Rheumatology: SLE

Dr. Meg-angela Christi Amores

Systemic Lupus Erythematosus (SLE)

• autoimmune disease in which organs and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes

• 90% are women in childbearing years• all ethnic groups are susceptible

Pathogenesis

• Interactions between susceptibility genes and environmental factors result in abnormal immune responses– (1) activation of innate immunity– (2) lowered activation thresholds of adaptive

immunity cells – (3) ineffective regulatory and inhibitory CD4+ and

CD8+ T cells– (4) reduced clearance of apoptotic cells and of

immune complexes

• result in abnormal immune responses • generate pathogenic autoantibodies and immune complexes

that deposit in tissue, activate complement• cause inflammation• lead to irreversible organ damage

Pathogenesis

• The result of these abnormalities is sustained production of pathogenic autoantibodies :

• ANA (antinuclear antibodies)• Anti-dsDNA• Anti-Sm• Anti-RNP• Anti-Ro• Anti-La• Antihistone

Pathogenesis

• SLE is a multigenic disease• In most genetically susceptible individuals,

normal alleles of multiple normal genes each contribute a small amount to abnormal immune responses

• if enough variations accumulate, disease results

Pathogenesis

• Female sex is permissive for SLE• make higher antibody responses than males• Women exposed to estrogen-containing oral

contraceptives or hormone replacement have an increased risk of developing SLE

• environmental stimuli may influence SLE :– Exposure to ultraviolet light – some infections

Diagnosis

• based on characteristic clinical features and autoantibodies

• Most patients experience exacerbations interspersed with periods of relative quiescence

• Antinuclear antibodies (ANA) are positive in >98% of patients during the course of disease; repeated negative tests suggest that the diagnosis is not SLE

diagnosis

• Mnemonics: SOAP BRAIN MD– Serositis– Oral ulcers– Arthritis– Photosensitivity– Blood (all are low, anemia, etc)– Renal (protein, nephritis)– ANA– Immunologic (ds DNA)– Neurologic (seizures)– Malar rash– Discoid rash

• > 4 out of 11 suggests SLE is highly likely

Manifestations

• Arthritis – polyarthritis– soft tissue swelling and tenderness in joints, most

commonly in hands, wrists, and knees• Myositis with clinical muscle weakness

Manifestations

• Dermatitis• Discoid rash - roughly circular

with slightly raised, scaly hyperpigmented erythematous rims and depigmented, atrophic centers

• Malar rash - photosensitive, slightly raised erythema, occasionally scaly, on the face (particularly the cheeks and nose—the "butterfly" rash), ears, chin, V region of the neck, upper back, and extensor surfaces of the arms

Manifestations

• Neprhritis– most serious manifestation of SLE– leading causes of mortality in the first decade of

disease• Nervous system manifestations– cognitive dysfunction, including difficulties with

memory and reasoning– seizures

Manifestations

• Vascular occlusions• Pleuritis with or without pleural effusion• Pericarditis• Anemia, Leukopenia, Lymphopenia,

Thrombocytopenia

Treatment

• There is no cure• physician should plan to control acute, severe

flares and then develop maintenance strategies

Treatment

• Conservative strategies: (for non-life threatening cases)– suppression of symptoms– Analgesics and antimalarials • NSAIDs are useful analgesics/anti-inflammatories,

particularly for arthritis/arthralgias• Antimalarials (hydroxychloroquine, chloroquine, and

quinacrine) often reduce dermatitis, arthritis, and fatigue

Treatment

• Life-threatening:– systemic glucocorticoids • methylprednisolone sodium succinate • Prednisone• doses are tapered as rapidly as the clinical situation

permits

– Cytotoxic/immunosuppressive agents added to glucocorticoids