Indications for the administration of antiplatelet agents, anticoagulants, and fibrinolysis activators are changes in the coagulogram indicating a tendency to thrombosis or consumption coagulopathy.

The goal of therapy is to correct the parameters of the vascular-platelet link of hemostasis.

A combination of anticoagulants (sodium heparin or calcium nadroparin), antiplatelet agents (pentoxifylline, dipyridamole) and fibrinolysis activators (nicotinic acid) should be prescribed.

Sodium heparin is administered intravenously or subcutaneously (4 times a day) at a rate of 100-150 U/kg under control of APTT values. Calcium nadroparin is administered subcutaneously once a day at a rate of 80-150 anti-Xa U/kg. The duration of treatment with direct anticoagulants is 21-24 days, followed by the administration of indirect anticoagulants (warfarin).

Pentoxifylline is administered intravenously at a rate of 20 mg/kg 2 times a day for 21-30 days.

Dipyridamole is prescribed orally at a dose of 5-7 mg/kg per day, divided into 4 doses. The duration of administration is at least 3 months.

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

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 is 30-40 minutes);
• antibiotics are administered according to generally accepted rules for each drug;
• symptomatic therapy (detoxification, cardiotropic) as indicated;
• pentoxifylline is dissolved in 0.9% sodium chloride solution (the daily dose is divided into 2 doses);
• normal human immunoglobulin is administered intravenously in accordance with the instructions for use;
• sodium heparin is administered intravenously (around the clock) or subcutaneously 4 times a day, subcutaneous injections of calcium nadroparin are administered once a day;
• Nicotinic acid in a daily dose of 5-10 mg is dissolved in a 0.9% sodium chloride solution and administered intravenously 2 times a day.

In the presence of severe effusion in the joints, intra-articular injections of corticosteroids (methylprednisolone, betamethasone, triamcinolone) are performed.

Doses of glucocorticoids for intra-articular administration

Joints	The drug and its dosage
Large (knee, shoulder, ankle)	Methyprednisolone (1.0 ml - 40 mg); betamethasone (1.0 ml - 7 mg)
Middle (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 glucocorticoid therapy in juvenile rheumatoid arthritis

Indications and conditions of use	Conditions for prescribing methylprednisolone	Conditions for prescribing betamethasone
Synovitis with predominant exudation	Small, medium, large joints	Arthritis of large and medium joints; tendovaginitis; bursitis
Synovitis and systemic manifestations	Lymphadenopathy, hepatosplenomegaly, low-grade fever, rash	Febrile, hectic fever, rash, carditis, polyserositis
Synovitis, Cushing's syndrome with concomitant treatment with prednisolone	Indicated (does not increase adrenal insufficiency)	Undesirable (increases adrenal insufficiency)
Constitution type	Shown for all types of constitution	Not recommended for lymphatico-hypoplastic constitution
Joint pain syndrome with predominant proliferation	Indicated (does not cause soft tissue atrophy)	Undesirable (causes soft tissue atrophy)

Of the NSAIDs, diclofenac is most often used at a dose of 2-3 mg/kg per day. In case of severe systemic manifestations, NSAIDs should be avoided, as they can provoke the development of macrophage activation syndrome.

Doses of nonsteroidal anti-inflammatory drugs used in pediatric rheumatology practice

Preparation	Dose, mg/kg per day	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
Meloxicam	0.3-0.5	15	1
Sulindak	4-6	300	2-3
Tolmetin	25-30	1200	2-3
Surgam	-	450	1-4
Flugalin	4	200	2-4

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

Treatment of juvenile rheumatoid arthritis (seropositive and seronegative)

Among NSAIDs, the preferred use is diclofenac at a dose of 2-3 mg/kg, selective cyclooxygenase-2 inhibitors - nimesulide at a dose of 5-10 mg/kg per day, meloxicam in children over 12 years of age at a dose of 7.5-15 mg per day.

Intra-articular administration of PS is performed in the presence of severe effusion in the joints.

Immunosuppressive therapy: early administration (within the first 3 months of the disease) of methotrexate at a dose of 12-15 mg/m2 ^of body surface per week subcutaneously or intramuscularly is indicated.

If methotrexate is insufficiently effective at the indicated dose for 3-6 months, it is advisable to increase its dose to 20-25 mg/m2 ^of body surface per week if well tolerated.

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

• for children weighing >30 kg - 100 mg once a day for 3 days, then at a dose of 20 mg once a day;
• for children weighing <30 kg - 50 mg per day for 3 days, then no more than 10 mg per day.

Leflunomide treatment can be administered without the 3-day loading dose at a dose of 0.6 mg/kg per day, as well as monotherapy with leflunomide in case of methotrexate intolerance and the development of side effects.

If combination therapy is ineffective for 3-6 months, it is advisable to use a biological agent - infliximab. The drug is administered intravenously according to the following scheme: 0th, 2nd, 6th 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, infliximab can be administered according to the above scheme, but the dose of the drug can be increased and / or the interval between infusions can be reduced to 4-5 weeks. Infliximab treatment is carried out in combination with methotrexate at a dose of 7.5-15 mg / m ² of body surface per week.

If immunosuppressive and biological therapy are ineffective, parenteral administration of corticosteroids may be administered orally at a dose of no more than 0.25 mg/kg per day in combination with the treatment methods listed above.

Treatment of oligoarticular (pauciarticular) juvenile rheumatoid arthritis

Among NSAIDs, the preferred use is 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 over 12 years of age at a dose of 7.5-15 mg per day.

In the presence of severe effusion in the joints, intra-articular injections of corticosteroids are administered: methylprednisolone, betamethasone, triamcinolone.

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

For the early-onset subtype, early administration (within the first 3 months of the disease) of methotrexate at a dose of 7.5-10 mg/m2 ^of body surface per week is recommended.

If standard doses of methotrexate are ineffective, it is possible to increase its dose to 15 mg/m2 ^of body surface per week or prescribe infliximab in combination with methotrexate according to the scheme described above.

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

In case of persistence of joint syndrome activity and development of uveitis remission against the background of cyclosporine treatment, it is advisable to use combined immunosuppressive therapy with methotrexate and cyclosporine. Methotrexate is prescribed at a dose of 10-15 mg/m2 ^of body surface per week (subcutaneously or intramuscularly), cyclosporine - 4.5-5.0 mg/kg per day.

If combination therapy is ineffective and uveitis is highly active, infliximab plus methotrexate or cyclosporine is indicated. Infliximab is administered intravenously according to the following schedule: at 0, 2, 6 weeks, 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. If ineffective, infliximab can be continued according to the above schedule, but the dose of the drug can be increased and/or the interval between infusions can be reduced to 4-5 weeks. Infliximab treatment is performed in combination with methotrexate at a dose of 7.5-15 mg/m2 ^of body surface per week or cyclosporine at a dose of 4.5 mg/kg.

In the 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 be started with a dose of 125-250 mg per day (depending on the child's weight). The sulfasalazine dose is increased to the calculated dose by 125 mg once every 5-7 days under the control of clinical and laboratory parameters (clinical blood test, urea levels, creatinine, transaminase activity and total bilirubin concentration in the blood serum).

If sulfasalazine is ineffective, therapy with a biological agent, infliximab, is carried out for 3-6 months.

For uveitis, dexamethasone and betamethasone drops are used locally, subconjunctivally, retrobulbarly, and drops with anti-inflammatory drugs and mydriatics are also used (treatment of uveitis should be carried out by an ophthalmologist).

Surgical treatment of juvenile rheumatoid arthritis

The main types of surgical treatment are joint replacement, tenotomy, and capsulotomy.

Indications for surgical treatment of juvenile rheumatoid arthritis:

• severe joint deformations, significant limitation of movement in the joints;
• ankylosis of joints (joint prosthetics are performed);
• development of aseptic necrosis of the femoral heads (hip joint endoprosthetics are performed);
• severe joint contractures that do not respond to medication and conservative orthopedic treatment (tenotomies and capsulotomies are performed).