Systemic lupus erythematosus (SLE) is an autoimmune disease in which organs and cells undergo damage mediated by tissue binding autoantibodies and immune complexes. 90 % of patients at diagnosis are women of childbearing age groups. Highest prevalence is in black women and lowest is in white men.

1. Recent Advances in Diagnosis &
Management of SLE
Speaker- Dr. Shadab Ahmad

2. Definition
Systemic lupus erythematosus (SLE) is an autoimmune disease in which
organs and cells undergo damage mediated by tissue binding
autoantibodies and immune complexes.
• 90 % of patients at diagnosis are women of childbearing age groups.
• Highest prevalence is in black women and lowest is in white men.

3. Risk factors
• Female sex
• Black ethnic groups
• Exposure to UV light
• Epstein-Barr virus (EBV) infection
• Tobacco smoking
• Prolonged occupational exposure to silica

4. Female sex is permissive for SLE because
• Hormone effects
• Genes on X- chromosome
• Epigenetic differences between genders
• Estradiol binds to receptors on T and B lymphocytes, increasing
activation and survival of those cells, thus favoring prolonged immune
response.
• So, women exposed to estrogen containing OCPs and hormone
replacement therapy have an increased risk of developing SLE.
• People with more X- chromosome (XXY karyotype, Klinefelter’s
syndrome) have a significantly increased risk for SLE.

5. Pathogenesis

6. Autoantibodies in SLE
Antibodies Antigen Recognized
ANA Multiple nuclear antigens
Anti-dsDNA dsDNA
Anti-Sm Protein complexed to 6 species of nuclear U1 RNA
Anti-RNP Protein complexed to U1 RNA-gamma
Anti-Ro (SS-A) Protein complexed to hY RNA (60 kDa, 52 kDa)
Anti La (SS-B) Protein complexed to hY RNA (47 kDa)
Anti-histone Histone associated with DNA(in nucleosome, chromatin)
Antiphospholipid Phospholipids, beta-2 glycoprotein 1 cofactor,
prothrombin
Antierythrocyte Erythrocyte membrane
Antiplatelet Surface and altered cytoplasmic antigens on platelets
Antineuronal (anti-glutamate receptors) Neuronal and lymphocyte surface antigens
Antiribosomal P Protein on ribosomes

7. New Antibodies
Antibodies Used as marker of Role in SLE
Anti-nucleosome antibodies Disease activity and organ
involvement
Drug induced lupus, lupus
nephritis, lupus flares
Anti-C-1q antibodies Disease activity and organ
involvement
Nephritic flares
NMDA receptor antibody Neuronal damage Neuropsychiatric disease
Anti-Alpha actinin antibody Disease activity, renal involvement Lupus nephritis

8. Diagnosis of SLE
1. ACR criteria
2. SLICC criteria

9. ACR Criteria
Malar rash Fixed erythema, flat or raised, over malar eminence
Discoid rash Erythematous circular raised patches with adherent keratotic scaling and follicular
plugging; atrophic scarring may occur
Photosensitivity Exposure to ultraviolet light causes rashes
Oral ulcers Includes oral and nasopharyngeal ulcers, observed by physician
Arthritis Nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or
effusion
Serositis Pleuritis or pericarditis documented by ECG or rub or evidence of effusion
Renal disorder Proteinuria >0.5 g/d or 3+, or cellular casts
Neurologic disorder Seizures or psychosis without other causes
Hematologic disorders Hemolytic anemia or leukopenia (<4000/dl) or lymphopenia (<1500/dl) or
thrombocytopenia (<1,00,000/dl) in absence of offendidng drugs
Immunologic disorder Anti-dsDNA, anti-Sm, and/or anti-phospholipid
Antinuclear antibodies An abnormal titer of ANA by immunofluorescence or an equivalent assay at any point
in time in the absence of drugs known to induce ANAs
Sensitivity is – 75%
Specificity is – 95%

10. SLICC criteria
(Systemic Lupus International Collaborating Clinics Classification 2012 )
Clinical Criteria
Acute Cutaneous lupus Lupus malar rash, bullous lupus, toxic epidermal necrolysis variant of SLE, maculopapular lupus
rash, photosensitivity lupus rash (in absence of dermatomyositis)
Chronic Cutaneous lupus Classic discoid rash localized (above the neck) or generalized (above and below neck),
hypertrophic (verrucous) lupus, lupus panniculitis (profundus), mucosal lupus, chilblains lupus,
discoid lupus/lichen planus overlap
Oral Ulcers or Nasal
Ulcers
Oral: palate, buccal, tongue, nasal ulcers. In the absence of other causes, such as vasculitis,
Behcet’s disease, infection, inflammatory bowel disease, reactive arthritis, and acidic foods
Non-scarring alopecia Diffuse thinning or hair fragility with visible broken hairs, in the absence of other causes such as
alopecia areata, drugs, iron deficiency, and androgenic alopecia
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 more than 1 day or pleural effusion or pleural rub. Typical pericardial pain
(pain with recumbency improved by sitting forward) for more than 1 day or pericardial effusion
or pericardial rub or pericarditis by electrocardiography

11. SLICC criteria cont…
Clinical Criteria cont..
Renal Urine protein to creatinine ratio (or 24 hour urine protein) representing 500 mg protein/24
hour or red blood cell casts.
Neurologic Seizure, psychosis, mononeuritis multiplex (in the absence of other known causes such
primary vasculitis), myelitis, peripheral or cranial neuropathy (in the absence of other
known causes such as primary vasculitis, infection, and diabetes mellitus), acute confusional
state (in the absence of other causes, including toxic/metabolic, uremia, drugs)
Hemolytic anemia
Leukopenia (<4000/mm3) OR At least once: In the absence of other causes such as Felty’s syndrome, drugs, and portal
hypertension
Lymphopenia (<1000/mm3) At least once: In the absence of other known causes such as corticosteroids, drugs, and
infection
Thrombocytopenia
(<100,000/mm3)
At least once in the absence of other known causes such as drugs, portal hypertension, and
thrombotic thrombocytopenic purpura

12. SLICC criteria cont…
Immunologic
Criteria
ANA Level above laboratory reference range
Anti-dsDNA Antibody level above laboratory reference range (or 2-fold if tested by ELISA)
Anti-Sm Presence of antibody to Sm nuclear antigen
Anti-phospholipid
antibody
Positivity, as determined by
Positive test for lupus anticoagulant
False-positive test result for rapid plasma regain
Medium-or high titer anticardiolipin antibody level (IgA, IgG, or IgM)
Positive test result for anti-2-glycoprotein I (IgA, IgG, or IgM)
Low complement (C3, C4, or CH50)
Direct Coomb’s
test
(In the absence of hemolytic anemia)
Sensitivity is – 94%
Specificity is – 92%

13. Classify a patient as having SLE if..
ACR criteria
 If ≥4 of these criteria, well documented, are present at any time in a
patient’s history
SLICC criteria
 The patient satisfies four of the criteria including at least one clinical
criterion and one immunologic criterion
OR
 The patient has biopsy proven nephritis compatible with SLE and
with ANA or anti-dsDNA antibodies

14. Novel Biomarkers in SLE
Cellular markers Used as marker of Role in SLE
CD27 plasma cells Disease activity Distinguish a lupus flare up from infection
CD44v3/CD44v6-T cells Disease activity Lupus nephritis
CD4- CD8- (double
negative) t cells
Disease activity Lupus nephritis
Plasma MBL Disease activity Lupus nephritis (high level), Cutaneous lupus (low level)
Complement activation
products
Diagnosis or disease
activity
Diagnosis of SLE
Cytokines
IFN-𝛼, IFN-𝛾 Disease activity/flare Marker and potential predictive marker for anti-type I IFN therapy
MCP-1 Disease activity/flare
IL-2, IL-6, IL-10, IL-17, IL-23
TNF-𝛼, IFN-𝛼, TGF-B
Disease activity Diagnosis and progression of SLE
TWEAK Disease activity Lupus nephritis

15. Novel Biomarkers cont..
Genomic markers Used as marker of Role in SLE
Fc receptor gene polymorphism Disease susceptibility Diagnosis of SLE
DNA methylation markers (CD70,
CD154, Perforin)
Disease activity Diagnosis and monitoring
Micro RNAs Disease activity and effect of
treatment
Monitoring of SLE
New gene therapy strategies

16. Therapeutic classification
Mild Moderate
Muco-cutaneous
Butterfly rash
Photosensitivity
Maculopapular rash
Mild oral ulcer
Mild DLE
Severe oral ulcer
Severe DLE
Diffuse SCLE
Lupus profundus
Skin vasculitis
Articular Arthralgia
Mild polyarthritis
Disabiling polyarthritis

17. Cont…
Mild Moderate Severe
Renal Class I,II Class III,IV
LN
Neuropsychiatry Lupus headache Chorea
Peripheral neuropathy
Delirium
Encephalitis
Psychosis
Coma
Myelopathy
Hematological Platelet 30-100,000 Platelet 15-30,000
Hemolytic anemia
Leucopenia
Lupus adenitis
Platelet <15,000

18. Cont…
Mild Moderate Severe
Cardiopulmonary Pleurisy Pleural effusion
Pneumonitis
Pericarditis
Mild myocarditis
Severe pneumonitis with
respiratory failure
Pulmonary hemorrhage
Cardiac temponade
Severe myocarditis
Gastro-intestinal Mild hepatitis Pancreatitis
Peritonitis
Severe hepatitis
Colitis
Protein losing
enteropathy
Mesenteric vasculitis
Miscellaneous Responsive fever
Fatigue
Myalgia
Refractory/high fever

19. Treatment of SLE
Conventional therapies
• NSAIDs
• Anti-malarials
• Corticosteroids
• Immunosupressants
Targeted therapies
• Monoclonal antibodies

20. Drugs for management of SLE
Medication Dose range Adverse effects
NSAISs Upper limit of recommended
range
Aseptic meningitis, decreased renal function, vasculitis of skin,
myocardial infarction, ototoxicity, GI irritation
Topical glucocorticoids Mid potency for face
High potency- other area
Atrophy of skin, contact dermatitis, folliculitis, infection,
hypopigmentation
Topical sunscreens SPF 15 at least
30+ preferred
Contact dermatitis
Hydroxychloroquine 200-400 mg OD Retinal damage, agranulocytosis, thrombocytopenia, aplastic
anemia, ataxia, cardiomyopathy, ototoxicity, neuropathy, seizures
DHEA
(dehydrepiandrosterone)
200 mg OD Acne, menstrual irregularity
Methotrexate 10-25 mg once a week with
folic acid
Anemia, bone marrow suppression, leukopenia, infection,
thrombocytopenia, hepatotoxicity, nephrotoxicity, neurotoxicity,
pulmonary fibrosis, pneumonitis, teratogenic
Oral glucocorticoids
(Prednisone)
0.5-1 mg/kg/d- severe SLE
0.07-0.3 mg/kg/d- milder SLE
Infection, hypertension, hyperglycemia, hypokalemia, aseptic
necrosis of bone, cushingoid changes, osteoporosis, psychosis
IV glucocorticoids
(Methylprednisolone)
1 g *IV*OD for 3 days As oral glucocorticoids

21. Cont…
Medication Dose range Adverse effects
Cyclophosphamide 7-25 mg/kg once a month
for 6 months
Infection, bone marrow suppression, leukopenia, anemia,
thrombocytopenia, hemorrhagic cystitis, carcinoma bladder,
alopecia, ovarian and testicular failure, teratogenic
Mycophenolate
mofetil
2-3 g/d Infection, leukopenia, anemia, thrombocytopenia, lymphoma,
malignancy, alopecia, GI symptoms, hypertension,
hypokalemia, tremor, teratogenic
Azathioprine 2-3 mg/kg/d Infection, bone marrow suppression, leukopenia, anemia,
thrombocytopenia, pancreatitis, hepatotoxicity, malignancy,
alopecia, GI symptoms

22. Targeted therapy in SLE
Target Agent Role in SLE
B Cell depletion
Anti-CD20 Rituximab Effective in refractory SLE, no benefit in proliferative lupus
nephritis
Anti-CD22 Epratuzumab Reduction in corticosteroid dose in SLE
Anti-CD11 Efalizumab Improvement in cutaneous SLE
B Cell activation
Anti-B Lys Antibody Belimumab Reduction in SLE activity, reduce flares
Anti-B Lys+APRIL Atacicept Decrease in SLE autoantibodies
B Cell tolerogens
B cell tolerogen Abetimus,
Edratide
No long term benefit in lupus nephritis
T-Cell target blockers
Anti-CD40 antibodies Toralizumab Unproven role
CTLA4-Ig Fusion protein Abatacept Improvement in non-life threatening SLE
Cell surface receptor
activation inhibition
Sirolimus Role in refractory SLE

23. Cont…
Target Agent Role in SLE
Cytokine inhibition
Anti-TNF-𝛼 Infliximab Doubtful efficacy in lupus nephritis
Anti-IFN-𝛼/-𝛾 Sifalimumab
Rontalizumab
No result released
Anti-IL-1 Anakinra Improvement in SLE arthritis
Anti-IL-6 Tocilizumab Clinical and serologic improvements in SLE
Anti-IL-10 B-N10 Improvement in disease activity
Other targets
Anti-C5 monoclonal
antibody
Eculizumab Improvement in SLE
Soluble recombinant
complement C3
inhibitor
sCR1 Improvement in disease activity
Chemokine inhibitor Bindarit Improvement in disease activity

24. Diagnosis & Initial therapy of SLE

25. THANK YOU