Systemic lupus erythematosus

2021-02-06 12:00 AM

Usually mild fever, but there are also cases of high fever, unexplained persistent fever, accompanied by general symptoms such as weakness, fatigue, poor appetite.

Lupus has been known in medicine since the early nineteenth century but is only considered a non-dangerous skin disease. In 1828, BieHe described asymmetrical "erythema" and differentiated lupus as "deeply damaged" from "superficial". In 1845, Hebra described the skin lesion as a butterfly on her face. The noun "Lupus erythematosus" was introduced by Cazenave in 1851 with two forms: mild skin lesions and severe with internal damage.

By 1872, Kaposi divided systemic lupus erythematosus (SLE) into two clinical forms: discoid lupus and diffuse lupus. In the form of diffusion that Kaposi describes in addition to the skin manifestations, there are also other lesions such as blood, nerves, internal organs ... accompanied by a fever which he called toxic shock.

In 1895 - 1904, Osler was the first to describe the systemic manifestations of lupus erythematosus: arthritis, pneumonia, and kidney, nervous system ... at the same time he also reported internal damage. pericardium and the pericardium in the special disease group showed erythema.

The first half of the twentieth century recorded histological manifestations of the disease: glomerular lesions were seen in 23 cases and by 1942 Klemperer and Bachs led the research towards colloidosis.

In 1948, Hargraves and colleagues discovered the LE cell. In 1950, Hassik discovered the immune factor that plays an important role in the formation of LE cells, the notion of an autoimmune disease being formed.

Eventually, the discovery of antinuclear antibodies caused by Coons and Frion in 1957 led to the discovery of a series of other autoantibodies, which marked a milestone that confirmed lupus erythematosus is an autoimmune disease.

The appearance and good effects of corticosteroids have extended the patient's life and greatly changed the patient's prognosis (Hench 1948 - 1949), Dubois defines lupus as a non-causal syndrome. clearly, characterized by damage to multiple internal organs, there are severe progression alternating episodes of withdrawal. Diagnosis is based on the presence of antinuclear antibodies and Hargraves cells in the patient's serum. In 1968 the American Association of Arthritis (ARA) introduced 14 diagnostic criteria and today there are only 11 standards. Only 4 out of 11 criteria are needed for a positive diagnosis.

The annual incidence of lupus is difficult to determine. According to some research papers, that rate ranged from 1 to 10 new cases per 100,000 population (1955-1975) in the US and Nordic countries.

Immune abnormalities

Autoantibodies

Antibodies against the structure of the nucleus:

The positive rate of the antinuclear antibody (ANA) is as high as 90%, but specificity is low because ANA can be found in other diseases such as scleroderma and rheumatoid arthritis. Especially positive from 1- 3% in normal people, especially in the elderly.

Anti-DNA antibodies include 03 types:

Type I: Antibody to natural double-chain DNA (ds DNA, db DNA, n DNA), encounter rate 60-70%, high specificity.

Type II: Antibodies to both single- and double-chain DNA.

Typ III: Antibody to single-chain DNA (n-DNA), prevalence is 30%.

Antihistamine antibodies: seen in the cases of drug-induced lupus.

Insoluble nucleoprotein antibodies, detected by Hargraves cell.

Antibodies to soluble antigens:

Anti-Sm antibodies (the name of the patient first detected to have this antibody), the rate of exposure is 30-40%.

Antibodies to RNP (the corresponding antigen is ribonucleic-protein) have a high sensitivity and specificity. The Sm and RNP antibodies are usually associated, although the antigens are different.

Anti-SSA (anti-Ro) antibodies are encountered in 30% in systemic lupus erythematosus, 60% in Sjsgren-Gougerout syndrome. Very specific for the diagnosis of congenital lupus.

Antibodies to cells:

Anti-red blood cell antibodies: Coombs test is positive at a rate of 60% in lupus and often causes clinical anaemia manifestation.

Anti-leukaemia antibodies: decreased peripheral leukocytes. Studies show that it is predominantly damaged lymphocytes, a small proportion of polymorphonuclear leukocytes.

Antiplatelet antibodies are antibodies to antigens on the surface of platelets, causing mild to moderate thrombocytopenia; You may experience thrombocytopenic bleeding.

Antiphospholipid antibodies: is clinically manifested by a false positive syphilis reaction.

Antibodies to microorganisms:

Anti-ribosomal antibody: when appearing this antibody often shows psychotic manifestations.

Antibodies against the Golgi apparatus: very rare.

Immune complexes

Circulating immune complexes: encountered in the circulatory system.

Deposition complex: in tissues, subcutaneous organizations, glomerular basal membrane.

Complement

Deposition of immune complexes will activate the complement in the classical path. The activation will release the C3a - C5a fragments. This is an adaptive chemical factor that will pull polymorphonuclear leukocytes, macrophages to phagocytosis with immune complexes. In the process of phagocytosis will release inflammatory substances in places where immune complexes are deposited.

When the inflammatory reaction stimulates oxidation to produce free radicals, the ions are very toxic to connective tissue.

In addition to cells, damaging free radicals also have proteolytic enzymes derived from many different cells involved in tissue damage, connective organizations.

Causal factors

Congenital (genetic) factors

Family nature with an increased incidence of the disease among people of the same bloodline, especially in the first generation. Genetic factors are more evident in infants with the same egg, accounting for 63% while in other infants the incidence is 10%.

Nowadays, with advanced technology, lupus is often found in combination with HLA DR2 and HLA DR3.

Acquired factors

Virus:

When comparing young people with lupus with a healthy person, the Epstein-Barr infection serum frequency is significantly increased, but all attempts to isolate the virus in lupus patients have failed. It has been hypothesized that the virus is a gene trigger in the body that causes an immune system disorder.

Medicine:

Medicines to treat tuberculosis (INH, Rifampicin), antihypertensive drugs (Hydralazine, Procainamide), anticonvulsants (Phenytoin ...), anti-conception drugs ... are the causes of lupus erythematosus.

Sex hormones:

It is more common in women than men (8-9 / 1), the frequency is higher in reproductive age. Pregnancy process clearly affects the disease, especially the last 3 months of pregnancy.

Ultraviolet ray.

Fever

Usually, a mild fever is 37 ° 5 C - 37 ° 6C, but there are also cases as high as 39 - 40 ° C. Unexplained prolonged fever, accompanied by general symptoms such as weakness, fatigue, and poor appetite.

Manifestations in the skin and mucous membranes

Butterfly-shaped erythema on the face. Plaque, smooth scales, sometimes oedema, localized on the wings of the nose, cheeks and under the chin.

There may be erythema in the area of ​​the chest, back, fingertips around the nail.

Skin is sensitive to light.

Mouth and throat ulcers.

Hair loss can be diffuse or localized into plaques.

Manifestations in the musculoskeletal system

Muscle pain and joint pain are common signs and are often signs of the onset of illness.

Pure arthritis: May occur in one or more joints, can move from one joint to another. No morning stiffness, no red-hot swelling, no osteoarthritis deformation. On X-rays, there are no images of osteocalcin, osteocalcin or joint narrowing. It is possible to have diamond deformation, or deformation of the whole joint axis, forming a rheumatic disease like Jaccoud, but very rare.

Aseptic osteonecrosis: Common in the upper extremity of the femur, bone convex

thigh, trunk, or upper arm bone that is not caused by corticosteroids.

Myositis, muscular dystrophy: Leucocytosis can be seen through muscle biopsy and with increased muscle enzyme tests.

Infectious arthritis: Common in the knee joint, caused by bacteria-producing pus.

Expressed in the kidneys

Mainly damage to the glomeruli, often the cause of death of the disease. Kidney damage has the following characteristics:

An early injury in internal organs.

There is no match between kidney damage and the clinical picture.

There is no match between pathology and clinical presentation.

Common manifestations: oedema, low urination, proteinuria, may have red blood cells, white blood cells, urinary cylinder. Often there is acute glomerulonephritis, nephrotic syndrome and renal failure.

Glomerular lesions on kidney biopsy images include

Type I: The kidneys are optically normal, with no immunofluorescence deposition.

Type II: Vasodilatory glomerulonephritis.

Type III: Glomerulonephritis segment and proliferation drive.

Type IV: diffuse proliferative glomerulonephritis.

Type V: Epidural glomerulonephritis.

Type VI: Fibromyalgia.

Clinically, kidney damage is manifested by:

Acute glomerulonephritis syndrome: gross or microscopic haematuria, low or anuria with urea and creatinine increased rapidly, can lead to acute renal failure.

Nephrotic syndrome

Big oedema.

Protein / urine above 3.5g / 24h.

Blood protein decreased below 60g / l in which albumin decreased below 30g / l.

Increased lipids (triglycine, cholesterol).

Chronic renal failure: anuria, high blood pressure, anaemia, oedema, and creatinine in the blood increase in different degrees. This is the cause of death.

Bladder injury: very rare, manifested mainly by cystitis (thickening of the wall of the bladder). This is a severe lesion with a high prognosis of death when present.

Cardiovascular manifestations

Expressed in the heart

Pericarditis is the most common manifestation of heart damage, accounting for 20-40%. Pericardial effusion is usually not so much that it compresses the heart.

Libman-Sacks endocarditis: Depression of the heart valves and ventricular septum.

Clinical is sometimes difficult to detect, detected by echocardiography, encountered in 15 to 20% of cases of Osler.

Myocarditis: 10 - 15% clinically encountered, manifestations of arrhythmias, conduction block, complete arrhythmia.

Expression in the vascular system

Raynaud's syndrome occurs in 20-30%.

Coronary artery damage: Presented by angina or myocardial infarction.

Venous thromboembolism: Common in 8-20% of cases, often easily causing embolism, commonly seen in the venous area of ​​the limbs, but also in the vein of the viscera or vena cava ... often related to anti- Freezing circulation.

Expressed in the respiratory system

Pleurisy: can be one or two sides, seen in the progression of the disease with the rate of 25-50%. There is serous hydrocephalus, the quantity of fluid is usually not much.

Parenchymal injury: difficult to detect and has many different clinical manifestations.

Lupus pneumonia: symptom very noisy, acute but the rate of encounter is not high. Alveolar bleeding: is a very serious injury that causes acute respiratory failure and leads to rapid death. Chest radiograph shows "white embryo".

Manifestation in the nervous-mental system

Headache, general or local epilepsy convulsions are common symptoms. Good response to anticonvulsants and corticosteroids.

Mental disorder is one of the manifestations of the disease, with a poor prognosis. It should be differentiated from psychosis caused by corticosteroids.

In addition, there may be encephalitis, meningitis, transverse myelitis syndrome.

Manifestation in blood and hematopoietic organization

Anaemia occurs in at least 50% of patients, possibly an onset of the disease.

Thrombocytopenia is also a common manifestation.

Disorders of blood clotting with the risk of increased blood clots causing venous thrombosis.

Spleen and lymphadenopathy at many points.

Expressed in the digestive system

Commonly, anorexia, nausea, and vomiting occur during the course of the disease.

Gastrointestinal bleeding 1.5 to 6.3%, including drug causes (corticosteroids), also ulcers of the small intestine, colon due to ischemia.

Enlarged liver occurs in 8-12% of patients, usually painless on examination except in a few cases in the advanced stage of the disease.

In addition, in the clinical setting, there may be pancreatitis, surgical pseudomembranous colic syndrome, easily causing misdiagnosis.

Expression in eyes

Retinitis, congestive conjunctivitis.

Retinal artery occlusion, optic neuritis, tear gland atrophy syndrome, atrophy of eye connective tissue.

Tests are nonspecific

Blood formula: Slightly decreased 3 lines of red blood cells, white blood cells, and platelets. Blood sedimentation increased.

Protein electrophoresis: A / G reversible, α-globulin increased.

General analysis of urine showed protein - cells - cylinders.

Specific tests

Antinuclear antibodies ANA, ds DNA.

Hargraves cells.

Antiphospholipid antibodies: anti-Cardiolipin antibodies cause false reactions with syphilis.

Skin biopsy by immunofluorescence shows the deposition of immunoglobulins and the skin - epidermal connecting complement.

Kidney biopsy.

Diagnostic standards of the American Association of Arthritis (ARA) 1982

(1) Butterfly-shaped board on the face.

(2) Disc board.

(3) Light sensitivity.

(4) Mouth sores.

(5) Polyarthritis.

(6) Inflammation of the lining of the heart or pleura.

(7) Kidney damage: Protein / urine> 0.5 g / 24 h; red blood cells; urinary cylinder.

(8) Neurological - mental damage.

(9) Blood disorders.

Haemolytic anaemia.

WBCs below 4000 / mm3.

Platelets less than 100,000 / mm3.

10) ANA immune disorder; ds DNA.

Hargraves cells.

Antibodies to Sm.

A false-positive syphilis reaction lasts more than 6 months and during those 6 months, there must be no manifestation of syphilis.

(11) Antinuclear antibodies are at an abnormal titer.

Only 4 out of 11 criteria are needed for a positive diagnosis.

Disease forms

Chronic form: benign because the damage is localized only, there is no internal damage.

Acute form: severe because of internal damage.

However, the chronic form can become acute if there are favorable factors such as stress, drug allergy ...

Differential diagnosis

Prolonged fever in a number of other diseases such as cancer, infection, malaria, viral fever ...

Chronic lupus - discoid lupus: benign because the damage is localized only.

Rheumatoid arthritis: in the early stages if there is only joint pain and fever is easy to mistake. However, in rheumatoid arthritis, joint damage is very characteristic, accompanied by osteoarthritis.

Progressive systemic scleroderma: for a positive diagnosis there is systemic scleroderma and Raynaud's syndrome.

Treatment

Nonsteroidal anti-inflammatory drugs

Used in the early stages of the disease for its anti-inflammatory, analgesic, antipyretic effects. Often used drugs of the groups salicylic, indomethacin, pyrazole, ibuprofen.

Antimalarial drugs

Used to treat lupus since the late twentieth century. Very effective in the treatment of skin damage in cases of lupus as well as other systemic symptoms (fever, fatigue, loss ...). The therapeutic dose usually starts from 200mg twice a day, after a month of no response can increase the dose to 600mg in one day. The maintenance dose is 200mg. However, anti-malarial drugs have side effects on the eyes, and patients should be advised to have their eyes examined twice a year.

Corticoid

Introduced in lupus treatment since 1950. Has a pronounced anti-inflammatory and immunosuppressive effect.

In the early stages of the disease, use a low dose of 5-15mg / 24h, then lower the dose every 15 days to reduce 1mg. In severe cases, dose of 1-2mg / kg / 24h. Can be used orally or by infusion. Use the attack dose for 2-3 weeks long, then reduce the dose every 7 days, 5-10mg each time. Monitor the outcome of treatment based on clinical, laboratory, and drug side effects.

Immunosuppressants

In cases of glomerular damage but high doses of corticosteroids still do not work, immunosuppressants can be used. Cyclophosphamide for oral use, dosage from 1-4mg / kg / 24h. Good progress was found after 10 weeks of treatment with cyclophosphamide. However, during treatment, renal function must be monitored, and when stopping the drug, there may be a more severe outbreak.

Symptomatic treatment

Antibiotics if there is an infection.

Sedation if there is nervous system damage.

Anticoagulant if thrombophlebitis is present.

Hypotension in case of severe kidney damage.

Topical drugs such as Betnovate cream, Betamethasone cream.

Prognosis

The prognosis is not clear, the disease lasts many years, must use the drug continuously and as directed by the doctor.