SYSTEMIC LUPUS ERYTHEMATOSUS

PHARMACOTHERAPEUTICS OF SLE

1. Systemic Lupus Erythematosus Dr. V. S. Swathi Assistant Professor

2. Definition It is an autoimmune disease associated with autoantibody production which will affect multiple organs

3. Epidemiology In the world, around 5 million people are affected with the SLE In India, 3 people per 1,00,000 population are affected with this problem

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. Clinical Presentation Acute/sub acute Cutaneous lupus/ malar rash/ photosensitive rash Chronic Cutaneous lupus/ discoid rash Oral/ nasal ulcers Non scarring alopecia Tenderness, swelling and pain in joints Fatigue Depression Headache Weight loss Nausea Abdominal pain Seizures Lymphadenopathy Heart murmurs Pleuritic pain Shortness of breath Hematuria Dry eyes Confusion Memory loss Reynaud’s phenomenon

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

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

10. 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

11. Non Pharmacological Treatment Protection from sun Exercise Smoking cessation Counselling Avoid exposure lo live vaccines

12. Treatment Algorithm of SLE General disease NSAID Anti malarial drugs Glucocorticoids Cyclophosphomide Methotrexate Mycophenolate Mofetil Rituximab Belimumab Calcineurin inhibitors IV immunoglobulins Plasmapheresis

13. Treatment Algorithm of SLE Continued…. Lupus Nephritis NSAID Anti malarial drugs Glucocorticoids IV immunoglobulins Plasmapheresis Glucocorticoid+ Mycophenolate Mofetil+ Cyclophosphomide-Induction Therapy Mycophenolate Mofetil+ Azathioprine- Maintenance Therapy

14. Treatment Algorithm of SLE Continued… Neuropsychiatric Lupus Anti malarial drugs Antidepressants Antipsychotics Anticonvulscents Azathioprine Cyclophosphomide

15. Treatment Algorithm of SLE Continued…. Cutaneous Lupus Erythematosus Topical corticosteroids Topical Calcineurin inhibitors Anti malarial drugs Methotrexate Mycophenolate Mofetil Dapsone Thalidomide IV immunoglobulins Plasmapheresis

16. 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

17. 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

18. 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

19. Resources https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505936/pdf/pmed.1002800.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523351/pdf/cells-08-00323.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456110/pdf/medi-98-e15030.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420100/pdf/dddt-13-857.pdf https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC6417005/pdf/dddt-13-845.pdf