How is Juvenile Systemic Scleroderma Treated?

Non-drug treatment of systemic scleroderma

The patients are shown physiotherapy, massage and physiotherapy exercises, which help maintain the functional capabilities of the musculoskeletal system, strengthen the muscles, expand the amplitude of movements in the joints, and prevent the growth of flexion contractures.

Medicamentous treatment of systemic scleroderma

As a basic therapy, glucocorticosteroids, cytotoxic agents and antifibrotic drugs are used.

Means with glucocorticosteroid activity

In the presence of clinical and laboratory signs of inflammatory and immunological activity in the early phase of systemic scleroderma, glucocorticosteroids - prednisolone or methylprednisolone at medium doses of 15-30 mg / day are shown with their subsequent decrease when the therapeutic effect is achieved and complete withdrawal. Glucocorticosteroids can stabilize the skin process, stop the manifestations of arthritis, active myositis, serositis, and alveolitis. With severe fibrosis, in the late stage of the disease, glucocorticosteroids are not only ineffective, but also enhance sclerotic processes.

There are separate reports on the effectiveness of pulse therapy with glucocorticosteroids in systemic scleroderma in the treatment of pulmonary hypertension due to the involvement of lung vessels in the absence of thrombosis and interstitial lesions.

Cytotoxic agents

Cyclophosphamide is a cytotoxic drug from the group of alkylating agents, a drug of choice for the treatment of interstitial lung disease, a diffuse form of juvenile systemic scleroderma of rapidly progressing flow.

Various schemes for the use of cyclophosphamide in adults have been proposed, the effectiveness of which has been proved in retrospective studies.

• Pulse therapy (intravenous injection of the drug in megadoses): 1 time monthly for 6 months, then with a positive dynamics of pulmonary functional tests - 1 time in 2 months, while maintaining positive dynamics - 1 time in 3 months.
• Administration of cyclophosphamide is combined with daily intake of glucocorticosteroids at a dose of 0.5-0.8 mg / kg for 8 weeks, then the dose is reduced to 0.3 mg / kg for 12-18 months; duration of pulse-therapy cyclophosphamide - at least 2 years.
• Cyclophosphamide 750 mg (IV drip) in combination with methylprednisolone at a dose of 125 mg per infusion, which is performed every 3 weeks for 6 months.
• Cyclophosphamide inside at 1-2 mg / kg per day in combination with prednisolone inside at 40 mg / day through day was recognized as a promising method of treatment of the initial stages of interstitial lung injury in systemic scleroderma.

Both regimes of pulse therapy of cyclophosphamide are associated with serious side effects: leukopenia, anemia, hepatotoxicity, hemorrhagic cystitis, hair loss, nausea, vomiting.

Methotrexate is effective in treating early (<3 years from the onset of the disease) diffuse systemic scleroderma with subcutaneous injection and ingestion. Methotrexate is indicated for severe damage to the joints, muscles, periarticular contractures, and widespread skin lesions. It does not affect visceral lesions. Methotrexate is prescribed in a dose of 10 mg / m ² once a week together with folic acid in a standard dose (daily, except for the day of taking methotrexate).

Initially, methotrexate treatment was combined with taking glucocorticosteroids at a dose of 0.5 mg / kg per day for 6-8 weeks, with a dose reduction up to a maintenance dose of 0.1-0.25 mg / kg for 12-18 months, followed by a complete cancellation. Caution should be used to prescribe methotrexate to children with chronic foci of infection, to temporarily discontinue the drug if intercurrent diseases occur. Treatment with methotrexate is carried out for at least 2 years. It is necessary to monitor the safety of treatment, monitoring the hemogram quarterly, the biochemical indicators of liver function.

There is evidence of greater efficacy of methotrexate, used in children in large doses - 20-25 mg / m ² per week intramuscularly or subcutaneously.

Cyclosporine is used in the treatment of systemic scleroderma, but potential nephrotoxicity limits the wide use of the drug in clinical practice, since it requires careful monitoring of the state of renal function and the level of blood pressure.

Cyclosporine at a dose of 2-3 mg / day has a positive effect on systemic scleroderma skin changes, without affecting the condition of internal organs.

There are some reports of the effectiveness of cyclosporine in the treatment of progressive interstitial lung lesions in systemic scleroderma with cyclophosphamide ineffectiveness.

Azathioprine in combination with low doses of glucocorticosteroids can be used in the treatment of interstitial lung disease in systemic scleroderma, which leads to stabilization of lung function and improvement in patients with systemic scleroderma. This is shown in the pilot studies.

Antibiotic therapy of systemic scleroderma

Penicillamine is the most widely used drug of this group in the treatment of systemic scleroderma. It breaks the synthesis of collagen, splits the cross bonds between the newly formed molecules of the tropocollagen, promotes its removal from the body, inhibits the work of fibroblasts. The drug is prescribed initially in small doses on average 3 mg / kg per day, with good tolerability, the dose is gradually increased to 8-10 mg / kg daily (250-375 mg / day), which the patient takes for 3-5 years. Antifibrotic action of penicillamine is realized slowly, a pronounced clinical effect is observed after 6 months from the beginning of treatment. With rapidly progressive scleroderma, diffuse skin induration, fibrosis of internal organs, penicillamine is combined with glucocorticosteroids at a dose of 0.5 g / kg for 8 weeks. Further, the dose of glucocorticosteroids is gradually reduced to complete cancellation after 12-18 months.

The benefits of treatment with high doses of penicillamine are not confirmed. The drug in medium doses is usually well tolerated by patients, but with the development of side effects (dyspeptic disorders, aphthous stomatitis, skin rashes, nephropathy, eosinophilia, cytopenia, etc.), it is necessary to reduce the dose or stop taking.

Other medicines

The effectiveness of colchicine, as well as a- and y-interferons, which were previously used as antifibrotic agents, has not been confirmed in open trials, which does not allow them to be recommended for use.

Correction of microcirculatory disorders

Use drugs of various groups - vasodilators, disaggregants, if necessary - anticoagulants. Indications for the appointment - Raynaud's syndrome and its complications (ischemia, necrosis), pulmonary, renal hypertension.

• Calcium channel blockers lead to a moderate but significant decrease in the incidence and severity of vasospasm attacks. The choice of calcium channel blockers in children is carried out taking into account the individual tolerability, age and weight of the child. Short-acting drugs - nifedipine, long-acting drugs - nifedipine (Corinfar retard), amlodipine (norvask), the purpose of which is preferable.
• Angiotensin converting enzyme (ACE) inhibitors - captopril, enalapril - are prescribed to patients with a true scleroderma kidney, accompanied by severe vasoconstriction and hypertension. In adults, captopril is used in 12.5-50 mg 3 times a day, enalapril - 10-40 mg per day.
• The selective serotonin reuptake inhibitor-ketanserin at a dose of 60-120 mg / day showed efficacy in treating Reynaud's syndrome in placebo-controlled studies in adults.
• Angiotensin II receptor antagonists are losartan, 25-100 mg per day. In a pilot study, the efficacy of losartan (50 mg / day) and nifedipine (40 mg / day) was compared for 12 weeks for the treatment of secondary Reino syndrome in systemic scleroderma. There was a decrease in the severity of vasospasm attacks, more pronounced with losartan than with nifedipine, while a decrease in the frequency of seizures was noted only with losartan. Used for prolonged treatment.
• Sympatholytics, in particular prazosin, give a temporary effect, which disappears in a few weeks.
• In clinical practice, pentoxifylline (trental) is widely used in large doses (in adults - up to 400 mg 3 times per day), but there are no controlled studies to evaluate the results of its use.

For the treatment of severe Raynaud's syndrome, low molecular weight heparins are used. The effect occurs after 4 weeks of treatment.

In recent years, the synthetic analogue of prostaglandin E1 alprostadil (w / v of 0.1-0.4 μg / kg per min) and iloprost in minutes), which allows you to quickly improve the condition of patients. Course treatment consists of an average of 7-10 infusions.

Local treatment of systemic scleroderma

Externally apply the application of 20-30% solution of dimethyl sulfoxide with the addition of vasodilating, anti-inflammatory drugs to the affected areas of the skin. Phonophoresis is used to administer the drugs. Apply ointments containing corticosteroids - methylprednisolone aceponate (advantan), mometasone (elokom); vasotropic drugs - heparin ointment, troxerutin (troxevasin); means for improving trophism of tissues - chondroitin sulfate (chondroxide), actovegin \ solcoseryl. Contractubex and others.

Surgical treatment of systemic scleroderma

Practically, children do not use surgical treatment.

Indications for specialist consultation

With the localization of scleroderma foci on the head and face, patients need to consult an oculist (examination by a slit lamp), a neurologist.

Indications for hospitalization

• The newly diagnosed juvenile systemic scleroderma for a complete examination and selection of treatment.
• Necessity of monitoring the state of the child and monitoring the treatment, assessing its effectiveness and tolerability.
• The appearance of signs of disease progression and the need for correction of treatment.

Forecast

The prognosis for life in children with systemic scleroderma is much more favorable than in adults. Mortality in children with systemic scleroderma under the age of 14 years is only 0.04 per 1000 000 population per year. The five-year survival rate of children with systemic scleroderma is 95%. Causes of death - progressive cardiopulmonary insufficiency, scleroderma renal crisis. Possible the formation of pronounced cosmetic defects, disability of patients in connection with the violation of the function of the musculoskeletal system and the development of visceral lesions.

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