Systemic lupus erythematosus

Systemic lupus erythematosus is a multi-system   autoimmune disease which is characterized by   production of antinuclear antibodies. 

SLE is the prototypic human immune complex disease.

Epidemiology  

Incidence – 4 to 7 new cases per 100,000 per year

Prevalence – 1: 2,000 population

Age – Peak onset 15 to 45 years old

Female:Male ratio – 4 to 10 : 1

Black:White ratio – 3:1

Prevalence in all women ages 15 to 64 is 1/700 Prevalence in black women of same age is 1/245

Other populations commonly affected: Hispanics ,Chinese

? Low socioeconomic status>>High

Etiology

Associated with DR2, DR3 and C4A deficiency

25-50% concordance in monozygotic twins

5% concordance in dizygotic twins and

  non-twin siblings

This twins discordance is probably 2o to environmental   factors such as:  infection,hormones, uv irradiation 

  which activates and modifies the immune   response, resulting in the immune system   inappropriately targeting self as non-self.

Pathogenesis and Pathophysiology

Lesions

  1.  Immune complex deposition with inflammation

  (vasculitis)

  2.  Vascular leukoocclusion

  3.  Thrombosis mediated by anti-phospholipid

  antibody

Non-lesions

  1.  Autoantibodies to cells or cell precursors

  2.  Inflammatory cytokines which suppress bone

  marrow

Serositis

Pleuritis,

Pericarditis or

Peritonitis

Oral Ulcers

Can affect all mucosal surfaces

Painless (which distinguishes them from   aphthous ulcers)

Arthritis

Clinically indistinguishable from RA

Nonerosive

Symmetric

Inflammatory

  > 2 peripheral joints

-Skin Rash From UV irradiation

Blood Dyscrasias

Coombs + hemolytic anemia with reticulocytosis or

Leukopenia- <4,000 on 2 occasions or

Lymphopenia- <1,500 on 2 occasions or

Thrombocytopenia- <100,000 on 2 occasions 

Renal Disorder

Persistent proteinuria > 0.5 grams/day  

  or

Cellular casts

  or

10 RBC/HPF

and urine must be sterile

Lupus Renal Histology

WHO designation:

I:    Normal  light microscopy, but immuoglobulin

   and /or complement deposits

II:    Mesangial Lupus Nephritis

III:  Focal Proliferative Glomerulonephritis –not as bad

IV:   Diffuse Proliferative Glomerulonephritis - worst

V:    Membranous Nephritis – bad

VI:  Sclerotic Kidney

Antinuclear Antibody

Significant titer is > 1:80

Found in 95% SLE patients but also-

Interstitial pulmonary fibrosis

  MCTD

  PSS

  Polymyositis

  Procainamide/Hydralazine/Dilantin

  RA

  Sjögren's syndrome 

  Normal population

Immunologic Disorder

anti-ds DNA antibody (anti-native DNA ab) or

anti-SM antibody or

antiphospholipid antibody based on either:

  abnormal serum IgG or IgM anticardiolipin ab

or

  lupus anticoagulant

or

  false positive RPR or VDRL for > 6 months and

  confirmed by t. Pallidum immobilization

or

  fluorescent treponemal antibody (FTA)

  absorption test. 

Anti-DS-DNA Antibody

Also known as anti-native DNA antibody.

Antibodies to DS-DNA are not sensitive but   are very specific for SLE.

They indicate patients at increased risk for   significant SLE renal disease.

DS-DNA levels may parallel lupus activity in   individual patients.

Any titer is significant. 

Anti-Sm Antibody

Smith (Sm) is an extractable nuclear antigens   (ENA).

Antibodies to Sm are not sensitive but are

  as specific as DS-DNA for SLE.

Antiphospholipid Syndrome

Directed against phospholipids in the body.

Occurs as IgG, IgA or IgM isotypes.

Antibodies to phospholipid bind to platelet   surfaces and activate platelets resulting   in aggregation and thrombosis.

Therefore: antiphospholipid antibodies are   procoagulants.

Antiphospholipid Syndrome Clinical Associations

Clinically associated with:

1.  Recurrent vascular thrombosis (IgG).

  2.  Recurrent fetal loss (IgM).

  3.  False + RPR (or VDRL).

  4.  Falsely prolonged PTT

  (lupus anticoagulant).

  5.  Libman-Sachs endocarditis of SLE.

  6.  Livedo Reticularis.

  7.  Thrombocytopenia

Neurologic Disorder

Seizures

Psychosis

Malar Rash

Fixed erythema

Flat or raised

Spares the nasolabial folds

Discoid Rash

Raised patches

Adherent keratotic scaling

Follicular plugging

Older lesions may cause scarring

Other SLE Rashes

Palmar Erythema and Rash

Subacute Cutaneous Lupus   Erythematosus (SCLE)

Bullous Lupus Dermatitis

Neonatal Lupus

Raynaud’s Phenomenon

Therapy

Serositis  

NSAID 

Corticosteroids

Immunosuppressive

Arthritis 

NSAIDs

Hydroxychloroquine

DMARDs

Corticosteroids

Immunosuppressive Drugs

Blood dyscrasias 

Corticosteroids

Immunosuppressive Drugs

Renal, Neurological, Rash Therapy

Renal

Corticosteroids

Immunosuppressive

Neurologic

Symptomatic

Corticosteroids

Immunosuppressive

Rash 

Topical Corticosteroids

Systemic Steroids

Hydroxychloroquine

Methotrexate

Immunosuppressive Drugs