Systemic Lupus Erythematosus (SLE)

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Introduction

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.

The Case of...

a simple case introducing clincial presentation and calling for a differential diagnosis to get students thinking.

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Causes and Risk Factors

SLE has an incidence 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.

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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

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

Can be chronic cutaneous lupus.

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Signs and Symptoms

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):

Serositis - pleuritis, pericarditis, peritonitis
Oral ulcers - usually painless
Arthritis - nonerosive, usually involving two or more joints; characterized by tenderness, swelling, or effusion
Photosensitivity - needs to be unusual skin reaction, not sunburn
Blood changes - autoimmune cytopenias (RBC, WBC, platelets), antiphospoholipid antibodies, causing clotting
Renal involvement (nephritic syndrome: proteinuria, hematuria, or cellular casts)
ANA
Immunological changes Sm, phospholipid antibody testing
Neurological signs (seizures, psychosis, peripheral neuropathies)
Malar rash
Discoid rash