SLE PRESENTATION presentatiomn (1).pptx

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1. SYSTEMIC LUPUS ERYTHEMATOSUS BY, DR.LAKSHMIPRIYAGOWTHAMAN PG-II MD GENERAL MEDICINE

2. DEFINITION Systemic Lupus Erythematosus is a chronic Multisystem , autoimmune disease In which organs and cells undergo damage Initially mediated by tissue binding autoantibodies and immune complexes. Females is more common affected than males. Common in Reproductive age group Prevalence of SLE in united states is 81-144 Per 1 lakh population. Less prevalence in Africa and Australia.

3. PATHOGENESIS Of sLE AUTOANTIBODY PRODUCTION: B cells of the immune system produce autoantibodies that Target the body’s own cells and tissues Autoantibodies commonly found in SLE is Antinuclear antibodies. IMMUNE COMPLEX FORMATION: Binding of autoantibodies to self antigens leads to formation of Immune complexes. Immune complexes consist of autoantibodies can circulate in the blood and deposit in various tissues including kidneys, skin,joints and blood vessels.

4. COMPLEMENT ACTIVATION: Immune complexes formed in SLE can activate the classical pathway of complement system. Thus results in release of Inflammatory mediators such as C3a,C5a and the formation of Membrane attack complex(MAC) ,which can directly damage cells INFLAMMATION AND TISSUE DAMAGE: Deposition of Immune complexes in tissues and activation of complement system leads to chronic inflammation due to release of Inflammatory mediators like cytokines, chemokines. Neutrophils, macrophages and other immune cells contribute to tissue damage through release of enzymes, reactive oxygen species and pro Inflammatory molecules. This chronic inflammation can affect multiple organ systems.

5. ABNORMAL T CELL FUNCTION: In SLE, there is an imbalance of T cell subsets, particularly increase in Autoreactive CD4 + Tcells . Autoreactive T cells can recognise self antigens presented by APC and provide help to B cells, leading to production of autoantibodies. It directly contribute to tissue inflammation by releasing Pro Inflammatory cytokines like Interleukin-17(IL-17). DEFECTIVE CLEARANCE OF APOPTOTIC CELLS: In SLE, there is a defect in clearance of apoptotic cells. The release of self antigens from these dying cells can trigger an immune response and contribute to production of autoantibodies.

6. TYPE 1 INTERFERON PRODUCTION: SLE is characterised by increased production of type 1 Interferons, particularly Interferon-Alpha. Type 1 Interferons are cytokines that play a crucial role in the immune response to viral infections. In SLE, there is activation of Plasmacytoid dendritic cells which are specialized immune cells that produce large amounts of Interferon- Alpha in response to immune complex formation. The increased production of Type 1 Interferons can further stimulate the immune system , enhance the presentation of self antigens, and promote inflammation.

7. CLINICAL MANIFESTATIONS OF SLE MUSCULOSKELETAL : Arthralgia and Non erosive arthritis are most common (>85%). It commonly involves PIP and MIP joints of the hand along with wrist and knees. About 10% of patients, Deformities result from damage to Periarticular tissue causing JACCOUD’S ARTHROPATHY .

8. CUTANEOUS MANIFESTATIONS CLASSIC MALAR RASH : Acute Manifestation Erythematous( Flat or raised) Facial rash with a butterfly distribution across the malar and nasal prominences and sparing of the nasolabial folds It is triggered by Sun exposure. Generalized photosensitivity and alopecia.

9. DISCOID LUPUS: Chronic presentation,Benign variant of lupus in which only the skin is involved Discoid rash consists of erythematous, slightly raised patches with adherent keratotic scaling and follicular plugging The rash is primarily seen in scalp and face.

10. MUCOCUTANOUS MANIFESTATIONS Recurrent crops of small, Painful ulcerations on the oral or nasal mucosa. Dryness secondary to Sjogrens syndrome.

11. HAEMATOLOGICAL MANIFESTATIONS Antibodies that Target each of the cellular blood elements are responsible for haematological changes. RBC: Normocytic normochromic anaemia and hemolytic anaemia WBC: Leukopenia particularly Lymphopenia . . PLATELET: Idiopathic /immune thrombocytopenic purpura induced by Antiplatelet antibodies. CLOTTING FACTORS: Impaired clot formation and haemorrhage.

12. NEUROPSYCIATRIC MANIFESTATIONS COGNITIVE DYSFUNCTION HEADACHE SEIZURES DEPRESSION AND PSYCHOSIS NEUROPATHY VASCULOPATHY

13. CARDIAC MANIFESTATIONS Most frequent- PERICARDITIS Serious Manifestation- MYOCARDITIS AND LIBMAN SACK ENDOCARDITIS Due to Accelerated atherosclerosis and vasculitis – INCREASED RISK FOR MYOCARDIAL INFARCTION.

14. PULMONARY MANIFESTATIONS MOST COMMON PLEURAL LESION - PLEURISY WITH OR WITHOUT PLEURAL EFFUSION. Pleural effusion – Exudative with low C3, ANA test positive in pleural fluid. LUNG LESION- PNEUMONITIS, SHRINKING LUNG SYNDROME, INTERISTITAL INFLAMMATION LEADING TO FIBROSIS AND INTRA ALVEOLAR HAEMORRHAGE.

15. GASTROINTESTINAL MANIFESTATIONS: Non specific diffuse Abdominal pain – AUTOIMMUNE PERITONITIS/ INTESTINAL VASCULITIS. MESENTRIC VASCULITIS OCULAR MANIFESTATIONS: COMMON MANIFESTATION- SICCA SYNDROME AND NON SPECIFIC CONJUNCTIVITIS. SERIOUS MANIFESTATION- RETINAL VASCULITIS AND OPTIC NEURITIS.

16. RENAL MANIFESTATIONS Kidney may be involved in 30-50% of SLE Patients. Often asymptomatic in most of the lupus patients. Characterized by Proteinuria (>500 mg/24 hours) and or cellular (red cell) casts. Urinalysis should be done in any person suspected of having SLE followed by regular urinalysis and blood pressure monitoring.

17. OTHER MANIFESTATIONS KIKUCHI-FUJIMOTO DISEASE- SPLENOMEGALY AND LYMPHADENOPATHY. ANTIPHOSPHOLIPID SYNDROME OSTEOPOROSIS COMPLEMENT DEFICIENCIES NON HODGKIN’S LYMPHOMA LUNG AND HEPATOBILIARY CANCERS.

18. LABORATORY INVESTIGATIONS AUTOANTIBODIES DETECTION: ANTINUCLEAR ANTIBODY: Best screening test and >90% of the patients show positive test . It is not specific for SLE. ANTI-DOUBLE STRANDED DNA- Common in SLE Patients. ANTI SMITH ANTIBODIES- Highly specific for SLE Patients. RHEUMATOID FACTOR- Positive in 30% of patients

19. COMPLETE BLOOD COUNT: ANAEMIA, LEUCOPENIA, LYMPHOPENIA AND THROMBOCYTOPNephritis -. ACTIVATED PARTIAL THROMBOPLASTIN TIME: Prolonged in the presence of Antiphospholipid antibodies ERYTHROCYTE SEDIMENTATION RATE- Monitoring the disease activity. URINALYSIS: Active Nephritis- PROTEINURIA, HAEMATURIA AND CELLULAR OR GRANULAR CASTS. COMPLEMENT LEVELS: Low levels of C3 indicate active disease especially nephritis LE CELL: Phagocytic leukocyte (Neutrophil or macrophage) that has engulfed the denatured nucleus of an injured cell is positive.

20. IMAGING CHEST X RAY- To exclude other pathology ,for pulmonary and cardiac pathology. HIGH RESOLUTION CT: To demonstrate Fibrotic lung. MRI BRAIN AND SPINAL CORD ECHOCARDIOGRAPHY: To diagnose Pericardial and endocardial involvement RENAL BIOPSY: INDICATIONS: Confirmed proteinuria of >1gm/ 24 hours. Proteinuria >0.5gm/day plus hematuria or cellular casts .

21. MANAGEMENT OF NON LIFE THREATENING DISEASE. NSAID’S are useful analgesics/ anti inflammatories , particularly for Arthralgia/ Arthritis. Adverse effects: NSAID’S INDUCED ASEPTIC MENINGITIS, ELEVATED SERUM TRANSAMINASES, HYPERTENSION AND RENAL DYSFUNCTION. HYDROXYCHLOROQUINE: : Reduces disease symptoms, prolongs survival, reduces occur of tissue damage including renal damage BELIMUMAB AND ANUFROLUMAB- Effective in persistent disease activity and fatigue despite Standard therapies. TOPICAL SUNSCREEN, ANTIMALARIALS, TOPICAL GLUCOCORTICOIDS AND TACROLIMUS- LUPUS DERMATITIS.

22. MANAGEMENT OF LIFE THREATENING SLE

23. DRUG INDUCED LUPUS Drug induced lupus is a type of ANA positive Lupus that appears during therapy with certain Medications and biological agents. Drugs like Antiarrythmics ( Eg.Procainamide , Diltiazem,disopyramide and propafenone ), Antihypertensive ( Eg.Hydralazine ), Methyldopa, Angiotensin- Converting Enzyme inhibitors, beta blockers,Anti thyroid Propylthiouracil , Antipsychotic – Chlorpromazine,lithium , Anticonvulsants- Carbamazepine and phenytoin . Commonly associated with ANTI HISTONE ANTIBODIES. Predominant in whites, less female predilection. Rarely involves kidneys and brain. Treatment – Resolves over several weeks after discontinuation of offending medication.

24. PREGNANCY AND LUPUS Rate of fetal loss is increased approximately 2-3 fold in women with SLE. Fetal demises is higher in mother with high disease activity , Antiphospholipid antibodies, Hypertension and/or Active nephritis. Active SLE in pregnant women should be controlled with Hydroxychloroquine and if necessary Prednisone/Prednisolone at the lowest effective doses for the shortest time require. Azathioprine may be added if these treatments do not supress disease activity. Glucocorticoids should be used with caution because of the adverse fetal effects at high doses. Direct oral anticoagulants should avoid in pregnancy. In SLE patients with Antiphospholipid antibodies and prior fetal losses , treatment with LMWH + Low dose aspirin as significantly increase the proportion of live births.

25. NEONATAL LUPUS Rash and /or Congenital heart block with or without Cardiomyopathy. Presence of ANTI –RO Cardiac manifestations of Neonatal lupus are life threatening hence requires vigilant monitoring of fetal heart rate. Treatment- HYDROXYCHLOROQUINE treatment of Anti-Ro postive mother whose prior infant developed Congenital heart block significantly reduces the chance that subsequent fetuses will develop heart block. DEXAMETHASONE treatment of mother in whom fetal first or second degree heart block detected in utero sometimes prevents progression of heart block.

26. LUPUS DERMATITIS Exposure to Ultraviolet light. Topical GLUCOCORTICOIDS AND ANTIMALARIALS (EG:HYDROXYCHLORQUINE) are effective in reducing lesion severity. Systemic treatment with RETINOIC ACID is a useful strategy in patients with inadequate improvement after these interventions on adverse effects are potentially severe. Extensive Pruritic, bullous or ulcerating dermatitides usually improve Promptly after institution of systemic Glucocorticoids

27. PREVENTION Patient receiving >20 mg of Prednisone daily may be protected from pneumocystis infections with trimethoprim- Sulfamethoxazole or atovaquone . Postmenopausal women can be partially protected from steroid induced osteoporosis with calcium supplementation, vitamin D and either bisphosphonates or denisumab . Statin therapies reduce all cause deaths in SLE Patients.

28. EXPERIMENTAL THERAPIES Depletion of B cells with OBINITUZUMAB Inhibition of B cells by blocking more than one receptor for BAFF (TELACICEPT) Elimination of Plasma cells. B cells inhibition through inhibition of BTK Inhibition of B/T cell second signal coactivation with CTLA-Ig or anti- CD 40L. Inhibition of Innate immune activation via TLR7 or TLR7 and TLR9. Induction of regulatory T cells with peptides from immunoglobulin or autoantigens. Inhibition of T effector cells through CD6. Targeting lymphocyte migration by modulation of S1P1 receptor. Inhibition of lymphocyte activation by blockade of JAK/ Stat

29. POOR PROGNOSTIC FACTORS MALE SEX OLDER AGE AT PRESENTATION BLACK RACE HYPERTENSION ANTIPHOSPHOLIPID ANTIBODY SYNDROME DIFFUSE PROLIFERATIVE GLOMERULONEPHRITIS

30. CAUSES OF DEATH IN SLE INFECTIONS AND RENAL FAILURE THROMBOEMBOLIC EVENTS CARDIOVASCULAR DEATH