Treatment of systemic scleroderma

At the heart of the treatment of systemic scleroderma is the administration of drugs with an antifibrotic effect of penicillamine (coulenyl) in combination with arterial vasodilators and antiplatelet agents. In the treatment of cardiovascular disease with heart damage, the effectiveness of oxygen therapy, slow calcium channel blockers and ACE inhibitors has been demonstrated.

Treatment of pulmonary arterial hypertension associated with systemic scleroderma is a very difficult task, as it is characterized by a small selection of medications. Treatment consists of general measures, medication and in some cases, surgical treatment.

General recommendations are aimed at minimizing harmful external influences in patients with PAH. Patients are advised to avoid such potentially dangerous symptoms as severe shortness of breath, fainting and chest pain. Only on an asymptomatic level is the load possible to maintain an adequate physical form. Physical activity should be avoided after taking the lishy and at elevated air temperature. Since hypoxia can aggravate vasoconstriction, patients with PAH should avoid hypobaric hypoxia, which develops at an altitude between 1500 and 2000 m, which is equivalent to the flight of airplanes, so patients are advised to avoid air flights,

The basic principles of the use of oral anticoagulants in patients with PAH are based on the presence of both traditional risk factors for venous thromboembolism, such as heart failure, a sedentary lifestyle, the presence of a predisposing hematogenous thrombophilia to thrombosis, and thrombotic changes in the microcirculatory bed and pulmonary artery,

Treatment with diuretics can improve the patient's condition, but no specific randomized clinical trials for their use have been conducted. According to the latest data, 49-70% of patients take diuretics. With pulmonary arterial hypertension, the preferred class of diuretics is not defined, so the doctor can choose a diuretic and its dose in a specific clinical situation. Patients receiving diuretic treatment, it is necessary to monitor the content of electrolytes that reflect the function of the kidneys.

Oxygen therapy in patients with PAH should be used to continuously maintain oxygen saturation of more than 90%. Yet at the present time there is no data on the beneficial effects of prolonged inhalation of oxygen.

The use of such traditional vasodilators, as slow calcium channel blockers, is based on a reduction in pulmonary vascular resistance, which leads to a reduction in pulmonary artery pressure. However, favorable clinical and prognostic effects of high doses of slow calcium channel blockers have been shown in patients with a positive response to an acute test with vasodilators, which is observed in only 10-15% of patients with pulmonary hypertension. In recent studies, mainly nifedipine and diltiazem were used. Their choice depends on the heart rate: with relative bradycardia, nifedipine should be given, with initial tachycardia - diltiazem. The highest efficacy of these drugs is observed with the appointment of high doses of drugs: the daily dose for nifedipine should be 120-240 mg, for diltiazem - 240-720 mg. The factors limiting the use of slow calcium channel blockers are systemic hypotension, edema of the shins and feet. Adding digoxin and / or diuretics in some cases can reduce the side effects of slow calcium channel blockers.

Prostacyclin, produced mainly by endothelial cells, is a potent endogenous vasodilator. It was shown that prostacyclin causes selective pulmonary vasodilation (reduction of pulmonary vascular resistance and pulmonary artery pressure) in patients with secondary pulmonary hypertension in the presence of pulmonary fibrosis. Prolonged intravenous prostacyclin promotes a two-year survival rate of up to 80% compared with 33% in traditional treatment, improves the quality of life of patients, improves exercise tolerance and reduces the manifestations of pulmonary hypertension.

The clinical use of prostacyclin is associated with the synthesis of its stable analogs, which possess different pharmacokinetic, but similar pharmacodynamic properties. The greatest experience is now accumulated with the use of epoprostenol. Beraprost is the first stable analog of prostacyclin for oral administration. In our country from the group of prostanoids for the treatment of patients with pulmonary arterial hypertension only prostaglandin E1 - alprostadil (vasaprostan) is used.

Endothelin-1 is a peptide produced predominantly by endothelial cells, which has potent vasoconstrictor and mitogenic properties against smooth muscle cells. Endothelin-1 causes pulmonary and systemic vasoconstriction, acting on smooth muscle cells, causing their spasm and hypertrophy of the wall, has a negative inotropic effect. Bozentan is the first drug from the class of receptor antagonists to endothelin, which in randomized studies in patients with pulmonary hypertension has shown the ability to improve exercise tolerance, FK, hemodynamic and echocardiographic parameters. Bozentan serves as a drug of choice for patients with pulmonary hypertension with prostatoid intolerance. The drug is recommended for the treatment of patients with PAH III and IV FC in the US and Canada. In Europe - only for patients with III FC and PAH associated with SSD without significant pulmonary fibrosis.

Sildenafil is a potent selective inhibitor of cGMP-phosphodiesterase-5 for oral administration. Its effect is associated with the accumulation of cellular pGMF within the cell, which leads to relaxation and suppression of proliferation of smooth muscle cells. Favorable effects of sildenafil have been shown in patients with pulmonary arterial hypertension associated with SSD. Treatment of systemic scleroderma with sildenafil must be assumed in those patients with pulmonary hypertension, in which other medicamentous effects are ineffective.