Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies that result in damage to multiple organs, primarily affecting young women between ages 20-30. The prevalence is notably higher among African-American and Afro-Caribbean women, with risk factors including family history, smoking, and infections. Diagnosis involves clinical presentation and various lab tests, while treatment options range from immunosuppressants to corticosteroids depending on the severity and specific symptoms.

1. Systemic Lupus Erythematosus
Dr Ganesh G
DNB PG Resident
Department of General Medicine
District Hospital Chikkaballapur

2. Definition
• It is an autoimmune disease in
which organs & cells undergo
damage mediated by tissue
binding autoantibodies and
immune complexes

3. Epidemiology
• In the world, around 5 million people are affected with the SLE.
• Prevelance is higher in African-American , afro-carrebean women than
white men
• In India, 3 people per 1,00,000 population are affected with this
problem
• Usually occurs in young women b/w 20 to 30yrs

4. Risk factors
• Family history of SLE
• Smoking
• Infections like Epstein Barr Virus
• Persons who are using Immunosupressants and Biological drugs
• Stress
• Women

5. Etiology
• Epigenetic regulation of HLA-D2, D3, and D8 gene
• Environmental factors
• Hormones- Estrogen and Progesterone
• Abnormalities in immune cells and cytokines

6. Pathogenesis
Patients with risk factors
Exposed to triggering factors
Abnormal expression of genes responsible for immunity
• Activation of T cells and B cells
• Formation of inflammatory mediators like Interleukins, Cytokines,
Cytotoxins and TNF-α
Formation of auto antibodies
Antibody and antigen complex formation
Accumulation of above complex in multiple organs
Damage of multiple organs

7. • Autoantibody production – B cells of immune system produce antinuclear
antibodies that target the body’s own cells & tissues
• Immune complex formation – consists of autoantibodies bound to target
antigens , they circulate in blood and deposit in various tissues
• Complement avtivation – immune complexes formed in SLE activate
complement system with the release of C3a, C5a and formation of
Membrane attack complec which damage the cells directly
• Defective clearance of apoptotic cells –in SLE apoptotic cells may not be
cleared efficiently, the release of self antigens from dying cells can trigger
autoimmune response & contribute to production of autoantibodies
Pathophysiology

8. Pathophysiology continued…
• Inflammation and tissue damage – immune complexex, complement activation leads
to chronic inflammation with the release of mediators like cytokines, chemokines
contribute to tissue damage.
• Abnormal T-cell function – in SLE there is imbalance in T-cell subsets, increase in
autoreactive CD4+ T cells. It can recognize self antigens presented by antigen
presenting cells and provide help to B cells to produce autoantibodies. They also cause
tissue inflammation by release of IL-17
• Type 1 interferon (IFN) production – type 1 IFN-α play a crucial role in immune
response to viral infections. In SLE there is activation of plasmacytoid dendritic cells
that produce large amount of IFN-α in response to immune complex stimulation
which leads to further stimulation of immune system, enhance presentation of self
antigens.

10. Clinical Presentation
• Systemic – fatigue, malaise, fever,anorexia, nausea, weight loss
• Musculoskeletal- arthralgis, non-erosive polyarthritis, Jaccoud’s arthropathy
• Mucocutaneous – Malar rash, discoid rash, alopecia, Raynaud phenomenon, splinter hemorrhages
• Hematological – anemia, leukopenia, lymphopenia, thrombocytopenia,splenomegaly, hemolytic
anemia
• Neuropsychiatry – delirium, psychosis,seizures, polyneuropathy, mood disorders, stroke
(thromboembolic)
• Cardiopulmonary – pericarditis, myocarditis, Libman-Sacks endocarditis, congenital heart block
(neonatal lupus), shrinking lung syndrome
• Renal – proteinuria, nephrotic syndrome, renal failure
• Others- cutaneous vasculitis, antiphospholipid antibody syndrome, sicca syndrome

12. Renal manifestations in SLE
ISN/RPS Classification of LUPUS NEPHRITIS
Class 1 – minimal mesangial lupus nephritis
Class 2 – Mesangial proliferative LN
Class 3 – Focal Lupus nephritis
Class 4 – Diffuse lupus nephritis
Class 5 – Membranous lupus nephritis
Class 6 – Advanced sclerosing lupus nephritis

13. Complications
• Arthritis
• Pancytopenia
• Hypertension
• Stroke
• Pericarditis/ Myocarditis
• Lupus nephritis
• Anxiety
• Mood disorders
• Depression
• Neuropathy
• Pleuritis
• Vasculitis

15. Diagnosis
• Medical history
• Clinical presentation
• Complete blood count
• Lab tests based on complications
• Serology test for
• Auto antibodies (ANA)
• Antiphospholipid antibodies
• Complement proteins

16. Diagnosis Continued…..
• C Reactive protein
• Erythrocyte sedimentation rate
• Urine microscopy
• Chest x ray
• CT/MRI of brain/ lung/ chest- depending on effected organ
• ECG
• Renal biopsy
• Lumbar puncture

17. Diagnosis
SLE is characterized by production of autoantibodies , some are antinuclear, anticytoplasmic, some are specific
against surface antigens of of blood cells.
Autoantibodies in patients with SLE
• Antinuclear antibodies (ANA)
• Anti-double strand DNA
• Anti-Smith
• Anti Ribonuclear protein
• Anti-Ro
• Anti-La
• Anti Histone
• Antiphospholipid
• Antierythrocyte
• Antiplatelet
• Antineuronal
• Antiribosomal

18. • ANA is the best screening test, more than 90% patients show positive. However it is not specific
for SLE
• Anti – dsDNA and Anti Sm are relatively specific for SLE
• Rising levels of anti – ds DNA and low levels of complement C3 and C4 usually reflect disease
activity.
• ESR is raised in some patients
• CRP unlike ESR does not rise with disease activity unless there is arthritis or serositis.
• APTT is prolonged in patients with lupus anticoagulant (APLA)
• With active nephritis urine analysis show proteinuria, hematuria & cellular or granular casts.
Renal biopsy confirms renal involvement.
• Low levels of C3 & C4 indicate active disease especially nephritis.
• LE cell – phagocytic leukocyte (neutrophil or macrophage) that has engulfed the denatured
nucleus of an injured cell

19. American college of Rheumatology criteria for Systemic Lupus Erythematous
Entry criterion -
ANA at a titre of ≥ 80 on HEp – 2 lines or an equivalent positive test
Additive criteria
(A total score of 10 or more is considered to classify as SLE with entry criterion is a must)
Immunological domain & criteria weight
APLA - Anticardiolipin or
Anti β2 glycoprotein 1 or
Lupus anticoagulant
2
Complement proteins – Low C3 or C4 3
Low C3 & C4 4
SLE specific antibodies – Anti ds DNA antibody or 6
Anti Smith antibody

20. Clinical domain & criteria weight
Fever 2
Hematological - Leukopenia 3
Thrombocytopenia 4
Autoimmune hemolyses 4
Neuropsychiatry – delirium 2
Psychosis 3
Seizure 5
Mucucutaneous – non sparing alopacia 2
Oral ulcers 2
Subacute cutaneous or discoid lupus 4
Acute cutaneous lupus 6
Serosal – pleural or pericardial effusion 5
Acute pericarditis 6
Musculoskeletal – joint involvement 6
Renal – proteinuria > 0.5g/24h 4
Renal biopsy class II or V lupus nephritis 8
Renal biopsy class III or IV lupus nephritis 10
Note : additional criteria within
same domain will not be counted
Classify as SLE with a score of 10
or more (from both clinical &
immunological criteria)
along with Entry Criterion ANA
rising titre is a must

22. Non Pharmacological Treatment
• Protection from sun
• Exercise
• Smoking cessation
• Counselling
• Avoid exposure to live vaccines

23. Treatment of SLE
Initial management of SLE –
Sunscreen, SBE prophylaxis
Arthritis – NSAIDs, HCQ, if persistant add Methotrexate
Mucocutaneous symptoms , fatigue, alopecia – HCQ
Fever – indomethacin, if persistant ad Glucocorticoids
CNS symptoms – high dose steroids or IV cyclophosphamide
Renal involvement biopsy confirmed :
1. Class II – trial of moderate Glucocorticoids
2. Class III or IV – high dose Glucocorticoids , IV Cyclophosphamide, Mycophenolate mofetil,
azathioprine
3. Class V – trial of Glucocorticoids, MMF, cyclosporine
4. Class VI – close monitoring, dialysis, Renal transplant
Alveolitis – systemic GC + MMF or IV cyclophosphamide , then add rituximab or IV Ig, maintain with
azathioprine or mycophenolate
Antiphospholipid syndrome – anticoagulation, with or without HCQ, then add direct thrombin inhibitor.
Uncomplicated digital or cutaneous vasculitis – systemic GC, with or without HCQ, with or without
Methotrexate, then add Azathioprine or MMF then switch to IV cyclophosphamide.

24.  Immunosuppressive agents – azathioprine, methotrexate, cyclophosphamide,
mycophenolate mofetil are used in controlling severe disease. They are particularly useful
in patients with renal involvement..
 A combination of IV cyclophosphamide and steroids is most effective.
 Following IV cyclophosphamide, oral MMF is an alternative to maintain remission.
 Drugs targeting B-cell pathways such as Belimumab & rituximab are used in refractory
cases.
 New update : Antifrolumab, a human monoclonal antibody against IFN receptors
subunit1 was approved by US FDA for treatment of moderate to severe disease.

25. Drugs used in treatment of SLE
Drug Category Mode of action Dose Adverse effects
Prednisone Corticosteroids Control inflammation by
stabilizing lysosomes at
cellular level
0.1-1.5mg/kg/day-PO  Hypertension
 Diabetes
 Poor wound healing
 Osteoporosis
 Weight gain
Methyl Prednisolone Corticosteroids Control inflammation by
stabilizing lysosomes at
cellular level
100-1000mg-TID  Hypertension
 Diabetes
 Poor wound healing
 Osteoporosis
 Weight gain
Hydroxychloroquine Anti malarial drug Impairs complement
dependent antigen and
antibody reactions
200-400mg-PO-OD  Muscle weakness
 Leukopenia
 Thrombocytopenia
 Retinal damage
 Alopecia

26. Drugs used in treatment of SLE Continued..
Belimumab Biological agents Inhibit production of
antibodies from plasma cells
10mg/kg- IV-3 doses in 2 weeks
10mg/kg- IV-once in every 4 weeks
 Infusion reactions
 Diarrhea
 Pyrexia
 Nasopharyngitis
 Bronchitis
Cyclophosphomide Immunomodulator Produces irreversible T cell
apoptosis
500-1000mg-IV-once in every 6 months  Alopecia
 GI toxicity
 Leukopenia
 Amenorrhea
 Sterility
Mycophenolate
Mofetil
Immunosuppressant Inhibit T and B cell
production
0.5-3g/day-PO  Hyperglycaemia
 Hypercholesterolemia
 Hypomagnesaemia
 Dyspnoea
 Back pain
Azathioprine Immunomodulator Inhibit T and B cell
production
1.5-2mg/kg/day-PO  Leukopenia
 Infections
 Lymphoma
 Abdominal pain
 Alopecia

27. Drugs used in treatment of SLE Continued..
Methotrexate Immunomodulator Inhibit T cell replication 15-25mg-PO-Once
weekly
 Arachnoiditis
 Erythema
 Hyperurecemia
 Stomatitis
 Glossitis
Rituximab Monoclonal antibody Induces B cell lysis 500-1000mg- IV  Angioedema
 Pruritis
 Abdominal pain
 Leukopenia
 Infections
Aspirin NSAID Inhibit prostaglandin
synthesis
2.1-7.3g/day-OD-PO  Angioedema
 Bronchospasm
 CNS alteration
 Alopecia
 GI bleeding