SLE Flashcards
SLE
Systemic Lupus Erythematosus
Lupus latin for
wolf
What is SLE?
chronic autoimmune disease
remission and flares/exacerbation
severity can range from mild to threatening
no cure
gender dynamics
women: men
10: 1
ANA
anti-nuclear antibody
non specific for antibodies against self
if positive = might have lupus (thus test Anti-dsDNA and/oe anti-sm antigen)
Reference range…<1:40 = negative
Anti-dsDNA (anti-double stranded DNA)
auto antibodies to DNA
more specific for SLE
can show disease activity
will increase in a flare
increased in lupus nephritis
anti-sm antigen
auto antibodies to RNA splicing proteins
antibody most specific to SLE
antiphospholipid antibody
*very important
increases clotting factors
if positive, may be at higher risk for clots
Lupus nephritis (LN)
deadliest aspect of SLE
occurs in 40 - 60% of pts w/ SLE
terrible prognosis in colored people
MOA: damage and inflammation of the glomerulus
S/Sx: hematuria, proteinuria causing foamy urine; increased Scr, HTN, edema
specific txs target pts with LN
Lupus Cerebritis (CNS Lupus)
brain being attacked by body
decreased blood flow to the brain
S/Sx: anxiety, depression, psychosis, seizures
monitoring: lumbar puncture, MRI
minocycline
can cause DIL (drug induced lupus)
Most common offenders of DIL
quinidine
procainamide
hydralazine
(other agents: minocycline, isoniazid, methyldopa, carbamazepine, chlorpromazine)
DIL course of disease
- no hx of SLE
- development of ANA
- > /= 1 clinical feature of SLE
- Stop offending agent
- Symptom improvement
How to diagnose lupus
ACR (American college of rheumatology)
SLICC (systemic lupus international collaborating clinics)
ACR criteria
“DOPAMINE RASH”
- must have >/= 4 of these symptoms to be diagnosed with SLE*
- Discoid rash
- Oral ulcers
- Photosensitivity
- Arthritis
- Malar rash
- Immunologic involvement
- NEurologic involvement
- Renal involvement
- Antinuclear antibody positive
- Serositis
- Hematologic involvement
SLICC Criteria
biopsy-proven lupus nephritis with systemic lupus:
- positive ANA
- positive anti-dsDNA
or
> /= 4 total immunologic AND clinical criteria (must have at least 1 from each group!)
SLICC Clinical Criteria
acute cutaneous lupus
chronic cutaneous lupus
non-scarring alopecia
oral/nasal ulcers
joint disease
serositis
renal involvement
neurologic involvement
hemolytic anemia
leukopenia
thrombocytopenia
SLICC immunologic criteria
elevated ANA
elevated anti-dsDNA
anti-sm antigen
antiphospholipid antibody
low complement
direct coombs test
Goals of Tx
induce and maintain remission of disease
reduce inflammation caused by SLE
prevent flares and treat them when they occur
control symptoms like joint pain and fatigue
prevent organ damage
minimize drug toxicity
improve quality of life
Non-pharmacologic
sun protection (broad spectrum, UV-A + UV-B, spf >/= 55)
nutrition (pts may require higher caloric intake during flares)
exercise
immunizations (NO live vaccines can be given to SLE patients due to immunosuppression)
smoking cessation (has been shown to reduce frequency of flares)
NSAIDS
FIRST LINE THERAPY
MOA: reversibly inhibits COX-1 and COX-2
NSAID examples
naproxen 440-550 mg PO BID
ibuprofen 400 - 800 mg PO q6 - 8h
NSAIDS ADRs
gastrointestinal
cardiovascular
renal
hepatic
bleeding, gastritis, perforation
increased BP, worsened heart failure, cardiovascular events
increased Scr, renal toxicity
hepatotoxicity
NSAID monitoring
baseline: Scr, urinalysis, CBC, LFTs, BP
annual: Scr, CBC, LFTs, BP
antimalarials
FIRST LINE if no relief from NSAIDs
antimalarial examples
hydroxychloroquine (plaquenil) 200 - 400 mg PO QD/divided
Chloroquine (aralen) 250 - 500 mg PO QD
antimalarial MOA
inhibits movement of neutrophils and eosinophils
impairs complement-dependent antigen antibody reactions
antimalarials ADRs
Retinal Toxicity Corneal deposits (“Bulls Eye maculopathy”)
Dermatologic
Rashes
Pigment Changes (hair/skin)
CNS
Headache, anxiety, insomnia
Gastrointestinal
Abdominal pain, decreased appetite, nausea, vomiting, diarrhea
antimalarial monitoring: baseline
Ophthalmologic
Serum Creatinine (SCr)
Complete Blood Count (CBC)
Liver Function Tests (LFTs)
antimalarial monitoring: periodic
Ophthalmologic exam 3 months after therapy initiation
Hydroxychloroquine q 12 months
Chloroquine q 3 months
corticosteroids (TOPICAL)
MOA: anti-inflammatory, suppress immune response
corticosteroids (TOPICAL) place in therapy
SECOND LINE
Adjunctive treatment to other systemic agents
Presence of cutaneous symptoms
Helps decrease use of systemic therapies
corticosteroids (TOPICAL) High potency used for
Scalp, soles, palms
Clobetasol
corticosteroids (TOPICAL) Mid potency used for
Trunk and extremities
Triamcinolone acetonide
Betamethasone Valerate
corticosteroids (TOPICAL) low potency used for
Face
Fluocinolone acetonide
Hydrocortisone butyrate
corticosteroids (TOPICAL) pearls: Body
Creams and Ointments
corticosteroids (TOPICAL) pearls: Scalp
Foams and Solutions
corticosteroids (TOPICAL) ADRs
Skin Atrophy
Rosacea
Telangiectasis (spider veins)
Limit duration to avoid ADRs
corticosteroid (SYSTEMIC) facts
MOA: anti-inflammatory (suppress immune response)
corticosteroid (SYSTEMIC) place in therapy
SECOND LINE
Mild disease: if not responsive to NSAIDs/antimalarials
severe disease: nephritis, pneumonitis, myositis, vasculitis, CNS involvement
corticosteroid (SYSTEMIC) examples
Prednisone (maintenance therapy)
Methylprednisolone/Prednisone (pulse therapy)
corticosteroids (SYSTEMIC) ADRs
HTN
hyperglycemia
hyperlipidemia
hypokalemia
osteoporosis
wt gain
mood disturbances/psychosis
infection
cataracts
corticosteroids (SYSTEMIC) monitoring: baseline
BP, bone mineral density, BMP, FLP
corticosteroids (SYSTEMIC) monitoring: routine
BMP q 6 months
FLP q 6 months
bone mineral density q 12 months
cytotoxic agents
MOA: suppression of immune fxn
cytotoxic agents: place in therapy
SEVERE DISEASE
disease that threatens major organ fxn
cytotoxic agents used
cyclophosphamide
azathioprine
mycophenolate mofetil
cyclophosphamide for
lupus nephritis, refractory/life threatening disease
cyclophosphamide ADRs
myelosuppression
opportunistic infections
hemorrhagic cystitis
bladder cancer
infertility
azathioprine for
renal flares (long term suppression therapy), to decrease dose of corticosteroid
commonly used as adjunct w/ steroids
azathioprine ADRs
myelosuppression
opportunistic infections
hepatotoxicity
ovarian failure
thrombocytopenia
mycophenolate mofetil for
Lupus nephritis
Cutaneous symptoms
Arthritis
Hematologic symptoms
Commonly used as adjunct with corticosteroids
mycophenolate mofetil ADRs
Myelosuppression
Nausea/vomiting
Diarrhea
BP changes
CNS effects
Metabolic effects
Renal/hepatic concerns
Biologic agents for
Place in therapy: SEVERE DISEASE…DISEASE THAT THREATENS MAJOR ORGAN FXN
MOA: B-cell reduction
Biologic agent examples
belimumab (benlysta)
rituximab (rituxan)
Biologic agent pearls
No live* vaccines 30 days before or during therapy
Don’t use more than ONE biologic agent at a time
Examples of live-attenuated vaccines
measles, rotavirus, smallpox, tuberculosis, varicella, intranasal influenza vaccines, and yellow fever
Belimumab (benlysta) USE
Positive autoantibody active SLE
Adjunctive to standard treatment
Belimumab (benlysta) MOA
Human IgG antibody binds to BLyS
Promotes apoptosis of B cells
Rituximab (rituxan) USE
Lupus nephritis
Possibly more effective in AA pts or with cyclophosphamide
Rituximab (rituxan) MOA
Chimeric monoclonal antibody directed at the CD20 antigen on B-cells –> killing of B-cells
Additional Therapies
methotrexate
TNF-alpha inhibitors
calcineurin inhibitors
Voclosporin (Lupkynis®) Info
Approved in 2021 for the treatment of active lupus nephritis. Used in combination with corticosteroids and mycophenolate mofetil
MOA: Calcineurin inhibitor, leads to inhibition of lymphocyte proliferation, T-cell cytokine production, and expression of T-cell activation surface antigens
Voclosporin (Lupkynis®) AE
Hypertension Decreased glomerular filtration rate Diarrhea Anemia Headache Cough
Voclosporin (Lupkynis®) Contraindications
Concomitant use with CYP3A4 inhibitors
Pregnancy should be…
…avoided in active disease
Active SLE increases the risk for:
Miscarriage Preeclampsia Pre-term labor Fetal growth retardation Maternal mortality Increased risk of exacerbation
Pregnancy and lupus facts
Patients should stay exacerbation-free for 6 months prior to pregnancy
Estrogen-containing contraceptives should be avoided due to increased risk of clots!
Antiphospholipid syndrome can increase the risk of maternal thrombosis or spontaneous fetal death
Antiphospholipid syndrome (APS)
Systemic autoimmune disease characterized by venous or arterial thrombosis and/or pregnancy loss in the presence of persistent expression of antiphospholipid antibodies
Antiphospholipid syndrome (APS): Prophylaxis
No prior fetal losses: aspirin 81 mg daily
Recurrent fetal losses: aspirin 81 mg daily +/- low-dose heparin or low-molecular weight heparin (LMWH)
Antiphospholipid syndrome (APS): Acute Thrombotic Events/Hx of Thrombosis
Therapeutic heparin or LMWH
WARFARIN CONTRAINDICATED IN PREGNANCY
SLE Pharmacologic Summary
Mild SLE: NSAID +/- antimalarial
Moderate SLE: NSAID + antimalarial +/- maintenance systemic steroids
Severe SLE/Lupus Nephritis/CNS Lupus: NSAID + antimalarial +/- maintenance systemic steroids +/- cytotoxic agent
Refractory SLE: NSAID + antimalarial + maintenance systemic steroids +/- cytotoxic agent +/- biologic agent
For ALL Severities: topical corticosteroids for cutaneous symptoms; high-dose steroids for flares
