SLE UPDATED

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SYSTEMIC LUPUS ERYTHEMATOSUS
By Dr Tapan Moderator Dr Ajit Kumar Surin
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Outline

• Introduction
• Aetiology Pathogenesis
• Diagnosis
• Autoantibodies in Lupus.
• Systemic Manifestations
• Management

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INTRODUCTION

• Inflammatory multisystem disease.
• WomengtMen- 91 ratio.
• 90 cases are women of childbearing age.
• African AmericansgtWhites.
• Onset usually between ages 15 and 45 years, but
  can occur in childhood or later in life.
• Highly variable course and prognosis, ranges from
  mild to life threatening.
• Characterized by flares and remissions.
• Tissue-binding autoantibodies and immune
  complexes.

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Systemic Lupus

• Incidence Prevalence increasing
• Improved survival, diagnosing milder cases.

• Geographical variability
• African-Americans gt Caucasians (3x)
• Asian-American and Hispanics gt Caucasians
• Age at diagnosis
• 16-55 years of age 65 of cases
• lt 16 20
• gt 65 15

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Lupus History

• Lupus means wolf in Latin.
• 10th century- 1st used medically in case reports.
• Described clinically in the 19th century
• Butterfly rash in 1845
• Arthritis in 1892
• Nephritis in 1895 by Osler
• Serologic tests become available in the 20th
  century
• LE cell in 1948
• ANA in 1954
• 1971- First set of classification criteria.

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Pathogenesis
Genetics
Abnormal Immune response
Environment
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Environmental Triggers

• UV light (A2 and B component)
• Gender ( female gt male, Estrogen)
• EBV
• Vitamin D deficiency
• Other organic compounds.
• Silica dust, solvents, petroleum products,
  Smoking.
• Drugs
• Long list Sulfonamide, Hydralazine, Isoniazid,
  d-Penicillamine, Antiarrhythmic drugs
  Propafenone, procainamide, disopyramide
• Interferons and TNF inhibitors.

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Pathogenesis

• Activation of innate immunity.
• Lowered activation thresholds and abnormal
  activation pathways.
• Ineffective regulation of CD4 and CD8 T cells,
  B cells and myeloid derived suppressor cells.
• Reduced clearance of immune complexes and
  apoptotic cells.

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Pathogenesis
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Development of Autoantibodies
Formation of Antinuclear antibodies
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Mechanisms of organ damage
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Organ damage

• Cytokines involved in tissue injury / organ
  damage in lupus include
• B cell maturation/survival cytokines B-Lymphocyte
  Stimulator (BLyS/BAFF).
• Interlukin 6, 17, 18.
• Pro-inflammatory type 1 and 2 interferons (IFNs)

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Autoantibodies in SLE
Antibody Prevalence Antigen recognized
ANA 98 Multiple nuclear antigens
Anti-dsDNA 70 Double stranded DNA
Anti-Sm 25 Protein complexed to 6 species of nuclear U1 RNA
Anti-RNP 40 Protein complexed to U1 RNA
Anti-Ro (SS-A) 30 Protein complexed to hY RNA (60kDa and 52 kDa)
Anti-La (SS-B) 10 Protein complexed to hyRNA (47 kDa)
Antihistone 70 Histone proteins associated with DNA.
Antiphospholipid 50 ß2G1, Phospholipids, prothrombin
Antierytherocyte 60 RBC membrane
Antiplatelet 30 Surface and altered cytoplasmic antigens on platlets
Antineuronal 60 Neuronal and lymphocyte surface antigens
Antiribosomal P 20 Ribosomal protein
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Clinical relevance Autoantibodies

• ANA
• High sensitivity, low specificity.
• Best screening test
• Repeated negative tests makes SLE unlikely
• Can be positive in upto 10-15 of normal
  individuals.
•  Immunofluorescent technique (IF) more reliable
  than ELISA and/or bead assays.

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Clinical relevance Autoantibodies

• Anti dsDNA
• High titers Specific
• 60 sensitivity.
• In some, Correlates with disease activity
  (Nephritis, vasculitis)
• Anti- Sm
• Specific to SLE.
• More common in Blacks and Asians.
• No definite clinical correlation.

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Clinical relevance Autoantibodies

• Antiphospholipid Antibodies
• Ig G Anticardiolipin High titres(gt40 IU),
  Increased risk for clotting
• Anti ß2 glycoprotein.
• Lupus anticoagulant (By DRVVT)
• Anti Ro/SS-A
• Non Specific
• Associated with Sicca syndrome, Neonatal Lupus,
  Subacute cutaneous lupus
• Decreased risk for nephritis

Women with childbearing potential and SLE should
be screened for both Antiphospholipid and anti-Ro
antibodies
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Clinical relevance Autoantibodies

• Anti RNP
• Non Specific, association with RA (Rhupus),
• black gt white.
• Anti La/SS-B
• Decreased risk for nephritis, associated with
  anti Ro.
• Anti histone
• Drug induced lupus.
• Antineuronal
• Positivity in CSF Active CNS Lupus
• Antiribosomal P
• Positivity in Serum Depression, Psychosis in
  Lupus.

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Diagnosis SLE

• American Rheumatism Association (ARA) in 1982
  (revised in 1997) proposed criteria for
  classification "and not for diagnosis.
• Pitfalls of ACR 1997
• Overly biased and weighted toward cutaneous
  lupus, with four cutaneous criteria.
• Omission of Hypocomplementemia.
• Only psychosis and seizure were included.
• Biopsy-proven nephritis compatible with SLE was
  not included

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Systemic Lupus International Collaborating
Clinics (SLICC) classification

• 11 clinical and 6 immunological criteria
• The patient should satisfy atleast four of the
  criteria including at least one clinical
  criterion and one immunologic criterion.
• Biopsy-proven nephritis compatible with SLE in
  the presence of ANA or anti-dsDNA antibodies even
  in the absence of other lupus features is
  regarded as sufficient for a patient to be
  diagnosed as having lupus.

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SLICC What's new

• Non scarring alopecia added as new entity.
• Old Hematological criteria divided into 3.
• Inclusion of mononeuritis multiplex, myelitis,
  and acute confusional state in CNS manifestation.
• Biopsy proven lupus nephritis
• Addition of Low complement levels in immune
  criteria.
• Antiphospholipid antibodies.

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Performance of the SLICC as compared to old ACR
criteria

• SLICC Sensitivity and specificity were 94 and
  93.
• ACR 1997 Sensitivity and specificity were 86
  93.
• The new criteria retains the goal of simplicity
  of use, yet reflects current knowledge of SLE
  obtained in 29 years since the initial ACR
  criteria.

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Systemic Manifestations Overview
Manifestations
Prevalence,
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Musculoskeletal

• Intermittent polyarthritis
• soft tissue swelling and tenderness in joints
  and/or tendons (hand, wrist, knee)
• Joint deformities develop in only 10
• Individuals having rheumatoid-like arthritis with
  erosions who fulfill criteria for both RA and SLE
  ("rhupus") may be coded as having both diseases.

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Renal Manifestations

• One of most serious manifestation.
• Classification of Lupus Nephritis is purely
  histologic.
• Renal biopsy indicated in every SLE patient with
  evidence of nephritis.
• UPCR gt0.5, RBC casts.
• Nephrotic Syndrome
• ESRD

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ISN/RPS classification of lupus nephritis
Class I Minimal mesangial lupus nephritis (Light microscopy Normal glomeruli)
Class II Mesangial proliferative LN (few isolated subepithelial/endothelial deposits visible by IF or electron microscopy)
Class III Focal lupus nephritis (lt50 glomerulli, sub endothelial deposits)
III A Active lesions
III A/C Active and Chronic Lesions
III C Chronic Lesions
Class IV Diffuse lupus nephritis( gt50 glomeruli involved, Segmental and Global lesions)
IV S (A) Active lesions - Diffuse segmental proliferative lupus nephritis
IV G (A) Active lesions - Diffuse global proliferative lupus nephritis
IV S (A/C) Active chronic lesions - Diffuse segmental proliferative sclerosing lupus nephritis
IV G (A/C) Active chronic lesions - Diffuse global proliferative sclerosing lupus nephritis
IV S (C) Chronic inactive lesions with scars - Diffuse segmental sclerosing lupus nephritis
IV G (C) Chronic inactive lesions with scars - Diffuse segmental global lupus nephritis
Class V Membranous lupus nephritis
Class VI Advanced sclerosing lupus nephritis
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RENAL MANIFESTATIONS

• Patients with dangerous proliferative forms of
  glomerular damage(ISN III and IV) usually have
  microscopic hematuria and proteinuria (gt500 mg
  per 24h)
• If diffuse proliferative glomerulonephritis(DPGN)
  is inadequately treated, virtually all patients
  develop ESRD within 2 years of diagnosis.
• Patients with class V and nephrotic range
  proteinuria should be treated in the same way as
  those with classes III or IV proliferative
  disease.

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Neurological Manifestations

• Cognitive dysfunction
• Difficulty with memory and reasoning
• Headaches, when excruciating, often indicates SLE
  flare
• Psychosis must be distinguished from
  glucocorticoid induced psychosis.
• Disabling myelopathy.
• Stroke, TIAs
• Aseptic meningitis.

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Cutaneous

• Photosensitivity
• Malar rash
• Oral Ulcers
• Alopecia
• Discoid Rash
• Vasculitis rash
• Urticaria

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Oral or Nasal Ulcers

• Oral palate, buccal mucosa, tongue
• Nasal ulcers
• In the absence of vasculitis, Behcets disease,
  infection (herpesvirus), inflammatory bowel
  disease, reactive arthritis, and acidic foods.

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Acute Cutaneous Lupus OR Subacute Cutaneous Lupus

• Acute cutaneous lupus lupus malar rash, bullous
  lupus, TENvariant of SLE, maculopapular lupus
  rash, photosensitive lupus rash (in the absence
  of dermatomyositis).
• Subacute cutaneous lupus nonindurated
  psoriatiform and/or annular polycyclic lesions
  that resolve without scarring.

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Malar Rash
Photosensitive lupus rash
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Chronic Cutaneous Lupus

• Classic discoid rash localized (above the neck)
  or generalized (above and below the neck)
• Hypertrophic (verrucous) lupus
• lupus panniculitis (profundus)
• Mucosal lupus
• lupus erythematosus tumidus
• chilblains lupus
• discoid lupus/lichen planus overlap

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Classic Discoid Rash
Nonscarring alopecia Diffuse thinning or hair
fragility with visible broken hairs.
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Hypertrophic (verrucous) lupus
Hypertrophic (verrucous) lupus
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Lupus profundus
Lupus affecting the fat underlying skin aka
lupus panniculitis.
Dented scar and Nodule.
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lupus erythematosus tumidus

• Tumidus dermal form of lupus.
• Characteristically photosensitive
• Red, swollen, urticaria-like bumps and patches
• Ring-shaped (Annular)

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Cardiopulmonary

• Pleuritic Chest pain, pleural effusion.
• Pericarditis, pericardial effusion, tamponade.
• Myocarditis
• Coronary artery disease.
• Lupus pneumonitis.
• Interstitial fibrosis.
• Pulmonary HTN
• Alveolar hemorrhage, ARDS.

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GASTROINTESTINAL MANIFESTATIONS

• Autoimmune peritonitis and/or intestinal
  vasculitis.
• Increases in serum AST and ALT are common when
  SLE is active
• Aggressive immunosuppressive therapy with
  high-dose glucocorticoids is recommended

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Hematologic

• Anemia (chronic disease)
• Leukopenia (lt4000/mm3)
• Lymphopenia(lt1000/mm3)
• Thrombocytopenia (lt100,000/mm3)
• Lymphadenopathy
• Splenomegaly
• Auto Immune Haemolytic anemia

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Life threatening complications

• Cutaneous Digital Gangrene
• Cutaneous Necrosis
• Thrombocytopenia
• Autoimmune Hemolytic Anemia
• Catastrophic Antiphospholipid Syndrome.
• Pericardial Tamponade
• Myocarditis
• Pulmonary Alveolar Hemorrhage
• Myelitis
• Mesenteric Vasculitis

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ISN/RPS classification of lupus nephritis
Class I Minimal mesangial lupus nephritis (Light microscopy Normal glomeruli)
Class II Mesangial proliferative LN (few isolated subepithelial/endothelial deposits visible by IF or electron microscopy)
Class III Focal lupus nephritis (lt50 glomerulli, sub endothelial deposits)
III A Active lesions
III A/C Active and Chronic Lesions
III C Chronic Lesions
Class IV Diffuse lupus nephritis( gt50 glomeruli involved, Segmental and Global lesions)
IV S (A) Active lesions - Diffuse segmental proliferative lupus nephritis
IV G (A) Active lesions - Diffuse global proliferative lupus nephritis
IV S (A/C) Active chronic lesions - Diffuse segmental proliferative sclerosing lupus nephritis
IV G (A/C) Active chronic lesions - Diffuse global proliferative sclerosing lupus nephritis
IV S (C) Chronic inactive lesions with scars - Diffuse segmental sclerosing lupus nephritis
IV G (C) Chronic inactive lesions with scars - Diffuse segmental global lupus nephritis
Class V Membranous lupus nephritis
Class VI Advanced sclerosing lupus nephritis
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Management SLE

• No cure.
• Complete sustained remission, rare.
• Mainstay Supress symptoms and prevent organ
  damage.
• Prevention of complications of disease and its
  treatment.
• Depends on severity of disease.

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Management Algorithm
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Management SLE

• Non life- or organ threatening.
• Non Pharmacological conservative, Risk factor
  modification.
• Addition of Low dose Corticosteroids, belimumab.
• Life- or organ threatening.
• Nephritis, Myelitis, vasculitis.
• High dose iv steroids Immunosuppressant.
• Special conditions
• Pregnancy, Dermatitis, Thrombotic crisis.

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Therapies Available

• Glucocorticoids.
• Antimalarials.
• NSAIDs (Asprin)
• Biologicals.
• Cyclophosphamide
• Mycophenolate mofetil
• Azathioprine
• Methotrexate
• Tacrolimus
• LefLunomide
• IV Ig

FDA approved.
Off label but standard of care
Borrowed drugs
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Nonpharmacological management

• Sunscreens, SPF atleast 30, prefered 55.
• Smoking cessation.
• Weight loss.
• Exercise.
• Optimal Blood pressure control.
• Supplemental Vit D.
• Avoid High-dose oestrogen therapy, Oral
  contraceptive
• Avoids culprit meds Sulphonamides.
• Avoid pregnancy

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• Pharmacological therapies

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NSAIDs

• For minor symptoms.
• Arthralgia, musculoskeletal, fever, headaches and
  mild serositis.
• Short periods only.
• Adverse effects Aseptic meningitis,
  Transaminitis, Decreased renal function, GI
  bleed, Vasculitis. (NSAID)
• All esp. COX 2 inhibitors increase risk of MI

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Glucocorticoids

• Rapidly reduce inflammation.
• Modulate innate and adaptive immune response.
• Dosages depend on severity.

Low dose prednisone (0.10.2 mg/kg) Mild SLE Cutaneous and musculoskeletal symptoms
Medium dose prednisone (0.5 mg/kg) Moderate SLE Pleuropericarditis or Hematological manifestsations
High dose oral prednisone (1.01.5 mg/kg) or IV methylprednisolone (1 g or 15 mg/kg) Severe disease renal or neuropsychiatric manifestations or vasculitis
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Glucocorticoids (Contd)

• long-term adverse effects
• Infections, HTN, Hyperglycaemia, Acne, Aseptic
  necrosis of bones, Cushing's syndrome, CHF,
  Fragile Skin, Insomnia, Menstrual irregularities,
  osteoporosis, psychosis
• Add calcium (1,500 mg /day) vitamin D (800
  IU/day), if prednisone or equivalent 5 mg /day.

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Antimalarial agents

• MOA Inhibit endosome function ? Disrupt class
  II MHC Decreasing antigen presentation.
• Activates endosomal TLR decrease IFN a.
• Use constitutional, musculoskeletal, skin and
  mild pleuritic symptoms.
• Dose 200-400 mg daily.
• Adverse effects Retinal damage, agranulocytosis,
  aplastic anemia, cardiomyopathy, myopathy,
  peripheral neuropathy, pigmentation of skin,
  Quinacrine diffuse yellow skin.

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Cyclophosphamide

• Alkylating agent, Cross-links DNA and suppress
  DNA synthesis, Prevents division of cells.
• For lupus nephritis, neuropsychiatric lupus,
  severe systemic vasculitis.
• Dosing Protocols.
• NIH I/V CPM (0.51.0 g/m2 bsa) once /month X
  6 months, f/b once / 3 months for 2 years.
• Euro Lupus I/V CPM 500 mg / 2 weeks X
  3 months, f/b AZA or NIH regimen as maintenance.

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Cyclophosphamide

• In comparative study no significant difference
  between NIH and Euro Lupus.
• Adverse reactions Severe infections, alopecia,
  lymphomas and bladder Ca and infertility.
• I/V mesna decrease risk of bladder Ca.
• Gonadotropin releasing hormone use prevents
  premature ovarian failure.

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Azathioprine

• Purine analogue, inhibits synthesis of xanthylic
  and adenylic acids, supress DNA synthesis.
• Use systemic features of lupus, maintenance
  dose for Lupus Nephritis, ISN class III IV.
• Option as induction agent in patients with LN,
  concerned with risk of infertility with CPM.

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Azathioprine

• Dosage For Induction 2 - 3 mg/kg/day PO
• For maintenance 1 -2 mg/kg/day
• If CrCI lt50 ml/min, decrease frequency.
• Adverse effects BM suppression, GI intolerance,
  hypersensitivity and hepatotoxicity. induction
  therapy for selected

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Mycophenolate Mofetil

• Monophosphate dehydrogenase Inhibitor, blocks
  synthesis of guanosine nucleotides and
  proliferation of T and B cells.
• Use Induction and maintenance therapy in lupus
  nephritis moderate to severe SLE.
• NB More effective in Hispanic,
  African-Americans and non-Asians, non white races
  with lupus nephritis, compared to CPM.

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Mycophenolate Mofetil

• Dosages MMF
• For Induction 2-3 g/d PO.
• For maintenance 1 -2 g/d.
• Adverse Effects Nausea, abdominal pain,
  diarrhoea, myelosuppression and infections.

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Methotrexate

• Folate antimetabolite, inhibits DNA synthesis.
• Use for musculoskeletal manifestations, also
  good for serositis.No role in nephritis.
• Dosage 10-25 mg/week PO or SC along with folic
  acid. Requires dose modification renal
  impairment.
• Adverse Effects stomatitis, bone marrow
  suppression, hepatitis, alopecia and pneumonitis,
  pulmonary fibrosis.

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Biologicals
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Belimumab

• Fully human monoclonal antibody against B
  lymphocyte stimulator (BLyS), important for
  survival of B cells. FDA approved.
• Use reduce disease activity in SLE patients
  with mildmoderate disease, without severe renal
  or central nervous system. (FDA approved)

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Belimumab

• Dose 10 mg/kg IV wks 0, 2 and 4, then monthly.
• Generally, well tolerated, not associated with a
  high rate of adverse events.

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IV Immunoglobulin

• Off -label use in catastrophic antiphospholipid
  syndrome.
• Mechanism of action of IVIG in SLE t/t not clear.
• Small clinical trials, have reported variable
  efficacy of IVIG.
• Off label in patients with refractory SLE,
  concomitant infection.

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• Therapy for specific SLE manifestations

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Management Algorithm
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• Mainstay of treatment for any inflammatory
  life-threatening or organ-threatening
  manifestations of SLE is systemic
  glucocorticoids.
• Pulse, 1 g of methylprednisolone IV daily for 3
  days followed by high dose (0.5- 1 mg/kg/day)
  prednisone or equivalent.

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Lupus Nephritis

• In Mild disease Start with hydroxychloroquine,
  RAAS blockers, manage proteinuria and
  hypertension.
• Treatment with hydroxychloroquine have higher
  rates of renal response, fewer relapses, and
  reduced accrual of renal damage.

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Lupus Nephritis

• Patients with ISN grade III or IV disease,
  treatment with GCs and CPM reduce progression to
  ESRD and death.
• For Induction GCs CPM or MMF
• Both CPM and MMF were found to be equally
  effective.
• MMF preferred in Hispanic, African-Americans and
  non-Asians, non white races .

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Lupus Nephritis

• Azathioprine (AZA) may be effective for induction
  but is slower to influence response and
  associated with more flares.
• For Maintenance either MMF or AZA can be used,
  in some studies MMF was found more efficacious.
• For Refractory cases consider rituximab /
  alternate therapy.

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Crescentic Lupus Nephritis

• Crescents in glomeruli have got worse prognosis.
• Currently only High dose CPM with High-Dose GC,
  in induction phase is recommended.

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Membranous Lupus Nephritis

• Classified as ISN class V, have proliferative
  changes.
• In pure Membranous variant, immunosuppression is
  not recommended unless proteinuria in nephrotic
  range.
• ACE inhibitors and ARBs are recommended.
• Alternate day GCs plus CPM/ MMF / Cyclosporine
  all effective in reducing proteinuria.

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Pregnancy and Lupus

• Lupus does not affects fertility.
• Rate of fetal loss increased.
• Demise is higher in mothers with
• high disease activity
• SLE nephritis
• APLA
• Women with AntiRo SSA need additional monitoring,
  high risk for neonatal Lupus.
• APLA with SLE treated with heparin and low dose
  Asprin.

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Pregnancy and Lupus

• Glucocorticoids are Category A
• Cyclosporin, Tacrolimus Rituximab in Category C
• AZA, HCQs, MMF, CPM as category D (benefits
  outweighs risk)
• MTX is Cat X (risk outweighs benefits)
• Mgx HCQs and if required prednisone at lowest
  dose for short time.
• AZA may be added.
• Breast feeding should be avoided (
  glucocorticoids and immunosuppressants get into
  breast milk).

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Neonatal Lupus

• Rare condition
• Not true lupus, passively transferred autoimmune
  disease
• Transplacental transfer of IgG anti SSA or SSB
  antibodies
• 5-7 transient rash, resolves by 6-8 months
• 2 cardiac complications, congenital heart block.

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Neonatal Lupus

• Trans-placental fluorinated corticosteroids,
  dexamethasone and betamethasone.
• Hydroxychloroquine during pregnancy associated
  with reduced rates of NLS.
• IVIg was reported to prevent recurrence of CHB in
  one study, but two large RCTs failed to show any
  beneficial effect.

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Drug Induced Lupus

• Appears during therapy.
• Fever, malaise, arthritis, intense arthralgia,
  myalgia, serositis, and or rash (less common).
• ANA positivity very high.
• Differs from SLE
• White predominance, less female predilection,
  rare involvement of kidneys or brain.
• Commonly antihistone antibody positive, Anti
  dsDNA and RNP rare
• Management
• Withdraw offending drug
• Low doses of systemic corticosteroids if severe
  disease.

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Micro vascular Thrombotic Crisis

• Haemolysis, thrombocytopenia, and micro vascular
  thrombosis in kidneys, brain and other tissues.
• High mortality.
• LAB PS shows schistocytes, LDH is elevated,
  Antibodies to ADAMS13.
• Management Plasma exchange, along with GC
  therapy.

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Lupus and antiphospholipid syndrome

• Repeated fetal losses, venous or arterial
  clotting, with atleast 2 positive tests for
  APLA(12 weeks apart).
• Target INR
• Between 2.0 2.5 (One episode of venous
  clotting).
• Between 3.0 3.5 (recurring clots or arterial
  clotting)
• Heparin and Warfarin.
• Statins, hydroxychloroquine, and rituximab might
  be useful.

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Disease Activity Assessment

• WHY IMPORTANT..??
• For quantification of lupus disease activity
  primarily to check effectiveness of a new drug.
• Not used in routine medical practice.

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• The most effective instrument to measure SLE
  disease activity is still open to debate.
• Several validated measures are
• SLEDAI (SLE disease activity index)
• BILAG (British Isles Lupus Assessment Group)
• SLAM (Systemic Lupus Activity Measure)
• LAI (Lupus Activity Index)
• ECLAM (European Consensus Lupus Activity
  Measurement)

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SLEDAI

• 24 lupus manifestations
• Parameters scored only if present ( ie active
  lupus)
• 16 Clinical, 8 lab parameters.
• Manifestation items are weighted with scores 1 to
  8.
• Total score is sum
• Mild 0-5
• Moderate 6-12
• Severe 13-20
• Score reduction requires complete resolution.
• 3 to 7 point reduction clinically meaningful
  improvement.

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SLEDAI Limitations

• Cannot measure partial improvement of individual
  parameter.
• Cannot measure worsening of an existing
  abnormality
• Some items are unfairly scored (eg
  thrombocytopenia)

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BILAG

• Measures improvement/ worsening in disease
  activity by organ system domain.
• Individual parameters grouped into 9 organ
  domains and scored 0,1,2,3,4 meaning not
  present, improving , same , worse and
  new respectively.
• made with intention to treat.
• Scores A to E, A severe disease activity E
  no activity.

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Composite Responder Indices

• For assessing disease activity in response to
  therapy.
• Identify both improvement and worsening in same
  and different organ system.

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Take home message

• SLE Multifactorial disease.
• No cure, but disease activity can be limited if
  detected early and remissions can be reached.
• Management requires both lifestyle modification
  and pharmacotherapy.
• Severe disease managed by GCs and
  Immunosuppressants.
• Disease activity assessment For future
  prospects.

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