Download Systemic Lupus Erythematosus

Systemic Lupus Erythematosus
Intended Learning Objectives (ILOs)
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Identify definition and causes of SLE.
Understand pathogenesis of SLE.
Know the clinical presentation and features of SLE.
Discuss the pathological changes of SLE on different body
organs.
• Understand the diagnostic criteria for SLE.
* Definition: chronic
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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
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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
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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
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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.
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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
* Criteria for the 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
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, homogeneousappearing inclusion, itself
derived from nuclear material
of degenerating leukocytes and
coated with antinuclear
antibody; a characteristic of
lupus erythematosus