Lupus Flashcards
lupus is 9x more common in ____
women
mortality ratio for SLE is _____ than the general population
2-3x higher
______ tend to have more severe disease
men and children
_______ patients with lupus nephritis have reduced survival
african american
name some effects lupus has on the body
unexplained fever, alopecia, chronic fatigue, scalp sores, butterfly rash, anemia/blood clotting, chest pain, Raynaud’s, joint pain, muscle aches, hand and feet swelling, mouth/nose sores, skin changes/sun sensitivity
lupus is a _____ disease with _____ flares
chronic disease with acute flares
lupus can mimic what disease?
Rheumatoid arthritis
interactions between _____ and _____ result in abnormal immune responses
susceptibility genes and environmental factors
who is at higher risk for SLE
people with first degree relatives with SLE
etiology of SLE is _____-factorial
multi
abnormal clearance of ______ stimulates an immune response
apoptotic debris
autoantibodies cause _____
tissue destruction
what are some examples of organ damage from SLE
renal failure, atherosclerosis, pulmonary fibrosis, stroke
what is drug-induced lupus?
lupus-like findings in a patient with no history of SLE/onset at least 1 month after initiation of a drug; improvement within days to months after stopping the drug
true or false: a combo of genetic factors & environment play a role in SLE etiology
true
what are some diagnostic criteria used for SLE
EULAR/ACR 2019
SLICC 2012
why is SLICC criteria different
it does not require the presence of ANA
antinuclear antibodies (ANA) are positive in _____ of patients during the course of disease
> 98% (but ANA is not specific to lupus it can mean anything autoimmune)
what antibodies are more specific for SLE?
high-tier IgG antibodies to double-stranded DNA and antibodies to the Sm antigen
true or false: the presence of multiple antibodies without clinical symptoms should be considered diagnostic for SLE
FALSE
what are some clinical presentation of SLE
fever, fatigue, weight loss, neuro, renal, heme, cardiac, skin, MSK
what are the constitutional symptoms present in most lupus patients?
fever, fatigue, weight loss
85% of patients with SLE will have ____ and _____
arthritis and arthralgias
difference between RA and SLE arthritis/arthralgias?
in SLE it is not permanent
characteristics of arthritis/arthralgias in SLE
migratory, polyarticular, symmetrical
who more commonly has skin manifestations in lupus
women
a ______ usually appears after sun exposure
butterfly rash
______ is a common theme for skin lesions and can trigger a skin rash
photosensitivity
what are some pulmonary manifestations of SLE
pleuritis and pleural effusion, interstitial inflammation leading to fibrosis
what is the leading cause of death in patients with SLE?
cardiovascular disease
what is the most common cardiac manifestation of SLE?
pericarditis
what are other cardiac manifestations of SLE
myocarditis, hypertension, premature atherosclerosis
what are GI manifestations of SLE
nausea, vomiting, diarrhea (can be part of a flare, or side effects of medications)
what are hematologic manifestations of SLE?
anemia, leukopenia, neutropenia, thrombocytopenia
what are nervous system manifestations of SLE?
memory and reasoning difficulties, headache/migraine (flare), seizures, mood disorders (anxiety, depression), psychosis
psychosis in SLE must be distinguished from ____
glucocorticoid psychosis: occurs during first few weeks of glucocorticoid therapy
lupus nephritis is more common in who
men
lupus nephritis is a significant cause of______
morbidity and mortality
selena gomez had a ____ transplant
kidney
how does lupus nephritis happen
antibodies deposit in kidney; triggers autoimmune response that attacks kidneys— damage leading to proteinuria, albuminuria
what are the 3 antiphospholipid antibodies
anticardiolipin, antiB-2-glycoprotein I, lupus anticoagulant
what is antiphospholipid syndrome (APS)
systemic autoimmune disorder characterized by thrombosis in presence of antiphospholipid antibodies
APS increases the risk of _____ and _____
thrombosis and stroke
immunologic lab tests for SLE
ANA +/- anti-dsDNA +/- Anti-sm
antiphospholipid antibodies
ESR and CRP
complement
anemia work up for SLE
CBC with diff + BMP
renal work up for SLE
SCr, urinalysis with sediment
goals of treatment
prevent flares, limit involvement of other organs and prevent damage, reduce disease activity, achieve and maintain remission, reduce use of steroids
pharm treatment consists of _______ AND ______
immunosuppression AND symptomatic therapies
self care measures for lupus?
- hats in the sun
- sunscreen always (UVA and UVB, SPF 15 minimum but 30 preferred)
- stop smoking
- exercise
- stress coping
- lots of sleep
- immunizations (try to give before starting immunosuppressive therapies)
pharm options?
anti-inflammatory, anti-malarial, corticosteroids, cytotoxic immunosuppressives
anti inflammatory agents
NSAIDs, ASA
antimalarial agents
hydroxychloroquine
corticosteroid agents
prednisone, methylprednisolone
cytotoxic immunosuppressives
azathioprine, methotrexate, mycophenolate, cyclophosphamide, voclosporin, calcineurin inhibitors, JAK inhibitors
biologics
rituximab, benlysta, saphnelo
what is the mainstay of lupus treatment
hydroxychloroquine
what is cutaneous lupus erythematosus (CLE)
skin involvement
first line for CLE
topical therapy first line; most commonly topical corticosteroids
for thin skin areas like face and groin, use ____
low potency steroids
for trunk and extremities, use ____
mid potency
for thick skin areas like scalp, soles, and palms use _____
high potency
adverse drug reactions of topical corticosteroids
skin atrophy, telangiectasias, steroid-induced dermatitis
use the lowest ___ and ____ for topical corticosteroids
potency and duration
in addition to topical corticosteroids, you can use ____ for CLE
topical calcineurin inhibitors
SLE with no specific disease manifestations– what treatment?
NSAIDs
NSAIDs are first line for what
arthritis, musculoskeletal complaints, fever, serositis but no major organ invovement
NSAIDs are NOT ____
disease modifying; but they do help w/ symptoms
try NSAIDs for up to __ weeks and re-assess
4
potential side effects for NSAIDs
GI effects, CV effects, renal
hydroxychloroquine dose
200-400 mg PO daily (max 5 mg/kg/day)
effects of hydroxychloroquine
anti-inflammatory, immunomodulatory, antithrombotic
counseling for hydroxychloroquine
may take 2-8 weeks to see effects and 3-6 months for maximum efficacy.
who should receive hydroxychloroquine
all patients
hydroxychloroquine allows corticosteroid doses to be ____
decreased
benefits of hydroxychloroquine
prevents flares, improves survival, protects against bone mass loss, protects against thrombosis and organ damage, benefits lipids and fasting BG, decreases infections
mech of hydroxychloroquine
reduces concentrations of inflammatory cytokines; alters antigen presentation and T-cell proliferative responses, decreases activation of TLR
hydroxychloroquine elimination
renal
hydroxychloroquine T1/2
40-50 days
ADRs of hydroxychloroquine
GI and skin reactions (nausea, vomiting, rash, alopecia), QT prolongation, retinal toxicity
____ screening required for hydroxychloroquine at baseline and then annually after 5 years
eye
place in therapy for glucocorticoids
monotherapy or adjunct; control flares and maintain low disease activity
onset of glucocorticoids
rapid
dose options for glucocorticoids
high IV dose pulse to control flare, high dose oral to control severe disease, low dose oral for maintenance
early ADRs for glucocorticoids
weight gain, hyperglycemia, infection risk, mood changes, dyspepsia
chronic use ADRs for glucocorticoids
osteoporosis, infections, cataracts, glaucoma, hyperglycemia/diabetes, fat redistribution, sleep/mood disturbances, thinning of skin (topical)
what if no sustained response from NSAIDs, antimalarials, or glucocorticoids?
go to immunosuppressives
azathioprine MOA
purine analog, inhibits nucleic acid synthesis and affects cellular and humoral immune functions
what testing to have prior to using azathioprine
TPMT testing (if TMPT activity is low, they can’t metabolize the drug= risk for myelosuppression)
azathioprine is metabolized to ___
mercaptopurine
place in therapy for azathioprine
for refractory mild disease, mild nephritis, or a steroid-sparing agent
less effective but less toxic
ADRs of azathioprine
hepatotoxicity, pancreatitis, myelosuppression, N/V, infection
monitoring for azathioprine
LFTs q6 months, CBC q2 weeks with dose increases then monthly
methotrexate MOA
inhibition of dihydrofolate reductase, which is needed for DNA synthesis and cell proliferation
place in therapy of methotrexate
steroid-sparing drug, MSK/skin/serosal disease
ADRs of methotrexate
bone marrow suppression, increased LFTs, infection, cirrhosis, diarrhea, N/V, mouth sores, GI/pulmonary/nephrotoxicity
how to reduce toxicities of methotrexate
administer folic acid 1-5 mg daily
mycophenolate mofetil (MMF) MOA
inhibits IMP dehydrogenase, which results in decreased B and T cell proliferation and decreased antibody production
active form of MMF
mycophenolic acid
onset of MMF
3-16 weeks
place in therapy for MMF
induction, maintenance
ADRs of MMF
GI complaints most common, infections, leukopenia, anemia, thrombocytopenia
evidence suggests that who responds better to MMF
hispanic and black patients with lupus nephritis
cyclophosphamide MOA
alkylating agent, inhibits B and T cell proliferation and antibody production
place in therapy of cyclophosphamide
induction agent for patients with severe disease or refractory organ involvement including lupus nephritis, neuropsychiatric lupus, severe systemic vasculitis, hematologic disease
dosage forms of cyclophosphamide
IV or PO, IV is preferred
onset of cyclophosphamide
3-16 weeks
toxicity of cyclophosphamide
hemorrhagic cystitis and bladder cancer (greater risk with PO administration)
cyclophosphamide is only for ____
induction
how to prevent bladder toxicity with cyclophosphamide
intermittent pulse IV doses, hydration, frequent voiding, or giving with mesna
____ and ____ are preferred for maintenance therapy
azathioprine and mycophenolate
ADRs of cyclophosphamide
myelosuppression, increased infection risk, cardiac/hepatic/pulmonary toxicity, decreased fertility, teratogenic, urinary/renal toxicity
monitoring for cyclophosphamide
baseline and monthly CBCs and urinalysis
voclosporin MOA
calcineurin inhibitor– blocks activation of T cells, cytokine release, and costimulation of B-cells with release of autoantibodies; helps maintain glomerular filtration barrier in kidneys
voclosporin is the first drug to be FDA-approved for _____
treatment of active lupus nephritis
voclosporin is used in combo with
mycophenolate and steroids
belimumab brand name
benlysta
belimumab MOA
B-lymphocyte stimulator (BLyS): cytokine that is important for B-cell survival, maturation, and differentiation
belimumab is a ________ antibody
fully human monoclonal
belimumab is FDA approved for ____
treatment of autoantibody-positive SLE in addition to standard therapy
benefits of belimumab
prevents the survival of B- lymphocytes by blocking the binding of BLsY to receptors on B lymphocytes
promotes apoptosis of B-lymphocytes
reduces activity of B-cell mediated immunity and the autoimmune response
onset of belimumab
8 weeks for action on B cells, 16 weeks for clinical improvement
belimumab dosage forms
IV or SubQ
place in therapy for belimumab
decreases flares, disease activity, and steroid use
belimumab ADRs
nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, pharyngitis, injection site reaction
limitations for use of belimumab
not been evaluated in patients with severe CNS lupus; not recommended
data does not support safety and efficacy of belimumab with concomitant use of ____
rituximab or other biologics
FDA warnings of belimumab
mortality (serious and fatal infections reported); progressive multifocal leukoencephalopathy (PML); hypersensitivity reactions (anaphylaxis), depression and suicidality; live vaccines should not be given concurrently
rituximab MOA
IV chimeric monoclonal antibody directed at the CD20 antigen on B cells
rituximab place in therapy
use in SLE being investigated, potential for use in refractory lupus nephritis/ severe hematological lupus/ CNS manifestations
rituximab ADRs
infusion reactions, mucocutaneous reactions, allergy, infection, PML, hepatitis B virus reactivation
rituximab FDA warnings
fatal infusion reaction within 24 hours of infusion, tumor lysis syndrome, severe mucocutaneous reactions, PML
anifrolumab brand name
saphnelo
anifrolumab MOA
fully human IgG1-Kappa monoclonal antibody that blocks type 1 interferons through binding the type I interferon receptor subunit I, leading to reduced inflammation
anifrolumab ADRs
nasopharyngitis, URTIs, bronchitis, infusion reactions, herpes zoster and cough
limitations of use anifrolumab
efficacy has not been evaluated in patients with severe active lupus nephritis or severe active CNS lupus; use not recommended for use with other biologic therapies
rule of thumb for biologics
never use them together
FDA warnings anifrolumab
serious infections, hypersensitivity reactions, malignancy, avoid use of live or live-attenuated vaccines
class I and II lupus nephritis
minimal mesangial and mesangial proliferative
all patients with nephritis should receive __
hydroxychloroquine 200-400 mg/day to reduce damage and flares +/- NSAIDs/glucocorticoids
Class III and IV nephritis
more severe kidney involvement
induction treatment for Class III/IV
high dose IV glucocorticoids then PO
+ induction with PO mycophenolate or cyclophosphamide
continue by 6 months
maintenance treatment nephritis class III/IV
mycophenolate 1-2 g/day or azathioprine 2 mg/kg/day +/- PO low dose glucocorticoids. if no response then belimumab or voclosporin
what is nephritis class V
membranous lupus nephritis and nephrotic range proteinuria >3 g/day
treatment of class V induction
PO prednisone + induction with PO mycophenolate continue x 6 months
if no response: switch induction to cyclophosphamide and IV pulse glucocorticoids then prednisone x 6 months
maintenance class V nephritis
mycophenolate or azathioprine +/- PO glucocorticoids
continue 3-5 years
neuropsychiatric lupus treatment
hydroxycloroquine is preferred. anticonvulsants, antidepressants, antipsychotics as needed. glucocorticoids alone or in combo for inflammation/neurotoxic damage
can you have positive antiphospholipid antibodies without APS?
yes
what makes you considered to have APS
positive antiphospholipid antibodies and a clot/thrombotic event
positive antiphospholipid antibodies/no clot: prophylaxis?
aspirin 81 mg PO daily
women avoid estrogen
address modifiable risk factors
TREATMENT for people that do have APS (antibodies + clot)
warfarin with INR goal 2-3, if they are pregnant use LMWH
all patients taking prednisone should take
calcium and vitamin D
hydroxychloroquine in pregnancy _____ recommendent
IS
highest risk drug-induced SLE
procainamide, hydralazine
moderate risk drug-induced SLE
isoniazid, quinidine, sulfadiazine
low risk drug-induced SLE
methyldopa, chlorpromazine, carbamazepine, prophylthiouracil, minocycline, captopril
