How is reactive arthritis treated?

Principles of treatment of reactive arthritis:

• the development of differentiated therapy taking into account the detected infections, the duration of the course and the degree of activity of reactive arthritis;
• monotherapy with antibiotics (macrolides, tetracyclines in children older than 10 years) with acute reactive arthritis associated with chlamydial infection;
• the appointment of combined therapy with immunomodulators and antibiotics (macrolides, tetracyclines in children older than 10 years) with a chronic course of reactive arthritis against persistent chlamydia infection;
• administration of antibiotics (aminoglycosides) to patients with acute and chronic course of post-enterocolitis variant of reactive arthritis and serological markers of intestinal infections;
• carrying out antibiotic therapy before the appointment of immunosuppressive drugs. If the child already receives immunosuppressive therapy, during the time of antibiotic therapy a temporary cancellation of the basic treatment is performed;
• treatment of NSAIDs and intra-articular injection of HA are used in patients with reactive arthritis as symptomatic therapy as needed.

Three types of treatment for reactive arthritis.

• Etiotropic.
• Pathogenetic.
• Symptomatic.

Etiotropic treatment of reactive arthritis

Due to the fact that Chlamydia is an intracellular parasite, the choice of antibacterial drugs is limited by their ability to accumulate intracellularly. Drugs of choice: macrolides, tetracyclines and fluoroquinolones.

However, tetracyclines and fluoroquinolones are toxic, have side effects that limit their use in children's practice. In this regard, most often for the treatment of chlamydia in children use macrolides (azithromycin, roxithromycin, spiramycin, josamycin). Teens can use doxycycline (children over 12 years).

Antibiotic treatment is more effective in the acute stage of Reiter's syndrome (chlamydia actively multiply, and the metabolically active reticular body is sensitive to antibacterial drugs).

In chlamydia, antibiotics of the penicillin series are not prescribed because of the possibility of chlamydia transition to L-like forms and development of chronic persistent chlamydial infection.

Etiotropic treatment of reactive arthritis associated with intestinal infection

For reactive arthritis associated with intestinal infection, there are no unambiguous recommendations for antibiotic therapy. It is assumed that at the beginning of the manifestation of arthritis the infection has already been stopped and there is no need for treatment with antibacterial agents. According to some rheumatologists, the prognosis for reactive arthritis and the possibility of its transformation into a chronic form, juvenile spondylitis, psoriatic arthritis are associated with the patient's genetic predisposition and the etiology of the disease, but does not depend on the antibiotic therapy. To all children with reactive arthritis, when antibodies to intestinal bacteria are detected in diagnostic titers or bacteria of the intestinal group, bacteriologic examination of the feces is advisable to perform antibiotic therapy. The drugs of choice are aminoglycosides (amikacin).

Antibacterial therapy allows to achieve seroconversion, clinical remission in the majority of patients and makes it possible to prescribe immunosuppressive drugs if necessary.

Pathogenetic treatment

Monotherapy with antibiotics is not sufficient in the long and chronic course of reactive arthritis associated with persistent chlamydial infection.

During this period, as a rule, only the joint syndrome recurs, and not the entire triad of symptoms. Taking into account the peculiarities of the interaction of the micro- and macroorganism, it is expedient to use various immunomodulating agents for the treatment of chronic chlamydial arthritis.

In patients with chronic persistent chlamydial infection, the immune system does not function adequately, and a full-fledged immune response is not formed or formed too slowly. Protective reactions are dominated by immunopathological ones. Given these features, the use of various immunomodulating agents affecting the immune response of the macroorganism is shown. Immunomodulators activate the immune response and indirectly induce the activity of the microorganism, which makes it accessible to antibiotics.

It should be noted that preparations with absolute specificity of action do not exist. However, if they existed, then due to the multicomponent and interconnectedness of various elements of the immune system, any highly specific drug would inevitably cause in this system a complex of complex successive changes.

Groups of drugs depending on the effect on the system of immunobiological surveillance:

• preparations, mainly stimulating nonspecific protective factors: (adaptogens and preparations of plant origin, vitamins);
• preparations, mainly stimulating monocytes / macrophages: (preparations of microbial origin and their synthetic analogs);
• preparations, mainly stimulating T-lymphocytes: (synthetic immunostimulants, thymus preparations and their synthetic analogues, IL-2, IL-1b);
• drugs that predominantly stimulate B-lymphocytes.

For the treatment of reactive arthritis of chlamydial etiology in children, therapy schemes have been developed and tested using the thymus extract, azoxime.

Scheme of combined treatment with thymus extract (tactivin) and antibiotic in patients with chronic course of reactive arthritis associated with chlamydial infection

Thymus extract subcutaneously to 1.0 ml every other day, the total number of injections - 10.

Antibiotic prescribe on the 5th day of treatment, i.e. After the second injection of the thymus extract. It is possible to use any antibiotic that has anti-chlamydial activity: macrolides (azithromycin, roxithromycin, josamycin) at age doses. Children under 12 years of age may use doxycycline. The course of antibiotic treatment is 7-10 days for the blockade of 2-3 life cycles of chlamydia.

Thymus extract (up to 10 injections) after completion of the course of antibacterial treatment.

The total duration of the course of combined antichlamydia therapy is 20 days.

Control of the general blood test is expedient to be carried out once in 7 days, biochemical indicators to monitor before and after the start of treatment.

Scheme of combined treatment of glucosaminyl muramyl dipeptide and antibiotics in patients with chronic course of reactive arthritis associated with chlamydial infection

Glucosaminyl muramyl dipeptide in the form of sublingual tablets. Children under 5 years of age should be prescribed 1 mg 3 times a day, children older than 5 years - 2 mg 3 times a day. The course of treatment is 24 days.

Antibiotic on the 7th day of taking glucosaminyl muramyl dipeptide. It is possible to use any antibiotic that has anti-chlamydial activity: macrolides (azithromycin, roxithromycin, josamycin) at age doses. In children older than 8 years, the use of doxycycline is possible. The course of treatment with antibiotic 7-10 days to cover 2-3 life cycles of chlamydia.

Glucosaminyl muramyl dipeptide up to the 24th day after the completion of the course of antibacterial treatment.

Control of the general blood test once every 7 days, control of biochemical parameters before and after treatment.

The scheme of combined treatment with azoxime (polyoxidonium) and antibiotics in patients with chronic course of reactive arthritis associated with chlamydial infection

Azoxymer intramuscularly at 0.03 mg per administration. The drug is administered every other day, the total number of injections is 10.

Antibiotic after the second injection of azoxime, that is on the 4th day of treatment. It is possible to use any antibiotic with anti-chlamydial activity: macrolides (azithromycin, roxithromycin, josamycin, etc.) in the dose levels (given above). In children older than 8 years, the use of doxycycline is possible. The course of treatment with an antibiotic for at least 7-10 days to cover 2-3 life cycles of chlamydia.

Azoximer (up to 10 injections) after completion of antibiotic therapy.

Control of the general blood test once every 7 days, control of biochemical parameters before and after treatment.

On the 5th-7th day from the beginning of treatment with immunomodulator in patients with chronic reactive arthritis, there may be an exacerbation of the joint syndrome, which is manifested by an increase in exudation in the joint, increased pain syndrome, and a violation of joint function. A number of patients may also experience an increase in temperature.

Exacerbation of the joint syndrome can be regarded as the transition of the inactive phase of the life cycle of chlamydia to the active one due to the stimulation of the immune response against the background of immunomodulator treatment. Activation of intracellularly located chlamydia leads to their intensive division, destruction of macrophages with subsequent exacerbation of joint syndrome. This phenomenon is a positive effect of treatment with an immunomodulator, due to the fact that during this period the microorganism becomes sensitive to the effects of antibacterial drugs.

For relief of acute inflammatory changes in joints, intra-articular administration of rjhnbrjcnthjbljd, application of NSAIDs in age-related doses is advisable.

Control of the effectiveness of pathogenetic and etiotropic treatment is carried out not earlier than 1 month later, optimally - 3 months after the treatment.

If the course of combined treatment is ineffective, repeated courses of treatment with the replacement of immunomodulators and antibiotics are recommended.

In some cases, after successful treatment, re-infection is possible, which requires the re-appointment of antichlamydia therapy.

An important factor in the successful treatment of a child with reactive arthritis associated with chlamydial infection is the diagnosis and treatment of family members of the patient.

Symptomatic treatment

For the treatment of articular syndrome with reactive arthritis, NSAIDs are used.

Within the framework of treatment, the most effective drug with the best tolerability is selected. When using NSAIDs in rheumatology, it should be remembered that the development of the anti-inflammatory effect lags behind the analgesic. Anesthesia occurs in the first hours after admission, while the anti-inflammatory effect appears only on the 10-14th day of a regular, regular intake of NSAIDs.

Treatment begins with a minimal dose, increasing it after 2-3 days with good tolerability. In recent years, there has been a trend towards an increase in single and daily doses of drugs characterized by good tolerability, while maintaining restrictions on the maximum dose of acetylsalicylic acid, indomethacin, piroxicam.

With prolonged course treatment, NSAIDs are taken after meals (in rheumatology). To obtain a rapid analgesic and antipyretic effect, NSAIDs are prescribed 30 minutes before meals or 2 hours after meals, with a 0.5-1 glass of water. After taking NSAIDs for 15 minutes, it is advisable not to lie down in order to prevent esophagitis. The time of taking the drug is determined by the time of the most pronounced symptomatology, taking into account the chronopharmacology of the drugs, which allows achieving a greater effect at a lower daily dose. In the morning stiffness, the earliest possible intake of rapidly absorbed NSAIDs or the appointment of long-acting drugs for the night is appropriate.

Non-steroidal anti-inflammatory drugs used in pediatric practice and recommended doses

A drug	Dose, mg / kg per day	The maximum dose	Number of receptions
Diclofenac-sodium	2-3	100	2-3
Indomethacin	1-2	100	2-3
Naproxen	15-20	750	2
Piroxicam	0.3-0.6	20	2
Ibuprofen	35-40	800-1200	2-4
Nimesulide	5	250	2-3
Meloksikam	0.3-0.5	15	1
Surgham	-	450	1-4
Flugalin	4	200	2-4

Glucocorticoids

Corticosteroids - the most powerful anti-inflammatory drugs used in the treatment of reactive arthritis in the acute period and the period of exacerbation of the joint syndrome. However, their use is limited primarily to the intra-articular route of administration.

Intra-articular administration of sustained-release corticosteroids is an important component of the complex treatment of reactive arthritis. Methylprednisolone and betamethasone have a pronounced local anti-inflammatory effect.

Currently, corticosteroids have been synthesized for intraarticular administration; their use has significantly increased the effectiveness and safety of local therapy. Drugs of prolonged action: Methylprednisolone acetate - medium-duration drug, betamethasone acetate + betamethasone sodium phosphate and betamethasone propionate + betamethasone sodium phosphate - long-acting agents.

Corticosteroids injected into the joint cavity have a rapid local and systemic anti-inflammatory effect. This is indicated by a statistically significant decrease in inflammatory changes in punctured and unpaired joints, the number and severity of extra-articular manifestations in all patients already within the first 12-24 hours after drug administration. The general anti-inflammatory effect of local therapy with glucocorticosteroids is a consequence of systemic absorption of hormones introduced into the joint, which is 30-90%. The rapid therapeutic effect of topical administration of prolonged glucocorticosteroids allows the acute inflammatory changes to be controlled in reactive arthritis.

Glucocorticosteroids are injected into the joint cavity or around it only at signs of exudation. Preference is given to methylprednisolone. If it is insufficiently effective or short-lived, in order to achieve a more pronounced and stable effect, it is optimal to use betamethasone containing a rapidly and slowly absorbed fraction of betamethasone (the immediate development of the effect and its prolongation, respectively).

With high therapeutic efficacy, local corticosteroid therapy does not have any significant side effects.

Side effects due to violation of the rules of application for local therapy of glucocorticosteroids:

• atrophy of the skin, subcutaneous tissue, muscle when the drug is injected subcutaneously;
• Cushing's syndrome;
• hormone dependence, hormone resistance;
• infectious complications in violation of the rules of asepsis and antiseptics in the course of arthrocentesis;
• proliferative reactions.

Adverse reactions, traditional for all glucocorticosteroids, develop with frequent, uncontrolled intra-articular injection of drugs. They are most pronounced when using betamethasone, which refers to a strong long-acting glucocorticosteroid.

The frequency of administration of glucocorticosteroids determines the activity of the joint syndrome, but not more often than 1 time per month.

Immunosuppressive therapy

Immunosuppressive therapy is used for the chronic course of arthritis, the appearance of spondyloarthritis, especially in HLA-B27 positive patients with high laboratory ESR, serum concentrations of C-reactive protein, IgG. The drug of choice is sulfasalazine, less often methotrexate.

Sulfasalazine is used in patients with acute and chronic course of reactive arthritis, threatened with development of spondyloarthritis, HLA-B27 positive patients, with clinical signs of interest in sacroiliac joints and spine. The main pharmacological effects of the drug are anti-inflammatory and antibacterial (bacteriostatic). In children with a risk of developing juvenile spondylitis, sulfasalazine is used as a disease-modifying drug (basic therapy). Sulfasalazine is the drug of choice in spondyloarthropathies associated with a chronic inflammatory process in the intestine (ulcerative colitis and Crohn's disease). The drug is recommended for use in oligoarticular and polyarticular variants of articular form of juvenile rheumatoid arthritis.

If there are indications and to prevent the occurrence of side effects, it is necessary to start treatment with low doses - 250 mg per day (125 mg twice a day). The dose of the drug is gradually increased under the control of clinical and laboratory indicators (the number of leukocytes, erythrocytes, platelets, serum urea concentration, creatinine, transaminase levels, serum bilirubin) at 125 mg in 5-7 days before the therapeutic dose. Recommended doses of 30-40 mg / kg of body 1 time per day to 60 mg / kg 2 times a day during meals or after meals, washed down with milk. The clinical effect comes to the 4th-8th week of treatment.

Current and forecast

In most children, reactive arthritis results in complete recovery. This outcome is typical in the case of development of reactive arthritis associated with iersiniosis and campylobacter infection. In some patients, episodes of reactive arthritis recur, there are signs of spondyloarthritis, especially in HLA-B27 positive patients. In the literature, there are data that in 3 out of 5 patients, positive for HLA-B27 after suffering from reactive arthritis caused by salmonellosis, psoriasis develops. According to our data, in some patients with reactive arthritis, during the course of the observation, transformation into a typical juvenile rheumatoid arthritis occurs, with all the relevant clinical and radiological changes.

[1], [2], [3]