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Systemic Lupus Erythematosus
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Intended Learning Objectives (ILOs)
• Identify definition and causes of SLE.Identify definition and causes of SLE.
• Understand pathogenesis of SLE.Understand pathogenesis of SLE.
• Know the clinical presentation and features of SLE.Know the clinical presentation and features of SLE.
• Discuss the pathological changes of SLE on different body Discuss the pathological changes of SLE on different body organs.organs.
• Understand the diagnostic criteria for SLE.Understand the diagnostic criteria for SLE.
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* Definition: chronic multisystem, autoimmune disease
most commonly affecting young women. • Any organ of the body may be involved . • Course of the disease is remissions and exacerbations.
• With good management, the ten years survival may be over 90%.
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Etiology and Pathogenesis of SLE
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A) Genetic factor• Certain genes permit a little immune over-response,
or presentation of high quantities of target antigens in certain tissues.
• Many studies have described familial aggregation of SLE.
• lupus have at least one first or second degree relative with lupus.
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B). Environmental factors
1. UV light, flares SLE in most patients .There is good evidence
that exposure of skin to UV light alters the location and
chemistry of DNA
2. Drug-induced lupus. Drugs ( hydralazine, procainamide,
beta-blockers, isoniazid, penicillamine) can induce lupus.
Generally, lupus that is caused by a drug exposure goes away
once the drug is stopped.
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3. Infection.
- There has been continuing interest in the possibility that
infectious agents might initiate or flare SLE.
- Mechanism might include molecular mimicry between external
Ag and a self-Ag, nonspecific activation of T or B cells. There
has been recent interest in Epstein Bar virus, Cytomegalovirus.
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c). Sex hormones• Female: Male=9:1
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D). Abnormal immune system
1-Sustained presence of autoantigens.
2-Hyperactivity of B and T lymphocyte.
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3. Autoantibodies to DNA, RNA.
4. Circulating immune complexes (Ag &Ab
complexes) are frequently observed and these may
deposit in the kidney, skin, brain, lung, and other
tissues. It causes inflammation and tissue damage by a
number of mechanisms, notably fixation and activation
of the complement system which cause damage in the
tissues.
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Clinical manifestations of SLE
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General symptoms
The most common symptoms listed as initial complaints are fatigue, fever, and weight loss.
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• Fatigue
Low grade fever, anemia, or any source of inflammation can result in fatigue.
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Dermatological involvement• Up to 85% of SLE• Butterfly rash• Maculopapular eruption• Discoid lupus• Relapsing nodular non-suppurative panniculitis• Purpuric lesions• Alopecia• Oral ulcer
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Malar rash: This is a "butterfly-shaped" red rash over the cheeks below the eyes and across the bridge of the nose. It
may be a flat or a raised rash.The rashes are made worse by sun exposure
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Maculopapular eruption
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Discoid lupus These are red, raised patches with scaling of the overlying
skin.
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Alopecia
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Oral ulcer:
• Sores in the nose or mouth.
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Musculoskeletal system
• The arthritis of lupus is usually found on both sides
of the body and does not cause deformity of the
joints. Swelling and tenderness must be present.
• The most frequently involved joints are those of the
hand, wrists and knees,.
• The muscle involvement was reported in 30-50% of
lupus patients
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Kidney system
• Haematuria• Proteinura (>0.5g protein/d or 3+ )
R.B.Cs Casts in urine
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Nervous system
• The brain, nerve problems and psychiatric syndromes are
common in lupus affecting up to two-thirds of people.
• Potential disorders include seizures, nerve paralysis, severe
depression, and even psychosis.
• Spinal cord involvement in lupus is rare and occurs primarily
when there is clot formation in a critical vessel that supplies
blood to the spinal cord.
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Hematological abnormalities • Red blood cells
a normochromic, normocytic anemia is frequently
found in SLE. They appears to be related to
chronic inflammation, drug-related haemorrhage.
haemolytic anemia due to presence of a serum
antibody which attack red blood cells.
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• White blood cell
leucopenia:
- Its cause is probably a combination of destruction of white cells by autoantibodies, decreased marrow production.
- It should also noted that the immunosuppressive drugs used in the treatment of SLE may cause a marked leucopenia.
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Vasculitis
• Vasculitis in arteries throughout the body can account for signs and symptoms from a variety of organ involvements. Seen here is an artery with extensive vasculitis with chronic inflammatory cells.
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Pulmonary manifestations
• Pleurisy• Pleural effusion: - Pleural effusions may occur in SLE patients either due to
direct pleural injury or secondary to nephrotic syndrome, infection, cardiac failure.
• Acute lupus pneumonia. • pulmonary hemorrhage.
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Cardiovascular manifestations
• Pericarditis is the most common cardiac manifestation of SLE.
• Myocarditis. • (Libman-Sacks endocarditis ).• Hypertension. • Heart failure
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Libman-Sacks endocarditis: reddish-tan vegetations spreading over the mitral valve and chordae
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Gastrointestinal and hepatic manifestation
• Esophagitis, dysphagia, nausea, vomiting: (drug related in most cases).
• Chronic intestinal obstruction, mesenteric vasculitis, protein-loosing enteropathy.
• Pancreatitis.
• Lupus hepatitis.
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Secondary sjogren’s syndrome
• Dry eyes.
• Dry mouth.
- The exocrine glands were infiltrated with lymphocytes
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Deep venous thrombosis
• Notice the contrast between the involved left leg and the normal right leg. Redness, swelling, and warmth combined with discomfort in the involved leg are cardinal manifestations of a deep venous thrombosis.
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Diagnosis of SLE
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1. Malar rash: Fixed erythema over malar areas
2. Discoid rash: Erythematous raised patches with keratotic scaling .
3. Photosensitivity: Skin rash after exposure to sunlight.
4. Oral ulcers: Oral or nasopharyngeal, painless.
5. Arthritis: Tenderness, swelling, effusion in 2 or more peripheral joints
6. Serositis: A) pleurisy or B) pericarditis
* Criteria for the diagnosis of SLE* Criteria for the diagnosis of SLE
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7. Renal disorder A) proteinuria >0.5g/24hour
8. Neurological disorder: A) seizures or B) psychiatric disorder.
9. Haematological disorder:
-A) haemolytic anaemia.
-B) leucopenia.
-C) thrombocytopenia
10. Positive antinuclear antibodies: anti-dsDNA, antibodies to
nuclear antigen (anti-Sm), positive LE cells
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Autoantibodies in SLE• Antibodies to cell nucleus component anti-dsDNA, antibodies to nuclear antigen (anti-Sm) • Antibodies to cytoplasmic antigens anti-SSA, anti-SSB• Cell-specific autoantibodies lymphocytotoxic antibodies, anti-neurone antibodies,
anti-erythrocyte antibodies, anti-platelet antibodies• Antibodies to serum components antiphospholipid antibody
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Anti-nuclear antibodies• The lupus
erythermatosus (LE) cell: Is a mature neutrophilic
polymorphonuclear leukocyte, which has phagocytized a spherical, homogeneous-appearing inclusion, itself derived from nuclear material of degenerating leukocytes and coated with antinuclear antibody; a characteristic of lupus erythematosus