Autoimmune: SLE therapeutics

What is Systematic Lupus Erythematosus (SLW)?

a CHRONIC autoimmune disease associated with a lot of different clinical manifestations.

T/F With SLE, multiple organ systems are affected

TRUE

Who is at a greater risk for developing SLE?

women during their reproductive years (15-45 years)

How do symptoms usually manifest for a patient with SLE (chronic/acute)?

acute flares

NOT CONSTANT

The etiology is not completely understood but what factors contribute to SLE?

genetic (suspectibilty genes) and environmental factors

remember- genetic loads the gun and environmental pulls the trigger!

With SLE there's _______ component with ________ triggers

genetic, environmental

Name a few examples of enviromental factors that can trigger/exacerbate SLE

- viruses

- SMOKING

- pollen

- metals

ALSO, it is though that hormones contribute to disease exacerbation (predominantly in females)

What cells are increased in SLE?

PLASMA CELLS so autoantibodies are present

Problem with plasma cells increasing in SLE

they can be dorminant for YEARS which can cause organ damage

autoantibodies can also interact with proteins and tissues

What is DILE?

Drug-Induced Lupus

- certain drugs can trigger an autoimmune response

What factors differentiate DILE from SLE?

onset is ONE MONTH after treatment was intiated and improvements are often seen once the medication is discontinued.

T/F The time-frame for DILE is variable

TRUE! Drugs vary!

What are th two diagnostic criterias for SLE?

1. EULAR/ACR 2019

2. SLICC 2012

Which diagnostic criteria REQUIRES A POSITIVE ANA?

EULAR/ACR

Whicg diagnostic can use ANY immunological criteria (not just strictly ANA)?

SLICC 2012

T/F patient with a positive ANA automatically has SLE

FALSE!!!

A positive ANA only tells you there's autoimmune dysfunction present... NOT SPECIFIC!

What is required for SLE to be considered as a diagnosis

ANA WITH CLINICAL SYMPTOMS/MANIFESTATIONS

Which immunologic tests are more SPECIFIC for SLE?

1. dsDNA

2. antibodies to SM antigen

What are the three most non-specific HALLMARK symptoms of SLE?

1. Fever

2. Fatigue

3. Weight Loss

What clinical presentation on the skin is associated with SLE?

"butterfly" rash

- tells you the patient is photosensitive

What are the most COMMON MSK (musculoskeletal) symptoms associated with SLE?

Note: these are one of the earliest clinical manifestations of SLE

arthritis and arthralgia

T/F arthritis and arthralgia are specific signs of SLE

FALSE!

think about it: arthralgia and arthritis can be anything lol

T/F there is skin involvement with SLE

TRUE!

"butterfly rash"

What is the most serious complication of SLE that is the leading cause of death?

CV!

T/F patients with SLE are at higher risk of having a coronary event

TRUE

T/F SLE is associated with manifestation of premature atherosclerosis

TRUE

What s/sx are associated with flares?

1. N/V

2. EXCRUTIATING headaches

What is the most common blood disorder associated with SLE?

ANEMIA

What nervous system side effect of SLE is also linked to corticosteroid usage?

PSYCHOSIS!

What is a major organ complication associated with SLE?

Lupus Nephritis

Is Lupus Nephritis more common in males or females?

males

Selena Gomez is rare beauty

Explain Lupus Nephritis

Antibody/Antigen complexes go into different areas of the kidney leading to deposits of protein in the urine

What is a nephrology finding in patients with Lupus Nephritis

PROTEINURIA

tells you the kidneys aren't filtering or working properly

How do we treat Lupus Nephritis?

by TREATING THE LUPUS!

It's LUPUS-induced

What antibodies are associated with SLE?

Antiphospholipid Antibodies

What are the three types of Antiphospholipid Antibodies?

1. Anticardolipin

2. AntiB-2-glycoprotein 1

3. Lupus anticoagulant

T/F a patient needs ALL antiphospholipid antibodies positive for diagnosis of SLE

FALSE!

T/F Antiphospholipids Antibodies are always seen in patients with lupus

FALSE

What does a positive antiphospholipid antibody put an SLE patient at risk of?

A CLOT!

T/F Antiphospholipid positive and Antiphospholipid syndrome mean the same thing

FALSE

What's Antiphospholipid SYNDROME?

patient has antiphospholipid antibodies PLUS A CLOT

What's Antiphospholipid positive?

Patient has antiphospholipid antibodies but DOES NOT HAVE A CLOT

What are screening tools used for in SLE?

To determine DISEASE SEVERITY

What do we use to determine disease severity of SLE?

1. SLEDAI

2. BILAG

What are some clinical manifestations we look for in patients to diagnose SLE?

- butterfly rash

- fever

- protein in urine

- Arthritis/Arthralgia

- Photosensitivity

- LUPUS NEPHRITIS

What are our goals for treatment for SLE?

1. Prevent disease flares

2. Limit organ damage

3. Achieve and maintain remission

4. Decrease disease activity

5. REDUCE use of corticosteriods

6. Improve QOL

7. Minimize ADE and costs

T/F pharmacological intervention cures SLE

FALSE

LUPUS IS A CHRONIC DISEASE- THERE IS NO CURE

What is the stepwise approach for SLE treatment

1. Evaluate disease severity (need to know this before treating)

2. Establish Non-pharmacological treatment plan

3. Establish Pharmacological treatment plan

4. MONITOR

T/F Everyone with SLE gets non-pharmacological intervention

TRUE!

What consists treatment for SLE?

IMMUNOSUPRESSANTS + SYMPTOMATIC THERAPY

What are the non-pharm treatment plans?

1. SPF (15 is ok but 30 preferred)

2. Wear protective clothing (hats, sunglasses)

3. AVOID photosensitizing medications (ex. DOXYCYCLINE)

4. SMOKING CESSATION

5. AEROBIC exercise

6. Staying up to date with vaccines

7. SLEEP

8. medidation

What's the MAIN treatment for SLE?

ANTI-MALARIAL Hydroxychloroquine (HCQ)!!!!

What are potential add-on therapies to HCQ with SLE?

- corticosteroids (topical or oral)

- cytotoxic immunosupressants (methotrexate, Cyclophosphamide, Mycophenolate)

- Biologics "MABS"

What is our first line for skin rash and NO OTHER symptoms?

TOPICAL CORTICOSTEROIDS

Does potency matter for topical steroids?

YES!

In what places would we want to use LOW POTENCY topical corticosteroids?

FACE, GROIN

In what areas of the body would we be ok with using HIGHER potency topical corticosteroids?

Soles of the feet, palm of hands

What is the key counseling point for topical corticosteroids?

USE....

1. THE LOWEST DURATION

2. LOWEST DOSE POSSIBLE

What is the first-line therapy for CLE?

TOPICAL CORTICOSTERIODS

CLE- CUTANEOUS- SKIN!!!

What is the primary treatment for non-renal SLE treatment?

HCQ +/ glucocorticoids

no symptom improvement- then methotrexate, azathioprine, or mycophenate and taper GC

if no improvement add biologics MAB

When do we want to use NSAIDs in patients with SLE?

ARTHRITIS, FEVER

T/F NSAIDs are disease-modifying

FALSE

THERE'S NO AUTOIMMUNE COMPENENT ON NSAIDS! JUST TREATS SYMPTOMS!

Why would we want to add on glucocorticoids for SLE treatment with HCQ?

WORKS FAST!

HCQ takes AWHILE to work!

What is the oral glucocorticoid dosage goal (prednisone)?

LESS THAN 5MG/day MAINTENANCE

When is high IV glucocorticoid considered?

patient has FLARE

What is the IV glucorticoid?

Methyprednisolone

What drug is preferred for SLE and is recommended for ALL PATIENTS?

Hydrochloroquine (HCQ)

Down sides about Hydrochloroquine HCQ

TAKES LONGER TO WORK (2-8 WEEKS)

MAX EFFICACY 3-6 MONTHS

we might need to add NSAIDS or GC

What type of damage is ASSOCIATED WITH HYDROXYCHLOROQUINE (HCQ)

EYE DAMAGE!!!

KNOW THAT HYDROXYCHLOROQUINE CAUSES

EYE DAMAGE!!!

What is required for patient to receive HCQ?

EYE SCREENING at baseline then anually after 5 years!!

Why does patient need eye screening for HCQ?

causes IRREVERSIBLE RETINAL TOXICITY

What test is required for patients to get BEFORE starting immunosupressive drugs? Why?

TB- blood or skin

HIV, HepA, HepB

TB can be reactivated if taking immunosuppresants and cause disease!

Who is at high risk for HIV/hepatitis?

1. IV drug use

2. Men who have s*x with men

What are the common cytotoxic immunosuppressants?

1. Azathioprine (AZA)

2. Methotrexate (MTX)

3. Mycophenate mofetil (MMF)

4. Cyclophosphamide (CYC)

which cytotoxic immunosupressant are steroid-sparing?

1. Azathiprine (AZA)

2. Methotrexate (MTX)

Which cytotoxic immunosupressant is used for INDUCTION PHASE ONLY? (NOT LONG-TERM) Why?

Cyclophosphamide (CYC)

GIVEN IV (due to risks)

INCREASED risk of bladder cancer and hemorrhagic cystitis

T/F cyclophosphamide can be used for maintainence therapy

FALSE

INDUCTION ONLY!

Which cytotoxic immunosuppresant can be used for BOTH maintanence and induction?

MYCOPHENOLATE

M=MAINTENANCE TOO!!

Properties of Azathioprine (AZA)

- a purine analogue

- TMPT testing is REQUIRED

- Steriod paring- helps people get off of steroids

- associated with HEPATOTOXICITY

What is a major counseling point for Azathioprine (AZA)

TAKE AFTER FOOD to help with N/V

ADEs associated with Azathioprine (AZA)

- HEPATOTOXICITY

- pancreatitis

- myelosuppression

- N/V

- infection

Which immunosuppresant requires TMPT testing?

AZA (Azathioprine)

How is methotrexate dosed in patients with SLE?

WEEKLY

What should be added on to methotrexate to reduce toxicities?

FOLIC ACID!

we see methotrexate and folic acid used together to reduce metho's toxicity!

What population benefits from Mycophenolate over Cyclophosphamide?

African American

What cytotoxic immunosuppresant is used in SLE patients on the verge of KIDNEY FAILURE?

Cyclophosphamide (CYC)

REMEMBER ONLY SHORT-TERM!! (INDUCTION)

T/F Cyclophosphamide is used for maintanence and induction therapy

FALSE

ONLY MYCOPHENOLATE

Which medication was first oral FDA-approved drug to treat lupus nephritis

Voclosporin

What black box warning does Voclosporin contain?

increased risk of Malignancies and infections

What are the Biologic agents used in SLE?

Benlysta (Belimumab)

Saphnelo (Anifrolumab)

Rituximab

T/F Benysla and Saphnelo can be used together

FALSE

NEVER USE BIOLOGICS TOGETHER!

What type of vaccines are contraindicated in patients on biological therapy?

LIVE VACCINES

What are our treament options for Lupus Nephritis?

1. Low IV cyclophosphamide and Glucorticoids

2. Mycophenolate and gc

OR combination therapies with belimumab plus cyclophosphamide ot mycophenolate

OR

combination therapy with Calcineurin Inhibitrs PLUS mycophenolate

ALOT BUT MAIN ONES: MYCOPHENOLATE AND CYCLOPHOSPHAMIDE +/ GLUCOCORTICOIDS

for HOW LONG should lupus nephritis be treated?

at LEAST THREE YEARS

BUT NOT WITH CYCLOPHOSPHAMIDE- CAN ONLY BE USED FOR INTITIAL TREATMENT!!! (INDUCTION)

what is the drug of choice for neuropsychiatric lupus

HCQ!!!

GC with cyclophosphamide depending on neurotoxicity

Stroke: Antiplatelets/anticoagulants

T/F Anfrolumab and belimuab are recommended for severe neuropsychiatric involvement

FALSE NO!

MABS ARE LAST LINE FOR NEUROPSYCH!!!

Does a patient have to be on HCQ forever?

depends if they can stay in remission!

What drug do we taper first for SLE?

GLUCOCORTICOIDS

When is a patient considered to be in remission?

Clinical SLEDAI of ZERO

GC dose