SYSTEMIC LUPUS ERYTHEMATOSUS

June 1& 8, 2015

Outline Introduction : Definition, epidemiologyPathogenesis : Etiology, Risk factors, pathology.Diagnosis : SLICC 2012 v/s ACR 1997.Autoantibodies in Lupus.Systemic Manifestations : overview and life threatening

complications.

Management : Therapies old and new, special

conditions, monitoring disease activity, Flare definition

and management, pipeline therapies.

Systemic Lupus• Inflammatory multisystem disease.• Women>Men- 9:1 ratio.• 90% cases are women of childbearing age.• African Americans>Whites.• 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.

Systemic Lupus

• Incidence & Prevalence : increasing– Improved survival, diagnosing milder cases.

• Geographical variability :•African-Americans > Caucasians (3x) •Asian-American and Hispanics > Caucasians •Age at diagnosis:

• 16-55 years of age: 65% of cases • < 16: 20%• > 65: 15%

US UK JapanIncidence(per 100000 per year)

5.1 3.8 2.9

Prevalence(per 100000)

52.2 26.2 28.4

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• Lupus anticoagulant in 1952• ANA in 1954

• 1971- First set of classification criteria.

Pathogenesis

Genetics

AbnormalImmuneresponse

Environment

Genetic Factors

Environmental Triggers• UV light (A2 and B component)• Gender ( female > 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.

• 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.

Development of Autoantibodies

Failure : accumulation of nuclear particles

Capturing by antigen presenting

cells

Attract Macrophages and

dendritic cells.(Phagocytes the

complex)

Circulating immune cells engulf and

Release “find me” signal

Early Apoptotic

cells(“eat me”

signal)

Formation of

Antinuclear antibodies

Mechanisms of organ damage

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.– Proinflammatory type 1 and 2 interferons (IFNs)

Autoantibodies in SLEAntibody 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 β2G1, Phospholipids, prothrombinAntierytherocyte 60 RBC membrane

Antiplatelet 30 Surface and altered cytoplasmic antigens on platlets

Antineuronal 60 Neuronal and lymphocyte surface antigens

Antiribosomal P 20 Ribosomal protein

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.

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.

Clinical relevance : Autoantibodies

• Antiphospholipid Antibodies– Ig G Anticardiolipin : High titres(>40 IU), Increased

risk for clotting– Anti β2 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

Clinical relevance : Autoantibodies• Anti RNP

– Non Specific, association with RA (Rhupus), black > white.• Anti La/SS-B

– Decreased risk for nephritis, associated with anti Ro.• Anti histone

– Drug induced lupus.• Antierythrocyte

– Measured by DCT• Antiplatelet

– Not useful clinically • Antineuronal

– Positivity in CSF : Active CNS Lupus• Antiribosomal P

– Positivity in Serum : Depression, Psychosis in Lupus.

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

Systemic Lupus International Collaborating Clinics (SLICC) classification

• 11 clinical and 6 immunological criteria• The patient should satisfies 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 in the absence of other lupus features is regarded as sufficient for a patient to be diagnosed as having lupus.

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 psoriaform and/or annular polycyclic lesions that resolve without scarring.

Malar Rash Photosensitive lupus rash

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

Classic Discoid Rash

Hypertrophic (verrucous) lupus

Hypertrophic (verrucous) lupus

Lupus profundus

Lupus affecting the fat underlying skin aka ‘lupus panniculitis’.

Dented scar and Nodule.

lupus erythematosus tumidus

• Tumidus dermal form of lupus.• Characteristically photosensitive• Red, swollen, urticaria-like

bumps and patches• Ring-shaped (Annular)

Oral OR Nasal Ulcers

• Oral: palate, buccal, tongue• Nasal ulcers• In the absence of vasculitis, Behcet’s disease,

infection (herpesvirus), inflammatory bowel disease, reactive arthritis, and acidic foods.

• Nonscarring alopecia– Diffuse thinning or hair fragility with visible broken

hairs.• Synovitis involving 2 or more joints

– Characterized by swelling or effusion OR tenderness in 2 or more joints and at least 30 minutes of morning stiffness

• Serositis– Typical pleurisy for > 1 day OR pleural effusions OR

pleural rub– Typical pericardial pain (pain with recumbency

improved by sitting forward) for > 1 day OR pericardial effusion OR pericardial rub OR pericarditis by electrocardiography.

• Renal– Urine PCR (or 24-hour urine protein) > 500 mg

protein/24 hours OR RBC casts.

Neurologic

• Seizures, psychosis, mononeuritis multiplex.

• Myelitis, peripheral or cranial neuropathy.

• Acute confusional state.

• Hemolytic anemia.

• Leukopenia (<4000/mm3) OR Lymphopenia

(<1000/mm3).

• Thrombocytopenia (<100,000/mm3).

IMMUNOLOGIC CRITERIA

• ANA > reference negative value.• Anti-ds DNA• Anti-Sm• Anti phospholipid• Low serum complement• Positive direct Coomb’s test

SLICC : What's new

• Non scarring alopecia added as new entity.• Old Hematological 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.

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 retain the specificity while being more sensitive.

• 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.

Systemic Manifestations : Overview

SLE

9580

856060

5040

1515

Others Thrombosis GastrointestinalRenal Cardiopulmonary NeurologicHematologic Cutaneous Musculoskeletal

Prevalence, %

Man

ifest

ation

s

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.

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 >0.5, RBC casts.• Nephrotic Syndrome• ESRD

ISN/RPS classification of lupus nephritisClass 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 (<50% glomerulli, sub endothelial deposits)

III A Active lesions

III A/C Active and Chronic Lesions

III C Chronic Lesions

Class IV Diffuse lupus nephritis( >50% 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

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.

Cutaneous

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

Cardiopulmonary

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

Gastrointestinal

• Nausea, vomiting, diarrohea, pain abdomen.• Transaminitis.• Mesenteric Vasculitis• pancreatitis

Hematologic

• Anemia (chronic disease)• Leukopenia• Lymphopenia• Thrombocytopenia• Lymphadenopathy• Splenomegaly• Auto Immune Haemolytic anemia

Life threatening complications

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

Management : SLE

• No cure.• Complete sustained remission, rare.• Mainstay : Supress symptoms and prevent

organ damage.• Depends on severity of disease.• Prevention of complications of disease and its

treatment.

Management : Algorithm

1.• Symptom complex suggestive of SLE• Order tests : ANA, CBC, Urine Me, Platelets

2.• All results normal, Symptoms subside: No SLE• Results normal, symptoms persist : Repeat ANA & anti dsDNA, anti Ro. (3)• ANA positive : SLICC criteria, ≥4: Definite SLE, <4 : Probable SLE (Treatment)

3.• Repeat ANA, Anti dsDNA and Anti Ro : All negative. NO SLE• Some Positive : SLICC ≥4 : Definite SLE (Treatment)

Management : Algorithm

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.

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

FDA approved.

“Off label” but standard of care

“Borrowed drugs”

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

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

Pharmacological therapies

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

Glucocorticoids

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

Low dose prednisone (0.1–0.2 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 (1.0–1.5 mg/kg) or IV methylprednisolone (1 g or 15 mg/kg)

Severe disease

renal or neuropsychiatric manifestations or vasculitis

Glucocorticoids (Contd…)– long-term adverse effects

– Infections, HTN, Hyperglycemia, Acne, Asptic

necrosis of bones, Cushings 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.

Antimalarial agents– MOA : Inhibit endosome function ? Disrupt

class II MHC Decreasing antigen presentation.– Activates endosomal TLR: decrease IFN α.– 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.

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 (0.5–1.0 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.

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.

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.

Azathioprine• Dosage : For Induction : 2 - 3 mg/kg/day PO;• For maintenance : 1 -2 mg/kg/day;• If CrCI <50 ml/min, decrease frequency.• Adverse effects : BM suppression, GI

intolerance, hypersensitivity and hepatotoxicity. induction therapy for selected

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.

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.

Methotrexate• Folate antimetabolite, inhibits DNA synthesis.• Use : for musculoskeletal manifestations, also

good for serositis and to some extent for skin manifestations.

• 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.

Biologicals

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 mild–moderate disease, without severe

renal or central nervous system. (FDA

approved)

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.

Rituximab

• Chimeric mouse/human monoclonal antibody

specific for human CD20.

• Selectively Depletes CD20+ mature B cells

from circulation.

• Use : For non responders to above therapy.

Rituximab

• Currently, not approved for SLE.• Only in patients with refractory disease esp.

cytopenia, nephritis or neuropsychiatric lupus.• Dose : 375 mg/m2/wk x 4 or 1g/2 wks x 2,

along with corticosteroids and other immunosuppressive agents.

• Infection (including PML), infusion reactions, headache, arrhythmias, allergic responses.

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.

Therapy for specific SLE manifestations

• 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.

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.

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

effictive.– MMF preferred in Hispanic, African-Americans and

non-Asians, non white races .

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.

Crescentic Lupus Nephritis

• Crescents in glomeruli have got worse prognosis.

• Currently only High dose CPM with High-Dose GC, in induction phase is recommended.

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 ARB’s are recommended.• Alternate day GC’s plus CPM/ MMF /

Cyclosporine all effective in reducing proteinuria.

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.

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).

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.

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.

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.

Microvascular Thrombotic Crisis

• Hemolysis, thrombocytopenia, and microvascular thrombosis in kidneys, brain and other tissues.

• High mortility.• LAB : PS shows schistocytes, LDH is

elevated, Antibodies to ADAMS13.• Management : Plasma exchange, along with

GC therapy.

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.

Disease Activity AssessmentWHY IMPORTANT..??• For quantification of lupus disease activity

primarily to check effectiveness of a new drug.

• Not used in routine medical practice.

Disease Activity AssessmentMost commonly used disease activity instruments• SLEDAI

– SLEDAI, SLEDAI-2000, SRI-50– SELENA-SLEDAI

• BILAG– Classic and BILAG 2004

• Composite indices– SRI– BICLA

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.

SLEDAI Limitations• Cannot measure partial improvement of

individual parameter.• Cannot measure worsening of an existing

abnormality• Some items are “unfairly” scored (eg

thrombocytopenia)

SELENA-SLEDAI

• Seizures that are due to past irreversible central nervous system damage are excluded.

• Some other descriptors were modified like “cerebrovascular accident” was modified to exclude hypertensive cause.

• Detects less severe items than SLEDAI 2K.• Easy to use.

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.

Composite Responder Indices

• For assessing disease activity in response to therapy.

• Identify both improvement and worsening in same and different organ system.

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 GC’s and

Immunosuppressants.• Disease activity assessment : For future

prospects.