Pathology of systemic lupus erythematosus

2021-01-26 12:00 AM

Special forms of lupus need to distinguish from diseases with similar symptoms: thrombocytopenic haemorrhage, glomerulonephritis, nephrotic syndrome.

Define

The disease with the highest rate in the group of colloid diseases (60%) manifests diffuse or scattered inflammation in the connective tissue, caused by autoimmune.

Epidemiology

The disease is seen mainly in young women, the ratio of female / male: 8/1.

The highest prevalence of the disease is between the ages of 20 and 40.

Blacks have morbidity and mortality rates three times higher than whites, high morbidity rates: black, Asian, and white.

Causes and mechanisms

Today is considered an autoimmune disease on a special site.

Evidence of autoimmunity

In the patient's fluid, there are many autoantibodies: antinuclear antibodies, anti-nuclear antibodies (AND, RNA), anti-blood cells (red blood cells, white blood cells, platelets). There was a marked decrease in the amount of complement in the blood (CH50, C3, C4), a false positive BW reaction, and detection of immune complexes in the blood and organ.

Lymphoid B and T rates change in the blood.

Can cause disease in animals by immunological methods.

Treatment with immunosuppressants has results.

Mechanical factors

Young women.

HLA-DR3 is significantly higher than the average person.

Some cases are of a family nature.

Causal factors

The direct cause of the disease is unknown. However, there are some factors as follows:

Some drugs can cause lupus: Hydralazine, hydralazine, procainamide, Acebutolol, D penicillamine, quinidine, Isoniazid, chlorpromazine, sulfasalazine, minocycline, carbamazepine, interferon α and γ.

Industrial products: Formaldehyde, isocyanate and anhydride phtalique.

Cytokines such as interfon, agranulocytosis stimulant, antibodies used in clinical practice such as anti TNF.

Infectious agents: such as parvovirus B19.

New trends in the pathogenesis of Luput

Identify the genes that can lead to this disease:

The C4A gene is involved in lupus expression.

Deficiency of the Fc YRIIa - H131 segment is related to lupus nephritis.

Abnormalities in T cells or TCR:

T cells in lupus patients lack protein kinase A (PKA).

Phosphorylation of cellular proteins can alter homeostasis and even impair immune function.

B-cell overactivity and autoantibody production are characteristic of lupus:

Lupus progression is associated with an increase in interleukin product 10.

Apoptosis is involved in the development of cell reduction and the release of components of the cell nucleus, substances that can stimulate the immune system to produce autoantibodies.

Symptoms

Clinical

In clinical practice, it is mainly subacute.

Onset

Most start slowly, gradually increase: unexplained persistent fever, joint pain or arthritis resembling VKDT.

In some cases, the onset is rapid, the symptoms are complete at an early stage.

Sometimes the disease appears after favourable reasons: infection, trauma, stress, using drugs that can cause lupus.

Damage to many organs.

Body: Persistent fever, fatigue, weight loss.

Musculoskeletal: Pain, inflammation, joint deformity, muscular dystrophy, bone necrosis.

Mucous skin: Butterfly-shaped erythema on the face, disc-like erythema on the skin, sunburn due to sunburn, ulceration of the oral mucosa, nose, alopecia, subcutaneous capillary inflammation.

Blood and hematopoietic organs: Prolonged anaemia, bleeding under the skin, enlarged spleen, lymphadenopathy.

Psychiatric disorders: Mental disorders, epilepsy.

Circulatory, respiratory: Epidural effusion, pleura, myocarditis, endocarditis, Raynaud's syndrome, interstitial pneumonia, thrombophlebitis, veins.

Kidney, liver: Proteinuria, cylindrical cells, ascites, liver dysfunction.

Eyes: occlusion of tear glands (Sjogren's syndrome) conjunctivitis, retinitis.

Test

Nonspecific tests:

Blood count: Decreased partial or total blood flow, extrapyramidal reduction:

Reduced red blood cells (usually haemolytic anaemia): 65%.

WBCs decreased, mostly neutrophils: 32%.

Thrombocytopenia: 10%.

Blood sedimentation rate increases by 92%, fibrinolysis increases: 45%.

Serum electrophoresis: γ Globulin increased by 86%.

Found immune complexes in the blood.

Reaction BW (+).

Specific tests:

Hargraves cells (LE): polymorphonuclear leukocytes have the phagocyte fragments of other cells personnel have been destroyed by human antibodies appear in lupus.

It is common to calculate the percentage of LE cells to total white blood cells in the blood. The rate of 5% is valid for diagnosis. In lup 60% - 90% have LE cells.

Look for translation antibodies:

Antinuclear antibody: considered positive when the serum dilution is> 1/32.

Anti-DNA antibodies are very specific in lupus.

Antibodies against soluble etiologist: KT resistant to Sm (+) in 50%.

Antibody to red blood cells, anti-lymphoid cells, anti-platelet

Complement decreased in the blood.

Reduced rate of Lymphocytes compared with B cells.

Biopsy:

Skin biopsy: deposition of immunoglobulins: IgM, IgG and complement into a layer between the epidermis and dermis of the skin (+ 70%).

Kidney: glomerulonephritis, basal membrane thickening due to the deposition of IgG, IgM and complement.

Synovial membrane: the lesions closely resemble rheumatoid arthritis.

Development

Depending on the type of disease

Acute: Severe organ damage, rapid progression and death after a few months due to kidney, nerve, and lung damage.

Chronic: Less visceral damage, mild skin manifestations, slow progression, good prognosis.

Subacute: Progressing in waves, getting worse and worse. Severe illness if pregnancy, infection, injury, surgery, stress, drug abuse. Often fatal from complications in the kidneys, nerves, infections. The average life span of 5 - 10 years.

Sharp syndrome: A mixed disease between lupus and scleroderma, with signs of polyarthritis, Raynaud's syndrome, swollen fingers, lumpy swollen, oesophageal stenosis, polymyalgia. Due to less visceral manifestations, better prognosis and steroid sensitivity.

Diagnose

Implementing the quadrants

Based on 11 standards of the American Low School Association, improved in 1997, the diagnosis is determined when there are at least 4 standards:

Butterfly-shaped erythema on the face.

Discoid erythema on the face and body.

Sun exposure.

Mouth or nasopharyngeal sores.

Polyarthritis.

Inflammation of the lining of the heart or pleura.

Kidney damage: Proteinuria> 0.5g / 24 hours or urinary retention.

Neurological damage: Seizures or psychosis.

Blood disorders:

Haemolytic anaemia (reticulocytosis); WBCs <4000 / mm3.

Lymphoid <1500 / mm3 or platelets <100,000 / mm3.

Immune disorder: T blood weed has:

Anti-DNA antibody or anti-Sm antibody.

Abnormal concentration of IgG or anti-Cardiolipin IgG, or presence of circulating anticoagulant factor (anticoagulant circulant).

Antinuclear antibodies (+).

Differential diagnosis

Rheumatoid arthritis.

Rheumatoid arthritis.

Diseases in the colloid group: scleroderma, polymyositis, inflammation of the nodes around the arteries.

With special forms of lupus need to distinguish from diseases with similar symptoms: thrombocytopenic haemorrhage, glomerulonephritis, nephrotic syndrome. Pleural pericarditis due to another cause.

Reality

When the following 5 factors appear in a young female patient, there is a tendency to diagnose lupus

Long-term, persistent fever with no cause found.

Inflammation of many joints.

Butterfly-shaped erythema on the face.

Proteinuria.

High blood sedimentation rate.

Treatment

Common to all cases of lupus: Educate patients to avoid harmful things like tobacco, avoid direct or indirect sunlight, avoid family planning, and avoid substance abuse.

Indications for treatment depend on the severity of the disease:

Light form

Damage to the skin - joints.

Medicines: Aspirin and nonsteroid anti-inflammatory, synthetic anti-malarial drugs.

Aspirin and AINS: most of the side effects are gastrointestinal, renal, and sensorineural.

Hydroxychloroquine: 400mg / day for many years.

Effect of treatment of skin and joint damage, preventive effects appear new episodes, and are resistant to thrombosis.

Monitor eyes regularly: visual acuity, colour vision, retinal electrophoresis.

Other rare side effects: agranulocytosis, neuromuscular disease or atrioventricular block with prolonged treatment.

With the above treatment, joint symptoms persist, possibly supporting prednisone <0.3 mg / kg / day.

Heavy form

Damage to internal organs.

Corticoid therapy:

In severe episodes: often begins in the form of bolus.

Methylprednisolone 1g IV in 90 minutes (after blood potassium and ECG test) for 3 consecutive days. Then use orally.

Prednisone: 1 mg / kg / day in multiple organ lesions (proliferative kidney disease, diffuse nerve damage, thrombocytopenia or severe haemolysis) and 0.5 mg / kg / day in milder forms. Initially, the corticoid dose was divided into 2-3 times a day. Later, it is only used once in the morning. When the disease has been controlled, give it 1 time in the morning. When the disease has been controlled, give it once every 2 days at a double dose, usually indicated in children to protect growth.

Intensive corticoid therapy is indicated for 4 weeks. Then reduce the dose gradually (reduce 10% dose / every 10-15 days).

Hydroxychloroquine is used when the dose of prednisone <0.5 mg/kg.

Maintenance steroid therapy (0.15 - 0.25 mg / kg / day) is usually prescribed long term, depending on the severity of the initial severity or previous relapses.

Immunosuppressants:

Treatment of these drugs is controversial, although their benefits are well recognized in proliferative kidney diseases. It serves two purposes: to improve the disease in resistant to corticosteroids, allowing to reduce the amount of corticoid.

The potential risk, especially infection and tumor formation, is limited in some serious organ damage. The two commonly used drugs are:

Cyclophosphamide: Currently rarely used orally because there are many side effects, but often used by intravenous interrupt with a dose of 0.5 to 0.8 g / m2 depending on renal function and white blood cell count.

Azathioprine: 2 - 4 mg / kg / day orally.

Other than cyclophosphane is not a threat to sexual function and is not contraindicated during pregnancy.

The majority of authors treat immunosuppressants in combination with steroid therapy in proliferative kidney diseases and non-anemic CNS lesions, especially in the case of relapses. The usual regimen is: IV cyclophosphamide IV every month for 6 months, then every 3 months for 2 years. For azathioprine, duration of administration is from 12 to 24 months.

Other immune interventions:

Only occupies a limited position in lupus treatment.

Cyclosporine A: has a favorable effect in a limited number of Série.

Methotrexate: Unlike in the treatment of rheumatoid arthritis, beneficial in some cases of kidney damage and myositis.

Plasma dialysis: Results were contradictory in lupus nephritis. Unproven benefit in the treatment of attacks of severe kidney disease.

Current intravenous immunoglobulin is only used in some cases of severe thrombocytopenia.

New treatments are currently underway:

Monoclonal antibodies against interleukin 10.

Test for Bromocriptine and stem cell transplantation in severe and resistant to other treatments.

Prognosis

The prognosis of systemic lupus has improved for 20 years, now the 10-year survival rate exceeds 90%.

A number of factors with severe prognostic significance are: male, of a black race, childhood-onset, kidney, nerve damage or combined antiphospholipid syndrome.

The cause of death is somewhat increased due to opportunistic infections, increased coronary artery steatosis and neoplastic tumours, the risks of prolonged use of corticosteroids and immunosuppression should be emphasized.

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