SYSTEMIC LUPUS

ERYTHEMATOSUS
Prepared by: Joycemay
G. Andaya.
 TOPICS TO DISCUSS

•Pathophysiology of
1 SLE

•Drugs for SLE

2
THE IMMUNE SYSTEM
THE CULPRIT CELLS:
 MECHANISM OF AUTOANTIBODY
PRODUCTION AND TISSUE INJURY IN LUPUS

https://www.sciencedirect.com/science/article/pii/S0952791512001616
 FOUR TYPES OF LUPUS
1) Systemic lupus erythematosus

2) Cutaneous lupus erythematosus

3) Drug-induced lupus erythematosus

4) Neonatal lupus
 SYSTEMIC LUPUS
ERYTHEMATOUS (SLE)
 Systemic lupus erythematosus (SLE) is a
chronic inflammatory disease that is
characterized by an autoantibody response to
nuclear and cytoplasmic antigens.
 It can affect the skin, joints, kidneys, brain,
and other organs.

https://medlineplus.gov/ency/article/000435.htm
 CUTANEOUS LUPUS ERYTHEMATOSUS
 In this autoimmune disease, the body’s
immune system attacks healthy
skin. Cutaneous lupus is
sometimes diagnosed in people who
have systemic lupus erythematosus

Three Main Types

1. Acute cutaneous lupus (Acute Skin Lupus)
2. Subacute cutaneous lupus (Subacute Lupus)
3. Chronic cutaneous lupus (Discoid Lupus)
https://jamanetwork.com/journals/jamadermatology/fullarticle/1843885
 THREE MAIN TYPES OF
CUTANEOUS LUPUS ERYTHEMATOSUS
1. Acute cutaneous lupus (Acute Skin
Lupus) - Often a sign of systemic lupus
erythematosus. The rash associated with acute
cutaneous lupus appears in a recognizable
butterfly pattern that spreads across the nose
and cheeks that usually appears after sun
exposure.
2. Subacute cutaneous lupus (Subacute
Lupus) - May be a sign of systemic lupus, but
it can also develop on its own. Most of the time,
lesions aren’t itchy or painful, and they rarely
cause scarring after they heal.
https://nyulangone.org/conditions/cutaneous-lupus/types
 THREE MAIN TYPES OF
CUTANEOUS LUPUS ERYTHEMATOSUS
 Chronic cutaneous lupus (Discoid
Lupus) - There are several types of chronic
cutaneous lupus, with discoid lupus being
the most common.
 “Discoid” refers to the round shape of the
sores or lesions that develop. These are thick,
raised, scaly patches that are often pink and
may flake or form a crust on the surface of the
skin.
 DRUG-INDUCED LUPUS
ERYTHEMATOSUS
 Drug-induced lupus erythematosus (DILE) is an
autoimmune disorder like systemic lupus
erythematosus (SLE) and both can present with
arthralgia, myalgia, fatigue, and serositis.
 Most common drugs that cause DILE;
 Hydralazine (20% risk)
 Procainamide (roughly 20%, 5-8% if taken for 1 yr)
 Isoniazid
 Quinidine
 Diltiazem
 Minocycline
 Targeted Immunotherapy

https://emedicine.medscape.com/article/1065086-overview#a5
 PATHOGENESIS OF DILE
Three theories about DILE
 Drug Metabolites – metabolites of the drug are
subjected to oxidative metabolism and serve as a
substrate for myeloperoxidase, which is activated in
polymorphonuclear neutrophils.

 Decreased T-cell Methylation - an overexpression

of lymphocyte function–associated antigen (LFA-1)
occurs. T cells with hypomethylated DNA become
autoreactive and cause antibody formation.

 Genes - genetic differences in an individual’s P450

system causes drugs to be metabolized differently,
which results in the generation of toxic metabolites
that may facilitate autoimmunity.

https://emedicine.medscape.com/article/1065086-overview#a4
 SEVERAL BROAD DRUG CATEGORIES
LINKED TO DILE:
 Antiarrhythmics - Procainamide and Quinidine
 Antibiotics – Minocycline , Isoniazid, Rifabutin
 Antifungals - Griseofulvin and Voriconazole
 Anticonvulsants - Valproate, Ethosuximide,
Carbamazepine, and Hydantoins
 Anti-inflammatory - Penicillamine and sulfasalazine
 Antihypertensives - Hydralazine, methyldopa, and
Captopril
 Antipsychotics - Chlorpromazine
 Cholesterol-lowering agents - Lovastatin, Simvastatin
(DISCLE), Atorvastatin, and Gemfibrozil
 Inhalers - Tiotropium bromide inhaler
 Other drug categories - Ophthalmic timolol
 ADDITIONAL DRUGS THAT MAY CAUSE
DILE INCLUDE THE FOLLOWING:
 Acebutolol  Hydrochlorothiazide  Phenytoin
 Amiodarone (SLE (DISCLE)  Practolol
and SCLE)  Imiquimod (DISCLE)  Propylthiouracil
 Atenolol  Lamotrigine  Reserpine
 Bupropion  Lansoprazole  Rifampin
Cefepime (DISCLE)
  Rifamycin
Diltiazem  Leflunomide

(DISCLE)  Sertraline
 Doxorubicin Terbinafine
(DISCLE)  Lithium 
(DISCLE)
Doxycycline  Mephenytoin
  Tetracycline
(DISCLE)  Methimazole (bullous
SLE)  Ticlopidine
 Esomeprazole
(DISCLE)  Nitrofurantoin  Trimethadione
 Fluorouracil  Olanzapine
 Glyburide  Omeprazole
 Gold salt (DISCLE)
 Hydroxychloroquine  Oral contraceptives
DIFFERENCE BETWEEN SLE AND DILE
 NEONATAL LUPUS

 Neonatal lupus is not a true form of lupus. It is

a rare condition that affects infants of women
who have lupus and is caused by antibodies from
the mother acting upon the infant in the womb.
Most infants of mothers with lupus are entirely
healthy.
 SIGNS AND
SYMPTOMS

https://ghr.nlm.nih.gov/condition/systemic-lupus-erythematosus
 CAUSES OF SYSTEMIC LUPUS
ERYTHEMATOSUS
 Hormones - Because nine of every 10
occurrences of lupus are in females, researchers
have looked at the relationship between estrogen
and lupus.
 Genetics - Researchers have now identified
more than 50 genes which they associate with
lupus. These genes are more commonly seen in
people with lupus than in those without the
disease.
 Environment – Most commonly cited are
ultraviolet light (UVA and UVB); infections
(including the effects of the Epstein-Barr virus),
and exposure to silica dust in agricultural or
industrial settings.
https://www.lupus.org/resources/what-causes-lupus
 HOW TO DIAGNOSE?
 Laboratory tests
 Complete blood count
 Hemoglobin - In men: 135-175 grams/L In women: 120-
155 grams/L
 WBC - 3,500 to 10,500 cells/mcL

 Erythrocyte sedimentation rate

 0-22 mm/hr for men and 0-29 mm/hr for women.
 Kidney and liver assessment.
 Urinalysis.
 Antinuclear antibody (ANA) test
 Normal titer levels: 1:40 to 1:60

https://www.mayoclinic.org/diseases-conditions/lupus/diagnosis-treatment/drc-20365790
 HOW TO DIAGNOSE?

 Imaging Tests
 Chest X-ray
 Electrocardiogram

 Biopsy
 Other Tests
 Anti-dsDNA Antibody
 Anti-Smith Antibody
 Anti-U1RNP Antibody
 Anti-Ro/SSA and Anti-La/SSB Antibodies
 Anti-Histone Antibodies
 Serum (blood) Complement Test

https://www.hopkinslupus.org/lupus-tests/lupus-blood-tests/
 ALGORITHM
FOR
DIAGNOSIS
OF SYSTEMIC
LUPUS
ERYTHEMATO
SUS

https://www.aafp.org/afp/2003/1201/p2179.html
HOW TO CONFIRM A DIAGNOSIS? (11
SIGNS)

1. Malar rash 11. Abnormal antinuclear

2. Discoid rash antibody (ANA)
3. Photosensitivity
4. Oral ulcers
5. Arthritis
6. Serositis
7. Kidney disorder
8. Neurological disorder
9. Blood disorder
10. Immunologic disorder
DRUGS FOR SYSTEMIC
LUPUS ERYTHEMATOSUS
 NON-PHARMACOLOGIC
APPROACH/THERAPY TO SLE
 Avoid exposure to sunlight
 Use SPF 50+ sun block or wear protective
clothing
 Avoid “Live” vaccination of immunosuppressive
agents
 Get regular exercise

 Smoking Cessation

 Eat a healthy diet

 Ask your doctor if you need vitamin D and

calcium supplements
 ANTI-MALARIAL DRUGS:
CHLOROQUINE AND HYDROXYCHLOROQUINE

 Mechanism of Action:  Therapeutic Use:

1. several 4-
aminoquinoline 1. Discoid and Systemic
derivatives Lupus Erythematosus
2. intercalation with DNA, 2. Rheumatoid Arthritis
inhibition of heme 3. Suppressive and Acute
polymerase or by treatment of malaria
interaction with Ca++–
calmodulin-mediated
mechanisms
 ANTIMALARIAL DRUGS:
CHLOROQUINE AND HYDROXYCHLOROQUINE

Adverse Effects:  Contraindications:

1. Dizziness 1. Psoriasis
2. Headache 2. Porphyria
3. Itching (Dark skinned
people)
4. Skin rash
5. Vomiting
6. Burring of vision
7. Exacerbation or
unmasking of lupus
erythematosus
8. Blindness due to chronic
use
 NONSTEROIDAL ANTI-INFLAMMATORY
DRUGS (NSAIDS):
IBUPROFEN (ADVIL), NAPROXEN
(NAPROSYN), ETODOLAC (LODINE), CELECOXIB (CELEBREX),
AND MELOXICAM (MOBIC)

Mechanism of Therapeutic Use:

Action: 1. Treat pain, swelling
and fever associated
Inhibition of with lupus
prostaglandin 2. Reduce inflammation
synthesis by COX-2. responsible for the
stiffness and
discomfort in muscle,
joints, and other
tissues
 NONSTEROIDAL ANTI-INFLAMMATORY
DRUGS (NSAIDS):
IBUPROFEN (ADVIL), NAPROXEN
(NAPROSYN), ETODOLAC (LODINE), CELECOXIB (CELEBREX),
AND MELOXICAM (MOBIC)

Adverse Effects:
1. Erosive Gastritis, Peptic Ulceration

2. Prolonged bleeding time

3. Renal failure

4. Decreased effectiveness of diuretics and

Hypertensives
5. Bronchospasm

6. Delayed parturition
 CORTICOSTEROIDS:
PREDNISONE, METHYLPREDNISONE

Mechanism of Action:  Therapeutic Use:

 inhibit leukocyte 1. Decrease
infiltration at the site of swelling, warmth,
inflammation, interfere tenderness and
with mediators of pain that are
inflammatory response, associated with
and suppress humoral inflammation.
immune responses.
 CORTICOSTEROIDS:
PREDNISONE, METHYLPREDNISONE

Adverse Effects:
1. Acne
2. Moon face
3. Weight gain
4. Fluid retention and Redistribution of fat
5. Easily bruising skin
6. Suppressed growth in children
7. Irritability, agitation, excitability, insomnia or
depression.
 DISEASE-MODIFYING ANTI-RHEUMATIC
DRUGS (DMARDS)
METHOTREXATE (RHEUMATREX)

Mechanism of Action: Therapeutic Use:

 A folate 1. Alleviate the joint pain
antimetabolite that and swelling of
inhibits dihydrofolate polyarthritis (arthritis
reductase and other involving multiple
folate-dependent joints) in lupus
enzymes in cells. 2. “gold standard“ for the
treatment of
rheumatoid arthritis.
3. Psoriatic arthritis

4. Pleuritis
 DISEASE-MODIFYING ANTI-RHEUMATIC
DRUGS (DMARDS)
METHOTREXATE (RHEUMATREX™)

 Adverse Effects:
1. Nausea
2. Stomatitis
3. GI discomfort
4. Rash
5. Diarrhea
6. Headache
 DISEASE-MODIFYING ANTI-RHEUMATIC
DRUGS (DMARDS)
LEFLUNOMIDE (ARAVA)

Mechanism of Action: Therapeutic Use:

 inhibits T-cell 1. Treat the swelling, pain,
proliferation by and stiffness that many
blocking de novo lupus patients feel due
pyrimidine synthesis to arthritis.
and inhibiting the
tyrosine kinases that
are associated with
certain cytokine and
growth factor
receptors.
 DISEASE-MODIFYING ANTI-RHEUMATIC
DRUGS (DMARDS)
LEFLUNOMIDE (ARAVA)

Adverse Effects: Contraindication:

1. Nausea 1. Pregnancy

2. Indigestion 2. Breastfeeding

3. Diarrhea 3. Renal or hepatic disease

4. Vomiting 4. Heavy alcohol use

5. Weight changes
6. Skin rashes
7. Pruritus
8. Reversible alopecia
 IMMUNOSUPPRESSANTS:
CYCLOSPORINE (NEORAL)
Mechanism of Therapeutic Use:
Action:
1. Treatment for
 inhibits calcineurin
phosphatase lupus nephritis
activity, which leads (Inflammation of
to a decreased kidneys caused by
synthesis and lupus)
release of several Adverse Effects:
cytokines, including
1. Nephrotoxicity
interleukins IL-2,
IL-3, IL-4, 2. Vasoconstriction
interferon-, and 3. Hypertension
tumor necrosis
factor.
 IMMUNOSUPPRESSANTS:
MYCOPHENOLATE MOFETIL (CELLCEPT®)

Mechanism of Therapeutic Use:

Action: 1. Prophylaxis of organ
 Penicillium-derived rejection in patients
immunosuppressive receiving renal, hepatic,
and cardiac transplants
agent
Adverse Effects:
 Blocks de novo
purine synthesis by 1. Nausea
noncompetitively 2. Abdominal cramps
inhibiting the 3. Diarrhea
enzyme inosine 4. Increase incidence of
monophosphate viral and bacterial
dehydrogenase. infections
 IMMUNOSUPPRESSANTS:
AZATHIOPRINE (IMURAN®)

Mechanism of Action: Therapeutic Use:

 Antagonizes purine 1. Blocks inflammation
metabolism and may pathways in lupus
inhibit synthesis of 2. Prevent rejection of
DNA, RNA, and kidney transplants
proteins. It may also 3. Helps lower steroid
interfere with dosage
cellular metabolism
and inhibit mitosis. Adverse Effects:
1. Pancreatitis

2. Hepatitis
CYTOTOXIC DRUGS (ALKYLATING AGENTS):
CYCLOPHOSPHAMIDE (CYTOXAN®)

Mechanism of Action of Alkylating agents:

1. attachment of alkyl groups to DNA bases, preventing
DNA synthesis and RNA transcription from the
affected DNA
2. DNA damage via the formation of cross-links (bonds
between atoms in the DNA) which prevents DNA
from being separated for synthesis or transcription,
and
3. The induction of mispairing of the nucleotides leading
to mutations.
 CYTOTOXIC DRUGS:
CYCLOPHOSPHAMIDE (CYTOXAN®)

 Therapeutic Use:  Adverse Effects:

1. Treatment of Lupus 1. Neutropenia
with serious kidney 2. Febrile neutropenia
problems 3. Fever
2. Treatment of 4. Alopecia
malignant lymphomas
5. Nausea
3. Multiple myeloma,
6. Vomiting
4. Adenocarcinoma of the
ovary 7. Diarrhea.
 CYTOTOXIC DRUGS:
CHLORAMBUCIL (LEUKERAN),
MECLORETHAMINE(MUSTARGEN)

 Therapeutic Use:  Adverse Effects:

1. Treat lupus symptoms 1. Maximal Leukopenia
but are not used as 2. Thrombocytopenia
commonly as Cytoxan 3. Alopecia
2. For patients who 4. Nausea
cannot tolerate 5. Vomiting
Cytoxan or who have 6. Diarrhea
an allergy to the 7. Amenorrhea
medication 8. Infertility
 ANTICOAGULANTS
ASPIRIN

Mechanism of Therapeutic Use:

Action: 1. Prevents blood clotting

2. Reduces pain
 Selectively inhibit 3. Manages lupus
the synthesis of symptoms
platelet TxA2 and Adverse Effects:
thereby inhibit
1. GI disturbances
platelet aggregation.
2. Drowsiness

3. Mild Headache
 ANTICOAGULANTS
HEPARIN (CALCIPARINE®, LIQUAEMIN®)

Mechanism of Therapeutic Use:

Action: 1. Prophylaxis and
treatment of venous
 Administered thrombosis
heparin binds 2. prevention of post-
reversibly to ATIII operative deep venous
and leads to almost thrombosis
instantaneous 3. pulmonary embolism
inactivation of Adverse Effects:
factors IIa and Xa 1. Bleeding
2. Heparin-induced
thrombosis
3. Alopecia
 ANTICOAGULANTS
WARFARIN (COUMADIN)

Mechanism of Therapeutic Use:

Action: 1. Long-term use for
chronic coagulation
 Antagonizes the 2. Chronic atrial
conversion of the fibrillation
precursors of 3. Rheumatic heart
vitamin K– disease
dependent clotting
factors II, VII, IX,
and X. Adverse Effects:
1. Minor Bleeding

2. Purple Toe Syndrome

 MONOCLONAL ANTIBODIES (MABS)
BELIMUBAB (BENLYSTA)

Mechanism of Action: Therapeutic Use:

 selectively binds to 1. Adjunct
soluble human B treatment for
lymphocyte stimulator auto-antibody-
protein (BLyS) so that positive active
BLyS is unable to bind to systemic lupus
receptors on B erythematosus.
lymphocytes. The binding
of BLyS to its receptor is
essential for the survival
of B lymphocytes.
 MONOCLONAL ANTIBODIES (MABS)
BELIMUBAB (BENLYSTA)

Adverse effects:
1. nausea
2. diarrhea
3. Pyrexia
4. Nasopharyngitis
5. Bronchitis
6. insomnia,
7. pain in extremities,
8. depression,
9. migraine,
10. pharyngitis.
 REPOSITORY CORTICOTROPIN
INJECTION (H.P. ACTHAR GEL)

Mechanism of Action: Therapeutic Use:

1. Verification of

 Porcine ACTH, Adrenal

stimulates adrenocortical Responsiveness
hormone production 2. Acute Exacerbations
of Multiple Sclerosis
3. Nephrotic Syndrome

4. Diagnostic testing
for adrenal cortex
function
 REPOSITORY CORTICOTROPIN
INJECTION (H.P. ACTHAR GEL)

Adverse effects:
1. Edema
2. Hypertension
3. Psychotic disorder
4. Disorder of skin
5. Hyperglycemia
6. Peptic ulcer disease
7. Immune hypersensitivity reaction
8. Muscle weakness
 DRUGS THAT ARE CONTRAINDICATED
TO LUPUS

 Bactrim

 Sulfa antibiotic (e,g Gantrisin, Septra)

 Sulfa antidiuretics (Aldactone)

Since these medications can

cause lupus flares by increasing
sun sensitivity and occasionally
lowering blood counts.
 COMPLEMENTARY/ALTERNATIVE
TREATMENTS FOR LUPUS
 Dehydroepiandosterone (DHEA)
 For fatigue and muscle pain
 Fish Oil
 Omega-3 fatty acids may help people with lupus
 Acupuncture
 Ease muscle pain associated with lupus
REFERENCES

 Lippincott - Modern Pharmacology With Clinical

Applications 6th Edition
 Lupus Foundation of America (2019)
(https://www.lupus.org/resources/types-of-lupus)
 Medscape (2019)
(https://reference.medscape.com/)
 Drugbank (2019) (https://www.drugbank.ca/)

 The John Hopkins Lupus Center (2019)

(https://www.hopkinslupus.org/)