Systemic Lupus Erythematosus

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 organs.Discuss the pathological changes of SLE on different body organs. Understand the diagnostic criteria for SLE.Understand the diagnostic criteria for SLE.

* 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%.

Etiology and Pathogenesis of SLE

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.

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.

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.

c). Sex hormones Female: Male=9:1

D). Abnormal immune system 1-Sustained presence of autoantigens. 2-Hyperactivity of B and T lymphocyte.

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.

Clinical manifestations of SLE

General symptoms The most common symptoms listed as initial complaints are fatigue, fever, and weight loss.

Fatigue Low grade fever, anemia, or any source of inflammation can result in fatigue.

Dermatological involvement Up to 85% of SLE Butterfly rash Maculopapular eruption Discoid lupus Relapsing nodular non-suppurative panniculitis Purpuric lesions Alopecia Oral ulcer

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

Maculopapular eruption

Discoid lupus These are red, raised patches with scaling of the overlying skin.

Alopecia

Oral ulcer: Sores in the nose or mouth.

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

Kidney system Haematuria Proteinura ( >0.5g protein/d or 3+ ) R.B.Cs Casts in urine

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.

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.

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.

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.

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.

Cardiovascular manifestations Pericarditis is the most common cardiac manifestation of SLE. Myocarditis. (Libman-Sacks endocarditis ). Hypertension. Heart failure

Libman-Sacks endocarditis: reddish-tan vegetations spreading over the mitral valve and chordae

Gastrointestinal and hepatic manifestation Esophagitis, dysphagia, nausea, vomiting: (drug related in most cases). Chronic intestinal obstruction, mesenteric vasculitis, protein-loosing enteropathy. Pancreatitis. Lupus hepatitis.

Secondary sjogren’s syndrome Dry eyes. Dry mouth. - The exocrine glands were infiltrated with lymphocytes

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.

Diagnosis of SLE

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

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

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

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