SLE Flashcards
- an autoimmune disease in which organs and cells undergo damage initially
mediated by tissue-binding autoantibodies and immune complexes - Ninety percent of patients are women of child-bearing years
- highest prevalence is in African-American and Afro-Caribbean women, and lowest prevalence is in white men
SLE
- Inducing activation of innate immunity
Autoimmunity
is a genetic “signature” in peripheral blood cells 4 of 50-80% of SLE patients
Upregulation of genes induced by IFNs
-present antigen and secrete IL6 and IL10, further promoting autoreactive cell survival
- favored by estrogen
B cell
reduced capacity to clear immune complexes, apoptotic cells, and their DNA/RNA/ Ro/La and phospholipid containing surface blebs
Lupus phagocytic cells
destruction mediated by complement activation and release of
cytokines/chemokines
Deposition of autoantibodies and/or immune complexes
PREDISPOSING FACTORS
GENES
- High Hazard Ratios (268);
+ Deficiencies of C1q, C2,C4 (rare)
+ TREX1 mutations affecting DNA
degradation (rare) - Affecting Ag presentation or persistence,
e.g., phagocytosis of immune complexes
+ HLA-DRB1 (*1501,°0301), ORS, DQOA2
+ CR2, FCGR2A/8 - Enhance Innate Immunity, including production of IFNs
+ TNFEFAIPS, IRFS/TNPOS, IRF7/PHRF1, ITGAM, ICAMs - Alter Adaptive Immunity B and/or T Cell Signaling
+ BANK1, STAT4, MSHS, IZKF3, TCF7
PREDISPOSING FACTORS
GENES FOR LUPUS NEPHRITIS
- HLA-DRS,
- STAT4,
- APOL1 (African Americans),
- FCGRBA,
- ITGAM,
- IRFS,
- IRF7,
- TNFSF4 (Ox40L),
- DNAse
PREDISPOSING FACTORS
ENVIRONMENT/ MICROENVIRONMENT
- Ultraviolet Light,
- Smoking.
- Crystalline Silica,
- EBV infection
- Femaleness
PREDISPOSING FACTORS
EPIGENETICS
- Hypomethylation of DONA: In CD4+T, B and monocytes
- Some affect IFN production
- Histone modifications: Some increase expression of predisposing genes and/or IFN production
- MicroRNaA affecting gene expression
is permissive for SLE
Female sex
Women exposed to ___ have an increased risk of developing SLE
estrogen-containing oral contraceptives or hormone replacement
binds to receptors on T and B lymphocytes, increasing activation and survival of those cells, especially autoreactive subsets, thus favoring prolonged immune responses
Estradiol
Genes on the X chromosome that influence SLE, such as ___, may play a role in gender predisposition
TREX-1
Most SLE patients have autoantibodies for ___ before the first symptoms of disease, suggesting that regulation controls the degree of
autoimmunity for years before quantities and qualities of autoantibodies, pathogenic B and T cells, and activated tissue-fixed cells such as macrophages cause clinical disease
3 years or more
Exposure to ___causes flares of SLE in ~70% of patients
ultraviolet light
may be one infectious
agent that can trigger SLE in susceptible
individuals
Epstein Bar Virus (EBV)
increases risk
for SLE
- Current tobacco smoking
- Prolonged occupational exposure to crystalline silica
reduces the risk of SLE
Drinking alcohol (2 glasses of wine a week or 1/2 of an alcoholic drink daily)
Any combination of____ in the clinical and one in
the immunologic category, well documented at any time during an individual’s history, makes it likely that the patient has SLE
four or more criteria,
with at least one
___ of patients have either continuing active disease (on current treatment) or one or more flares of active disease annually
85%
are present most of the time
fatigue, myalgias/arthalgia
varying from mild to _ disabling, characterized by soft tissue swelling and tenderness in joints and/or tendons, most commonly in hands, wrists, and knees
intermittent polyarthritis
rheumatoid-like arthritis with erosions and fulfill criteria for both RA and SLE
Rhupus
the most common reason that px increase their dose of glucocorticoids
Joint pain
- If pain persists in a single joint, such as knee, shoulder, or hip, a diagnosis of ___ should be considered
- prevalence is increased in SLE, especially in patients treated with systemic glucocorticoids
ischemic necrosis of bone (INB)
with clinical muscle weakness, elevated creatine kinase levels, positive magnetic resonance imaging (MRI) scan, and muscle necrosis and inflammation on biopsy can occur
Myositis
- common therapies
- rare therapies used for SLE
- Glucocorticoid therapies
- antimalarial
- most common chronic dermatitis in lupus
- roughly circular with slightly raised, scaly
hyperpigmented erythematous rims and
depigmented, atrophic centers in which all dermal appendages are permanently destroyed
Discoid Lupus Erythematous (DLE)
- most common
rash - acute SLE rash
- photosensitive, slightly raised erythema, occasionally scaly, on the face (particularly the cheeks and nose), ears ,chin, V region of the neck and chest, upper back, and extensor surfaces of the arms
- Worsening of this rash often accompanies flare of systemic disease
Butterfly-rash
consists of scaly red
patches similar to psoriasis, or circular flat redrimmed lesion
Subacute cutaneous lupus erythematosus (SCLE)
Other SLE rashes include:
- recurring urticaria
- lichen planus-like dermatitis
- bullae,
- panniculitis (“lupus profundus”)
- most serious manifestation of SLE, particularly since this and infection are the leading causes of mortality in the first decade of disease
- urinalysis should be ordered in any person suspected of having SLE
- is asymptomatic in most lupus patients
- renal biopsy is recommended with clinical evidence of this in SLE px
Nephritis
Classification of Lupus Nephritis (International Society of Nephrology and Renal Pathology Society)
Normal glomeruli by light microscopy, but mesangial immune deposits by immunofluorescence.
Class I: Minimal Mesangial Lupus Nephritis
Classification of Lupus Nephritis (International Society of Nephrology and Renal Pathology Society)
Purely mesangial hypercellularity of any degree or mesangial matrix expansion by light microscopy, with mesangial immune deposits. A few isolated subepithelial or subendothelial deposits may be visible by immunofluorescence or electron microscopy, but not by light microscopy
Class Il: Mesangial Proliferative Lupus Nephritis
Classification of Lupus Nephritis (International Society of Nephrology and Renal Pathology Society)
- Active or inactive focal, segmental or global endo- or extracapillary glomerulonephritis involving <50% of all glomeruli, typically with focal subendothelial immune deposits, with orwithout mesangial alterations.
- Class Ill (A): Active lesions - focal proliferative lupus nephritis
- Class Ill (A/C): Active and chronic lesions - focal proliferative and sclerosing lupus nephritis
- Class III (C): Chronic inactive lesions with glomerular scars - focal sclerosing lupus nephiritis
Class Ill: Focal Lupus Nephritis
Classification of Lupus Nephritis (International Society of Nephrology and Renal Pathology Society)
- Active or inactive diffuse, segmental or global endo- or
extracapillary glomerulonephritis involving 50% of all glomeruli, typically with diffuse subendothelial immune deposits, with or without mesangial alterations. - This class includes cases with diffuse wire loop deposits but with little or no glomerular proliferation.
Class IV: Diffuse Lupus Nephritis
Classification of Lupus Nephritis (International Society of Nephrology and Renal Pathology Society)
- Global or segmental subepithelial immune deposits or their morphologic sequelae by light microscopy and by immunofluorescence or electron microscopy, with or without mesangial alterations. - may occur in combination with class Ill or IV, in which case both will be diagnosed.
- may show advanced sclerosis
Class V: Membranous Lupus Nephritis
Classification of Lupus Nephritis (International Society of Nephrology and Renal Pathology Society)
> 90% of glomeruli globally sclerosed without residual activity
Class VI: Advanced Sclerotic Lupus Nephritis
