How is juvenile ankylosing spondylitis treated?

Non-pharmacological methods of juvenile ankylosing spondylitis

Particular emphasis in the treatment of juvenile ankylosing spondylitis should be given to teaching the patient a rational regimen, developing the right functional stereotype, carefully designed complex of therapeutic gymnastics (LFK), aimed at limiting static loads, maintaining proper posture, maintaining a sufficient volume of movements in the joints and spine. It is important to orient the patient to perform daily physical exercises in order to prevent progressive kyphosis. With care, it is necessary to treat the use of JIA patients with active (or subacute) manifestations of peripheral arthritis and / or enthesitis, intense FZT and, especially, balneological procedures, often provoking exacerbations. Magnetolaser therapy, especially in the treatment of coke, electrophoresis with 5% lithium chloride, hyaluronidase (lidaz) and other antifibrotic agents can be widely used.

Medication for juvenile ankylosing spondylitis

The objectives of treatment of juvenile ankylosing spondylitis:

• suppression of inflammatory and immunological activity of the process;
• relief of systemic manifestations and joint syndrome;
• preservation of the functional capacity of joints;
• prevention or slowing down of joint destruction, disability of patients;
• achievement of remission;
• improving the quality of life of patients;
• minimization of the side effects of treatment.

The therapeutic tactics of juvenile ankylosing spondylitis basically differ little from that of ankylosing spondylitis in adults. It depends, mainly, on the spectrum of clinical manifestations of the disease at one or another stage of it.

Nonsteroidal anti-inflammatory drugs

NSAIDs are indispensable in the treatment of juvenile ankylosing spondylitis as symptomatic agents that can reduce and even completely stop the manifestations of pain and inflammation in the joints.

The list of NSAIDs permitted for use in pediatric practice is very limited, especially for pre-school children, for whom the vast majority of NSAIDs serve as "off labell" drugs.

Given the wide range of adverse reactions induced by NSAIDs, preference should be given to a new class of non-steroidal compounds, the so-called selective inhibitors of COX-2. Among drugs of this class, only nimesulide can be used with little or no age restrictions, children are prescribed at a dose of 5 mg / kg per day. Meloxicam is allowed for use only in children over 12 years of age at a dose of 0.15-0.25 mg / kg per day.

These remedies are less toxic to the digestive tract and kidneys with good anti-inflammatory activity.

Nimesulide, in addition, possessing antihistamine and anti-bradykinin action, serves as a drug of choice for patients with concomitant allergic diseases and bronchial asthma, and it is considered as the most pathogenetically justified drug because it is a sulfonanilide derivative related to sulfasalazine. In patients with high disease activity, an accumulation of anti-inflammatory potential of selective COX-2 inhibitors is possible within 2-3 weeks. The pronounced anti-inflammatory effect of the drugs may not appear as quickly as with the use of indomethacin or high doses of diclofenac. However, after achieving a therapeutic effect, the anti-inflammatory effect of this agent is almost identical to that of diclofenac. It should be emphasized that in some patients with highly active juvenile ankylosing spondylitis, as well as in adults with ankylosing spondylitis, selective efficacy of indomethacin occurs with insufficient response to any other NSAIDs. This few patients are forced to take indomethacin, despite the highest of all NSAIDs, the incidence of adverse adverse reactions they cause.

Indomethacin is administered to children at a rate of 2.5 mg / kg of body weight per day. In a similar dosage (2.5-3 mg / kg), diclofenac is also used. With success, you can use naproxen in a dose of 10-15 mg / kg (for a short period to suppress the activity - 20 mg / kg) or piroxicam (0.3-0.6 mg / kg in children older than 12 years), without forgetting, however , about the high gastroenterological toxicity of the latter. Other NPVPI with JIA, as a rule, ineffective.

General recommendations on the duration of NSAID use in case of JIA - the orientation towards the preservation of signs of disease activity, in the first place, articular syndrome. After stopping the signs of activity, NSAID treatment should be continued for 1.5-2 months.

Basic anti-inflammatory treatment of juvenile ankylosing spondylitis

Indication for the appointment of disease-modifying (basic) drugs - persistent maintenance of the disease with peripheral arthritis, enthesitis, uveitis. Suitable and pathogenetically justified is the use as a basic drug of sulfasalazine from the calculation of 30-50 mg / kg per day (total not more than 2 g per day).

In order to prevent serious adverse reactions that are possible in a small part of patients with individual metabolic peculiarities (slow type of acetylation), a full daily therapeutic dose is achieved gradually, within 1.5-3 weeks, starting with 0.25 g / day under the control of overall health and analysis of peripheral blood. It is necessary to avoid the appointment of sulfasalazine in patients with IgA-nephropathy, as this can exacerbate the severity of the urinary syndrome.

In recent years, with juvenile ankylosing spondylitis, methotrexate at a dose of 10 mg / m ² per week was started as a basic drug , and in some patients the use of a combination of sulfasalazine and methotrexate was justified. Methotrexate is administered orally or intramuscularly (subcutaneously) on a fixed day of the week, and the parenteral route of administration characterizes better tolerability and higher efficacy due to better bioavailability compared to oral administration. The appointment of methotrexate is indicated in cases of persistent clinical and laboratory activity resistant to the treatment, especially in combination with erosive arthritis of small joints of the feet, recurrent uveitis, as well as in patients with IgA-nephropathy. To improve the tolerability of methotrexate, folic acid is also used. On the day of his admission, it is advisable to cancel NSAIDs (especially diclofenac) or to lower the dose.

In a significant proportion of patients with juvenile ankylosing spondylitis the basic treatment is not used either because of poor tolerance of sulfasalazine and the impossibility of taking methotrexate (for example, with concomitant foci of infection, frequent viral diseases, erosive gastroduodenitis) or due to lack of clinical indications for prescribing basal agents. Our experience, consistent with the opinion of most other researchers, suggests that base-action drugs are ineffective in isolated spinal injury (the so-called central form of juvenile ankylosing spondylitis).

Treatment with glucocorticoids of juvenile ankylosing spondylitis

Sometimes it becomes necessary to prescribe and koritkosteroids in a dose of 0.2-0.5 mg / kg per day, as equivalent to high doses of NSAIDs. The use of corticosteroids is justified in patients with a long persistent high activity of the disease with pronounced persistent shifts of the humoral immunity indices, as well as in the development of such systemic manifestations as IgA-associated nephropathy or uveitis, provided that the use of NSAIDs in adequate doses is ineffective. In patients with a predominance of axillary skeletal lesion symptoms, especially with severe inflammatory pains and stiffness in the spine, a 3-day pulse-therapy with methylprednisolone of 15 mg / kg (either by a single course or programmatically, for example, quarterly) is effective in reducing the respiratory excursion.

Of great importance is the implementation of intraarticular injections, as well as the introduction of cotritosteroids in the places of the most pronounced enthesites and tenosynovitis. For intraarticular injections, corticosteroids of prolonged action are used: preparations of betamethasone, triamcinolone, less often metiprednisolone. In European countries and North America, in pediatric practice, hexacetonide is used almost exclusively for triamcinolone intra-articular injection, which has repeatedly proved its superiority over other drugs in controlled studies.

Treatment with anticytokine drugs of juvenile ankylosing spondylitis

The constantly ongoing search for effective means of pathogenetic treatment of rheumatic diseases led to the introduction in recent years of clinical practice of anti-cytokine drugs, primarily tumor necrosis factor (TNF-a) blockers. Infliximab, which is a monoclonal antibody to TNF-a, and ethanercept (soluble TNF-a receptor). They were successfully used in the most severe variants of seronegative spondylitis in adults, the drugs are very effective in the highly active course of spondyloarthritis in children. The possibility of active use of these drugs is limited by age, since they are not registered for use in children and can be prescribed only in special clinical situations to overcome drug refractoriness in the absence of contraindications (foci of chronic infection, tubinfication, risk of tumors, etc.). Long-term experience with the use of infliximab in adults with spondyloarthritis has shown the possibility of a persistent decrease in the activity of the disease and an improvement in the prognosis. Infliximab is administered in an average dose of 5 mg / kg intravenously drip at intervals of 2 weeks, 4 weeks (between the second and third infusions) and then every 8 weeks. Contraindications to the use of infliximab are unsanitary infectious foci, especially tuberculosis infection.

The use of rational schemes of treatment of patients with juvenile ankylosing spondylitis, timely correction of it with ineffectiveness or the appearance of new symptoms allows to achieve control of the activity of the pathological process in the vast majority of patients and significantly improve the prognosis.

Evaluation of the effectiveness of treatment of juvenile ankylosing spondylitis

In clinical practice, the criteria for the effectiveness of treatment are a reduction in the frequency and severity of relapses of peripheral arthritis and entesis, a decrease in laboratory activity, and an improvement in the functional capacity achieved as a result of the use of drugs. The effect of the use of NSAIDs, corticosteroids (oral and intra-articular), and biological agents occurs in a short time - usually within the first few days. On the contrary, the disease-modifying effect of basic drugs is qualified to expect no earlier than in 2-3 months of admission with a gradual increase in efficacy as the cumulation of the drug during long-term use.

In scientific research and clinical trials, special methods are used to evaluate the effectiveness of treatment. In adults with AS, the combined index of BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) is used, assessing five clinical indicators based on the questionnaire of the patient using the 100-mm visual analogue scale of BASDAI: pain in the spine, joint pain, duration and severity of pain in the spine, fatigue, the degree of discomfort arising when palpation of any areas. The BASDAI index is not used in assessing the effectiveness of treatment in children due to lack of validation, as well as special versions of the questionnaires. In pediatric practice with JIA, a technique developed in recent years for JRA / JIA can be used for this. According to this method, six indicators are evaluated:

• number of "active" joints (consider 75 joints);
• number of joints with restriction of function ( 75 joints are taken into account );
• ESR and / or C-reactive protein;
• general assessment of disease activity according to the doctor (VAS);
• assessment of general well-being in the opinion of the patient or his parents (VAS);
• Assessment of functional capacity using the Childhood Health Assesment Quesionnare (CHAQ) questionnaire.

The dynamics of these indicators in the treatment process gives grounds to judge the degree of effectiveness: a 30% improvement in indices allows the effect to be considered to be moderately positive, 50% good; 70% - very good.

Complications and side effects of treatment of juvenile ankylosing spondylitis

Species of side effects of drug treatment are different and depend on the pharmacological group, as well as the specific medicinal product used.

To the spectrum of side effects, NSAIDs include the following, arranged in order of priority:

• gastropathy in the form of dyspepsia and / or development of NSAID-induced damage to the mucous membrane of the upper gastrointestinal tract, most characteristic of indomethacin, acetylsalicylic acid, piroxicam, diclofenac;
• hepatotoxicity, which is possible with the use of any NSAID, more often diclofenac;
• nephrotoxicity, encountered with the use of any NSAIDs, including selective inhibitors of COX-2;
• myelotoxicity, characteristic of phenylbutazone, indomethacin;
• adverse CNS reactions observed with the use of acetylsalicylic acid, indomethacin, and sometimes ibuprofen;
• increased chondrodestruction, characteristic of indomethacin.

The most important side effects of sulfasalazine and methotrexate are potential hepatotoxicity, as well as idiosyncratic side effects characteristic of the whole antimetabolite group, which depend on the individual characteristics of the individual patient. With the use of methotrexate, dyspeptic reactions occur, the frequency of which increases as the duration of the drug intake increases.

The use of biological agents, especially modern TNF-a blockers, is associated with a high risk of developing opportunistic infections, as well as a hypothetical risk of increasing the incidence of neoplasms.

To prevent the development of complications and a significant part of adverse reactions helps strict adherence to recommendations on indications and doses of medicines, as well as monitoring of side effects.

Errors and unreasonable appointments

The most common mistakes in the treatment of juvenile ankylosing spondylitis involve unreasonable prescription of glucocorticosteroids with the development of exogenous hypercorticism (most often in situations where the diagnosis is mistakenly interpreted as juvenile rheumatoid arthritis). Sometimes basic drugs are unreasonably used in case of overdiagnosis of spondylitis in patients with peripheral arthritis and spine pathology of non-rheumatic nature. Isolated lesion of the axial skeleton with a reliable juvenile ankylosing spondylitis is also not a sufficient basis for basic treatment, since the main point of application of the pathogenetic action of these drugs is peripheral arthritis and enthesitis. Serious consequences can cause the use of active physiotherapy and balneotherapy in patients with "active" peripheral articular syndrome and enthesitis. Underestimation of concomitant diseases before the appointment of immunosuppressive treatment with methotrexate and biological agents is fraught with potentially dangerous complications.

Surgical methods of treatment of juvenile ankylosing spondylitis

According to the conventional wisdom, the juvenile onset of spondyloarthritis causes an unfavorable prognosis for destructive lesion of joints, especially hip joints. In this regard, in 20-25% of patients with juvenile ankylosing spondylitis in adulthood, there is a need for endoprosthetics of large joints.

In children of childhood with fixed hip joint contractures, low-traumatic surgical methods of treatment can be successfully applied - myoaductophasciotomy, the use of a distraction system, which allows improving the function and delaying the implementation of endoprosthetics.

Forecast

The prognosis for life and long-term preservation of functional ability is generally favorable. For a long time ago juvenile ankylosing spondylitis, as a rule, already in adulthood the cause of development of disability can be destruction of the hip joints, requiring endoprosthetics, or ankylosing of the intervertebral joints of the cervical spine. Eye damage rarely has an adverse course; Aortitis worsens the prognosis and can be a cause of death, which is extremely rare. At the lethality with juvenile ankylosing spondylitis affects amyloidosis, in this regard, the timely and adequate treatment of the active inflammatory process becomes particularly important.

Possible ways of evolution of juvenile ankylosing spondylitis and its prognosis should be considered pediatric rheumatology for vocational guidance and social rehabilitation of adolescents. With older patients and their parents, it is advisable to discuss the problem of the genetic basis of the disease as a risk factor for future offspring. According to the literature data, the risk that HLA-B27-heterozygous father will transmit the disease to his son, is no more than 5%, and daughters - even less. Systematic long-term medical supervision with control of laboratory indicators and timely correction of treatment allows to significantly reduce the risk of complications of juvenile ankylosing spondylitis and improve the prognosis.

[1], [2], [3]