Systemic Lupus Erythematosus (SLE)

SLE is a chronic autoimmune disease which can affect multiple organ systems and is characterized by autoantibodies against the cell nucleus, leading to tissue injury.

 

Causes and Risk Factors

 

SLE has an ncidence 50-70/million/year, with a prevalence 500/million. It is more common in females (9:10), with peak onset of 15-25 years. Blacks, native american, and Asian people are more affected.

Twin studies demonstrate that genetic effects are involved, with monozygotic twins having 25% concordance. HLA A1, B8, DR3 may be important. complement deficiencies?

Environmental factors such as estrogen effects, sunlight, drugs, and infectious agents are all thought to play a potential role.

 

 

Signs, Symptoms, and Diagnosis

Lupus is known as the 'disease of 1000 faces'.

It most often affects the heart, joints, skin, lungs, blood vessels, liver, kidneys, and nervous system.

 

It is diagnosed with at least 4 of the following 11 signs and symptoms (SOAP BRAIN MD):

 

microvascular involvement can result in vasculitis

alopecia

Raynaud's phenomenon

 

 

Labs

ANA

anti-dsDNA occurs in 60-80% of patients. It is highly specific when present in high titres and can give an indication of disease activity. 

extractable nuclear antigens - Ro, La, Sm, RNP

low complement - can also be used to follow disease progression

rheumatoid factor


 

Discoid Lupus Erythmatosus (DLE)

DLE is a manifestation of lupus with no systemic symptoms.

Cutaneous lesions are either poorly defined malar erythema or large, sharply demarcated erythematous, scaling plaques.

They may develop or worsen with sun exposure. Epidermal surface is shiny or scaly, and lateral pressure can produce wrinking, a sign of epidermal atrophy. Thinned epidermis reveals dilated and tortuous vessels (telangiectasia).

 

Drug-induced: can see anti-histone antibody

 

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Pathophysiology

Autoantibodies are produced against:

nuclear antigens: DNA< histones, Sm/RNP, others

cytoplasmic antigens

phospholipids: cardiolipin, others.

cell surface: RBC, lymphocytes, endothelial cells, neuronal cells

 

Likely that apoptosis, and the resulting apoptotic blebs, plays some role in antibody production.

For example, UV light can induce apoptosis in keratinocytes, which can then cause antigenic insult.

 

Genetic and envt factorsa cause B cell activation with or without T cell defects

immune complex formation and tissue deposition can cause inf and cell/organ dysfunction.

Direct cell death through antibody binding can also directly result in organ problems.

 

Nephritis

Lupus nephritis is caused by immunocomplex deposition in the glomeruli or basement membranes, and can be present in as many as 85-90% of patients.

This activates complement deposition and recruitment of leukocytes, including lymphocytes, macrophages, and neutrophils. The histologic type and severity depends on antigen specificity, type of inflammatory response, and involvement of epithelial, endothelial, and mesangial cell deposition of matrix proteins.

 

classes of lupus nephritis:

class I: minimal mesangial nephritis

class II: mesangial proliferative nephritis

class III: focal nephritis - acute or chronic

class IV: diffuse proliferative or sclerosing lupus nephritis, active or chronic

class V: membranous nephritis

class IV: advanced sclerosis nephritis

 

 

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Treatments

 

Education and regular followup

photoprotection

NSAIDs

antimalarials

corticosteroids

immunosuppressive drugs: azathioprine, cyclophosphamide, methrotrexate, mycophenilate mofetil

B cell depletion (eg rituximab)

anticoagulation in people with anti-phospholipid antibodies (predisposes to thrombosis)

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Course

 

 

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Patient Education

 

 

 

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Community Resources

 

 

 

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