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Neuropsychiatric Lupus
Robin L. Brey, M.D.
Supported by NIH/NINDS
R01-NS35477 and NCRR
No other disclosures to report.
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Systemic Lupus
Erythematosus (SLE)
SLE is an inflammatory disease affecting
many organ systems
Prevalence = 130/100,000 in the U.S. Female to Male ratio = 5:1
African Americans affected 5-10 times and
Mexican Americans 2-3 times morefrequently than Non-Hispanic Whites.
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SLE Diagnosis
Malar Rash
Discoid Rash
Photosensitivity
Oral or Nasopharyngeal Ulcerations
Arthritis without deformity Serositis
Renal Disorder
Neurologic Disorder (seizures orpsychosis)
Hematologic Disorder
Immunologic Disorder
ANA Positive
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Neuropsychiatric SLE
Over 80% of SLE patients experiencesome type of nervous system manifestation
at some time during the disease course
Seizures and psychosis are the onlymanifestations that are part of the
diagnostic criteria for the diagnosis of SLE
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Diagnosis of Neuropsychiatric SLE
Primary SLE-mediated nervous systemdisease
Secondary manifestations related to
vascular disease, infection, kidney failure,medication side effects
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Prevalence of Neuropsychiatric
SLE NPSLE manifestations occur as single or
multiple events even dur ing per iods o f no
non-nervous sys tem disease act iv i ty
40% of NPSLE manifestations develop
before diagnosis of SLE
63% occur within first year of diagnosis
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Neuropsychiatric SLE: Risk
Factors
Antiphospholipid antibodies:thrombosis, thrombocytopenia,
recurrent fetal loss, cognitive problems Anti-ribosomal P antibodies: psychosis
Anti-glutamate receptor antibodies:
cognitive problems, depression Secondary effects of renal disease,
vascular disease infection and
medication side effects
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Scope of Problem
1976 Landmark study of Urowitz and colleaguesshowed bimodal mortality over time in SLE Early deaths due to SLE activity or infection
Late deaths due to cardiovascular disease
Risks for Cardiovascular disease higher in SLEpatients 6 to10X increase for Stroke in SLE
Stroke cause of death in 15% of SLE deaths
5 to 50X increase for MI in SLE MI cause of death in 20% of SLE deaths
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Major Issues to Consider
Premature atherosclerosis Role of traditional risk factors
Role of autoimmune disease process
Secondary effects of organ damage Role of inflammation
Role of corticosteroid therapy
Clotting Disorders
Antiphospholipid antibodies
Cardiac lesions
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Increased risk for Heart Disease and Stroke in
Women with SLE(Ward, Arthritis Rheum 1999;42:338)
Reason forHospitalization:
Age
18-44 years
d Risk
Age
45-64
d Risk
Age
65 years
d Risk
Heart AttackHeart Failure
Stroke
8.511.1
8.7
2.83.3
2.5
0.71.2
0.7
Heart Attack
Heart Failure
Stroke
8.5
13.2
10.1
2.9
3.7
2.7
0.8
1.3
0.7
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Cardiovascular Risk Factors in Women
with SLE vs. Controls(Bruce. Arthritis Rheum 2003;48:3159)
Risk Factor SLE
(N=250)
Controls
(N=250)
Risk
HTN 83 (33%) 32 (13%) 2.6X
Cholesterol 84 (34%) 91 (36%) No
Low HDL 33 (13%) 26 (10%) No
Current smoker 42 (17%) 49 (20%) No
DM 12 (5%) 2 (1%) 6X
Fam Hx CAD 49 (20%) 42 (17%) No
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Cardiovascular Risk Factors Fail to Fully
Account for Accelerated Atherosclerosis in
SLE(Esdaile. Arthritis Rheum 2001;44:2331)
After controlling for traditional vascular risk
factors 10-fold increased risk for nonfatal MI
17-fold increased risk for cardiac death
7.9-fold increased risk for stroke
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Hahn, B. H. N Engl J Med 2003;349:2379-2380
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Take Home Message
In addition to treating SLE, people with SLEneed to be sure to do all they can to lower
their traditional cardiovascular risks:
Control blood pressure Normalize cholesterol
Control diabetes
Stop smoking Exercise
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American College of Rheumatology
(ACR) Case Definitions (1999) Central
Nervous System Aseptic Meningitis
Cerebrovascular disease
Cognitive Disorders
Delirium (Acute confusional state) Dementia
Demyelinating syndrome
Headaches
Movement disorders (Chorea) Myasthenia Gravis
Psychiatric Disorders
Seizure Disorders
Transverse Myelopathy
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ACR Case Definitions (1999)
Peripheral Nervous System
Autonomic Neuropathy
Myasthenia Gravis
Peripheral neuropathy
Sensorineural Hearing Loss
Cranial neuropathy
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Overall NPSLE Prevalence Estimates
in Adults
Studies using the ACR Case Definitions
found a prevalence of 14% to over 80%:
Manifestation PercentHeadache 39%-61%
Seizures 8%-18%
Cardiovascular disease 2%-8%Psychosis 3%-5%
Cranial neuropathy 1.5%-2.1%
Movement disorder 1%
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NP-SLE Syndromes: Cognitive
Attention Concentration
Memory
Word-finding Importance of corticosteroid use
controversial
Cognitive impairment not alwaysprogressive
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Spectrum of NPSLE - Cognitive
Dysfunction
0
10
20
30
40
50
60
None Mild Moderate Severe
Cognitive Dysfunction
Percent
SALUDFinland
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Risk Factors for Cognitive
Dysfunction in SALUD
Hispanic ethnicity
Higher depression scores
Higher SLE-related damage score Higher SLE-related acute disease activity
scores
Consistent prednisone use Persistently positive antibodies
Antiphospholipid antibodies
Anti-Ribosomal P antibodies
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Morbidity and Mortality Associated with
NPSLE Manifestations
Decreased quality of life and increased
SLE-related organ damage is associated
with NPSLE manifestations in adults (Hanly.Arthritis Rheum 2007;56:265)
Mortality rate over a 20-year period was
45% in children with NPSLE and 17.4% in
those without them (Sibbitt. J Rheumatol 2002;29:1536.)
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NPSLE Treatment Issues
Is therapy directed at treating theimmune system indicated for a specificNPSLE manifestation?
Should this therapy for a short time orcontinued over a long time period?
Are treatments needed to treat
symptoms that are not effective at alsotreating the underlying disease?
Are other non-drug therapies needed?
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NPSLE Treatment
Approach to therapy begins with
making the most precise diagnosis
possible Everything is NOT SLE!
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Therapy for NPSLE
There are no specific drugs for NPSLEmanifestations.
Drugs used are the same ones we use to
treat other serious SLE manifestations Steroids
Immuran
Cytoxan Cellcept
Others
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Symptomatic Treatments Medications
Drugs used to treat headache, seizures, strokeand other NPSLE manifestations work as well inSLE patients as in people without SLE
Many SLE patients (up to 66%!) use alternative
medicines Non-Pharmacologic
Stress management
Life-style changes
Psychotherapy Cognitive rehabilitation
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Summary
1. NPSLE manifestations are an importantsource of morbidity for many patients
with Lupus and are still under-recognized
2. Predictors of specific NPSLEsyndromes must be identified
3. Lowering non-SLE risk factors forcardiovascular disease is crucial