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PDAT4 > 26 - SLE Lupus > Flashcards

26 - SLE Lupus Flashcards

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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

Study These Flashcards
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

Study These Flashcards
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

Study These Flashcards
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

Study These Flashcards
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

Study These Flashcards
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

Study These Flashcards
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

Study These Flashcards
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

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

Hematologic
neutropenia

Hepatotoxicity

Malignancies
lymphoma / skin CA

25
**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**
26
**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
27
**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**
28
**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
29
**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**
30
**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**
31
**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**
32
**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**
33
**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**
34
**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**
35
**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
36
**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**
37
**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**
38
**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**
39
**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
40
**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*
41
**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**

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