How is juvenile dermatomyositis treated?

Indications for hospitalization

Primary examination and treatment of patients with juvenile dermatomyositis is always performed in the conditions of a specialized rheumatological hospital.

Non-drug treatment of juvenile dermatomyositis

The patient with juvenile dermatomyositis shows early activation to prevent the formation of severe muscular dystrophy, contractures and osteoporosis. As the activity of the disease subsides, the dosed physical exercise is prescribed. Massage is not carried out until the inflammatory activity in muscles is completely suppressed. In the period of remission, rehabilitation therapy in special sanatoriums (sulphurous, radon, rap baths) is possible to reduce the severity of contractures.

Drug treatment of juvenile dermatomyositis

The pathogenetic (basic) immunosuppressive and anti-inflammatory therapy is shown.

The main treatment for juvenile dermatomyositis is aimed at suppressing autoimmune inflammation in the skin, muscles and other organs. The basis of pathogenetic therapy in juvenile dermatomyositis is glucocorticosteroids, according to indications, cytostatics are prescribed.

Symptomatic therapy is aimed at eliminating microcirculation disorders, metabolism, maintaining the functions of internal organs, preventing complications of the disease and therapy.

Principles of pathogenetic therapy:

• early appointment;
• an individual approach when choosing the most rational treatment regimen, taking into account the clinical manifestations, the degree of activity and the nature of the course of the disease;
• continuity (timely alternation of the suppressive and maintenance dose of drugs taking into account the phase of the disease);
• constant monitoring of the effectiveness and safety of the therapy;
• duration and continuity of treatment;
• gradual slow dose reduction;
• cancellation only against the background of persistent clinical and laboratory remission.

The basis for the treatment of juvenile dermatomyositis, like many other rheumatic diseases, is systemic glucocorticosteroids. Assign glucocorticosteroids inside, with dysphagia possible introduction through the probe, and with expressed - parenterally. Treatment of juvenile dermatomyositis is carried out by short-acting short-acting corticosteroids (prednisolone, methylprednisolone).

Treatment of juvenile dermatomyositis begins immediately after the diagnosis, since the early onset leads to a better outcome until the disease completely regresses. The maximum inhibitory dose of prednisolone in juvenile dermatomyositis is 1 mg / kg. With a high activity of the disease, a higher dose, but not more than 1.5 mg / kg, is acceptable. Preferably the combination of taking prednisolone at a dose of 1 mg / kg orally with other methods of treatment. The daily dose of the drug is divided, reception is appointed in the morning, focusing on the early morning hours. Alternating reception (every other day) with juvenile dermatomyositis is ineffective.

The maximum dose is prescribed for 6-8 weeks (depending on the activity of the disease), after which a gradual slow reduction of the dose to the maintenance dose begins (it is desirable to replace prednisolone with methylprednisolone because of its less pronounced mineralocorticoid activity, 5 mg of prednisolone is equivalent to 4 mg of methylprednisolone). The smaller the dose of prednisolone, the slower its reduction, and at the expense of a later reception. With a good response to glucocorticosteroids, a decrease in the dose of prednisolone is done so that after 6 months of treatment it is at least 0.5 mg / kg, and by the end of the first year of treatment - not less than 0.25-0.3 mg / kg from the initial ( 1 mg / kg). With signs of torpidity of the process, the rate of glucocorticosteroid dose reduction slows down, additional methods of treatment are added to overcome steroid resistance.

The duration of reception of glucocorticosteroids is calculated individually in each case, depending on the effectiveness of this type of treatment in this patient, determined by the timing of relief of clinical manifestations and the achievement of remission, the presence of relapses, the timeliness of the initiation of adequate therapy. But even with the early appointment of glucocorticosteroids, a good response to treatment and no relapse, the total duration of treatment is at least 3 years (on average 3-5 years), with torpid and / or recurrent course of 3 years or more. Cancellation of glucocorticosteroids is performed only against a background of persistent, long (> 1 year) clinical and laboratory remission.

With high activity of the disease (II-III degree of activity, crisis), life-threatening disorders, special indications increase therapy with the help of additional methods of treatment. These include pulse therapy with glucocorticosteroids, including in combination with plasmapheresis, cytostatic drugs, intravenous immunoglobulins.

Pulse-therapy - intravenous injection of ultrahigh, shock doses of the drug. Its use makes it possible to rapidly stop the high inflammatory activity of the disease as quickly as possible, and thus avoid the appointment of very high doses of oral glucocorticosteroids. Use methylprednisolone in a single dose of 10-15 mg / kg, an average of 2-5 procedures daily or every other day. The drug is diluted in 100-250 ml of physiological sodium chloride solution or 5% glucose solution and injected for 35-45 minutes. Open studies have shown the effectiveness of pulse therapy in patients with acute, active course of the disease; at an early appointment - a decrease in the degree of functional insufficiency and prevalence of calcification in the future. Pulse therapy with methylperdnisolone has proved to be very useful in relentless exacerbations of juvenile dermatomyositis, allowing to stop the increasing activity of the disease without increasing the dose of prednisolone. Severe exacerbations of juvenile dermatomyositis, however, always require an increase in the dose of oral glucocorticosteroids to the maximum.

In domestic controlled trials, the effectiveness of juvenile dermatomyositis of discrete plasmapheresis (PAF) has been proven, especially in combination with pulse therapy, the so-called synchronous therapy. Depending on the activity of the disease, 3-5 procedures of PAP are used every other day, 6 hours after each session, pulse therapy is performed at a rate of 10-12 mg / kg. The use of PAF without adequate immunosuppression leads to a worsening of the condition due to the development of the "rebound" syndrome. The indication for the synchronization of PAP with pulse therapy with glucocorticosteroids is a high activity of juvenile dermatomyositis (grade III, myopathic crisis), including in severe exacerbations (against a background of an increase in the dose of prednisone - up to 1 mg / kg). Other indications for synchronous therapy in juvenile dermatomyositis: a bright, widespread skin syndrome, a long-term untreated or inadequately treated process, torpidity of clinical symptoms against oral glucocorticosteroid therapy.

Modern tactics of managing patients with juvenile dermatomyositis implies the early administration of cytotoxic drugs with moderate and high disease activity, which makes it possible to achieve a stable clinical and laboratory remission more quickly, reducing the time taken for high doses of glucocorticosteroids. It must be remembered that cytotoxic drugs are ineffective as monotherapy, they are prescribed for juvenile dermatomyositis only in combination with glucocorticosteroids.

Traditionally, with juvenile dermatomyositis, methotrexate is used, in many guidelines for the treatment of inflammatory myopathies, it is indicated as a drug of choice from "second-line agents" in connection with the optimal "efficiency / toxicity" ratio. Methotrexate is considered to be an antiproliferative agent, but with low doses, it has a predominantly anti-inflammatory effect.

Methotrexate is prescribed 1 time per week, as a more frequent drug intake is associated with the development of acute and chronic toxic reactions. Children take methotrexate inside at a dose of 10-15 mg / m ² body surface 1 time per week. The dose is increased gradually under the control of a general blood test and the level of transaminases. To reduce the toxicity of the drug additionally prescribed folic acid at a dose of 1 mg / day daily, except for the day of taking methotrexate. The effect develops after 1-2 months of treatment, the duration of admission is 2-3 years until a stable clinical and laboratory remission is achieved, provided there are no complications.

Alternative cytotoxic drugs in juvenile dermatomyositis (eg, in the ineffectiveness of methotrexate) - azathioprine, cyclophosphamide and cyclosporine A. Azathioprine is less effective than methotrexate.

Cyclophosphamide is administered orally at a dose of 1-2 mg / kg or as intermittent pulse therapy (10-15 mg / kg per month) for life-threatening changes. The drug has proven itself in interstitial lung lesions with juvenile dermatomyositis.

In the case of a steroid-resistant variant of the disease, cyclosporin A, used at a dose of 3-5 mg / kg per day, is effective with a further transition to a maintenance dose of 2-2.5 mg / kg per day for several months or years until the clinical effect is achieved. Currently, the drug is successfully used for interstitial lung injury, including fast-progressive.

Aminoquinoline (antimalarial) drugs have no independent value in the therapy of juvenile dermatomyositis, their effectiveness in this disease is controversial. In foreign literature, there is an opinion that these drugs can be used to relieve exacerbations of skin syndrome with dermatomyositis without increasing the dose of glucocorticosteroids, and for "dermatomyositis without myositis" are effective as monotherapy. In some cases, they are used to maintain remission of the disease against a background of a low maintenance dose of glucocorticosteroids.

Data on the efficacy of new drugs such as mycophenolate mofetil, tacrolimus, fludarabine, biological drugs (infliximab, rituximab) in adult dermatomyositis and juvenile dermatomyositis are contradictory.

A separate place in the therapy of juvenile dermatomyositis is occupied by intravenous immunoglobulins (IVIG). In juvenile dermatomyositis, the effectiveness of IVIG has been demonstrated in several open studies, multicenter analysis of which was conducted by Rider L. And Miller F. In 1997. He showed that IVIG application at a dose of 2 g / kg per month for 3-9 months (on admission GK) allowed to stop the manifestations of skin syndrome in 29% and myopathic - 30% of 27 patients with juvenile dermatomyositis, resistant to glucocorticosteroid therapy. In 8 patients, the calcification decreased or disappeared. Mechanisms of immunosuppressive action of IVIG are considered inhibition of proinflammatory cytokines, blockage of the deposition of components of the complement system, competitive binding to macrophage Fc receptors, B-lymphocytes and target antigens, competition for the recognition of antigens by sensitized T cells. With dermatomyositis, the ability of IVIG to block the deposits of complement protein complexes (MAC) in endomysia capillaries due to C3b binding, preventing the activation of activated C3 protein in C5-convertase, is of the greatest importance.

A clear scheme of IVIG application in juvenile dermatomyositis has not been worked out. To achieve an immunosuppressive effect, IVIG is prescribed at a dose of 2 mg / kg per month, splitting this dose by 2 doses for 2 consecutive days (alternatively 0.4 mg / kg daily for 5 consecutive days). Treatment is carried out for 6-9 months until a significant clinical improvement, normalization of the level of enzymes "muscle decay" and the possibility to reduce the dose of glucocorticosteroids. IVIG are ineffective as starting and monotherapy of dermatomyositis, they are used as an additional agent for steroid-resistant variants of the disease.

IVIG is also used as a substitute for the development of intercurrent infections. In this case, the course dose is 200-400 mg / kg, the greatest effectiveness was observed with the combination of IVIG with antibacterial drugs.

Of great importance in the treatment of juvenile dermatomyositis is symptomatic therapy aimed at correcting disorders caused by the disease itself, preventing and treating complications of therapy.

In the acute period of juvenile dermatomyositis, infusion, detoxification therapy (glucose-salt solutions), drugs that improve microcirculation (pentoxifylline, nicotinic acid preparations), antiplatelet agents and anticoagulants should be prescribed. With pronounced vasculitis accompanying the antiphospholipid syndrome, after the course of direct anticoagulants (heparin sodium) is completed, the patient is transferred to oral anticoagulants (warfarin) with a dose adjustment according to the values of MHO. Possible long-term use of acetylsalicylic acid.

To improve microcirculation, when the activity of the process subsides, during the period of incomplete remission, vascular preparations (pentoxifylline, nicergoline, etc.) and antiplatelet agents are constantly receiving a glucocorticoid with a patient with juvenile dermatomyositis.

The most effective prevention of calcification is adequate therapy, which allows quickly to stop the inflammatory necrotic process in the muscles. However, additionally for the prevention and treatment of calcification, ethidronic acid is used, which has a moderate and moderate anti-osteoporetic effect. Ethidronic acid is used orally, in the form of applications with DMSO and electrophoresis on calcification sites. Unfortunately, the long-existing widespread calcification is practically not amenable to correction, but relatively fresh calcifications decrease or even completely dissolve.

It is necessary to timely connect the drugs that prevent the development of severe side effects of glucocorticosteroids. First of all, the prevention of steroid osteoporosis is carried out: during the entire period of treatment with glucocorticosteroids, the patient receives calcium preparations (but not more than 500 mg / day) in combination with colcalciferol and calcitonin. Against the background of taking prednisolone or methylprednisolone, especially in large doses, almost constant prevention of upper gastrointestinal lesions is needed - alternation of antacids and enveloping agents. Given the property of glucocorticosteroids to increase the excretion of potassium and magnesium, the patient must constantly receive appropriate drugs.

Surgical treatment of juvenile dermatomyositis

Recently in the literature there were data on a possible operative correction of severe disabling effects of juvenile dermatomyositis (calcifications, contractures).

Indications for consultation of other specialists

Patients with juvenile dermatomyositis, as well as all patients taking glucocorticosteroids, are shown to consult an oculist every 6 months, due to the fact that one of the rare side effects is cataract.

Forecast

In recent years, due to improved diagnosis and the expansion of the arsenal of medicines, the prognosis of juvenile dermatomyositis has improved significantly. With timely initiated and adequately conducted treatment, most patients succeed in achieving a stable clinical and laboratory remission. According to LA Isaeva, and MA. Zhvania (1978), who observed 118 patients, lethal outcomes were noted in 11% of cases, deep disability - in 16.9% of children. In recent decades, severe functional insufficiency develops in juvenile dermatomyositis in no more than 5% of cases, the share of deaths does not exceed 1.5%.

[1], [2], [3], [4], [5], [6]