Systemic lupus erythematosus (SLE) is an autoimmune disease where the immune system mistakenly attacks healthy cells and tissues. It is known as lupus and can affect multiple organ systems. SLE affects women more than men and prevalence is highest in Asian, African, and Hispanic populations. Symptoms can include butterfly rash, photosensitivity, arthritis, serositis, and involvement of major organs like the kidneys and brain. SLE is diagnosed based on meeting 4 out of 11 diagnostic criteria from the American College of Rheumatology including both clinical and immunological criteria. Treatment involves managing symptoms with medications like NSAIDs, hydroxychloroquine, corticosteroids, and immunosuppressive

3. • affects a number of
organ & tissues
Systemic
• Latin word, meaning
“wolf”
Lupus
• Redness of skin(as in
inflammation)
Erythmatosus

4.  An autoimmune disease
 Immune system fights infection by producing antibodies
 Affected individuals produce abnormal antibodies known
as “autoantibodies”

5. • 30-50/100,000 in Asian countries
Prevalence rate
• Women are affected 9 times more frequently than
men
• More frequent in African Americans and people of
Chinese and Japanese descent
Frequency
• can affect all ages
• most commonly begins from 20-45 years of age
Disease onset

6.  SLE is a chronic disease of variable severity

7.  can cause disease of the skin, heart, lungs, kidneys, joints and
muscles

8.  2 main types on the basis of site of infection:
Discoid lupus
• Affects only skin
• No internal
disease
SLE
• Internal organs
are involved

10.  Medicines can trigger SLE
 More than 90% cases occurs as a side effect of one of the following
6 drugs
DRUG USED FOR
1. Hydralazine (Apresoline) High BP
2. Procainamide abnormal heart rhythms
3. Phenytoin (Dilantin) epilepsy
4. Isoniazid (Nydrazid, Laniazid) TB
5. Quinidine (Quinidine Gluconate,
Quinidine Sulfate)
abnormal heart rhythms
6. d-penicillamine rheumatoid arthritis

12. MHC Genes
HLA Class II: Polymorphism
HLA Class III: C2 and C4 defects
Other Genes
TCRs
IL-6
SNPs involved fall into the intron region

13. Hypothalamo–pituitary–adrenal (HPA) axis
Gender
Females ( Estrogen, Androgens)
Males ( Estrogen, Androgens)
Exogenous Estrogen
Oral Contraceptives
HRT
> Th1
Cells
< Th2
Cells
< B Cells < Antibodies

14. Infections
EBV (mimic + resemble self-antigens)
Stress
Stimulates Glucocorticoids Reduces Auto-antibodies
Epigenetics
Demethylation (CD4 T Cells)
Hyperactive B cells
Sunlight
Flare-up of symptoms
Vit D deficiency
Defect

15. CD4 Cells
Self Recognition
> Th1 Cells > IL-2
Inflammation
Th Cells < IL-17
CD8 Cells
Fail to suppress self-B Cells
B-Lymphocytes
Infected By EBV
Recognize self-antigens

16. Dendritic Cells
Uptake of Apoptotic Bodies:
1. Tolerance Induction (pDCs)
2. Autoimmunity (mDCs)
• Engulf apoptotic
bodies
• Present peptide
to autoreactive T
and B cells
• Sustain IFN-
a
production
• IFN-a acts
on
monocytes
• Release
IFN-a
pDCs
Mature
DCs
Antigen
Presentati
on
Immune
Complexe
s (Plasma
cells)

18. “Any attribute which increases likelihood of a disease”
- Environmental factors (Sunlight, Chemicals, Lifestyle)
- Genetic factors (Family history)
- Hormonal factors

21. Genetic linkage of systemic lupus erythematosus with chromosome 11q14
(SLEH1) in African-American families stratified by a nucleolar antinuclear
antibody pattern
A H Sawalha, B Namjou, S K Nath, J Kilpatrick, A Germundson, J A Kelly, D Hutchings, J James and
J Harley
Studies related to Ethnicity and SLE

22. Familial aggregation of lupus and autoimmunity in an unusual
multiplex pedigree.
Sestak AL1, Shaver TS, Moser KL, Neas BR, Harley JB
The 8 affected females shared several disease features, including arthritis (8/8), antinuclear antibodies
(ANA) (8/8), pleuritis (6/8), malar rash (6/8), photosensitivity (5/8), and nephritis (4/8).
Conclusion:
The high rate of autoimmunity among both blood relatives and nonconsanguineous mates in this unusual
pedigree suggests a complex interaction of genetic and environmental factors contributing to disease.
http://www.ncbi.nlm.nih.gov/pubmed/10405936

23.  Viruses
Epstein-Barr virus, cytomegalovirus, and parvovirus-B1.
 Sunlight
- alter the structure of DNA in cells below the surface.
-The immune system perceives these altered skin cells as foreign
- trigger an autoimmune response
 Chemicals Chlorinated pesticides and crystalline silica are two suspects

24.  Cytokines, major immune factors that are active in SLE, are directly affected by
sex hormones
 Women with SLE may have lower levels of androgens
 Men who are affected by SLE may also have abnormal androgen levels

26.  Renal
 Alopecia
 Serositis
 Hemolytic Anemia
 Oral & Nasal ulcers
 Neurologic
 Synovitis
 Chronic cutaneous lupus (Discoid)
 Acute & Sub acute lupus
 Aeucopenia
 Platelets (Low)

27. 1. BUTTERFLY RASH (Malar Rash)
 Characteristic red, flat facial rash over the bridge
of the nose
2. PHOTOSENSITIVITY
 Rash after exposure to ultraviolet (UV) B
radiation coming from sunlight or fluorescent
lights.
3. DISCOID RASH
 Skin rash often found on the face and scalp.
Usually red and may have raised borders.

28. 4. ALOPECIA
Diffuse thinning, LUPUS HAIR, Fragility
5. RUPHUS
 SLE primarily affects the small joints of
the hands, wrists, and knees.
6. MYOSITIS
 Pain & tenderness in the muscles

29. 7. BRAIN INFLAMMATION
 Changes in personality, psychosis, seizures and
coma as well
8. SEROSITIS

32. Various symptoms and multiple organ
involvement
Combination of laboratory evidence and clinical
findings.
11 ACR Criteria's were designed

33. Serositis
Oral ulcers
Arthritis
Photosensitivity
Blood disorders
Renal involvement
Malar rash
Discoid rash
Antinuclear antibodies
Neurologic disorder
Immunologic phenomena (eg, dsDNA; anti-
Smith [Sm] antibodies)
 Anti-cardiolipin antibodies
 Lupus Anticoagulants

34. A person is diagnosed with SLE if:
 4 out of 11 criteria are a present, including 1 immunologic and 1 clinical
criteria,
 With biopsy proven nephritis, or anti dsDNA antibodies presence
 85% sensitive and 95% specific

35.  Complete blood count
 Anemia, low white blood cells, low platelet count
 Erythrocyte sedimentation rate
 Slightly faster ESR
 Kidney and liver function Tests
 Liver function tests
 Creatinine kinase Assay
 Urine analysis
 High protein levels and red blood cells
 Antinuclear antibody tests
 Positive for SLE

36.  Chest X-ray
 Echocardiogram
 Joint radiography
 Brain MRA/MRI
 Cardiac MRI

37.  Arthrocentesis
 Lumber puncture
 Renal biopsy
 Skin biopsy
 Nerve biopsy

39.  Major Goals of the therapies
 To stop or reverse the ongoing inflammation of different body organs
 To prevent the irreversible end-organ damage
 Requirement of vigilant management
 Because of potential toxicities of immunosuppressive drugs

40. NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)
Low-doses of corticosteroids (prednisolone)
Corticosteroid creams for butterfly rashes
Antimalarials (Hydroxychloroquine)
Immunosuppressive Drugs (Methotrexate etc.)
Monoclonal antibodies targeting specific pathways

41. • COX-2 inhibition leading to
prostaglandin inhibition
• COX-1 inhibition leading to
prohibition of prostaglandins
production involved in G
lining protection

43.  Efficient in people with arthralgia
 Mechanism unknown, have anti-inflammatory effects
 Block UV absorption (destructive for cutaneous lesions)
 Mostly recommended antimalarial: Hydroxycholoroquine
Immunosuppressive
Drugs
Mycophenolate
Methotrexate
Cyclophosphamide
Azathiprine

44.  Corticosteroids (CS) side effects include
 Hypertension, atherosclerosis, type 1 diabetes, osteoporosis and
depression
 Higher fatigue and lower EuroQol scores
 NSAIDs
 Inhibits the COX-1 pathway
 Leads to bleeding GI tract and blood stool
 Antimalarial drugs
 Dermatological & ophthalmic reactions, headache and psychosis
 Standard ophthalmic screening is recommended
 Immunosuppressive drugs
 Increased risk of other opportunistic infections such as cancers

45.  B-cell targeted
 Rituximab
 Veltuzumab
 Complement System targeting
 Eculizumab
 Cytokine Inhibitors
 Infliximab
 Recently approved: BELIMUMAB