The pathogenesis of SLE is: ______

The pathogenesis of SLE is: the deposition of immune complexes composed of DNA bound to anti-DNA antibodies in the basement membrane of multiple organs (kidney, lung, skin, brain)

The genetic basis of SLE is 1. ___ 2.___ 3.__

The genetic basis of SLE is UNCLEAR!

1. Non-Mendelian inheritance

2. Polygenetic

3. Concordance in monzygotic twins = 30%

SLE is a combination of genes, sex hormones (problems of estrogen metabolism?), and environment (no factors proven)

Butterfly” rash-spares the nasolabial fold. Occurs in a majority of patients Reversible and heals without scarring Rash is photosensitive

Photosensitivity: skin rash from sunlight (UVB light) (sun exposure can precipitate a flare of Lupus that was previously dormant and well controlled!)

SLE arthritis

- NON-erosive, inflammatory in two or more peripheral joints (Rheumatoid is erosive)

SLE serositis:

Pleuritis or pericarditis

SLE criteria: Immunologic disorders

- Antibodies to dsDNA or SM or positive antiphospolipid antibodies (IgG or IgM abs)

- Lupus Anticoagulant

- False positive serologic test for syphilis

Scarring rash that extends into the dermis. Associated with follicular plugging Lesions heal with scarring, hypopigmentation & skin atrophy

SLE Pulmonary complications:

- Pleuritis

- Pleural effusion

- Interstitial lung disease

- Pulmonary hemorrhage

SLE Cardiac Complications:

- Pericardium: inflammation, pericarditis, pericardial effusion

- Myocardium: Myocarditis (rare) - Coronary Arteries: Arteriosclerosis (MI is common cause of death)

- Endocardium: Libman-Sachs sterile vegetations usually on mitral valve

Anti Nuclear Antibodies and SLE

- ANA is seen in 95% of SLE

- ANA is NOT specific for SLE (it's seen in many inflammatory, infectious, and neoplastic diseases and 5-15% of normal people)

Anti ds DNA antibodies are:

-Seen in 60% of patients with SLE

-HIGHLY SPECIFIC for SLE

-Strongest clinical association is with nephritis (antibodies to single-stranded DNA is not useful in regards to SLE)

Anti-SM (Smith) Antibodies

- Seen in 10-30% of SLE patients

- 100% specific for SLE!

The SSA antigen is most prominent in the developing fetal heart. IgG anti-SSA antibodies cross the placenta and bind to SSA antigen causing congential heart malformations or neonatal complete heart block

C3, C4, and total hemolytic complement CH 50 can be consumed during active SLE (low serum complement)

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Anti-Nuclear Antibodies: "Homogeneous" or "Diffuse" staining

• Everything in the nucleus (RNA, DNA, histones, proteins) is stained
• Not very helpful diagnostically

SLE Endocardial involvement:

Libman-Sachs sterile vegetations (usually on mitral valve)

Anti-Nuclear Antibodies: "Nucleolar" staining

• 4S RNA is stained
• Not very helpful diagnostically (also seen in scleroderma)

Anti-Nuclear Antibodies: "Rim" or "Outline" staining

• DNA is stained
• Specific for SLE!

Anti-Nuclear Antibodies: "Speckled"  staining

• Ribonuclear proteins are stained
• Not very helpful diagnostically (Also seen in Sjogren's syndrome and scleroderma)