Module: Pharmacotherapy III Module Coordinator: Dr. Arwa M. Amin Mostafa Academic Level: Postgraduate, Master of Pharmacy in Clinical Pharmacy School: Dubai Pharmacy College Year of first presented in Class: 2018 This presentation is for Educational purpose. It has no commercial value.

1. SYSTEMIC LUPUS ERYTHEMATOSUS
(SLE)
Arwa M. Amin Mostafa
PhD, M.Pharm Clinical Pharm, Dip Mangt, B.Pharm.

2. OUTLINES
What is Systemic Lupus Erythematosus (SLE)?
What is the Etiology of SLE?
What is the pathophysiology of SLE?
What are the risk factors of SLE?
What are the Goals of Treatment of SLE?
What are the Non-Pharmacological
treatments of SLE?
What are the Pharmacological Treatments of
SLE?
Evaluation of SLE Management

3. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
 Systemic lupus erythematosus (SLE) is
heterogenous autoimmune disorder
associated with autoantibody
production and generalized
multisystem inflammation.
 SLE affects commonly young women
(Reproductive Years).
 Lupus is Latin word which means Wolf.
 The rash on a person's face makes the
person's face look like the wolf face.
 SLE is affected by Genetic, Hormones,
Immune system and Environment.

4. ETIOLOGY OF SLE
 Idiopathic: Un-known cause
 Common Triggers:
 Genetics and Epigenetics
> 30 genetic polymorphisms linked to Lupus
 Abnormalities in the Immune cells
 Environmental Stimuli
UV light exposure, Drugs, Infections
 Hormones
e.g. Estrogen

5. ETIOLOGY OF SLE
 Idiopathic: Un-known cause
 Common Triggers:
 Genetics and Epigenetics
> 30 genetic polymorphisms linked to Lupus
 Abnormalities in the Immune cells
 Environmental Stimuli
UV light exposure, Drugs, Infections
 Hormones
e.g. Estrogen
The disease may
occur or
exacerbated by
the interaction
between triggers

6. RISK FACTORS OF SLE
Sex:
 9 times higher in women than in men
(Estrogen)
Age:
 ↑↑ in women of Reproductive Age
 15 - 45 years old (↑↑ Estrogen)
 May occur in childhood and older age
as well
 SLE tends to be more severe in
Men, children, and those with onset
at a later age (over 50 years).

7. RISK FACTORS OF SLE
Ethnicity:
 4 times higher in non-whites than in
the white population.
 Common and severe in African
American, Hispanics, Asian, Arab, and
Chaldean background, and Native
Americans than in whites.

8. RISK FACTORS OF SLE
Family History (due to genetic factors)
Environmental factors
 UV light
 Smoking Cigarette
 Infectious diseases
 Epstein Barr Virus
 Emotional Stress
 Drugs
 Procainamide and Hydralazine

9. PATHOPHYSIOLOGY OF SLE
Genetic
Susceptibility
Environmental
Factors:
UV light
Infection
Drugs
Production of
Autoantibodies
Hormonal Trigger:
Estrogen
Overactivation
of B-Cells
Abnormal
Autoimmune
Response
T-Cell
Defect

10. PATHOPHYSIOLOGY OF SLE
Autoantibodies
– Antigen
Complex
Inflammation and Damage
Joints
Deposition of
the immune
complex in
Tissues
Kidney
Brain
Skin
Heart &
Blood
vessels
Lung

11. CLINICAL MANIFESTATIONS OF SLE
This Figure is adapted from Bel Marra Health, Vasculitis, inflammation of blood vessels and the risk of lupus, https://www.belmarrahealth.com/vasculitis-inflammation-of-
blood-vessels-and-the-risk-of-lupus/

12. SLE Video:
How Lupus Attacks Immune System?
https://www.youtube.com/watch?v=KaWBUgkd_oo
PATHOPHYSIOLOGY OF SLE

13. CASE DISCUSSION
 Mrs. A.B. is a 32-year-old woman who has
been having knee pain On and Off for about
2 years.
 She has been to the doctor a few times since
then with the same complaint.
 Workups showed no radiologic changes to
the knees, and the doctor settled on a
diagnosis of early arthritis.
 Despite scheduled Acetaminophen and
Ibuprofen throughout the day, the pain has
not decreased much.
 The pain seems to be Cyclical; it is very bad
for a period of weeks, and then it wanes over
time. It is also worse in the summer.

14. CASE DISCUSSION
 She thinks the rashes she gets now and then on her
face and arms have something to do with the pain,
since the rash happens around the same time of a
bad flare-up. She complained of photosensitivity.
 No matter how much sleep she gets, it does not seem
to be enough; a couple of sleep medications later,
she is no better than before she tried them.
 She has also noticed a darkening of her stool over the
past couple of months.
 She is married since 5 years and she stated that she
and her husband are trying to conceive.

15. CASE DISCUSSION: PMH & ROS
PMH
Knee pain × 2 years
HTN × 1 year
Depression × 3 years
Fatigue × 1 year
ROS
(+) Fatigue & rash
(–) fever, chills,
peripheral
oedema, or
alopecia
PMH: Past Medical History, HTN: Hypertension, ROS: Review of symptoms

16. CASE DISCUSSION: LABS
 Hgb 10 g/dL
 HCT 31%
 Fe 35 mcg/dL
 Ferritin 8 ng/mL
 TIBC 455 mcg/dL
 ESR 66 mm/hr
 ANA titer 1:320 (rim
pattern)
 C3 50 mg/dL
 C4 10 mg/dL
 Lupus anticoagulant (+)
 Anticardiolipin antibody
(+)
 ds DNA Antibody (+)
TIBC: Total Iron Binding Capacity, ANA: antinuclear antibodies. ds DNA Antibody:
Double stranded DNA Antibody, Complement Component 4: C4, Complement
Component 3: C3

17. CASE DISCUSSION
Current Medications:
Hydrochlorothiazide 12.5 mg PO once daily
Amlodipine 5 mg PO once daily
Fluoxetine 20 mg PO once daily
Ibuprofen 600 mg PO four times daily
Acetaminophen 500 mg PO three times daily

18. What are the Clinical Presentations of SLE?
How to Diagnose SLE?

19. CLINICAL PRESENTATIONS OF SLE
 SLE has variable symptoms that can overlap with other
diseases.
 Disease Manifestations fluctuate with flares, progression
and remission.
 Common Symptoms of SLE are:
 Joint Pain
 Fatigue
 Depression
 Sleep problems
 Weight loss
 Photosensitivity
 Headache
 Nausea and Abdominal Pain
 Symptoms can wax and wane over time

20. CLINICAL PRESENTATIONS OF SLE
 Signs of SLE are:
 Skin Rash; Butterfly Rash
 Fever
 Arthritis
 Oral and Nasal Ulcers
 Renal Dysfunction; Lupus Nephritis
 CVDs:
 CAD, HTN, Pericarditis/Myocarditis, Heart Murmur
 Hematological:
 Anemia, thrombocytopenia
 Lymphadenopathy
 Seizures
 Psychosis
 Pleuritis
 Hair Loss (Alopecia)
HTN: Hypertension, CAD: Coronary Artery Disease

21. TOP FIVE SYMPTOMS OF SLE
This Figure is adapted from “TriceEdneyWire.com”, Lupus’ disproportionate impact on women and minorities must be known,
http://www.philasun.com/health/lupus-disproportionate-impact-women-minorities-must-known/

22. DIAGNOSTICS TESTS OF SLE
Laboratory:
• Antinuclear antibodies (ANA)
• Antibodies which targets proteins within the
nucleus of the cell.
• ↑↑ indicates Autoimmune disease
• ANA Pattern: Peripheral (RIM) → suggests SLE
• Limitation: it has low specificity (increases in
other autoimmune diseases)
• Anti dsDNA antibody
• If present → suggests Lupus Nephritis
• Anti-Smith Antibody
• Doesn’t correlate with Lupus Nephritis
Figure of ANA staining pattern in SLE
Figure is adapted from the Library website of Health University of UTAH,
https://library.med.utah.edu/WebPath/IMMHTML/IMM003.html

23. DIAGNOSTICS TESTS OF SLE
Laboratory… cont.:
• Antiphospholipid antibodies (APA)
• Lupus Anticoagulant (LA)
• Anticardiolipin antibody (aCL)
• Presence of LA & aCL indicates predisposition of
Blood clotting.
• Complements C3 & C4
• Low levels of C3 & C4 → suggests active Lupus
• Inflammatory Biomarkers
• C-Reactive Protein
• Erythrocyte Sedimentation Rate (ESR)

24. DIAGNOSTICS TESTS OF SLE
• CBC
• Hematological conditions (e.g. Anemia)
Other Diagnostics Tests:
• ECG
• Cardiac assessment
• Radiology
• Joints with pain
• Chest to indicate pulmonary disease

25. ACR CRITERIA FOR SLE DIAGNOSIS

26. ACR CRITERIA FOR SLE DIAGNOSIS
4/11 Criteria → Definite SLE
3/11 Criteria → Probable SLE
2/11 Criteria → Possible SLE

27. What information (signs, symptoms, and laboratory
values) indicates the development of SLE in Mrs. A.B.?
BACK TO MRS. A.B. CASE DISCUSSION

28. Signs and Symptoms:
 Skin Rash
 Photosensitivity
 Joint Pain (Knee Pain)
 Fatigue
 Arthritis
 Depression
 Sleep Disturbances
 Darkening of Stool
 Cyclic Pain (very bad for a period of weeks, and then
it wanes over time.)
What information (signs, symptoms, and laboratory
values) indicates the development of SLE in Mrs. A.B.?

29. Laboratory Results:
ANA titer 1:320 (rim pattern) ↑↑
C3 50 mg/dL ↓↓
C4 10 mg/dL ↓↓
Lupus anticoagulant (+)
Anticardiolipin antibody (+)
ds DNA Antibody (+) Lupus Nephritis
ESR 66 mm/hr ↑↑
What information (signs, symptoms, and laboratory
values) indicates the development of SLE in Mrs. A.B.?

30. What information (signs, symptoms, and laboratory
values) indicates the development of SLE in Mrs. A.B.?
Laboratory Results:
Iron Deficiency Anemia:
Hgb 10 g/dL ↓↓
HCT 31% ↓↓
Fe 35 mcg/dL ↓↓
Ferritin 8 ng/mL ↓↓
TIBC 455 mcg/dL ↑↑

31. What are the Overall Goals of SLE Therapy?

32. SLE THERAPY: OVERALL GOALS
Prevent Disease Flares
 Decrease Disease activity
Prevent Organs Damage
Maintain Remission
Reduce Use of Corticosteroids (to ↓↓ SE)
Reduce Drugs adverse effects
Improve Quality Of Life
What are the Overall Goals of SLE Therapy?

33. NON-PHARMACOLOGICAL TREATMENT OF SLE
 Avoidance of overexposure to Sun
 Using Sun-screen Protection
 Educate patient to avoid live vaccination
while on immunosuppressive
 CVD risk Modification
 HTN & Hyperlipidaemia
 Osteoporosis Prevention
 Promote Exercise
 Smoking Cessation
 Avoid emotional stress
 Heat Therapy to reduce Joint Pain

34. PHARMACOLOGICAL TREATMENT OF SLE
Pharmacological Treatment should be
personalized based on Manifestations
SLE severity should be considered (Mild,
Moderate and severe)
Combination therapy:
 Symptomatic Therapy
 Suppurative Therapy
 Immunosuppressants

35. PHARMACOLOGICAL TREATMENT OF SLE
FDA approved drugs to treat SLE:
 NSAIDs: Aspirin
 Corticosteroids: Prednisone
 Antimalarial: Hydroxychloroquine
 Biologicals: Belimumab
Off-Label Drugs:
 Azathioprine
 Mycophenolate Mofetil
 Cyclophosphamide
 Methotrexate

36. This Table is adapted from Marianthi Kiriakidou (2013) Systemic Lupus Erythematosus http://annals.org/aim/article-abstract/1743105/systemic-lupus-erythematosus

37. This Table is adapted from Marianthi Kiriakidou (2013) Systemic Lupus Erythematosus http://annals.org/aim/article-abstract/1743105/systemic-lupus-erythematosus

38. PHARMACOLOGICAL TREATMENT OF SLE
Figure is adapted from D.Á. Galarza-Delgado and A.C. Arana-Guajardo, (2014) How I diagnose and treat Lupus, http://www.elsevier.es/en-revista-medicina-universitaria-304-
articulo-how-i-diagnose-treat-lupus-S166557961500006X

39. PREGNANCY IN SLE
• Mrs. A.B. discussed with her Doctor that she and
her husband would like to conceive
• Discuss Risks associated with pregnancy in active
SLE
• What are the contraindicated SLE drugs in
Pregnancy?

40. PREGNANCY IN SLE
• Active SLE can be harmful to Pregnancy due to
higher risk of:
• Maternal Mortality
• Cesarean delivery
• Preterm labor
• Preeclampsia
• Thrombotic Events
• Infections
• Hematologic complications
• Pregnancy planning is important
• SLE should be inactive or in Remission for 6
months before conception.
• Pregnancy in SLE requires Close Monitoring.
• Lupus Nephritis may worsen in Pregnancy
• Mother Renal Function should be stable and Normal

41. SLE PHARMACOLOGICAL TREATMENT IN
PREGNANCY
Table Source: The Rheumatologist: A Better Family Plan, http://www.the-
rheumatologist.org/article/a-better-family-plan/5/

42. EVALUATION OF SLE TREATMENT OUTCOMES
• Patients should be evaluated for SLE disease
activity and organ involvement,
cardiovascular risk factors, comorbidities,
and risk for infection.
• Clinical and laboratory assessments should
be performed every 6 to 12 months in
patients with inactive disease and no organ
damage, and more frequently if
abnormalities are found.91

43. What is the best SLE Treatment for Mrs. A.B.?
LET’S THINK