Systemic Lupus Erythematosus Flashcards
What is SLE?
chronic autoimmune disease with diverse clinical presentation
immune system attacks healthy tissues and organs throughout the body
Epidemiology
more ocmmon in women and in women of childbearnig age - peak incidence 15-45 yrs; more prevalent in non-whites
Etiology
exact etiology is unknown, but many pre-disposing factors
Pre-disposing factors
genetics: 1st degree relatives more likelt to develop SLE, or identical/fraternal twins
hormonal: estrogen production may modulate the incidence and severity of SLE
environment: cigaretter smoking, meds, UV light, air pollution, viruses (EBV), psychological stress, pesticides
Drug-induced lupus erythematosus
overreaction to certain meds; sx occur 3-6mo of drug initiation; resolution occurs within weeks of drug discontinuation
~10% of SLE cases are drug-induced
DILE examples
My Pretty Mala Marking Probably Has A Transient Quality
methimazole, propylthiouracil, methyldopa, minocycline, procainamide, hydralazine, anti-TNF agents (infliximab, etanercept), terbinafine, isoniazid, quinidine
Signs/symptoms
fatigue, depression, photosensitivity, joint pain, N/V, fever, weight loss, malar “butterfly” rash, discoid rash, raynaud phenomenon, lupus retinopathy, lupus nephritis
Raynaud phenomenon
exagerrated vascular response to cold temperature and emotional stress
pallor: constriction of blood flow, white; cyanosis: tissue hypoxia, blue; rubor: reperfusion, red
Diagnostic tools
SLICC
EULAR/ACR
SLICC
must meet >/=4 total features with 1 from each group OR biopsy proven lupus nephritis WITH systemic lupus (+anti-dsDNA antibodies or +ANA)
EULAR
only the highest weighted criterion score within a single domain is used
patient’s score is >/= 10 AND at least 1 clinical criterion is fulfilled
Key labs
anti-nuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), anti-smith antibody (anti-SM), and antiphospholipid antibody
these are all negative in a healthy pt and all positive in lupus pt
ANA not specific, anti-dsDNA and anti-SM are high specificity; antiphospholipid antibody increases clotting factors
Pharmacologic treatments
hydroxychloroquine, NSAIDs, glucocorticoids, immunosuppressants, biologics
Hydroxychloroquine
MOA: antimalarial - inhibits overative immune cells
for ALL pts with SLE
reduces flares + helps manage pain
Hydroxychloroquine dosing
200-400mg PO daily
max: 400mg daily
Hydroxychloroquine SEs
retinal toxicity (bull’s eye maculopathy), neuropsychiatric effects, QT prolongation, cardiomyopathy, hypersensitivity, hypoglycemia, hemolytic anemia (if G6PD deficiency)
G6PD deficiency
X-linked disorder (present more often in males) that causes RBCs to prematurely break down
G6PD deficient, won’t convert NADP+ to NADPH, which won’t make glutathione, which won’t fight free radicals that damage blood cells
Hydroxychloroquine monitoring
CBC, LFTs, SCr, EKG
eye exam
NSAIDs
MOA: inhibit COX1 and 2 to decrease the formation of prostaglandin precursor
benefits: antipyretic, anti-inflammatory, and analgesic - particularly helpful with fevers, serositis, myalgias, and arthralgias
1st line for mild sx
NSAIDs dosing
ibuprofen: 400-600 mg PO q6-8h
naproxen: 500 mg PO BID
NSAIDs SEs/monitoring
bleeding, gastritis, perforation, increased BP, worsening HF, CV events, increased SCr, renal toxicity, hepatotoxicity
monitor: CBC, LFTs, SCr, BP, s/sx of fluid retention and bleeding
Glucocorticoids
MOA: inhibit B and T cell responses
benefits: anti-inflammatory and helpful during flares; variable dosage forms
adjunctive treatment if not responsive to NSAIDs/antimalarial
Glucocorticoid dosing
oral: mild-mod disease: 5-30mg/day prednisone; severe: 1 mg/kg/day prednisone
IV: 500-1000 mg IV daily x 3-6 days of methylprednisolone, then PO prednisone
Glucocorticoids dosing topical - low-potency
fluocinolone valerate and hydrocortisone butyrate (face)
Glucocorticoids dosing topical - moderate-potency
triamcinolone acetonide and betamethasone valerate (trunk and extremeties)
Glucocorticoids dosing topical - high-potency
clobetasol (scalp sores and palms)
Glucocorticoids PO/IV SEs
glaucoma, increased BP, increased risk of osteoporosis, GI bleed, gastritis, psychosis/sleep disturbances, weight gain, increased BG, increased risk of infection, cushing syndrome
Glucocorticoids topical SEs
skin atrophy, rosacea, telangiectasis
Glucocorticoids monitoring
BP, BMP, FLP, bone mineral density
Immunosuppresants
MOA: suppression of immune function from attacking healthy cells
adjunct to steroid therapy to lower the dose; used if insufficient response to HCQ
methotrexate, azathioprine, cyclophosphamide, mycophenolate mofetil
Methotrexate dosing and SEs
5-15mg once WEEKLY
BMS, infection, only one with NO malignancy!
Mycophenolate mofetil dosing and SEs
1-1.5g BID
BMS, infection, malignancy, AIS
Cyclophosphamid dosing and SEs
1-1.5 mg/kg QD
BMS, infection, malignancy
Azathioprine dosing and SEs
50 mg QD
BMS, infection, malignancy
monitor: TPMT deficiency
If TPMT deficiency do not give
azathioprine
it will increase immunosuppressive effects because more 6-TGNs (active metabolites)
Biologics - last line
MOA: monoclonal antibodies that block B-cell mediated immunity
inadequate response to antimalarial and immunosuppressants; for severe disease
belimumab, rituximab, anifrolumab
Biologics clinical pearls
no live vaccines 30 days before starting therapy OR during therapy
do not use more than 1 biologic at the same time
Belimumab dosing and SEs
10 mg/kg every 2 weks x 3 doses
hypersensitivity and or infusion reactions
Anifrolumab dosing and SEs
300 mg every 4wks
hypersensitivity reactions
Rituximab dosing and SEs
1g on days 0 and 15 or 375mg/m2 once weekly for 4 doses
infusion reactions, Hep B reactivation
premedicate ~30 min prior
Additional therapies
calcineurin inhibitors: tacrolimus, pimecrolimus, voclosporin (1st FDA approved oral med for lupus nephritis)
Nonpharmacologic treatment
balance of rest and exercise, smoking cessation, limit sun exposure and use of sunscreen
Cutaneous lupus
presents on skin with rash and lesions
first line: topical agents - clobetasol, betamethasone, triamcinolone, hydrocortisone; tacrolimus, primecrolimus; HCQ; systemic GC
refractory: high dose GC, MTX, mycophenolate mofetil
Lupus nephritis
mild-mod nephritis: GC+/- another immunosuppressant (AZA, MMF, CNI)
severe nephritis: MMF (preferred) or cyclophosmadie +/- GC; triple therapy - belimumab + MMF or cyclophosphamide +/- GC or CNI + MMF +/- GC
Pregnancy and SLE
higher materal and fetal risk: miscarriage, fetal growth retardation, maternal mortality, preeclampsia
best prognosis is when pt achieves remission for >/= 6 mo before pregnancy - pregnancy can cause flares
contraception: avoid estrogen-containing contraception, screen for antiphospholipid syndrome (could increase clot risk)
Medications in pregnancy
hydroxychloroquine (drug of choice)
NSAIDs: d/c at 20 weeks or later b/c of premature closing of ductus ateriosus
glucocorticoids: choose lowest dose for shortest duration
Antiphospholipid antibody
autoimmune disorder characterized by antiphospholipid syndrome that can cause blood clots and miscarriages
prophylaxis: no prior fetal loss - aspirin 81mg, recurrent fetal loss - aspirin 81mg +/- LMWH
acute thrombotic event/hx of thrombosis: LMWH
NO warfarin!
