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PDAT4 > 26 - SLE Lupus > Flashcards

26 - SLE Lupus Flashcards

1
Q

Etiology - Risks/Causes
SLE

A

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

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2
Q

ANA Testing
SLE

A

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**
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3
Q

What Immunologic Abnormality is
Highly Specific for SLE?

A

ANTI dsDNA

Present in 70% of patients

Correlates w/ DISEASE ACTIVITY

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4
Q

Immunologic Abnormalities in SLE

A

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

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5
Q

Clinical Manifestations
SLE

A

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

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6
Q
  • *Additional LABS**
  • *useful @ diagnosis & routine monitoring for SLA**
A

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

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7
Q

Prognosis of SLE

A

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
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8
Q
  • *NON-PHARMACOLOGIC**
  • *SLE Treatment**
A

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**
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9
Q

General Treatment Aproach
MILD SLE
Skin / Joints

Therapy is based on:
organ system involved & activity/severity of disease
​SPECIFIC to each patient

A

HCQ
+/-
NSAIDS
+/
Short Term / Low Dose PREDNISONE
<7.5mg/d

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10
Q

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​

A

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)

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11
Q

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​

A

INDUCTION
HIGH DOSE IV STEROIDS + MMF or Cyclphosphamide
Rituximabforfailures of MMF or Cyclophophamide

  • *Maintanence**
  • reduce* steroids –> transition to MMF / AZA (PO)
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12
Q

Which SLE Drug can cause STERILITY?

A

CYCLOPHOSPHAMIDE
alkylating agent

Also:
Hemorrhagic Cystisis - HYDRATE

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13
Q

Which SLE Drug has the ADR of:
DEPRESSION / SUICIDAL THOUGHTS

A

BELIMUMAB

also do not use for:
Rena / ​CNS lupus

avoid live vaccinations

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14
Q

Drugs that are safe for
PREGNANCY & LACTATION
SLE

A

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*
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15
Q

NSAIDs for SLE

Indications / Concerns

A

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

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16
Q

When to Avoid LIVE VACCINES
for CorticoSteroid Users

A
  • 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

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17
Q

CorticoSteroids for SLE

Indication / Dosing

A

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
18
Q

HydroxyChloroQuine for SLE

Indication / ADR

A

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

19
Q

Methotrexate for SLE

Indication / MoA / Considerations

A

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

20
Q

Methotrexate for SLE

ADRs

A

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

21
Q

AZAthioprine for SLE

MoA / Consideration

A
  • *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
22
Q

AZAthioprine

ADR’s

A

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

23
Q

Mycophenolate (MMF) for SLE

MoA / Indication

A
  • 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

24
Q

Mycophenolate (MMF)

ADRs

A
  • *avoid LIVE Vaccines**
  • *Infections / opportunistic**
  • *GI - NVD**
  • may be SEVERE*

Hematologic
neutropenia

Hepatotoxicity

Malignancies
lymphoma / skin CA

25
Q

Belimumab

Indication / MoA

A

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**
26
Q

What Drug(s) can NOT be used in:
Lupus Nephritis // CNS Lupus

A

BELIMUMAB

Typically used are:

  • *MMF / Cyclophosphamide / AZA**
  • *Rituximab** is reserved for MMF & Cyclophosphamide FAILURES
27
Q

Belimumab

Labs / ADR

A

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

28
Q

Which SLE Drug is safest for people treated for
CANCER?

A

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

29
Q

Rituximab

MoA / Indications

A

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

30
Q

Rituximab

Labs / ADR

A
  • *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

31
Q

Cyclophosphamide

MoA / Indications

A
  • *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

32
Q

Cyclophosphamide

Labs / ADR

A

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

33
Q

Additional Considerations
for SLE Patients

A

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

34
Q

Cutaneous Lupus

Treatments

A

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

35
Q

CNS Lupus

Therapy

A

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

36
Q

Lupus Nephritis (LN)

Screening / Treatment / Management

A

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

37
Q

SLE & Pregnancy

A

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

38
Q

SLE + Pregnancy

Drug Considerations

A
  • *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
39
Q

Antiphospholipid AB = aPL
&
APLS = Antiphospholipid AB syndrome

A
  • *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

40
Q

Anticoagulation for
APLS-TE PROPHYLAXIS

A

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

41
Q

Drug-Induced LUPUS

A

+ 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**

PDAT4 (34 decks)

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