26 - SLE Lupus Flashcards
Etiology - Risks/Causes
SLE
Environmental Factors
infection / UV light / drugs
Immunologic Abnormalities
changes in T&B cell signaling
AUTOANTIBODY PRODUCTION -
Hyperactive B-cells –> against nuclear components of cell
Termed AntiNuclear AB’s = ANA
Hormonal Influences
estrogen / thyroid / prolactin
Genetics
ANA Testing
SLE
Often the FIRST TEST
- but it is NOT definitive for SLE*
- occurs in other diseases: sclerosis / RA / sjogen*
Titer = HIGHEST DILUTION LEVEL
that is able to detect AG response
Titer of 1:320 is a GREATER concentration of ANA vs 1:160
- *ANA titer of 1:80 = Positive**
- but they fluctuate and are not correlated w/ severity or activity*
- *ANA is NOT routinely monitored**
What Immunologic Abnormality is
Highly Specific for SLE?
ANTI dsDNA
Present in 70% of patients
Correlates w/ DISEASE ACTIVITY
Immunologic Abnormalities in SLE
ANA
Anti dsDNA
highly specific for SLE –> correlates with disease activity
RNA-Associated Antigens
checked INITIALLY, but NOT followed
Antiphospholipid AB (aPL)
blood clotting risk
Clinical Manifestations
SLE
Fatiue / Fever / Myalgia / Weight loss
ARTHRALGIAS
SKIN MANIFESTATIONS
butterfly rash - photosensitivity // discoid lesions
- *RAYNAUD PHENOMEON**
- *Vasospasm** of arteries in hands/feet –> ulcers/gangrene
- *HEMATOLOGIC**
- *Anemia** of chronic disease
- *Leukopenia / Thrombocytopenia**
AFFECTS ALL ORGANS
- *Additional LABS**
- *useful @ diagnosis & routine monitoring for SLA**
Complete Metabolic Panel = CMP
abnorbalities in BUN / Cr / LFTs
CBC w/ diff
- *Complements** (C4/Cd)
- reduction can indicate* flare / risk of flare
- *Anti-dsDNA**
- correlates w/ DISEASE activity –> want UNDETECTABLE levels*
Urinalysis
Urine Protein / Cr Ratio
Prognosis of SLE
Depends on WHICH ORGAN / System are affected
CNS or RENAL** = **POOREST prognosis
Skin / Musculoskeletal / Drug-Induced = GOOD prognosis
- Poor prognostic factors for SURVIVAL:*
- *RENAL Disease / HT**
- *MALE SEX** / young age / old age
- *African American**
- *APLS** or Antiphospholipid ABs present
- *NON-PHARMACOLOGIC**
- *SLE Treatment**
AVOID Sun exposure
use sunscreen > 30 SPF
Balanced diet –> replace VIT D when low
REST / EXERSISE
AVOID SMOKING
associated w/ disease activity
- Reduce Infection Risk*
- *vaccinate / treat infections fast**
General Treatment Aproach
MILD SLE
Skin / Joints
Therapy is based on:
organ system involved & activity/severity of disease
SPECIFIC to each patient
HCQ
+/-
NSAIDS
+/
Short Term / Low Dose PREDNISONE
<7.5mg/d
General Treatment Aproach
MODERATE SLE
Significant / non-organ threatening
constitutional / skin / musculoskeletal / hematologic
Therapy is based on:
organ system involved & activity/severity of disease
SPECIFIC to each patient
HCQ
+/-
Short Term Prednisone
7.5 -15 mg/day
Often will need an oral steroid-sparing agent:
MTX / AZA / MMF
Belimumab (reserved for more resistant cases)
General Treatment Aproach
SEVERE SLE
Life Threatening / MAJOR ORGANS involved
RENAL or CNS
Therapy is based on:
organ system involved & activity/severity of disease
SPECIFIC to each patient
INDUCTION
HIGH DOSE IV STEROIDS + MMF or Cyclphosphamide
Rituximabforfailures of MMF or Cyclophophamide
- *Maintanence**
- reduce* steroids –> transition to MMF / AZA (PO)
Which SLE Drug can cause STERILITY?
CYCLOPHOSPHAMIDE
alkylating agent
Also:
Hemorrhagic Cystisis - HYDRATE
Which SLE Drug has the ADR of:
DEPRESSION / SUICIDAL THOUGHTS
BELIMUMAB
also do not use for:
Rena / CNS lupus
avoid live vaccinations
Drugs that are safe for
PREGNANCY & LACTATION
SLE
AZA
for clinically active Lupus nephritis
HCQ
for H/O of LN + mild disease activity
Corticosteroids
- *NSAIDS** - ONLY for Lactation
- avoid after 32nd week for Pregnancy*
NSAIDs for SLE
Indications / Concerns
1st Line treatment for:
Arthritis / Muscoskeletal SX / Fever / Serositis
inflammation of lining membranes = Pleuritis / Pericarditis
LOW Dose ASA for patients with AntiPhospholipid AB
ADR:
can REDUCE renal function // incease cardiac events in @risk pts
Bleeding / Ulcers / Bronchospasm
When to Avoid LIVE VACCINES
for CorticoSteroid Users
- AVOID LIVE VACCINES for:*
- *PREDNISONE > 20mg/day**
Ideally:
taper down to LOWEST effective dose needed to maintain low disease activity
Use steroid sparing medications to elim steroids
except PRN for flares
CorticoSteroids for SLE
Indication / Dosing
Quickly control DISEASE FLARES & maintiain LOW disease activity
Flare = measurable increase in disease activity in 1+ organs
involving new or worse clinical s/sx +/- lab measurements
Mild Flare < 7.5mg/day
Moderate Flare > 7.5mg/day
- *Severe Flare**:
- *Prednisone 1-2mg/kg/day** or IV pulses of MP
HydroxyChloroQuine for SLE
Indication / ADR
ALL PATIENTS
should take HCQ unless contraindicated
Anti-inflammatory / immunomodulatory / antithrombotic
No Dose Adjustments or Lab Monitoring
200-400mg QD
ADR:
OCULAR TOXICITY
irreversible RETINOpathy, needs yearly eye exam
GI side effects - NVD
Methotrexate for SLE
Indication / MoA / Considerations
inhibits DIHYDROFOLATE REDUCTASE, needed for
DNA synthesis / growth
Primarily for:
Arthritis + Skin
- *Hepatic + Kidney (90%)**
- *Renal Impairment –> REDUCE DOSE**
AVOID LIVE VACCINES
when dose is >0.4 mg/kg MTX / week
Methotrexate for SLE
ADRs
avoid ALCOHOL
due to risk of hepatotoxicity –> LFTs / cirrhosis / fibrosis / failure
Bone Marrow Suppression
hematologic
RESPIRATORY
interstitial pneumonitis / pulmonary fibrosis / cough
Add FOLIC ACID to avoid ADRs:
Dermatologic - ALOPECIA / rash / skin sunsitivity
NVD / Stomatitis
AZAthioprine for SLE
MoA / Consideration
- *Imidazoyl Derivative of MERCAPTOPURINE**
- inhibits* DNA synthesis, reduces immune cell proliferation
- inactivated by:*
- *TMPT**
- if enzyme activity is low* –> more myelosuppression / hepatotoxicity
- *Xanthine Oxidase**
- inhibitors of XO –>* risk of myelosuppression / hepatotoxicity also
AZAthioprine
ADR’s
Common = GI NVD
take with food or divide doses
avoid LIVE vaccines
when dose is >3mg/kg AZA / day
Hepatotoxicity
increase LFT / Bilirubin, REVERSIBLE with D/C
- *Hematologic Toxicity**
- *DOSE related**
Pericarditis / PML / Pancreatitis / Athralgia / Myalgia / Infxn / Malignancy
Mycophenolate (MMF) for SLE
MoA / Indication
- inhibits* IMPDH
- -> inhibits De-novo synthesis of Guanosine nucleotides
- reduces* differentiation of T/B cells
Severe SLE - Induction W/ IV Steroids
Or
Moderate SLE - Oral Steroid Sparing Agent
Mycophenolate (MMF)
ADRs
- *avoid LIVE Vaccines**
- *Infections / opportunistic**
- *GI - NVD**
- may be SEVERE*
Hematologic
neutropenia
Hepatotoxicity
Malignancies
lymphoma / skin CA
Belimumab
Indication / MoA
Binds to soluble BlyS –> inhibits the binding of BLys –> B-cell Receptors
Increase Apoptosis of B-cells
decrease B-cells –> plasma cells
decrease Autoantibodies due to decrease of auto-reactive b-cells
Indicated / approved for:
Active & Antibody +
patients on std therapy (except Cyclophosphamide & ritixumab)
for Moderate SLE - reserved for RESISTANT cases
- do NOT use with patients with:*
- *CNS Lupus or Lupus NEPHRITIS**
What Drug(s) can NOT be used in:
Lupus Nephritis // CNS Lupus
BELIMUMAB
Typically used are:
- *MMF / Cyclophosphamide / AZA**
- *Rituximab** is reserved for MMF & Cyclophosphamide FAILURES
Belimumab
Labs / ADR
NOT used for Severe SLE or CNS lupus/nephritis
10mg/kg IV
LABS b4 initiation:
CBC w/ diff, TB , HEP B/C
avoid LIVE vaccines
ADR:
DEPRESSION & SUICIDAL THOUGHTS
N/D/Fever/Insomnia / Headaches
Infections / PML / Malignancy / INFUSION rxn
Which SLE Drug is safest for people treated for
CANCER?
RITUXIMAB
Can be used for patients treated within
cancer last 5 years
ALSO:
do not need to check for _TB_
HEP B+C screen at start though.
still avoid LIVE vaccines
Rituximab
MoA / Indications
Depletes B-cells by binding to CD20 Antigen
- *IV Dosage**
- does not require continuous therapy, last* 4mo -> year
Reserved for:
SEVERE SLE - failures of MMF & Cyclophosphamide
&
past 5 years treated - CANCER PATIENTS
Rituximab
Labs / ADR
- *SCr** / CBC / HEP B+C
- *does NOT need TB TEST**
- avoid LIVE vaccines*
Adr:
INFUSION REACTION
Infection / PML / SJS-Tens
Nephrotoxicity / Cardiac Arrythmias
common:
Fevers / chills / weakness / Cough / HA / rhinitis
Cyclophosphamide
MoA / Indications
- *Alkylating Agent**
- *cytotoxic / inhibits pre-synthesis**
Typically IV dosing, rarely PO
GI Side effect common –> take ONDANSETRON prior
Indicated for:
SEVERE SLE - Induction tx w/ High dose IV steroid
Cyclophosphamide
Labs / ADR
LFTs / CBC w-diff / UA / SCr
avoid LIVE vaccines
ADRs:
- *STERILITY**
- *hemorrhagic cytitis = hydrate**
N/V is common –> ONDANSETRON
ALOPECIA
Malignancy / infection / Hypersensitivity / Cardiac Toxicity
Leukopenia / Thrombocytopenia
Intertitial Pneumonitis / Pulmonary Fibrosis
Additional Considerations
for SLE Patients
IMMUNIZATIONS
when B-Cells are HIGHEST & b4 mABs
SLE patients are prone to HPV Human Papilloma Virus
consider vax –> but there is INCREASED risk for TE events post vax
Osteoporosis prevention
Evaluate at treat: HTN / Depression
Evaluate and treat sequalae of SLE:
Raynauds / APLS
Cutaneous Lupus
Treatments
3 Types:
- *Head/Neck** // Upper Trunk // Arms
- may be DISFIGURING*
Treatment:
- *Sunscreen** / avoid Sun
- *Corticosteroids + Calcineurin Inhibitors** (tacrolimus + Pimecrolimus)
- *HCQ** // Oral Corticosteroids
if UNCONTROLLED consider ADDING:
MTX / MMF / oral retinoids / dapsone
Thalidomide / IVIG / Rituximab
AZA / leflunomide / Cyclophosphamide
CNS Lupus
Therapy
Tx depends on nature of problem:
Inflammatory:
Glucocorticoids +/- IMS
Thrombosis or moderate/high titers of APL Antibody:
use ANTICOAGLANTS +/- Platelet aggratation inhibitors
Systomatic therapy:
anticonvulsants / antidepressants
Lupus Nephritis (LN)
Screening / Treatment / Management
BIOPSY
for all patients with evidence of ACTIVE LN
HCQ
for ALL patients with LN
Pts w/ proteinurea > 0.5g/24 hours should have ACE-I or ARB
BP target < 130/80
LDL >100mg –> STATIN
Pregnancy COunseling
SLE & Pregnancy
SLE often FLARES during pregnancy / post-partum
less likely if SLE is in remission @ conception
Prefer disease stable for > 6 months
Risk for Neonatal lupus increased in mothers with:
anti-Ro/SSA or anti-LA/SSB
DISCOURAGE pregnancy in pts with:
HTN / renal insufficiency / lung disease / Heart failure
or
6 months of severe flare / active LN / CVA
SLE + Pregnancy
Drug Considerations
- *D/C Teratogenic Drugs > 3MONTHS B4 Conception**
- *MTX / MMF / Cyclophosphamide**
AVOID Biologics for 3-6months+ prior to pregnancy
- *+LOW DOSE ASA+**
- reduces* risk for preclamsia & fetal loss
HCQ can be continued
- *Corticosteroids** –> use lowest effective dose
- reduces risk for* Gestational DM & PROM
AZA is SAFE in pregnancy
if IMS is needed, max dose 2mg/kg/day
- *Anticoagulate women w/ APL AB**
- *LMWH / UFH** for APLS
Antiphospholipid AB = aPL
&
APLS = Antiphospholipid AB syndrome
- *40% of SLE pts have aPL**
- but
- NOT ALL** patients with aPL have APLS
Diagnosis of APLS:
1 lab criteria + 1 Clinical Event
time between both must be
>12 weeks & <5 years
Lab Criteria:
Lupus Anticoagulant / Anticardiolipin AB or AntiB2 Glycoprotein
Positive at least TWICE and >12 weeks apart
Clinical Events:
Arterial or venous thrombosis (CVA / PE / DVT)
PREGNANCY COMPLICATION
unexplained fetal death after 10th week / premature birth due to ecamsia
preeclamsia // >3 spontaneous abortions @ <10 weeks
Anticoagulation for
APLS-TE PROPHYLAXIS
Low Dose ASA
patient WITHOUT h/o of Arterial or Venous thrombosis
Warfarin
AFTER a TE event
INR 2-3, lifetime anticoagulation
DOACS
available, but data is limited in APLS
Drug-Induced LUPUS
+ ANA** & **AB to Histones
+
without anti-dsDNA
D/C offending med –> sx typically resolve
Commonly seen:
rash / myalgias / arthralgias / fever / wt loss
- RARE:*
- *CNS / renal invovlement / hematologic**
