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1. SYSTEMIC LUPUS
ERYTHEMATOSUS(SLE)- A
BRIEF OUTLOOK
BY- VISHNU.R.NAIR
THIRD YEAR PHARM.D
KERALA UNIVERSITY OF HEALTH SCIENCES
(KUHS)
KERALA STATE.

2. A. GENERAL FEATURES:
• “Autoimmune disease, in which body’s immune system mistakenly
attacks healthy tissue”
• Can affect almost any part of body
• Follows a relapsing and remitting course
• Also has PROTEAN manifestations………………………

3. B. EPIDEMIOLOGY:
• Occurs in 5 out of every 10,000 people
• More frequent in Asian women than in Whites
• Higher rates reported in Blacks
• Highest in women aged 14-64 years
• 90% cases occur in women, mostly in the age of midwifery…………….

4. C. ETIOLOGY:
• A. FAMILIAL:
- 8% of affected patients have at least one first degree family member with SLE
- For identical twins : 24% chances
- For fraternal twins : 2% chance
B. GENETIC:
- 35 genes are known to increase risk for SLE
- Loci associated with SLE include:
a. TNF A1P3
b. BANK 1
- Human leucocytic antigen (HLA):
• HLA-A1, HLA-DR3 and HLA-88 are more common in patients with SLE
- Presence of null complement alleles
- Congenital abnormalities of complement (C2, C4)  Associated with SLE
risk

5. CONTINUED………………….
- DNAase 1 enzyme deficiency:
. Also known as “GARBAGE DNA”
. Enzyme  eliminates cellular debris, by chopping them into smaller fragments for easier disposal
. Enzyme deficiency  increases risk for SLE.
C. VIRUSES:
- EBV (Epstein-Barr Virus)  causes T-cell abnormality  failure in normal immunoregulation of B-
cell response (causes B cell hyperactivity)
D. ENVIRONMENT n MISCELLANEOUS CAUSES:
- Silica dust
- Cigarette smoking
- Estrogen  administered to post-menopausal women  increased SLE risk
- Decreased breast feeding
- Photosensitivity
- UV light  stimulates KERATINOCYTES  causes over-expression of nuclear ribonucleoproteins
(snRNPs) on their cell surface , and stimulates cytokine secretion leading to Auto-antibody
production…………………….

6. CONTINUED…………………..
E. NUTRITIONAL DEFICIENCY:
- Vitamin D deficiency  has three SLE related effects:
a. Increases auto-antibody production
b. B-cell hyperactivity
c. Interferon-alpha activity
F. DRUGS:
- Drugs , that increase SLE risk, include:
a. Hydralazine (APRESOLINE)
b. Quinidine sulphate / gluconate
c. Procainamide (PROCANBID)
d. Phenytoin (DILANTIN)
e. INH (LANIAZID)
f. D- Penicillamine………………………..

7. D. PATHOPHYSIOLOGY OF SLE:
• Mainly the flowchart of SLE can be summarized like this:
(INNATE SUSCEPTIBILITY with or without ENVIRONMENTAL STIMULI)
 AUTOIMMUNE PROLIFERATION  AUTO- ANTIBODY
PRODUCTION  Signs and symptoms of SLE, depending on the organ/tissue
targeted by the immune system…………………….
• Factors that come under INNATE SUSCEPTIBILITY include:
- HLA type (DR 3/2)
- Immunoregulatory genes (multiple)
- Complement levels
- Hormonal levels
• Factors that come under ENVIRONMENTAL STIMULI include:
- UV response
- Microbial response
- Drugs.

8. CONTINUED…………………………
• Factors that come under AUTOIMMUNE PROLIFERATION include:
- Hyperactive B and T cell activation
- High ratio of CD4:CD8 T cells
- Defective immune complex clearance
- Impaired tolerance
• Factors that come under AUTO-ANTIBODY PRODUCTION, include:
- Apoptosis
- Self-exposure
- Self-recognition
- Foreign antibody cross reaction………………………………..

9. E. SIGNS AND SYMPTOMS:
• SLE is a chronic auto-immune disease, that can affect any organ system
• Symptoms range from INDOLENT to FULMINANT
• For children:
a. Malar rashes
b. Ulcers
c. Renal manifestations
d. Proteinuria
e. Urinary cellular casts
f. Seizures
g. Thrombocytopenia
h. Hemolytic anemia
i. Fever
j. Lymphadenopathy….
• For adults:
- Raynaud’s pleuritis
- Keratoconjunctivitis sicca

10. CONTINUED………………….
• For midwives:
- Fever
- Joint pain
- Rashes
• GENERALIZED MANIFESTATIONS:
1. Constitutional symptoms:
- Fatigue
- Fever
- Arthralgia
- Weight changes
2. Musculoskeletal symptoms:
- Arthralgia
- Myalgia
- Arthropathy
- Frank arthritis
- Avascular necrosis

11. CONTINUED………………………..
3. Dermatologic symptoms:
- Malar rash
- Discoid lupus
- Photosensitivity
4. Renal symptoms:
- ARF
- CRF
- Acute nephritis disease (lupus nephritis)
5. Neuropsychiatric symptoms:
- Seizure
- Psychosis
6. Pulmonary symptoms:
- Pleurisy
- Pleural effusion
- Pneumonitis
- Pulmonary HTN
- Interstitial lung disease

12. CONTINUED………………………….
7. GI symptoms:
- Nausea
- Dyspepsia
- Abdominal pain
8. Cardiac symptoms:
- Pericarditis
- Myocarditis
9. Hematologic symptoms:
- Leucopenia
- Lymphopenia
- Anemia
- Thrombocytopenia……………………………..

13. F. DIAGNOSIS OF SLE
• Based on combination of clinical findings and lab evidence
• According to American College of Rheumatology (ACR), presence of ANY 4 of the following 11
criteriae makes the patient positive/ susceptible to SLE : (Remember code of criteria is SOAP BRAIN
MD)
- S: SEROSITIS
- O: ORAL ULCERS
- A: ARTHRITIS
- P: PHOTOSENSITIVITY
- B: BLOOD DISORDERS
- R: RENAL MANIFESTATIONS
- A: ANTI NUCLEAR ANTIBODIES
- I: IMMUNOLOGIC INVOLVEMENTS ( Example dsDNA, Anti-Smith antibodies)
- N: NEUROLOGIC DISORDERS
-M: MALAR RASH
-D: DISCOID RASH…………………

14. CONTINUED………………….
• LAB TESTS USED FOR SLE DIAGNOSIS:
- CBC , with differential counts
- Serum creatinine levels
- Microscopial urine analysis
- ESR/ CRP results
- Complement levels
- LFTs (LIVER FUNCTION TESTS)
- Creatine kinase assay
- (Spot protein/ spot creatinine ) ratio
- Auto antibody tests
• IMAGING TESTS USED FOR SLE DIAGNOSIS:
- Joint radiography
- Chest radiography
- Chest CT Scan
- Echocardiography
- Cardiac MRI

15. CONTINUED………………………..
• PROCEDURES PERFORMED ON PATIENTS TO DIAGNOSE SLE:
- Arthrocentesis
- Renal biopsy
- Lumbar puncture…………………………………..

16. G. MANAGEMENT OF SLE:
• Depends on patient’s disease severity and manifestations
• Here, we will discuss:
I. GOALS OF THERAPY
II. PHARMACOTHERAPY
III. NON-PHARMACOTHERAPY
IV. PATIENT COUNSELLING………………………………..

17. I. GOALS OF THERAPY:
• To prevent symptomatic flares
• To stress on self-care (Maintenance of healthy lifestyle)
• Organ damage prevention
• Minimizing ADRs
• Medication adherence
• Prevention of complication
• Reduce mortality and morbidity
• Improve QOL (QUALITY OF LIFE)……………………………..

18. 2. PHARMACOTHERAPY OF SLE:
• Here, we will include:
- Medication classification
- EULAR recommendations for SLE management
- Drug details………………………

19.  MEDICATION CLASSIFICATION 
• BIOLOGIC DMARDs (Disease modifying anti-rheumatoid drugs):
- Belimumab
- Rituximab
- Immunoglobulin i.v (IGIV)
• NON-BIOLOGIC DMARDS:
- Cyclophosphamide
- Methotrexate
- Azathioprine
- Mycophenolate
- Cyclosporine
• NSAIDs:
- Ibuprofen
- Naproxen
- Diclofenac
• CORTICOSTEROIDS:
- Methyl prednisolone
- Prednisone

20. CONTINUED…………………………..
• ANTI-MALARIALS:
- Hydroxychloroquine (HCQ)
- Chloroquine (CQ)
• ANTI-NEOPLASTIC (For cutaneous lupus erythematosus):
- Thalidomide………………………….

21.  EULAR RECOMMENDATIONS FOR SLE
MANAGEMENT 
• In 2007, the European League Against Rheumatism (EULAR) released
recommendations for SLE treatment
• Recommendations include:
- For SLE patients, without major organ manifestations Use glucocorticoids and
anti-malarial agents (mainly HCQ)
- Use NSAIDs for short periods to avoid risk of complications from these drugs
- Consider immunosuppressants (azathioprine, methotrexate) in refractory cases or
when steroid doses cant be decreased to levels for long term use
- Above guidelines also apply to patients with neuropsychiatric manifestations
- Cutaneous, musculoskeletal manifestations and serositis represent milder disease
- The above symptoms are controlled with the following medication regimen :
(NSAIDs / low potency immunosuppressants) + HCQ +/- Corticosteroids (short
course)
- For patients with vital organs (CNS, renal) involvement  Treat with more
aggressive immunosuppression…………………………………….

22.  DRUG DETAILS 
A. NSAIDS:
- Provide symptomatic relief for arthralgias, fever, headache, and serositis
- M.O.A(Mechanism of action):
Drug inhibits COX-1 and COX-2 (Cyclooxygenase pathway) Prostaglandin synthesis
inhibited  decreased pain
Drug has 4 actions that ultimately decrease inflammation:
a. Inhibition of neutrophil aggregation and activation
b. Chemotaxis inhibition
c. Decreased pro-inflammatory cytokine levels
d. Altered lymphocyte activity
- ADRs:
a. Cholestasis
b. BUN levels > 40 mg/dl
c. Hepatitis
d. Nephrotoxicity
e. Serum creatinine levels > 2 mg/dl

23. CONTINUED……………………………….
- Drug interactions:
a. NSAIDs + methotrexate  decreased renal clearance of methotrexate (MTX)  Increased MTX
levels MTX toxicity  severe hematologic and GI toxicity  death
b. NSAIDs + cortisone / prednisone  pharmacodynamics synergism  increases toxicity of one
another  increased GI ulceration
- Contraindications:
a. ARF patients
b. Active GI bleeding
- Ibuprofen (NEOPROFEN, ADVIL):
a. Drug of choice for mild-moderate pain
b. Dose: 400-800 mg P.O (per oral) every 6-8 hrs
- Naproxen (NAPROSYN):
a. For mild-moderate pain
b. Dose: 750-1000 mg/day (P.O)
- Diclofenac (CATAFLAM):
a. Take with food to avoid GI ADRs
b. Dose : 100 mg/day………………………….

24. CONTINUED……………………………
B. CORTICOSTEROIDS:
- Used predominantly for anti-inflammatory action, and as immunosuppressant
- Preparations include oral, i.v, topical and intra-articular injections
- ADRs:
a. Diabetes mellitus
b. Headache
c. Weight gain
d. Osteoporosis
e. Oral candidiasis
f. Hepatomegaly
- Contraindications:
a. Documented hypersensitivity
b. Systemic fungal infections
- Methyl prednisolone (A-METHAPRED):
a. Used for acute organ threatening exacerbations
b. Drug  suppresses Polymorphonuclear lymphocytes migration and reverses capillary
permeability leads to decreased inflammation…………………..

25. CONTINUED………………………
c. Drug interaction:
Methyl pred. + Loratadine  increased levels or effect of former
d. Dose : 0.5-1 g i.v over 1 hr. OD for 3 days ( for lupus nephritis)
- Prednisone (DELTASONE):
a. Mainly immunosuppressant
b. Drug has the following actions, that ultimately reduce inflammation:
• Suppresses PMN (Polymorphonuclear neutrophils) migration
• Reverses increased capillary permeability
• Stabilizes lysosomal membrane
• Suppresses antibody production
• Suppresses lymphocytes
c. For Mild SLE use low dose oral form
d. For severe SLE  use high doses of oral/ i.v form
e. Dose : 60 mg P.O for 1 week………………………….

26. CONTINUED………………………….
C. ANTI-MALARIALS:
- Cause immunomodulation without hyper immunosuppression
- Used to prevent and treat lupus like skin rashes, constitutional symptoms , arthralgias,
arthritis
- Prevent lupus flares
- Decreases morbidity
- Decreases mortality
- HCQ (PLAQUENIL):
a. According to LUMINA (Lupus in Minorities: Nature vs Nurture ) study and other trials,
 patients who have been given HCQ Showed decreased flares and prolonged life
b. Thus HCQ is also known as “cornerstone of SLE management”
c. Drug has 3 actions:
• Inhibits eosinophil chemotaxis
• Inhibits neutrophil locomotion
• Impairs complement dependent Antigen-antibody reactions
d. Dose : Hydroxychloroquine sulphate : 200 mg

27. CONTINUED………………………………
e. ADRs:
• Retinal toxicity
• Alopecia
• Pruritus
• Weight loss
f. Drug interactions:
• HCQ + Anakinra increased immunosuppressive effects increased
risk of infections
• HCQ + Digoxin  increased levels of digoxin
g. Contraindications :
• Porphyria
• Psoriasis………………………………….

28. CONTINUED………………………………
D. NON-BIOLOGIC DMARDs:
- Function as immunosuppressives, cytotoxic, and anti-inflammatory
medications
- Medications that we will discuss are:
1. Cyclophosphamide
2. Methotrexate
3. Azathioprine
4. Mycophenolate…………………………………….

29. CONTINUED…………………………..1. CYCLOPHOSPHAMIDE ( CYTOXAN):
- Due to increased toxicity, it is reserved only for severe organ threatening disease (CNS involvement, vasculitis,
lupus nephritis)
- Drug enters body forms active metabolite (4-aldophosphamide) in liver  causes DNA cross-linkage
- Drug shows function similar to nitrogen mustards (alkylating agents)
- ADRs:
a. Interstitial pulmonary fibrosis
b. Infertility, sterility
c. Secondary malignancies
- Contraindications:
a. Severe myelosuppression
b. Hypersensitivity
- Drug interactions:
Cyclo. + Allopurinol  increased toxicity of former
- Dose : (mainly for lupus nephritis)
a. For low dose : 500 mg. iv every 2 weeks for 6 doses + corticosteroids + maintenance with mycophenolate
mofetil / azathioprine
b. For High dose : 500-1000 mg iv monthly for 6 doses + corticosteroids……………………..

30. CONTINUED…………………………….2. METHOTREXATE (RHEUMATREX):
- Drug has 2 blocking actions, that increased anti-inflammatory adenosine concentration at sites of inflammation:
a. Blocks purine synthesis
b. Blocks 5-amino imidazole -4- carboxamide ribonucleotide (5-AICAR)
- Manages arthritis, serositis, cutaneous and constitutional symptoms
- ADRs:
a. BMT (bone marrow toxicity)
b. Nausea and vomiting
c. Anorexia
d. Renal failure
- Contraindications:
a. Pregnancy
b. Alcoholics
c. Bone marrow hyperplasia
-Drug interactions:
Aspirin+ MTX Increased levels of MTX (due to decreased renal clearance) increased MTX Toxicity
-Dose : 7.5-15 mg / week (for arthritis), and 10-25 mg weekly (for psoriasis)…………………………….

31. CONTINUED……………………………..
3. AZATHIOPRINE (IMURAN):
- Immunosuppressant
- Less toxic alternative to cyclophosphamide
- Used as steroid sparing agent in non-renal disease
- Drug converted to 6-mercaptopurine  antagonizes purine function, inhibits DNA, RNA ,Protein
synthesis decreases immune cell proliferation  decreased auto-immune activity
- ADRs:
a. Leukopenia
b. Infections
c. BMT
d. SWEET SYNDROME ( Acute febrile neutrophilic dermatosis)
- Drug interaction:
Febuxostat + Azathioprine decreased metabolism of latter increased levels of latter
- Contraindication:
a. Pregnancy
b. Documented hypersensitivity
- Dose: 2 mg/kg/day P.O with /without low-dose corticosteroids…………………………

32. CONTINUED………………………….
4. MYCOPHENOLATE ( MYFORTIC):
- Mainly used as maintenance therapy (in lupus nephritis)
- Drug inhibits inosine monophosphate dehydrogenase (IMPDH) ,
Suppresses purine synthesis by lymphocytes , Inhibits antibody production
- ADR:
a. DM
b. Back pain
c. Hypomagnesemia
- Drug interaction:
Cholestyramine + mycophenolate  decreased GI absorption of latter
- Contraindication:
Hypersensitivity
-Dose :
2-3 gram for 6 months, with glucocorticoids……………………..

33. CONTINUED………………………
E. BIOLOGIC DMARDs:
1. BELIMUMAB (BENLYSTA):
- Monoclonal antibody
- B-lymphocyte stimular specific inhibitor
- BLys (B-lymphocyte stimulator ):
a. Naturally occurring protein
b. Required for survival and development of B-cells into mature plasma B-cells, that
produce antibodies
c. In autoimmune diseases increased BLys levels  production of auto antibodies
d. Drug specifically recognizes and binds to Blys  inhibits Blys stimulation of
B-cell development restores potential for auto antibody producing cells to
undergo normal process of apoptosis (programmed cell death)
- Decreases disease activity, severe flares and corticosteroid need
- Used as combination therapy, with steroids, HCQ, azathioprine, MTX
- Used to treat auto-antibody positive SLE

34. CONTINUED……………………….
- ADRs:
a. Infusion reactions (nausea, headache, skin reactions)
b. Hypersensitivity
c. Diarrhea
- Drug interactions:
Hydroxyurea+ Belimumab  increased risk for infections
- Contraindicated in:
Hypersensitivity
- Dose:
(10 mg/kg iv every 2 weeks ) for 3 doses……………….

35. CONTINUED……………………………..2. RITUXIMAB (RITUXAN):
- Depletes B-cells
- Humanized monoclonal antibody
- Drug binds to CD20 antigen induces complement/ antibody mediated cytolysis
- Used for patients who do not respond to immunosuppressants
- Used in severe refractory SLE
- More effective, when used in combination with COSTIMULATION INHIBITORS
- ADRs:
a. Angioedema
b. Fever
c. Pruritus
- Drug interactions:
Rituximab + certolizumab pegol  increased immunosuppressive effects  increased risk of infections.
- Contraindications:
a. Hypersensitivity b. Angina
- Dose : 1000 mg iv infusion ( repeat after 2 weeks). Give glucocorticoids 30 minutes before giving
rituximab to decrease risk of infusion reactions………………….

36. CONTINUED…………………………….
3. IMMUNOGLOBULIN I.V (OCTAGAM, HIZENTRA):
- Used for immunosuppression, in severe SLE flares
- Has the following actions:
a. Neutralizes circulating myelin antibodies through anti- idiotypic
antibodies
b. Downregulates pro-inflammatory cytokines (interferon-gamma)
c. Blocks Fc receptors on macrophages
d. Suppresses inducer T and B cells
e. Augments suppressor T cells
f. Blocks complement cascade
g. Promotes remyelination
h. May increase CSF immune globulin (G) concentration by 10%

37. CONTINUED…………………………….
- ADRs:
a. Chills
b. Headache
c. Hypotension
- Drug interactions:
Immune globulin i.v + bacitracin  increased nephrotoxicity and
ototoxicity
- Contraindications:
a. Isolated IgA deficiency
b. Hypersensitivity to gamma-globulin, thiomersal
- Dose:
400 mg/kg i.v every 3-4 weeks……………………………

38. CONTINUED…………………………..
F. THALIDOMIDE (THALOMID):
- Good option for treatment of cutaneous lupus erythematosus
- Complete remission observed in 72% cases
- Drug actions:
a. Decreased expression of MHC (major histocompatibility complex) Class II
antigens on keratinocytes
b. Decreased expression of ICAM-1 on keratinocytes
c. May cause decrease in CD4+ T cells
- ADRs:
a. Teratogenicity
b. Neuropathy
c. Constipation
d. Drowsiness
e. Paresthesia in hands

39. CONTINUED……………………………….
- Drug interaction:
Thalidomide + Anakinra :
a. Increased toxicity of thalidomide
b. Increased infection risk
- Contraindications:
a. Pregnancy
b. Hypersensitivity
c. Venous thromboembolism (VTE)
- Dose:
Thalidomide (100-300 mg/day)  decrease dose gradually + prednisone
(15-60 mg/day)……………………………

40. III. NON-PHARMACOTHERAPY FOR SLE :
• Sufficient amount of sleep
• Carefully prescribed exercise to maintain muscle tone
• Avoid direct skin exposure
• Use sunscreens and sun protection clothing
• For skin rash, use DAPSONE and RETINOIC ACID (RETIN-A)
• For patients, with lupus cerebritis/ lupus nephritis  opt
PLASMAPHERESIS (Removes antibodies and other immune
substances from body)
• For patients, with ESRD associated with SLE: Go for DIALYSIS/
RENAL TRANSPLANTATION

41. CONTINUED…………………
• Diet:
- Low dose diet supplementation with omega-3-fish oils has 3 actions:
a. Decreased heart disease risk
b. Decreased disease activity
c. Decreased inflammation
- Consume more plant based foods
- Consume lean sources of protein
- DHEA (Dehydroepiandrosterone)  decreases fatigue , improves
thinking difficulties and improves QOL in SLE patients
- Consume Vitamin D supplements……………………………….

42. IV. PATIENT COUNSELLING TIPS FOR SLE:
1. Stress on the importance of medications and follow-up appointments
to detect and control SLE
2. Instruct SLE patients to seek medical care for evaluation of new
symptoms , including fever
3. Advise patients regarding increased risk of infection and
cardiovascular disease
4. Educate patient that lupus cant be cured, but symptoms can be reduced
, and QOL can be prolonged and made worthwhile
5. Educate patients regarding avoidance of sunlight / UV exposure
6. Encourage to receive non-live vaccines during stable periods of
disease, mostly against encapsulated organisms, like :

43. CONTINUED……………………
a. Pneumococcus
b. Meningococcus
c. H.influenzae
d. Influenza virus
7. Educate patients regarding aggressive B.P and lipid goals to decrease
risk for CAD (coronary artery disease)
8. Quit smoking
9. Carefully plan pregnancies

44. CONTINUED…………………………
10. During SLE in pregnancy avoid most medications during 1st
trimester
11. Opt progesterone only contraception (since estrogen is a risk factor for
SLE)
12. For steroid induced osteoporosis  use bisphosphonates
(alendronate,ibandronate,risedronate) , along with Vitamin. D supplements
13. For renal diseases  use ACE-inhibitors, ARBs (Angiotensin receptor
blockers), non-DHP (Dihydropyridines, most
safe)……………………………………………………………………….

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@RXVICHU