Scleroderma - a disease of the connective tissue, the main manifestations of which are associated with circulatory disturbance and compaction of organs and tissues. Among patients women prevail (approximate ratio of women and men - 6: 1).
Causes
The causes of the disease are unknown. It is believed that scleroderma develops under the influence of some external factors in people with certain genetic disorders. The external factors that can trigger the development of scleroderma include
- retroviruses (primarily cytomegalovirus),
- silica and coal dust,
- organic solvents
- vinyl chloride,
- certain drugs (bleomycin and several other drugs used for chemotherapy).
manifestations of scleroderma
As a systemic disease, scleroderma is characterized by the simultaneous defeat of the skin, vascular, musculoskeletal system and internal organs, including the heart, lungs, kidneys and gastrointestinal tract.
A characteristic feature of scleroderma is the earliest Raynaud's syndrome - transient episodes spasmodermia limbs exposed to cold or emotional stress. Raynaud's syndrome is clinically manifested clearly defined areas of discoloration of fingers. In early attack vasospasm brushes fingers become pale coloration, which in a few minutes is changed to a bluish purple color. After the resolution of spasm and restore blood flow occurs reddening of the skin and the skin becomes intensely pink.
In some patients, vasospasm episodes are accompanied by a sense of freezing hands, numbness, or sensory disturbances. In the phase of redness, patients may feel pain in fingers.
Vasoconstriction may also be subjected to blood vessels of the skin and other sites. In these cases, there is the characteristic color change tip of the nose, lips and ears, above the knee.
The most specific symptom of scleroderma is the skin lesions in the form of its thickening and seals, which are observed in the majority of patients. The severity and prevalence of skin seals vary in individual patients, but with seal skin scleroderma always starts with the hands fingers, and may further spread further out on a limb and torso.
Simultaneously with the fingers of hands is often observed skin lesion, resulting in smoothed nasolabial folds and frontal, thinning red border of the lips, around which there are radial wrinkles.
Long-term follow celebrated staging of skin lesions: edema, induration, thinning. thickening of the skin has a tendency to progression in the first 3-5 years of the disease. In later stages of the disease the skin becomes less dense, and the seal is only fingers.
Often feature of scleroderma is the intensive staining of the skin, limited or widespread, with areas of hypo- or depigmentation ( "salt and pepper").
A characteristic feature are ulcers on the fingers, which can be acutely painful. Ulcerative skin lesions are observed in other areas exposed to mechanical stress: over the elbow and knee joints in the ankles and heels.
As a result of circulatory disorders appear ridges on fingers, dot thinning areas of the skin ( "rat-bite"). Scars on fingers may arise after healing ulcers. Due to loss of hair follicles, sweat and sebaceous glands in skin seal areas becomes dry and rough, deprived of hair.
Joint pain and morning stiffness are common manifestations of scleroderma, especially in the early stages of the disease.
The result is the destruction of circulatory disorders of nail phalanges, manifested by shortening and deformity of the fingers.
The defeat of the muscles can lead to muscle weakness.
Involvement of the gastrointestinal tract develops in 90% of patients with scleroderma. The defeat of the esophagus manifested impaired swallowing, persistent heartburn, which increases after a meal. The defeat of the stomach and duodenum is manifested by abdominal pain, flatulence. The defeat of the small intestine often asymptomatic, but with marked changes develop impaired intestinal absorption syndrome diarrhea, flatulence and weight loss. The consequence of the defeat of the colon become constipation.
lung damage develops more than 70% of patients with scleroderma and shows increasing shortness of breath and a persistent cough.
Other common manifestations of scleroderma include Sjogren syndrome (20%) and thyroid disease (thyroiditis Hashimoto's thyroiditis or de Quervain), leading to a decrease in thyroid function.
Diagnostics
Approximately half the observed increase in ESR 20 mm / h. With the same frequency reveals signs of inflammatory activity in scleroderma: increasing content fibrinogen and seromucoid; less experienced higher rates of C-reactive protein.
In 10-20% of patients with anemia is detected, the cause of which may be iron deficiency and vitamin B12, renal failure or bone marrow directly. Of great importance is the identification of specific autoantibodies for scleroderma.
Among the many instrumental methods plays an important role Capillaroscopy nail bed. Microcirculation research methods, such as laser-Doppler flowmetry, plethysmography, and others, are of secondary importance in the diagnosis of scleroderma because of the considerable variability results.
scleroderma treatment
Therapy always appointed individually, depending on the shape and course of the disease, the nature and extent of lesions. Given the progressive in most cases of the disease, it is important to draw the patient's attention to the need for permanent medical supervision and routine screening for early signs of disease progression and possible correction therapy.
Therapy is aimed at:
- prevention and treatment of vascular complications;
- suppression of progression of fibrosis of the skin and internal organs;
- impact on immunoinflammatory mechanisms of scleroderma;
- prevention and treatment of visceral lesions.
Patients need to reduce the time spent in the sun, avoid prolonged exposure to cold, the local vibration. To reduce the frequency and severity of attacks of vasospasm recommended to wear warm clothes, including a heat retaining underwear, hats, wool socks and mittens (instead gloves). With the same purpose, the patient is advised to stop smoking, give up coffee and caffeinated drinks consumption.
The main areas of medical treatment of scleroderma are vascular, anti-fibrotic and immunosuppressive therapy.
vascular therapy It is conducted to reduce the frequency and severity of Raynaud's syndrome episodes and improve blood flow and It includes the application of vasodilator agents, as well as drugs that affect blood viscosity and bonding platelets.
The most effective vasodilating agents are calcium channel blockers (verapamil, gallopamil, nifedipine, amlodipine, nicardipine, isradipine, lacidipine, nimodipine, nitrendipine, Valium, felodipine, diltiazem, cinnarizine, flunarizine).
The drug of choice is nifedipine (synonyms: kaltsigard retard kordafen, cordipin, nifedeks, Nifecard), the effective daily dose which is 30-60 mg three or four times. Nifedipine reduces the frequency and intensity, and in some cases, and the duration of vasospasm episodes.
Approximately 1/3 of the patients treated with nifedipine develop characteristic for the majority of side effects, the most frequent heart palpitations, headache, Dizziness, facial flushing and swelling shins.
Recently, increasingly used long-acting forms of nifedipine (kaltsigard retard cordipin retard) that create relatively constant concentration of drug in the blood and thus reduce the blood pressure variations and related side exposure.
Intolerance to nifedipine may appoint other drugs. Amlodipine (amlovas, kalchek, Norvasc, normodipin) has a prolonged effect and is assigned to a single dose of 5-10 mg. The most common adverse influence of amlodipine is swelling of the ankles, which appears in approximately 50% of patients.
Isradipine (Lomir) is administered in a daily dose of 5 mg in two steps. With little effect and good tolerability of the daily dose can be increased to 10 mg. The most common complications in the treatment of isradipine are headache and facial flushing.
Felodipine (auronal, plendil, felodil) at a daily dose of 10-20 mg reduces the frequency and severity of vasospasm.
Diltiazem (altiazem PP, diazo, diltazem CP) in a therapeutic dose of 180 mg / day is less effective than nifedipine, but has a better tolerability. When receiving the high dose may cause swelling of the ankles and headaches.
If there are contraindications or intolerance calcium channel blockers, vasodilators applied to other groups. For example, alpha-adrenergic blockers (dihydroergotamine, doxazosin, nicergoline, prazosin, terazosin). Good results have been observed in the treatment of a standardized extract of Ginkgo biloba (tanakan - Tablets 40 mg 3 times a day). In severe cases (e.g., pulmonary hypertension, renal crisis, gangrene) a synthetic prostaglandin E1 (alprostadil) in a dose of 20-40 mg intravenously during 15-20 days or prostacyclin analogues (Iloprost).
The effectiveness of treatment of vascular manifestations of scleroderma is increased when incorporated in therapy of drugs which improve blood fluidity - antiplatelet drugs (acetylsalicylic acid, ginkgo biloba, dipyridamole, pentoxifylline, ticlopidine), anticoagulants and optionally (acenocoumarol, warfarin sodium heparin, sodium dalteparin, nadroparin calcium, enoxaparin sodium, ethyl biskumatsetat).
The combination of vasodilator and antiplatelet agents provides the ability to assign the minimum effective dose of each of these drugs, and thereby reduce the incidence of side effects. For this purpose, the most widely used pentoxifylline at a daily dose of 600-1200 mg. In cases of multiple and ustoychvyh to conventional treatment of ulcers shows a short course (10-15 days) treatment, preferably a low molecular weight heparin.
antifibrotic therapy assigned in diffuse scleroderma form. D-penicillamine - basic drug that inhibits the development of fibrosis, - gives collagen synthesis, cleaving cross-links between the newly synthesized molecules.
Penicillamine (artamin, kuprenil) affects different parts of the immune system. The effective dose is 250-500 mg / day. Penicillamine take only on an empty stomach. With the development of side effects (stomach discomfort, hypersensitivity, reduced leukocytes and / or trombofitov blood, autoimmune reactions, etc.). necessary dose reduction or abolition the drug. The basis for the selection is canceled penicillamine protein in the urine above 2 g / day. Due to the high incidence of side effects (25%), which are often dose-dependent manner, during the treatment must be carefully observe patients do blood and urine tests every 2 weeks during the first 6 months of treatment, and in the future - 1 time month.
Anti-inflammatory therapy (Diclofenac, ibuprofen, ketoprofen, meloxicam, nimesulide, piroxicam, tselikoksib) under standard therapeutic doses indicated for the treatment of musculo-articular manifestations of scleroderma, desk fever.
Hormone (Betamethasone, hydrocortisone, dexamethasone, methylprednisolone, prednisolone, triamcinolone - not more than 15-20 mg / day) assigned when obvious signs of inflammatory activity and early (edematous) stage scleroderma, but do not affect the progression of fibrosis. Receiving more high doses increases the risk of kidney damage.
With the defeat of the esophagus recommend frequent small feedings. To eliminate impaired swallowing short courses administered prokinetic: domperidone, meklozin, ondansetron, metoclopramide; at reflux esophagitis - proton pump inhibitors (omeprazole 20 mg / day, lansoprazole 30 mg / day, rabeprazole et al.). With the development of a hernia of an esophageal aperture card operative treatment.
When intestinal lesion antimicrobials used: Erythromycin (sinerit, erythromycin, eriflyuid), ciprofloxacin (Kvintor, sifloks, tsiprovin, tsipromed, ciprofloxacin), amoxicillin (ranoksil, flemoksin soljutab, hikontsil), metronidazole (metronidazole, trihopol).
Antibiotics need to be replaced every 4 weeks to avoid development of resistant microbes. In the early stage prescribed prokinetics.
If it affects the lungs prescribe low doses of prednisone and cyclophosphamide. Good effect is observed in most cases intravenous cyclophosphamide pulse therapy at a dose of 1 g / m2 / month in combination with prednisolone 10-20 mg daily. Cyclophosphamide pulse therapy is continued at the indicated dose of at least 6 months (in the absence of side effects). If the positive dynamics of the pulmonary function tests and radiographic changes the interval between pulse therapy with cyclophosphamide increased to 2 months, and while maintaining a positive dynamics - 3 months. Cyclophosphamide pulse therapy should be carried out at least for 2 years.
Forecast
The prognosis of scleroderma is among the most unfavorable systemic connective tissue disease, and largely depends on the shape and course of the disease. According to the results of 11 studies, five-year survival of patients with scleroderma ranges from 34 to 73% and an average of 68%.
Poor prognosis factors are:
- rasprostranennnaya form;
- age of onset of the disease over 45 years;
- male gender;
- pulmonary fibrosis, pulmonary hypertension, arrhythmia and kidney damage in the first 3 years of the disease;
- anemia, high erythrocyte sedimentation rate, urinary protein excretion at the beginning of the disease.
All patients with scleroderma are subject to dispensary observation. Medical examination is carried out every 3-6 months depending on the disease and the presence and severity of visceral lesions. At the same time hold general and biochemical blood and urine tests. Recommended study of respiratory function and echocardiography.
Patients taking warfarin should be monitored prothrombin index and the international normalized ratio, and in the treatment of cyclophosphamide - explore common blood and urine tests every 1 1-3 months.