Sle diagnosis & treatment

Systemic Lupus Eruthematosis- Diagnosis & Treatment

1. Systemic Lupus Erythematosis Diagnosis & Treatment Dr Suman Roy PGT - Midnapore

2. Abnormal Immune Responses Susceptibility Genes And Environmental Factors Activation of Innate Immunity Lowered Activation Thresholds Adaptive Abnormal Activation Pathways Immunity Cells Ineffective Regulatory CD4+ & CD8+ T Cells, B Cells And Myeloid-derived Suppressor Cells Reduced Clearance Of Immune Complexes And Apoptotic Cells

3. Self-antigens Nucleosomal DNA/Protein; RNA/Protein in Sm , Ro La & Phospholipids Recognized by Immune System in Surface Blebs of Apoptotic Cells Autoantigens , Autoantibodies , Immune complexes Inflammation & Ds IFN1 & 2 TNF- α IL 17 & B Cell-maturation/Survival Cytokines B Lymphocyte Stimulator ( Blys / Baff ) & IL-10.

4. Pathogenesis of SLE

5. SLE is a Multigene Disease + Environmental Factor Normal alleles of Multiple Gene -- each contribute a small -- if enough predisposing variations are present Disease Results. Approx 45 predisposing genes have been identified

6. Gene Polymorphisms Transcription/Epigenetic combinations influence Immune Responses External & Internal Environment Too High Too Prolonged And/or Inadequately Regulated Response Autoimmune Disease Results Role of X chromosome & Hormones

7. Pathology Deposition of Ig at (DEJ) Injury to basal keratinocytes Inflammation dominated by T lymphocytes -- DEJ -- around blood vessels -- dermal appendages. Clinically unaffected skin may also show Ig deposition at the DEJ.

8. PATHOLOGY Histologic abnormalities in blood vessels Shows Leukocytoclastic Vasculitis is most Common Patterns of vasculitis BUT are not specific for SLE Lymph node biopsies are usually performed to rule out Infection or Malignancies In SLE, they show nonspecific diffuse chronic inflammation.

9. Diagnosis Depends on C/F Auto-Antibody

10. To Diagnose Any 4 or More 1 Clinical Category 1 Immunologic Category (Well documented at any time during individual’s history) Specificity ~ 93% Sensitivity ~ 92%

11. Auto-Antibodies ANA positive in >98% of Patients Repeated Negative Tests Not SLE (By immunofluorescent method) Unless other Autoantibodies are present High- titer IgG Ab to dsDNA specific for SLE Ab to Sm -Ag Favor diagnosis in presence of compatible clinical manifestations

12. If only antibodies + ve Without Clinical symptoms Should not be considered Diagnostic for SLE Although such persons are at increased risk .

13. Antiphospholipid antibodies Not specific for SLE But their presence fulfills one classification criterion They identify patients at increased risk for Venous or Arterial Clotting Thrombocytopenia Fetal Loss. There are three widely accepted tests that measure different antibodies Anticardiolipin Anti-β2-glycoprotein Lupus anticoagulant

14. Antiphospholipid antibodies Women with child-bearing potential & SLE should be screened for Antiphospholipid Antibodies Anti-Ro Because Both antibodies have the potential to cause Fetal harm

15. STANDARD TESTS FOR DIAGNOSIS Screening tests for Complete Blood Count Platelet Count Urinalysis May Detect abnormalities that contribute to DIAGNOSIS and influence Management Decisions

16. TESTS FOR FOLLOWING DISEASE COURSE To See Any Organ Involvement Urinalysis for Hematuria Proteinuria Hemoglobin Levels Platelet Counts Serum Levels Of Creatinine or Albumin Levels Of Anti-DNA & Anti-c1q Antibodies Several Components of Complement (C3 is most widely available) activated complement products (including those that bind to the C4d receptor on erythrocytes),

17. IFN-inducible gene expression in peripheral blood cells, serum levels of BLyS (B lymphocyte stimulator, also called BAFF) and Urinary levels of TNF-like weak inducer of apoptosis (TWEAK ) Neutrophil gelatinase -associated lipocalin (NGAL ) or monocyte chemotactic protein 1 (MCP-1 ) None is uniformly agreed upon as a reliable indicator of flare or of response to therapeutic interventions.

18. Interpretation of Clinical Manifestation

19. Fever Malaise Weight-Loss Anorexia Fatigue

20. Jaccoud’s -like arthropathy . These hand deformities resemble those that develop in patients with a history of rheumatic fever and are caused by ligamentous and/or joint capsule laxity. Deformities in the hands, such as ulnar drift at the metacarpophalangeal joints, swan neck and boutonnière deformities, and hyperextension at the interphalangeal joint of the thumb, closely resemble the deformities seen in rheumatoid arthritis. Absence of erosions on radiographs and their reducibility distinguish this condition from the deforming arthritis of rheumatoid arthritis.

21.   Localized acute cutaneous lupus erythematosus ( malar rash, butterfly rash) This lesion is characterized by macular or papular erythema in a malar distribution, sparing the nasolabial folds.

22. Subacute Cutaneous manifestations

23. Chronic Cutaneous Manifestation

24. Discoid lupus erythematosus involving the dorsa of the hands. The lesions spare the proximal interphalangeal joints, a characteristic feature of lupus-specific rashes.

25.   Bullous lupus erythematosus . These lesions are a rare manifestation of lupus and are characterized by nonscarring bullous lesions.

26. Lupus Panniculitis as an Initial Manifestation of SLE

27. HEMATOLOGIC MANIFESTATIONS Anemia -- normochromic normocytic reflecting chronic illness. Hemolysis can be rapid in onset and severe, requiring high-dose glucocorticoid therapy, which is effective in most patients. Leukopenia is also common and almost always consists of lymphopenia , not granulocytopenia Thrombocytopenia may be a recurring problem Lymphadenopathy Splenomegaly Hemolytic Anemia

28. VASCULAR OCCLUSIONS The Prevalence of TIA, strokes, and MI increased But not exclusive to SLE patients With Antibodies to Phospholipids ( APLA ) which are associated with Hypercoagulability and Acute Thrombotic Events

29. VASCULAR OCCLUSIONS Appropriate tests for antiphospholipid antibodies and for sources of emboli should be ordered in such patients To estimate the need for intensity of and duration of Anti-inflammatory and/or Anticoagulant therapies. In SLE, Myocardial Infarctions are primarily manifestations of accelerated atherosclerosis. The increased risk for vascular events is three- to tenfold overall, and is highest in women <49 years old.

30. NEURO Cognitive Dysfunction including difficulties with Memory and Reasoning HEADACHES are also common When excruciating They often indicate SLE flare Seizures of any type often requires both Antiseizure and Immunosuppressive therapies Psychosis can be the dominant manifestation

31. Renal involvement NEPHRITIS is usually the most serious manifestation of SLE Asymptomatic in most lupus patients URINALYSIS should be ordered in any person suspected of having SLE. The classification of lupus nephritis is primarily histologic Renal biopsy is recommended for every SLE patient with any clinical evidence of nephritis results are used to plan current and near-future therapies .

32. International Society of Nephrology(ISN) and The Renal Pathology Society (RPS) classification addition of “a” for active and “c” for chronic changes gives information regarding the potential reversibility The system focuses on glomerular disease Although the presence of Tubular Interstitial and Vascular Disease is important to clinical outcomes

33. Classification of Lupus Nephritis (International Society of Nephrology and Renal Pathology Society) Class I Minimal Messangial Normal Glomeruli Messangial Immuno Deposie Class II Messangial Proliferative Mesangial Hypercellularity Matrix Expansion Few Subepithelial & Subendothelial Deposits Class III Focal Active Or Inactive Focal , Segmental Or Global Endo Or Extracapillary GN < 50% Of All Glomeruli Class IV Diffuse Active Or Inactive Focal , Segmental Or Global Endo Or Extracapillary GN > 50% Of All Glomeruli Class V Membranous Global Or Segmental Subepithelial Immune Deposits Or Their Morphologic Sequelae Class VI Advance Sclerotic >_ 90% Glomeruli Globally Sclerosed Without Residual Activity

34. PULMONARY MANIFESTATION PLEURITIS with or without pleural effusion. When Mild , may respond to treatment NSAIDs When More Severe , patients require glucocorticoid therapy. Pulmonary Infiltrates also occur as a manifestation of active SLE Life-threatening pulmonary manifestations include interstitial inflammation leading to fibrosis, shrinking lung syndrome , and intraalveolar hemorrhage

35. CARDIAC MANIFESTATIONS PERICARDITIS responds to anti-inflammatory therapy and infrequently leads to tamponade . More serious cardiac manifestations are Myocarditis and Fibrinous Endocarditis of Libman -Sacks. The Endocardial involvement can lead to valvular insufficiencies, most commonly of the mitral or aortic valves, or to embolic events.

36. OCULAR MANIFESTATIONS Sicca syndrome and nonspecific conjunctivitis are common in SLE rarely threaten vision Retinal Vasculitis and Optic Neuritis are serious manifestations Blindness can develop over days to weeks Aggressive immunosuppression is recommended

37. Management

38. Management No cure for SLE Complete sustained remission are rare. Physician should plan To induce remissions of acute flares Maintain improvements with strategies that Suppress symptoms to an acceptable level and Prevent organ damage

39. Management Therapeutic choices depend on Life-threatening or likely to cause organ damage justifying aggressive therapies 2. Whether Manifestations are potentially Reversible 3. To Preventing complications of Disease

40. Thank You