RESIDENTS.SLE

PEDIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS

Pediatric Rheumatology Red Team Resident Teaching Series

Systemic Lupus Erythematosus • Episodic, heterogeneous, multisystem autoimmune disease – Widespread inflammation of vessels and connective tissues – Presence of antinuclear antibodies – Variable clinical manifestations and course

– Incidence in adults: 2- 7.6 /100,000 per year • 18% have onset in childhood • Female to male ratio 8:1

Lupus in Children • • • •

Uncommon before age 4 Incidence 0.5-0.6 /100,000 per year Females>males Children have more organ involvement than adults • Compliance issues in adolescence dangerous • Prognosis guarded; 30% may progress to renal insufficiency depending on treatment

Current Theories Of Pathogenesis In SLE • • • • • • • • • • •

Etiology unknown Multiple genes involved Immune dysregulation of B and T cell responses Immune complex deposition Abnormalities of complement Decreased clearance of apoptotic debris Hormonal imbalance Environmental triggers including UV B light, infection Loss of tolerance to chromatin and other autoantigens Cross reactivity between bacterial and mammalian DNA Abnormal response to DNA?

These factors, acting alone or together, may trigger onset of disease in a genetically predisposed host.

APOPTOSIS Protease (caspase) cascade

Receptor ligation ex: TNF, Fas DNA fragmentation Chromatin condensation Cytoplasmic blebbing Clearance by phagocytes

Y AUTOREACTIVITY

Apoptotic bodies

Y

Immune complex disease • Antibodies can be against self (e.g. nuclear components in SLE) or foreign antigens (i.e. drugs or microorganisms in serum sickness) • Antibodies and antigens combine to form immune complexes • Immune complexes deposit in blood vessels and tissues and activate inflammatory response leading to tissue destruction

Immune complex formation

C’

Y

RBC

Y Endo BM

Intima

Complement fixation

RBC

Release of inflammatory, vasoactive and chemotactic mediators Disruption of endothelium

C’ Y

C’ Y

C’

Thickening of BM

Y Infiltration of inflammatory cells Tissue damage

1997 ACR CRITERIA FOR THE CLASSIFICATION OF SLE • Malar (butterfly) rash: – Fixed erythema, flat or raised, sparing the nasolabial folds

• Discoid lupus rash: – Raised patches, adherent keratotic scaling, follicular plugging; may cause scarring

• Photosensitivity: – Skin rash from sunlight

• Oral or nasal mucocutaneous ulcerations: – Usually painless

1997 ACR CRITERIA FOR THE CLASSIFICATION OF SLE (cont) • Inflammatory arthritis: – Nonerosive, in two or more peripheral joints

• Pleuritis or pericarditis

• Cytopenias: – Hemolytic anemia, leukopenia (