SLE - Block 1 Flashcards
What is systemic lupus erythematosus (SLE)?
An autoimmune dx that is associated with the production of autoantibodies
What are the predisposing factors of SLE?
- Genetic influences
- Epigenetic regulation of gene expression: inhibition of DNA methylation (hydralazine, procainamide) -> DI-lupus
- Environmental factors: Medications
- Hormones
What are 2 common drugs that can induce lupus?
Hydralazine and procainamide
Anti-arrhythmic that cause lupus?
- Procainamide
- Quinidine
- Amiodarone
- Mexiletine
Anti-thyroid that induce lupus?
Methimazole
Propylthiouracil
Anti-HTN that indue lupus?
Hydralazine
Methyldopa
Anti-infective that induce lupus?
Doxycycline, minocycline, tetracycline, isoniazid, nitrofurantoin
TNFa inhibitors that induse lupus?
- Adalimumab
- certolizumab pegol
- etanercept
- golimumab
- infliximab
Anti-siezure that induce lupus?
Carbamazepine, ethosuximide, lamotrigine, phenobarbital, phenytoin, zonisamide
Anti-psychotics that induce lupus?
Clozapine, chloropromazine, fluphenazine, perphenazine, thioridazine, thiothixene, trifluoperazine
PPIs that induce lupus?
Dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole
How do you diagnose drug-induced lupus?
Symptom onset of at least 1 month after initiation & symptom improvement within days to months after drug discontinuation
What are the characteristics of SLE?
- Dysfunction of the innate and adaptive immune system
- Altered activation and signaling of T and B lymphocytes
- Reduces clearance of apoptotic cellular debris -> stimulation of immune system
- Increases risk for infection
- Certain autoantibodies can be present for years prior to the clinical presentation of SLE
What are the complications of having autoantibodies to blood cells? Phospholipids?
Cytopenia; thrombosis and fetal loss
Stimulates B-cell production, along with autoantibodies, in renal cells, which can cause skin & join symptoms associated with SLE?
IL-10
Increased production from T cells, which is associated with disease activity & kidney/tissue damage?
IL-17
Important for T-regulatory cell function & inhibition of IL-17 and decreases concnetration in SLE?
IL-2
Secreted from plasmacytoid dendritic cells?
Type 1 interferon and interferon-γ
Interferon associated with mucocutaneous inflammation?
High concentrations of type 1 interferon
Interferon associated with nephritis and arthitis?
High concentrations of interferon-γ
increase B-cell survival & differentiation?
BLyS
Increases antibody production?
IL-6
What is the most common sign of lupus? Others?
Arthritis
Rash
Fever
Raynaud’s phenomenon
What is the most common sx of lupus? Others?
Fatigue
Joint pain/stiffness
T/F: Presence of ANA means a patient has SLE?
False: used as a screening test, but NOT specific for SLE
Examples of diagnostic tests for lupus?
Serology: autoantibodies, antiphospholipis antibodies, complement
Inflammatory markers: CRP, ESR
What is the 1st sign of systemic dx?
Skin manifestations via cutaneous lupus
What are the types of cutaneous lupus?
- Acute cutaneous lupus erythematosus (malar rash or butterfly rash)
- Subacute cutaneous lupus erythematosus
- Chronic cutaneous lupus erythematosus
- Intermittent cutaneous lupus erythematosus
Lupus nephritis are more common to what populations? Most prevelant in?
African American, Hispanic, Asian patients
More prevalent in men
Patients with lupud nephritis may also have ___ and are at risk for ____?
other cormorbities (HTN); accelerated atherosclerosis
What are the general approaches to treating SLE?
- ANti-malarial med (hydroxychloroquine)
- Lifestyle modifications (counseling, aerobic exercise, weight loss, sun protection, smoking cessation)
- Evalute and treat other comorbidies
What are the approaches of using NSAID for lupus?
- Are not disease modifying agents
- Onyl used to relieve sx control
- Low dose aspirin (81 mg PO QD) for patients with antiphospholipid antibodies
What are the approaches of using CS for lupus?
Monotherapy or adjunct therapy
High doses: pulse IV regimens
Maintenance doses: low as possible for SLE flares
* Assess for ADRs: ↑ BP/BG, glaucoma, cataracts, weight gain, osteoporosis, mood changes
* Evalutate patients with SLE for prevention and tx of GC-induced osteoporosis
Prednisone, Methylprednisolone
What is the preferred medication for all patients with SLE especially for pregnancy and lactation?
Hydroxychloroquine
Hydroxychloroquine
Therapeutic Effects, ADR, RF, Monitoring
Therapeutic effects:
* Improvements in SLE manifestations -> 2 – 8 weeks
* Maximum clinical efficacy -> 3 – 6 months
ADR: Retinal toxicity
RF for retinal tox:
* Therapy duration > 5 years
* daily doses > 5mg/kg ABW
* concurrent use of tamoxifen
* past medical history of renal dysfunction or macular disease
Monitoring for eye exams:
* Baseline testing -> within 1-2 months of initiation
5 years of therapy -> annual testing, except for high-risk patients (monitored annually earlier)
Belimumab
ADR, CI
CI:
* Don’t give with DMARD or live vaccines
* Pregnancy caution
* Africican America patients have a low response rate
ADR:
* Depression and suicidal ideation
* Infusion or hypersensitivity rx (anti-pyretic, anti-histamine agents
Rituximab
ADR, Caution
ADR: Infusion related rx
Caution:
* Don’t give with DMARD or live vaccines
* Screen High risk patients for HBC and HCV before initiating therapy
* Consider pre-medication with steroid, acetaminophen, & antihistamine before initiating therapy.
Cyclophosphamide
ADR, Counseling
ADR: hemorrhagic cystitis from increased concnetrations of acrolein
Counseling:
* Administer with IV fluids before drug
* Administer mesna to decrease bladder toxicity (binds to acrolein)
Mycophenolate mofetil
ADR, Counseling
ADR: GI complaints
Counseling:
* Undergoes enterohepatic recycling to convert to active form
* Consider a dose reduction or switch to enteric-coated form (Myfortic) to decrease sx
Azathioprine
CI
Recommended to screen patients for TPMT deficiency prior to initiating therapy
TPMT deficiency -. myelosuppression
How does mercaptopurine undergo metabolism?
Inactivated by thiopurine methytransferase (TPMT)
Methotrexate
Dosing, Counseling
Dosing: QW
Counseling: Administer w/ folic acid to reduce toxicities
What is the recommended daily dosae of VD3?
1000-2000 IU PO QD
What is the first line for lupus nephritis?
Hydroxychloroquine
What are the antibodies that can increase the antiphospholipid syndrome and promote clotting and pregnancy morbidity?
- Anti-cardiolipin
- Anti-β2-glycoprotein
- Lupus anticoagulant
How do you diagnose antiphospholid syndrome?
One laboratory feature:
* Presence of antiphospholipid antibodies on two (2) separate occasions, separated by 12 weeks
*High risk: presence of lupus anticoagulant, combination of 2-3 antiphospholipid antibodies, or presence of persistently elevated antiphospholipid antibody titers
*Low risk: positive anticardiolipin or anti-β2-glycoprotein I at low-medium titers
One clinical feature:
* Vascular events
* Obsteric complication
What is the tx for Thromboprophylaxis in Patients with SLE and Antiphospholipid Antibodies?
Low-dose aspirin (81mg PO daily) for both high and low risk
When would aspirn be switched to warfarin?
Patient has first VTE (INR goal 2-3)
What is the INR target range?
2-3
What do you do it INR is ≥6?
Refer to Vitamin K policy
Tx for Class I & II (minimal mesangial & mesangial proliferative) lupus nephritis?
Do NOT require immunosuppressive agents
Tx for Class III & IV (focal & diffuse) lupus nephritis?
Duration
Treat with immunosuppressive therapy & glucocorticoids.
* Caucasian & Asian patients -> recommend IV cyclophosphamide for induction therapy
* African American & Hispanic patients -> recommend mycophenolate mofetil for induction therapy
Duration of induction therapy -> 6 months
Tx of Class V mixed with Class III & IV lupus nephritis?
Duration
Recommend same treatment for patients with Class III & IV lupus nephritis:
* Caucasian & Asian patients -> recommend IV cyclophosphamide for induction therapy
* African American & Hispanic patients -> recommend mycophenolate mofetil for induction therapy
Duration of induction therapy -> 6 months
For lupus nephritis what does induction tx look like?
Start maintencance therapy (mycophenolate mofetil or azathioprine)
How long does lupus nephritis maintenance therapy go for?
Continue 3-5 years in complete renal remission
When can non-live vaccines be administered in patients with SLE?
2 weeks before initiating immunosuppressive therapies
When can live vaccines be administered in patients with SLE?
Administer at least 4 weeks before initiating immunosuppressive therapies
Can rZoster be given to SLE patients?
- Can be administered while on immunosuppressive therapies
- Avoid use in pregnancy!
Tx for Pure Class V (membranous) lupus nephritis?
- Recommend induction therapy with mycophenolate mofetil & glucocorticoids for 6 months.
- Improvement after induction therapy -> recommend mycophenolate mofetil or azathioprine
- Duration of maintenance therapy -> continue for 3 – 5 years in complete renal remission
Tx for Class VI (advanced sclerosing) lupus nephritis?
Consider renal replacement therapy.
When would we use ACEI/ARB?
proteinuria (≥ 0.5g/day) to delay dx progression and maintain BP of <130/80
When would be use statin therapy?
LDL > 100mg/dL for prevention of accelerated atherosclerosis
What is first line for cutaneuous lupus?
Topical CS
How do we select topical CS?
Low potency: thin skin regions on face & groin
Moderate potency: skin on trunk & extremities
High: thick-skin areas (scalp, soles, palms)
Use the lowest effective potency & shortest duration of therapy
What is the 1st line for severe, disseminated cutaneous lupus?
Hydroxychloroquine
What are medications that can bring about fertilitity issues while with SLE?
- Cyclophosphamide
- Estrogen-containing oral contraceptives
- Mycophenolate
What kinds of contraceptives are suitible for SLE women?
- COC
- Vaginal ring
- POP
- Progestin-IUD
What kinds of contraceptives are suitible for women with SLE and antiphospholid antibody (+)?
Avoid COC
What the approaches for SLE women wanting to get pregnant?
- Avoid attempting pregnancy within 6 months of a severe SLE flare
- Pregnancy has best outcomes in patients with inacitve SLE for at least 6 mpnths
- DC teratogenic meds
* Methotrexate & thalidomide: DC 1-3 months before conception, DC thalidomide 4 weeks before conception
* Mycophenolate: Discontinue > 6 weeks before conception (women).
* Cyclophosphamide: Discontinue 3 months before conception (men & women).
* Leflunomide: Initiate oral cholestyramine elimination procedure (8 grams PO TID for 11 days).
* Avoid fluorinated CS: dexamethasone, betamethasone
* NSAIDS: Avoid use in 1st trimester due to risk of miscarriage, Avoid use in 3rd trimester due to risk of premature closure of ductus arteriosus.
* HTN: DHP-CCB, beta-blockers, a2-agonists (Avoid ACEI/ARBs)
Hydroxychloroquine can be used during pregnancy
What is the difference between non-live/recombinant vs line-attenuated vaccines?
Non-live: safe for immunocompromised patients
Live: safe for immunocompromised patients
Are B-cell depleting therapies (rituximab) safe with immunizations?
- Decreases humoral immune response to vaccines.
Administer vaccines at least 6 months after & 4 weeks before next course of B-cell-depleting therapies
