Scleroderma pathology: Define, classification, treatment

2021-02-06 12:00 AM

Skin lesions are localized on the fingertips, from fingers to wrists, or from toe to knees, sometimes with hardening of the skin localized under the collarbone.

Scleroderma pathology

Define

Scleroderma is a disease that damages the entire connective organization, with damage in many different organs characterized by damage in arteries, small capillaries causing hardening and clogging of blood vessels in the skin, digestive tract, heart, lungs, kidneys and various organs.

Skin lesions are usually localized, where there is an increase in the production of colloids in the subcutaneous connective tissue. Visceral damage is a prognostic condition.

Classification

Pervasive skin lesions

Raynaud's syndrome for at least 1 year before skin damage occurs.

Skin damage to the base of the limbs and body.

Common and sometimes very early signs:

Damage to the interstitial organization of the lung.

Renal failure.

Lesions of the stomach - intestines spread.

Damage to the heart muscle.

Dilatation and destruction of capillaries. 

Local injury

Have Raynaud's syndrome many years ago.

Skin lesions are localized in the tip of the finger (from finger to wrist or from toe to knee), sometimes skin stiffness is localized in the area below the collarbone).

There is a risk of late pulmonary hypertension.

With or without the following symptoms:

Damage to the interstitial organization of the lung.

Trigeminal nerve pain.

Fibrosis and dilatation of capillaries in subcutaneous tissue.

CREST syndrome: includes 4 signs:

Raynaud's syndrome.

Lime.

Sclerosis of the extremities.

Vasodilation and sclerosis of the oesophagus.

Epidemiology

As a rare disease, the frequency varies between studies. But it is found that in the US there are between 2.3 and 16 new discoveries per 1 million people each year.

The disease usually starts from 40 to 50 years old, in women appearing earlier about 30-39 years old. Before the age of 20, people experience 10% of the cases studied. The average annual death rate in the US ranges from 2.1 to 2.8 cases per million population. This rate varies with age.

The majority of patients who die have an average progression of 5 years.

This is the time for an internal damage process to progress.

Mechanism of pathogenesis

Scleroderma is a disease with a complex mechanism. However, from many known mechanisms through research on the participation of many types of cells, many molecules (antibodies, intermediate active substances) ... The pathogenesis of scleroderma was modelled.

Pathology of colloids

Increasing the number of extracellular colloids such as proteoglycan, fibronectin, laminin ... creates the basic pathological anatomical damage of scleroderma, which is hardening and thickening of the skin.

Research through electron microscopy showed that the accumulation of fibrin fibres mixed with colloidal fibres appeared. This changes the structure of the skin due to increased deposition and adhesion.

Pathology of damage to blood vessels

In scleroderma, damage to the blood vessels is small in size (50 - 500 microns). Raynaud's syndrome is very common (90 - 95% of patients), this is considered to be the major microvascular damage in scleroderma.

There is a proliferation of endothelial cells, mesenchymal thickening, secondary fibrosis and colloid deposition causing microvascular occlusion due to small vessel lumen narrowing.

Nuclear degeneration and nuclear necrosis of endothelial cells. Loss of tight bonding of the vessel wall. Increases the process of vascular osmosis causing oedema, inflammatory cell infiltrates.

Immune system pathology

Cells of the immune system such as lymphocytes, macrophages and various cytokines are involved in the damage mechanism of blood vessels and connective organization.

Collaboration with individual gene lesions acts indirectly by stimulating fibroblasts and endothelial cells.

The centre of skin damage is the infiltration of T-CD4 and T-CD8 cells, most often in the surrounding blood vessels and nerves.

Stimulates B lymphocytes to produce large amounts of antibodies, mainly autoantibodies.

Diagnostic standards

Diagnostic criteria are based on the American Association of Arthritis (ARA) clinical standards for systemic scleroderma.

Main standard

Skin sclerosis of the extremities: tight, thick skin, not concave.

Secondary standard

Stiffness of the extremities: stiffness of fingers or feet, and restriction of folding and stretching of fingers.

Slowly scar the skin of the toe.

Basal pulmonary fibrosis.

(Note: To diagnose scleroderma, one primary criterion and two sub-criteria are required).

Common clinical symptoms

Raynaud's phenomenon

Meet in 95% of XCB cases and 4% to 5% in the population.

Pre-existing sign several months or years before scleroderma is present. Progress silently.

This is a disorder of vasomotor in the limb due to the action of cold and progresses in 3 stages.

The first stage in a few minutes, occurs quickly in one or more fingers of the hands, making the tip of the finger white, cold and less sensation. This is the stage needed for diagnosis.

Stage 2: Purple limb and pain due to blood stasis in the venous system.

Stage 3: Hands return to pink due to the dilatation of capillaries. The hand gets hotter.

Raynaud's phenomenon increasingly appears more, faster and more pronounced with the progression of the disease. The stage of heavy hand is always cold, purple and decreased feeling.

Damage to the skin and mucous membranes (skin, mucosa, nails) goes through 3 stages: oedema, stiffness, skin atrophy, loss of folds on the skin.

The skin of the forehead, around the eyes, is flat, lost wrinkles, thin lips stretch, expressionless face.

Hard skin in the finger area, thickening forming a dry patch of skin, sticking to the deep layer limits folds, reduces sweat production, hair loss, dry, broken and notched nails Sometimes there is atrophy in the skin clearly.

Ulcers and necrosis of the fingertips due to dystrophy and embolism, sometimes needing to remove the knuckles in severe and painful cases. Ulcers can be found in other skin areas due to dystrophy.

Mouth sores and gum abscesses are also common signs. Limit mouth opening due to hard, notched skin around the mouth.

Appears areas of depigmentation on the skin (30%), sometimes appear subcutaneous calcified areas at the fingertips or skin forearms, neck, knees. This deposition of calcium does not change skin colour. However, it is dense, uneven and ulcerative.

Damage to the digestive system

Board. Pathology of the digestive system in scleroderma

Mouth

Stomach

Stomach

Intestine

Mouth sores

Oesophageal reflux

Reduce motility

Infection

Tongue inflammation

Reduce motility

Gastric relaxation

Duodenal ulceration

Capillary dilatation

Stenosis of the oesophagus

Food retention

Reduce motility

Swallowing disorders

Oesophageal ulcers

Stomach ulcers

Small bowel ulcers

Tongue atrophy

 

Stomach bleeding

Perforation of the intestine

Tooth abscess

 

 

Intestinal necrosis

 

Kidney damage

Is the cause of death of XCB. Lesions are usually:

Acute renal failure (encountered with a frequency of 15 - 20%).

Proteinuria alone with hypertension, anaemia.

The histology of the damaged kidney has the following manifestations:

Overproduction of the intravascular layer of the inter-lobe arteries

Fibrinous necrosis in the arteries.

Hyperplasia of glomerular basal cells.

It is possible to detect the deposition of C3a and IgM by immunofluorescent methods on the damaged blood vessel wall, causing ischemia in the renal cortex, causing glomerular unit fibrosis. Injury is usually quiet, quiet, but the prognosis is very severe. Kidney failure is the main cause of death.

The cause of kidney damage is mainly due to the decrease in blood volume to the kidney, on the one hand, due to the hardening of the renal artery, especially the small blood vessels, on the other hand, the secretion of renin in the parathyroid organization causes vasoconstriction and decreases. flow in the kidneys.

Lung damage

Pulmonary fibrosis caused by interstitial fibrosis is the leading complication of scleroderma. Symptoms of dyspnea during exertion, dry cough without sputum, decreased alveolar barrier at the bottom of the lung.

Chest radiograph shows "reticular" images at an early stage, then appear alternating fuzzy nodules, concentrated in the umbilical area extending to the bottom of the lung. Occasionally appears a blistering pattern due to alveolar dilatation.

Lung tomography clearly shows the damage at an early stage when the X-ray images are in the normal range.

Exploring the pulmonary ventilation process allows early detection of signs of interstitial fibrosis of the lungs, before there are signs on the chest radiograph, the pulmonary fibrosis process will cause limited ventilation (reducing the air volume of the lungs).

Pulmonary hypertension: Pulmonary artery pressure measurement is necessary in cases of scleroderma. This is a late complication and a cause of death.

Heart damage

Clinical signs that are not specific to scleroderma are shortness of breath, nervousness, chest tightness, purple lips, and head extremities.

Common heart damage includes:

Pericarditis can be acute or chronic. The chronic form, often asymptomatic, only detected on echocardiography ... May be accompanied by effusion of pericardium in moderate or much quantity.

Cardiomyopathy in scleroderma is very common due to disorders of the microcirculation of the coronary arteries nourishing the heart muscle. Due to the hardening of the capillaries, spasm, narrowing of the capillaries causes a decrease in the perfusion of the heart muscle. This condition improves with treatment with calcium blockers such as nifedipine.

Automatic conduction disorder causes arrhythmia, bundle branch block, atrioventricular block.

Damage to bones and joints

Meet 45% to 90% of patients with advanced systemic scleroderma. Osteoarthritis is sometimes the first sign of disease:

Pain, symmetrical polyarthritis, and stiffness in the morning make people often think of rheumatoid arthritis.

Often painful and inflammatory in the knuckles, fingers, wrists, knee joints, may be accompanied by swelling, heat, redness.

Bursitis in painful joints, synovial fluid, infiltrates many mononuclear cells and lymphocytes.

Limit movement, have a feeling of stiffness when moving. This is sometimes caused by the hardening of the skin.

On a joint radiograph, one can observe thickening of the soft around joints, stenosis, osteoporosis, osteoporosis in joints.

Muscle damage

Start with increasing muscle pain.

A moderate increase in serum enzymes, this is a very significant sign.

Muscle biopsy found interstitial fibrosis, reduced diameter of muscle fibres, decreased the number of capillaries in the muscle tissue. However, muscle biopsy is not the recommended procedure because after biopsy there is a delay in scarring in patients with scleroderma.

Endocrine system damage

You may experience hypothyroidism or hyperthyroidism.

Antithyroid antibodies were found in patients with hypothyroidism.

Hypothyroidism is caused by fibrosis of the gland.

Atrophy of the adrenal glands described in scleroderma may be caused by prolonged steroid therapy or by the scleroderma itself.

Nerve damage

Can cause damage to the trilamus with symptoms: paraesthesia, pain in symmetry due to damage to the lower two branches of this nerve. Usually, there is no movement disturbance.

There may be damage to the central nervous system, accompanying psychosis. Peripheral nerve damage markers are also described. The nerve damage is exacerbated when there is a decrease in vitamin B12 due to poor absorption, calcification in the marrow or compression of the marrow.

Auto-nervous system damage is very common in damage to the stomach and intestines that causes gastric and intestinal motility disorders.

Test

Antinuclear antibodies in scleroderma

Some antinuclear antibodies were detected such as Anti - Histone in scleroderma, however, the determination of titter in disease diagnosis still needs to be studied a lot.

Other tests

Inflammatory syndrome in the test: increased blood sedimentation rate, increased gamma globulin, increased ferritin, increased CRP.

Anaemia, usually small red blood cell anaemia, hypochromic, sometimes with autoimmune haemolytic anaemia.

Skin biopsy showed proliferation of fibroblasts, colloid agents, subcutaneous capillary thickening, endothelial cell layer damage, microvascular obstruction, infiltration of inflammatory cells around blood vessels.

Progression and prognosis

The progression of systemic scleroderma is very variable and difficult to foresee. The overall prognosis depends on the degree of internal damage. The bad factor is the degree of damage to the kidneys and the heart, it also depends on the rapid spread of skin damage.

The most commonly discussed factor was lung injury with FEV1 <70% of its theoretical value and early signs of pericarditis or skin pigmentation disorder at the first visit.

Differential diagnosis

There are many sclerotic lesions very close to the skin lesions in scleroderma.

Hard skin oedema

The disease is rare, with some of the following characteristics:

Deposition of many mucopolysaccharide molecules in the epidermis, dermis.

Increased number of fibroblasts in the subcutaneous tissue.

There are many papules with a diameter of 2 - 3 mm on the skin of the wrists, back of hands, arms and face. Often combined with generalized skin stiffness.

Diagnosis is based on a skin biopsy.

Congenital atrophy of the skin

Werner syndrome: a familial disease. Appearance atrophy of the skin like scleroderma, muscle atrophy, bilateral cataract, coordination of artery diseases. On the skin, there are many ulcers, dystrophy in the legs or in combination with osteoporosis and diabetes.

Combination diseases

Gougerot - Sjugren syndrome: common with a low rate of 1.4 - 7.8%, patients often have enlarged parotid glands, reducing saliva secretion. In the gland, there is the infiltration of lymphocytes.

Dermatitis: Muscle damage associated with scleroderma is very common. Usually, there is an increase in muscle enzymes (CK, CKMP, GOT, GPT ...). Clinically, the phenomenon of muscle weakness, electromechanical disturbances, manifestations of myositis during muscle biopsy. Sometimes a clinical manifestation of dermatitis is also present.

Lupus erythema: In this pathology also common symptoms of scleroderma such as myalgia, arthralgia. However, anti-DNA antibodies are found in systemic lupus erythematosus with a higher frequency.

Shapr Syndrome: This is a syndrome that includes the signs of Raynaud's syndrome, stiff fingers, disfigured joint pain and myositis. This antibody is rarely found in scleroderma.

Systemic treatment

Do not take medicine

Quitting smoking is aimed at blocking the effects on the lungs and blood vessels.

Exercise daily, especially regular breathing to improve lung ventilation.

Massage and functional rehabilitation by hot bath methods, paraffin coated to restore movement, avoid muscle spasm, prevent muscle atrophy, enhance capillary circulation where damage.

Systemic corticosteroids

Alter the glued structure of the fibre.

Reduces inflammatory response in the skin, joints, muscles and lungs.

Treatment in scleroderma forms is accompanied by polymyositis, dermatitis, and lupus erythematosus

redness and in severe forms of localized scleroderma.

Corticosteroids are not the primary means of treating severe internal damage and contribute to the prognosis of scleroderma.

Daily dose 0.5 - 1mg / kg / 24, reduce dose thereafter.

Corticoids in place

Dermovat or Betamethasone ointment applied on the skin once / 24 hours in the form of skin damage is not too heavy and not too deep.

D - penicillamine

As a treatment for rheumatoid arthritis, scleroderma can also be used. It inhibits the bonding organization's colloidal synthesis. The daily dose ranges from 300-600mg. It can take up to 6 months. One can coordinate with corticosteroids in the treatment of scleroderma. Common undesirable effects when using D- penicillamine are gastrointestinal disturbances, thrombocytopenia, leukopenia, marrow dysplasia, renal failure, myasthenia gravis and allergy to drug components.

Methotrexate

Used for the purpose of inhibiting the production of colloidal agents from fibroblasts. A significant improvement was found in the degree of skin damage, the area of ​​skin damage, an improvement in oesophageal motility, and Raynaud's syndrome. In addition, a combination of plasma exchange with cyclophosphamide has also been suggested in the treatment of scleroderma.

Treatment depends on the number of lesions

Treatment of Raynaud's syndrome:

Mainly treats peripheral vascular damage, prevents overproduction of fibrous tissue and colloid.

For mild forms:

Avoid cold contact, avoid injury that can easily cause ulcers.

Avoid medications that easily cause Raynaud's syndrome or make it worse: Beta-blockers, casein, nicotine, cocaine, and other vasoconstrictors.

Skin hygiene to avoid ulcers, avoid superinfection. For severe ulcers can use a topical antibiotic ointment. When hands are wet, they should be dried.

Use nitro-glycerine (Lenitral) fat on the skin of the finger at the two sides of the finger where the small artery passes to dilate the capillaries, improve perfusion to the limbs.

For heavy types: 

Calcium channel blockers are commonly used and are effective: Nifedipine from 20mg to 80 mg/day for a long time. A common complication is decreased diastolic tone, which causes reflux of the oesophagus, stomach, so it is necessary to combine anti-H2 drugs.

Aspirin is used to prevent platelet aggregation.

Treatment of joints:

Pain relief, nonsteroidal anti-inflammatory or low dose of corticosteroids (≤ 5-10 mg/day).

Mobilization therapy, physical therapy, orthopaedic replacement if the deformity is severe and limited movement.

Heart damage:

Calcium channel blockers significantly improve the perfusion of the heart muscle by reducing constriction of small blood vessels.

Corticoids are used in combined effusion or pericardial mucosa.

Treatment in the digestive tract:

Treatment of damage to the oesophagus is mainly:

Using antacids is very effective in damage to the lining of the oesophagus.

Eat small, many meals.

Primperan is used in improving oesophageal motility.

Treatment of renal vasoconstriction:

This is a fatal acute injury. It can be treated with propranolol in addition to anticoagulants. Reduce blood pressure with ACE inhibitors.

The drug class captopril (Lopril) is effective in the treatment of renal vasoconstriction and pulmonary hypertension in scleroderma.

Treatment of pulmonary manifestations:

There is no effective treatment for pulmonary fibrosis. Lesions are usually worse and difficult to recover, in mild can use D - penicillamine, with severe methotrexate.

With drugs corticoid, D - penicillamine and immunosuppressants improve vital capacity on the exploration of respiratory function.

In the case of pulmonary fibrosis can use corticoid 20mg / 24h then reduce the dose and 125mg methotrexate in 3 months.