How is reactive arthritis treated?

Principles of treatment of reactive arthritis:

• development of differentiated therapy taking into account the identified infections, duration of the course and degree of activity of reactive arthritis;
• conducting monotherapy with antibiotics (macrolides, tetracyclines in children over 10 years of age) for acute reactive arthritis associated with chlamydial infection;
• the appointment of combination therapy with immunomodulators and antibiotics (macrolides, tetracyclines in children over 10 years of age) for chronic reactive arthritis against the background of persistent chlamydial infection;
• prescribing antibiotics (aminoglycosides) to patients with acute and chronic postenterocolitic reactive arthritis and serological markers of intestinal infections;
• conducting antibacterial therapy before prescribing immunosuppressive drugs. If the child is already receiving immunosuppressive therapy, the basic treatment is temporarily discontinued for the duration of antibacterial therapy;
• NSAID treatment and intra-articular administration of GC 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

Since 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 and have side effects that limit their use in pediatric practice. In this regard, macrolides (azithromycin, roxithromycin, spiramycin, josamycin) are most often used to treat chlamydia in children. Doxycycline can be used in adolescents (children over 12 years old).

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 case of chlamydia, penicillin antibiotics are not prescribed due to the possibility of chlamydia transitioning to L-like forms and the development of chronic persistent chlamydial infection.

Etiotropic treatment of reactive arthritis associated with intestinal infection

There are no clear recommendations for antibacterial therapy for reactive arthritis associated with intestinal infection. It is assumed that by the time arthritis manifests, the infection has already been stopped and there is no need for antibacterial treatment. According to some rheumatologists, the prognosis for reactive arthritis and the possibility of its transformation into a chronic form, juvenile spondyloarthritis, psoriatic arthritis are associated with the patient's hereditary predisposition and the etiology of the disease, but does not depend on the antibacterial therapy. Antibacterial therapy is advisable for all children with reactive arthritis if antibodies to intestinal bacteria are detected in diagnostic titers or intestinal bacteria are detected during bacteriological examination of feces. The drugs of choice are aminoglycosides (amikacin).

Antibacterial therapy allows for seroconversion and clinical remission in most patients and makes it possible to prescribe immunosuppressive drugs if necessary.

Pathogenetic treatment

Antibiotic monotherapy is insufficient in the case of protracted and chronic reactive arthritis associated with persistent chlamydial infection.

During this period, as a rule, only the articular syndrome recurs, and not the entire triad of symptoms. Given the peculiarities of the interaction of micro- and macroorganisms, it is advisable to use various immunomodulatory agents for the treatment of chronic chlamydial arthritis.

In patients with chronic persistent chlamydial infection, the immune system functions inadequately, and a full immune response is not formed or is formed too slowly. Immunopathological reactions prevail over protective reactions. Given these features, the use of various immunomodulatory agents that affect the immune response of the macroorganism is indicated. Immunomodulators activate the immune response and indirectly induce the activity of the microorganism, which makes it accessible to the action of antibiotics.

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

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

• drugs that primarily stimulate non-specific defense factors: (adaptogens and herbal preparations, vitamins);
• drugs that primarily stimulate monocytes/macrophages: (drugs of microbial origin and their synthetic analogues);
• drugs that primarily stimulate T-lymphocytes: (synthetic immunostimulants, thymus preparations and their synthetic analogues, IL-2, IL-1b);
• drugs that primarily stimulate B-lymphocytes.

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

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

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

The antibiotic is prescribed on the 5th day of treatment, i.e. after the second injection of thymus extract. It is possible to use any antibiotic with antichlamydial activity: macrolides (azithromycin, roxithromycin, josamycin) in age-appropriate doses. In children over 12 years old, doxycycline can be used. The course of antibiotic treatment is 7-10 days to block 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 antichlamydial therapy is 20 days.

It is advisable to monitor the general blood test once every 7 days, and monitor biochemical parameters before and after the start of treatment.

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

Glucosaminyl muramyl dipeptide in the form of sublingual tablets. For children under 5 years old, it is advisable to prescribe 1 mg 3 times a day, for children over 5 years old - 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 with antichlamydial activity: macrolides (azithromycin, roxithromycin, josamycin) in age-appropriate doses. In children over 8 years old, doxycycline can be used. The course of antibiotic treatment is 7-10 days to cover 2-3 life cycles of chlamydia.

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

Complete blood count once every 7 days, biochemical parameters before and after the start of treatment.

Scheme of combined treatment with azoximer (polyoxidonium) and antibiotics in patients with chronic reactive arthritis associated with chlamydial infection

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

Antibiotic after the 2nd injection of azoximer, i.e. on the 4th day of treatment. It is possible to use any antibiotic with antichlamydial activity: macrolides (azithromycin, roxithromycin, josamycin, etc.) in age-appropriate doses (given above). In children over 8 years old, doxycycline can be used. The course of antibiotic treatment is at least 7-10 days to cover 2-3 life cycles of chlamydia.

Azoximer (up to 10 injections) after completion of the course of antibacterial therapy.

Complete blood count once every 7 days, biochemical parameters before and after the start of treatment.

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

Exacerbation of the articular syndrome can be regarded as a transition from the inactive phase of the chlamydia life cycle to the active phase due to stimulation of the immune response against the background of treatment with an immunomodulator. Activation of intracellular chlamydia leads to their intensive division, destruction of macrophages with subsequent exacerbation of the articular 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.

To relieve acute inflammatory changes in the joints, it is advisable to administer rjhnbrjcnthjbljd intra-articularly and use NSAIDs in age-appropriate doses.

Monitoring the effectiveness of pathogenetic and etiotropic treatment is carried out no earlier than 1 month, optimally 3 months after the treatment.

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

In some cases, after successful treatment, reinfection is possible, which requires repeated administration of antichlamydial therapy.

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

Symptomatic treatment

NSAIDs are used to treat joint syndrome in reactive arthritis.

As part of the treatment, the most effective drug with the best tolerability is selected. When using NSAIDs in rheumatology, it is necessary to remember that the development of the anti-inflammatory effect lags behind the analgesic effect. Pain relief occurs in the first hours after administration, while the anti-inflammatory effect appears only on the 10-14th day of constant, regular use of NSAIDs.

Treatment begins with a minimum dose, increasing it after 2-3 days if well tolerated. In recent years, there has been a tendency to increase single and daily doses of drugs characterized by good tolerance, while maintaining restrictions on the maximum doses of acetylsalicylic acid, indomethacin, and piroxicam.

In long-term treatment, NSAIDs are taken after meals (in rheumatology). To achieve a quick analgesic and antipyretic effect, NSAIDs are prescribed 30 minutes before meals or 2 hours after meals, with 0.5-1 glass of water. After taking NSAIDs, it is advisable not to lie down for 15 minutes to prevent esophagitis. The time of taking the drug is determined by the time of the most pronounced symptoms, taking into account the chronopharmacology of the drugs, which allows for a greater effect with a lower daily dose. In case of morning stiffness, it is advisable to take rapidly absorbed NSAIDs as early as possible or prescribe long-acting drugs at night.

Nonsteroidal anti-inflammatory drugs used in pediatric practice and recommended doses

Preparation	Dose, mg/kg per day	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
Meloxicam	0.3-0.5	15	1
Surgam	-	450	1-4
Flugalin	4	200	2-4

Glucocorticoids

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

Intra-articular administration of prolonged-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 for intra-articular administration have been synthesized; their use has significantly increased the effectiveness and safety of local therapy. Prolonged-action drugs: methylprednisolone acetate is a medium-acting drug, betamethasone acetate + betamethasone sodium phosphate and betamethasone propionate + betamethasone sodium phosphate are long-acting agents.

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

Glucocorticosteroids are injected into the joint cavity or around it only if there are signs of exudation. Preference is given to methylprednisolone. If it is insufficiently effective or has a short duration of action, to achieve a more pronounced and lasting effect, it is optimal to use betamethasone, which contains a rapidly and slowly absorbed fraction of betamethasone (immediate development of the effect and its prolongation, respectively).

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

Side effects resulting from violation of the rules of application during local therapy with glucocorticosteroids:

• atrophy of the skin, subcutaneous tissue, muscles when the drug is administered subcutaneously;
• Cushing's syndrome;
• hormone dependence, hormone resistance;
• infectious complications due to violation of the rules of asepsis and antisepsis during arthrocentesis;
• proliferative reactions.

Side effects, traditional for all glucocorticosteroids, develop with frequent, uncontrolled intra-articular administration of drugs. They are most pronounced when using betamethasone, which is a strong long-acting glucocorticosteroid.

The frequency of administration of glucocorticosteroids is determined by the activity of the joint syndrome, but not more than once a month.

Immunosuppressive therapy

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

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

If indicated and to prevent side effects, it is necessary to start treatment with low doses - 250 mg per day (125 mg 2 times per day). The dose of the drug is gradually increased under the control of clinical and laboratory parameters (number of leukocytes, erythrocytes, platelets; serum concentration of urea, creatinine, transaminase level, serum bilirubin) by 125 mg every 5-7 days to a therapeutic dose. The recommended doses are 30-40 mg / kg of body weight once a day up to 60 mg / kg 2 times a day during or after meals, washed down with milk. The clinical effect occurs by the 4th-8th week of treatment.

Course and prognosis

In most children, reactive arthritis ends in complete recovery. This outcome is typical in the case of reactive arthritis associated with Yersinia and Campylobacter infection. In some patients, episodes of reactive arthritis recur, signs of spondyloarthritis appear, especially in HLA-B27 positive patients. There are data in the literature that 3 out of 5 patients positive for HLA-B27 after reactive arthritis caused by salmonellosis develop psoriasis. According to our data, in some patients with reactive arthritis, during observation, there is a transformation into typical juvenile rheumatoid arthritis, with all the corresponding clinical and radiological changes.

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