SM_232a: Systemic Lupus Erythematosus Flashcards
Describe systemic lupus erythematosus
Systemic lupus erythematosus
- Multi-system, inflammatory, autoimmune disease with diverse clinical and laboratory manifestations
- Characterized production of autoantibodies which deposit in tissues and fix complement leading to inflammation and tissue damage
- Variable course and prognosis - can be a mild, life-threatening, or anything in between
Lupus is most common in ____ and ____
Lupus is most common in women and African Americans
Risk factors for SLE are ____, ____, and ____
Risk factors for SLE are genetics, environmental, and female hormones/sex
- Genetics: usually deficiency in several genes, usually SNPs in non-coding regions of DNA, only account for 15% of SLE heritability
- Environmental: UV light, medications, viral infections (EBV), cigarette smoking
- Female: increased disease activity in pregnancy
UV light promotes SLE through ____ and ____
UV light promotes SLE through DNA damage and keratinocyte apoptosis
Medications such as hydralazine and procainamide promote SLE through ____, leading to ____
Medications such as hydralazine and procainamide promote SLE through decrease DNA methylation, leading to altered gene expression
Describe SLE pathogenesis
SLE pathogenesis
- Genetic, environmental, immunoregulatory, hormonal, and epigenetic factors interact
- Immune complexes, antibodies, and cytokines released and T cells activated
- Various organs damaged
Describe immune dysregulation in SLE
SLE immune dysregulation
- Impaired apoptosis with decreased clearance of apoptotic cells
- Dendritic cells present self determinants -> stimulate activation and proliferation of autoreactive T cells and B cells, produce large amounts of interferon and B cell activating factors that sustain inflammatory response
- T-cells: increased Th17 and Th2 cells (pro-inflammatory), decreased Tregs (anti-inflammatory)
- Autoreactive B cells have defective selection and signaling: differentiate to plasma cells and produce autoantibodies
- Immune complex formation between autoantibodies and self-antigen -> deposit in tissues -> activate complement cascade -> promote increased local inflammation and organ damage
Describe events of immune dysregulation in SLE
SLE immune dysregulation
- Genetic alterations and environmental exposures
- Impaired apoptosis
- Abnormally functioning dendritic cells, increased Th17 and Th2, decreased Treg, abnormally functioning B cells
- Production of autoantibodies, immune complex, and pro-inflammatory molecules
- Tissue injury
Describe disease-related immune events and associated polymorphisms in SLE
SLE disease-related immune events and associated polymorphisms
- Decreased clearance of apoptotic cell debris with nucleoprotein autoantigens
- Dendritic cell maturation, antigen presentation, cytokine proliferation
- T cell activation and B cell stimulation
- Plasma cell differentiation and autoantibody production
There is a _____ between the innate and adaptive immune systems
There is a feedforward loop between the innate and adaptive immune systems
All SLE patients have ____
All SLE patients have antinuclear antibodies (ANA)
(against various components of cell nucleus, detection by immunofluorescence, and reported as titer)
ANA is ____ but not ____ for SLE
ANA is sensitive but not specific for SLE
- Patient with negative ANA is unlikely to have lupus even when presentation is suggestive because of high sensitivity
- Most useful when pre-test probability for lupus is high because of low specificity
_____ and _____ are autoantibodies that are highly specific for SLE
Anti-dsDNA and anti-Sm are autoantibodies that are highly specific for SLE
SLE is characterized by _____ where autoantibody detection precedes diagnosis by many years
SLE is characterized by preclinical autoimmunity where autoantibody detection precedes diagnosis by many years
Pathogenic autoantiboidies are usually _____ and function to _____ and _____
Pathogenic autoantiboidies are usually IgG and function to form circulating immune complexes and directly target cells through cross-reactivity with other antigens
Anti-dsDNA causes kidney damage in renal lupus by _____, _____, and _____
Anti-dsDNA causes kidney damage in renal lupus by entrapping circulating immune complexes in the basement membrane, directly binding to basement membrane antigens, and directly binding to renal tubular cells
Anti-dsDNA _____ deposits are found in membranous disease while _____ deposits are found in proliferative disease
Anti-dsDNA subepithelial deposits are found in membranous disease while subendothelial deposits are found in proliferative disease
Anti-SSA and anti-SSB are associated with _____, _____, and _____
Anti-SSA and anti-SSB are associated with subacute cutaneous lupus, neonatal lupus, and complete heart block in utero
Describe signs and symptoms of SLE
SLE signs and symptoms
- Malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, glomerulonephritis, neurologic disorder
- Other rashes, non-scarring alopecia, lymphadenopathy, sicca (dry eyes and mouth), Raynaud’s phenomenon, fever, transverse myelitis / mononeuritis multiplex, inflammatory myositis or myocarditis, interstitial lung disease
- Pain, fatigue, memory thief / brain fog, depression
SLE is characterized by periods of _____ and _____
SLE is characterized by periods of flare (increased disease activity and inflammation) and remission (low level disease activity)
(variable flare rates for patients, labs are predictive of flare rates)
Describe SLE disease severity
SLE disease severity
- Severe disease characterized by abrupt onset of symptoms, increased renal / neurologic / hematologic / and serosal involvement, and rapid accrual of organ damage (irreversible organ injury)
- Factors associated with more severe disease: younger age of onset, male sex, race/ethnicity, lower socioeconomic status
SLE mortality is _____
SLE mortality is bimodal
- Early causes: severe SLE disease activity, infections
- Late causes: CVD, organ failure, infection, malignancy
Goals of therapy for SLE are ____, ____, and ____
Goals of therapy for SLE are induction of remission, maintenance therapy, and supportive therapy
- Induction of remission: stop and reverse ongoing organ inflammation
- Maintenance therapy: prevent or limit irreversible end-organ damage
- Supportive therapy: prevent long-term complications from disease and treatment
Current therapy involves _____, _____, _____, and _____
Current therapy involves corticosteroids, hydoxychloroquine, immunosuppresants, and antiplatelet/anticoagulation (if antiphospholipid positive)
(also supportive therapy such as couseling on sun avoidance, liver function abd blood count surveillance, prophylactic antibiotics and vaccines, cardiovascular screening, age appropriate cancer screening, and osteoporosis screening and prevention)
Patients with SLE on treatment need to be monitored vigilantly because of the effects of _____
Patients with SLE on treatment need to be monitored vigilantly because of the effects of immunosuppressive medications
(liver dysfunction or drug-induced cytopenias, infection, cancer, infertility/birth defects)
_____ and _____ need to be monitored in SLE
Liver function and blood count need to be monitored in SLE
____ is a side effect of methotrexate
Transaminitis is a side effect of methotrexate
- Monitor liver function
Positive ____ test is non-specific but common to patients with SLE
Positive ANA test is non-specific but common to patients with SLE
Cardinal pathogenic features of SLE is _____
Cardinal pathogenic features of SLE is development of autoantibodies that form circulating immune complexes and can also cause direct tissue inflammation
Combination of ____ and ____ is used to decrease disease activity and prevent organ damage in SLE
Combination of corticosteroids and DMARDs is used to decrease disease activity and prevent organ damage in SLE
(supportive therapies and monitoring strategies reduce preventable, long-term complications of disease)
