SLE

Clinical Care

what is SLE

• autoimmune disease of an unknown cause in which the bodys immune system attacks healthy body tissue

• chronic and causes pain and inflammation in any part of the body

SLE has the presence of which autoantibody

anti-nuclear antibodies

antibodies against a persons own proteins or immune system

clinical presentation of SLE

• joint pain and swelling (the joints of fingers, wrists, hands and knees are affected

• cardiac involvement (chest pain and vascular manifestations

• skin rash (butterfly rash seen over cheeks and bridge of nose. may worsen with sunlight)

• renal involvement (lupus nephritis)

• arthralgia

• sensitivity to light

what are the constitutional symptoms in SLE

fever, fatigue, and weight loss

patients with lupus have what sensitivity to light

photosensitive

preventing sunburns is very important

risk factors for lupus

• family history

• gender: more common in women

• african american, hispanics, native americans and asians

• age: 15-44

drug induced lupus

• brought by overreaction to a medication

• takes several months of taking the drug to see lupus symptoms

drugs that definitively are associated with lupus

• chlorpromazine

• hydralazine

• isoniazid

• methyldopa

• minocycline

• procainamide

• quinidine

  • anti-tumor or necrosis factor alpha therapy and interferon alfa have been implicated in drug-induced. lupus

subacute cutaneous lupus has ben associated with which medications

CCBs, ACE, HCTZ, leflunomide, and terbinafine

which 3 medications are the top contributors of drug induced lupus

hydralazine, procainamide, quinidine

GOT of SLE

• relieve symptoms and prevent damage and complications (lupus nephritis)

• control autoimmune activation and inflammation

• improve QOL

• induce remission

Non-pharm SLE

• patient education

• immunizations (flu, avoid live vaccines)

• avoid prolonged sun exposure: wear protective hat and clothing, and use sunscreen with SPF >/= 30

• eat a heart healthy diet and exercise (anaerobic exercise good)

• smoking cessation

why are patients with SLE at an increased risk of osteoporosis

• due to reduced sun exposure

• patients should supplement with vitamin D (at least 1000IU) and calcium (if their intake is not at least 1200mg/day total from all sources)

pharmacological measures of SLE

• topical therapies

• NSAIDs

• anti-malarials

• CTS sparing agents

• CTS

why does SLE treatment vary so much

because lupus can affect any organ system meaning that treatment will be targeted depending on symptoms

topical therapies used in SLE

• mild local rashes can be treated with topical CTS or CI (tacrolimus, pimecrolimus)

• patients with more refractory skin disease may require systemic therapy

• most people do not respond to first line

indication for NSAIDS in SLE

• as needed for joint pain (in patients with arthritis) and pleuritic chest pain (in patients with pleuritis or pericarditis)

• all NSAIDs increase risk of MI or stroke

high doses of NSAIDs may be associated with the development of what condition

aseptic meningitis

should be limited for short periods of time for symptom control

pleuritis

inflammation of tissue that surround lungs and line chest wall

pericarditis

inflammation of lining of heart (pericardium)

which drug is first line in SLE

• hydroxychloroquine

• initiated in everyone with SLE unless contraindication

HCQ benefits in SLE

• improves photosensitive rashes, arthritis, fatigue

• can combine with other medications such as CTS and immunosuppressants

• can reduce accumulated organ damage if used early enough

• lipid and glucose lowering effects

• reduction in blood clots

disadvantages of HCQ

• withdrawal of these agents has been linked to disease flares in stable patients

• need to have regular ophthalmologic assessments to prevent irreversible retinopathy

• risk factors: high dose, therapy 5-7 years, existing liver/kidney disease, advanced age, obesity, pre-existing ophthalmologic disease

HCQ is contraindicated in what pre-existing conditioning

• those with pre-existing retinopathy or ophthalmologic disease

steroids are used in what dosage forms for SLE

IM, IV, PO

when are steroids used in SLE

as bridging therapy to obtain rapid control of acute inflammation (induce remission) and for flare ups as needed

combined with antimalarials

doses of prednisone for SLE should be kept at what dose or completely withdrawn when possible

</= 5 mg/day

due to side effects like increased risk of infection

high dose steroids are used when

• life/organ threatening conditions

• IV pulse methylprednisolone 250-1000 mg daily for 1-3 days then move down to 0.3-0.5 mg/kg/day

which agents are corticosteroid sparing in SLE

• azathioprine

• methotrexate

• cyclophosphamide

should be initiated early to minimize steroid related toxicity

which agents are used for mild-moderate lupus

azathioprine and methotrexate when therapy with HCQ (± steroids) is ineffective

MTX is effective in

refractory arthritis, skin disease, myositis, pleuritis, or pericarditis

azathioprine is also used in

maintenance therapy after induction with more potent agents in patients with severe lupus affecting the kidneys, NS, or patients with vasculitis

cyclophosphamide is indicated in

inductive therapy to treat severe lupus involving the kidneys, NS, or vasculitis

used to minimize damage and induce remission

mycophenalite is used when

• induction in proliferative nephritis

• preferred in patients who want to preserve their fertility

• more effective than azathioprine for maintenance in patients with nephritis

mycophenalate is more effective than cyclophosphamide for with ethnicities

hispanic and african backgrounds

when is rituximab used in SLE

refractory disease (lupus nephritis or severe hematologic involvement)

when is belimumab is used

in combo with standard therapies for treating active autoantibody positive SLE or used in combo to treat and maintain refractory proliferative lupus nephritis

when is anifrolumab used

• used in combination with standard therapies for treatment of severe skin disease

belimumab and anifrolumab can be considered in those

who cannot tolerate or who are unresponsive to HCQ with or without gluticocorticoids

can be considered first line in severe non-renal SLE but with extensive disease

tacrolimus and cyclosporine are used

• to treat and maintain refractory proliferative lupus nephritis and severe nephritis with proteinuria

• cyclosporine is equivalent to azathioprine for remission maintenance following induction therapy

which has a better AE profile, tacrolimus or cyclosporine

tacrolimus > cyclosporine due to AE profile (lower incidences of HTN, hyperlipidemia, gingival hyperplasia, hirsutism)

max dose of HCQ to minimize retinopathy risk

400mg/day

target dose is 5mg/kg/day based on actual body weight

what are the most common AE of HCQ

• nausea, cramps, diarrhea

rare but serious AE of HCQ

retinal deposition and ocular toxicity

cardiomyopathy

DI with HCQ

• may increase digoxin levels

• enhance AE of beta blockers

rituximab AE

mild to severe infusion reactions

rare: PML (progressive, multifocal leukoencephalopathy)

prevention of infusion reactions with rituximab

• premedicate with acetaminophen and antihistamine prior to infusion

• monitor for hypersensitivity reactions

benefits of treatment with rituximab may be delayed by how long

3-9 months

AE of corticosteroids

• acne, skin fragility, striae, GI upset, weight gain, glucose intolerance, mood swings, myopathy, glaucoma, hypertension, osteoporosis, adrenal suppression, increases susceptibility to infections

prophylaxis should be considered for what condition when using steroids

• drug-induced osteoporosis in patients taking >/= 30 mg/day or > 5 g/year

corticosteroid injection is called

methylprednisolone injectable

belimumab AE

• nausea, diarrhea, fever

• CNS: anxiety, depression, insomnia

• infusion reactions and hypersensitivity

anifrolumab AE

• nasopharyngitis, UTI, URTI, infusion reaction, headache, herpes zoster

safety and efficacy of belimumab and anifrolumab are not evaluated in

severe active lupus nephritis or severe active central nervous system lupus

smoking may affect efficacy of which biologic

belimumab

cyclophosphamide AE

• nausea, vomiting, infertility, potential for malignancy, increased risk of infection, cytopenias

• modified dosing is required in caucasian populations

AE MTX

• nausea, malaise, alopecia, oral ulcers, diarrhea, cytopenias, hepatotoxicity, pneumonitis

DI with MTX

NSAIDS/penicillins: may increase serum concentrations but not clinically significant

sulfonamides may decrease MTX clearance, alcohol increases risk of hepatotoxicity

abortogenic and teratogenic

MTX has an increased risk of toxicity in patients with which conditions

lupus nephritis and renal impairment

AE of mycophenalate

• anemia, leukopenia, thrombocytopenia, hyper/hypotension, edema, hyperglycemia, hypercholesteremia, hypokalemia, nausea, vomiting, headache, dizziness

DI with mycophenalate

• antacids, iron, magnesium and cholestyramine decrease absorption

• decreases efficacy of oral contraceptives

  • increased drug concentrations with probenacid

monitoring with mycophenalate

CBC, LFTs, and creatinine

acid likely equivalent in efficacy to mofetil

AE azathioprine

• N/V/D, fever, malaise, hepatotoxicity, increased LFTs, hepatotoxicity, leukopenia, infection, malignancy

azathioprine drug interactions

• allopurinol may increase azathioprine toxicity (monitor and decrease dose to 25-33%)

• warfarin/other anticoagulants: hypothrombinemic response may be inhibited

• ACEi: increase risk of neutropenia

  • use with immunosuppressants increases risk of infection

azathioprine takes up to how many months to reach effectiveness

3 months

monitoring for azathioprine

• CBC, LFT, and creatinine

pregnancy should be avoided when

in active disease especially if organ dysfunction because of increased risk of miscarriage and flares

SLE should be in remission for 6 months on pregnancy compatible medications before attempting conception

which drug is the only drug in SLE recommended in pregnancy

HCQ

selective use of drugs in pregnancy

• AZA (max dose 2mg/kg/day)

• prednisone (<10mg/day)

• cyclosporine

• tacrolimus

drugs CI in pregnancy

• CYC during 1st trimester

• mycophenalate

• leflunoamide

• methotrexate

biologics should be used how in pregnancy

with caution

which medications are considered compatible in breastfeeding

• HCQ, AZA, prednisone, cyclosporine, tacrolimus, and biologics

monitoring parameters SLE

• symptom control/remission

• organ funciton

• infection risk

• CV risk

• drug specific side effects (ophthalmology, OP, cancer screening)

sulfatrim in SLE

• can induce disease flares and photosensitive rashes

estrogen therapy should be avoided in

those with antiphospholipid antibodies or a history of thrombosis

HRT is associated with

increase of mild to mod flares

F/U in SLE is generally

Q 6 months once stable