SYSTEMIC LUPUS ERYTHEMATOSUS

Definition Epidemiology Pathophysiology Classification and diagnosis Clinical Features Lupus related syndromes Treatment Prognosis

Inflammatory autoimmune disorder affecting multiple organ systems characterized by the production of autoantibodies directed against cell nuclei

Prevalence influenced by age, gender, race, and genetics

Prevalence: 1:2000 Peak incidence 14-45 years African /Asian Female predominance 10:1 HLA DR3 association, Family History

UV light

Infectio n

Self Ag

Skin cell
APC T cell T cell
IC

External Ag

Genetic susceptibility

APC

B cell

Ab

Target

Defective IC clearance

Fatigue Fever Arthralgia

 Malar Rash (butterfly erythema) Discoid rash Photosensitive rash Subacute cutaneous LE Livedo reticularis Alopecia Raynauds

Vasculitic ulceration Oral ulceration Nasal septal perforation Nailfold capillary changes

Fixed erythema, flat or raised, over the malar eminences Tending to spare the nasolabial folds

Erythematous raised patches with adherent keratotic scaling and follicular plugging; Atrophic scarring may occur in older lesions

Alopecia

Subacute Cutaneous Lupus

Acute Cutaneous: Malar Rash Note Sparing of Nasolabial Folds

Chronic Cutaneous:Discoid Note Scarring, Hyperpigmentation

Follicular Plugging

Livedo Reticularis

ACR

Oral or nasopharyngeal ulceration Usually painless, observed by a physician

SLE - VASCULOPATHY
Small vessel vasculitis Raynauds phenomenon Antiphospholipid antibody syndrome

Arthritis is NONEROSIVE, transient, symmetrical, affecting small joints, seldom deforming, less severe than RA Most common presenting feature of SLE

Jaccouds Arthopathy: Nonerosive

 Synovitis-90% patients, often the earliest sign Osteoporosis From SLE itself and therapy (usually steroids) Osteonecrosis (avascular necrosis) Can occur with & without history of steroid therapy

 Conjunctivitis Photophobia Monocular blindness-transient or permanent Blurred vision Cotton-Wool spots on retina-degeneration nerves fibers due to occlusion retinal blood vessels

Pleuritis/Pleural effusion Acute lupus pneumonitis Pulmonary hemorrhage Shrinking lung - diaphragm dysfunction Restrictive lung disease

 Pericarditis in majority of patients Libman Sacks endocarditis Cardiac failure Cardiac Arrythmias-common Valvular heart disease Coronary Artery Disease

SLE can be associated with endocarditis. Shown here is LibmanSacks endocarditis in which there are many flat, reddishtan vegetations spreading over the mitral valve and chordae.

A) B) C) D)

Hemolytic anemia - with reticulocytosis Leukopenia Lymphopenia Thrombocytopenia

Behavior/Personality changes, depression Cognitive dysfunction Psychosis Seizures Stroke Chorea Pseudotumor cerebri Transverse myelitis Peripheral neuropathy

 Severe abdominal pain syndromes in SLE often indicate mesenteric vasculitis Chronic intestinal pseudo-obstruction Diverticulitis may be masked by steroids Hepatic abnormalities more often due to therapy than to SLE itself

 Develops in up to 50% of patients 10% SLE patients go to dialysis or transplant Hallmark clinical finding is proteinuria Advancing renal failure complicates assessment of SLE disease activity

Nephritis remains the most frequent cause of disease-related death.

Gross hematuria Nephrotic syndrome Acute renal failure Hypertension End stage renal failure

Class I Class II IIA IIB Class III

Class IV
Class V Class VI

Normal Mesangial Minimal alteration Mesangial glomerulitis Focal and segmental proliferative glomerulonephritis Diffuse proliferative glomerulonephritis Membranous glomerulonephritis Glomerular sclerosis

The American College of Rheumatology has designated 11 criteria for diagnosis. To receive the diagnosis of lupus, a person must have 4 or more of these criteria:

American College of Rheumatology 4/11 criteria (sens 85%, specif 95%) SOAP BRAIN MD Serositis heart, lung, peritoneum Oral ulcers painless esp palate Arthritis non-erosive Photosensitivity

Blood disorders - RBC (Coombs +), PLT, WCC, Lymphocytes Renal involvement proteinuria / casts ANA titer > 1:160 Immunologic phenomena LE cells, antidsDNA Ab, anti-Sm Ab, antiphospholipid Ab, false WR + Neurological disorders seizures/ psychosis Malar rash cheeks + nasal bridge Discoid rash rimmed with scaling, follicular plugging

Complete blood count

Anemia Leukopenia Lymphopenia Thrombocytopenia

Urine Analysis
Hematuria Proteinuria Granular casts

ANA - 95-100%-sensitive but not specific for SLE Anti -ds DNA-specific(60%)-specific for SLE, but positive to other non lupus conditions 4 RNA associated antibodies
Anti-Sm (Smith) Anti Ro/SSA-antibody Anti La/SSB-antibody Anti-RNP

Antiphospholipid antibody

Depressed serum complement Anti hystones antibodies

Biologic false + RPR Lupus anticoagulant-antibodies tocoagulation factors. risk factor for venous and arterial thrombosis and miscarriage. Prolonged aPTT Anti-cardiolipin

Management and treatment

1. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) symptomatic relief for arthralgias, fever, and mild serositis Eg: Ibuprofen
Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis

2. Antimalarials preventing and treating lupus skin rashes, constitutional symptoms, arthralgias and arthritis. also help to prevent lupus flares and have been associated with reduced morbidity and mortality in SLE. Eg. Hydroxychloroquine
Inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions

3. Corticosteroids used predominately for anti-inflammatory activity and as immunosuppressants a) Methylprednisolone Used for acute organ-threatening exacerbations. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

b) Prednisone Immunosuppressant for treatment of autoimmune disorders. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.

4. Immunosuppressant Agents act as immunosuppressives and cytotoxic and anti-inflammatory agents. a) Methotrexate
For managing arthritis, serositis, cutaneous, and constitutional symptoms. Blocks purine synthesis and AICAR, thus increasing anti-inflammatory adenosine concentration at sites of inflammation.

b) Cyclophosphamide

c) Azathioprine

Used for immunosuppression in cases of serious SLE organ involvement, especially severe CNS involvement, vasculitis, and lupus nephritis. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Immunosuppressant and less toxic alternative to cyclophosphamide and as steroid-sparing agent in nonrenal disease. Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.

d) Immune globulin intravenous

Used for immunosuppression in serious SLE flares. Neutralizes circulating myelin antibodies through anti-idiotypic antibodies. Down-regulates proinflammatory cytokines, including INF-gamma. Blocks Fc receptors on macrophages, suppresses inducer T and B cells, and augments suppressor T cells. Blocks complement cascade, promotes remyelination, and may increase CSF IgG (10%).

Patient Education Photosensitivity: Instruct patients with SLE to avoid exposure to sunlight and ultraviolet light.

Medication toxicity: Monitor the use of NSAIDs and salicylates because of increased renal and hepatic toxicity.

Opportunistic infections: Instruct patients with SLE to seek medical care for evaluation of new symptoms, including fever. CAD: Educate patients with SLE regarding aggressive lipid and blood pressure goals to minimize the risk of CAD. In addition, teach patients to recognize the signs and symptoms of myocardial infarction.