This document provides an overview of systemic lupus erythematosus (SLE). It discusses the definition, epidemiology, pathogenesis, diagnosis, clinical manifestations, management, and complications of SLE. The pathogenesis involves genetic susceptibility and environmental triggers leading to abnormal immune responses and autoantibody production. Diagnosis is based on the SLICC classification criteria. Management involves controlling symptoms, preventing organ damage, and treating flares and complications using medications like glucocorticoids, antimalarials, immunosuppressants, and biologics. Life-threatening complications can include renal disease, neurological involvement, hematological abnormalities and vasculitis.

1. SYSTEMIC LUPUS
ERYTHEMATOSUS
PRESENTOR - DR S.K.GHINTALA
MODERATOR- DR.K. BHATTACHARJEE
(ASSOCIATE PROFESSOR)

2. Outline
Introduction : Definition, epidemiology
Pathogenesis : 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.

3. 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.

4. 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 INDIA Japan
Incidence
(per 100000
per year)
5.1 3.8 0.9-3.1 2.9
Prevalence
(per 100000)
52.2 26.2 3.2-19.3 28.4

5. 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.

6. Pathogenesis
Genetics
Abnormal
Immune
response
Environment

7. Genetic Factors

8. 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.

9. • 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.

10. 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

12. Mechanisms of organ damage

13. 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)

14. 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 β2G1, 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

15. 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.

16. 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.

17. 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

18. 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.

19. 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

20. 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.

22. 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.

23. Malar Rash Photosensitive lupus rash

24. 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

25. Classic Discoid Rash

27. Lupus profundus
Lupus affecting the fat
underlying skin aka ‘lupus
panniculitis’.
Dented
scar and
Nodule.

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

29. 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.

30. • 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

31. • 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 >0.5 or 24-hour urine protein > 500 mg
OR RBC casts.

32. Neurologic
• Seizures, psychosis, mononeuritis multiplex.
• Myelitis, peripheral or cranial neuropathy.
• Acute confusional state.

33. • Hemolytic anemia.
• Leukopenia (<4000/mm3) OR Lymphopenia
(<1000/mm3).
• Thrombocytopenia (<100,000/mm3).

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

35. 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.

36. 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.

37. Systemic Manifestations : Overview
95
80
85
60
60
50
40
15
15
SLE
Others Thrombosis Gastrointestinal
Renal Cardiopulmonary Neurologic
Hematologic Cutaneous Musculoskeletal
Prevalence, %
Manifestations

38. 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.

39. 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

40. 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 (<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 global sclerosing lupus nephritis
Class V Membranous lupus nephritis
Class VI Advanced sclerosing lupus nephritis

41. 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.

42. Cutaneous
• Photosensitivity
• Malar rash
• Oral Ulcers
• Alopecia
• Discoid Rash
• Vasculitis rash
• Urticaria

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

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

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

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

47. 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.

48. 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
3.
• Repeat ANA, Anti dsDNA and Anti Ro : All negative. NO SLE
• Some Positive : SLICC ≥4 : Definite SLE (Treatment)

49. Management : Algorithm

50. 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.

51. 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”

52. 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

53. 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

54. Pharmacological
therapies

55. 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

56. 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

57. 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.

58. 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.

59. 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.

60. 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.

61. 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.

62. 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

63. 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.

64. 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.

65. 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.

66. Biologicals

67. 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)

68. 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.

69. 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.

70. 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.

71. 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.

72. Therapy for specific SLE
manifestations

73. • 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.

74. 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.

75. 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 .

76. 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.

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

78. 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.

79. 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.

80. 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).

81. 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.

82. 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.

83. 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.

84. 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.

85. 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.

86. 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.

87. Disease Activity Assessment
Most commonly used disease activity
instruments
• SLEDAI
– SLEDAI, SLEDAI-2000, SRI-50
– SELENA-SLEDAI
• BILAG
– Classic and BILAG 2004
• Composite indices
– SRI
– BICLA

88. 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.

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

90. 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.

91. 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.

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

93. 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.

94. 1.Which of the following drugs most likely to
cause systemic lupus-like syndrome?
a.Baclofen
b.Methotrexate
c.Procainamide
d.Sulfasalazine

95. 2. A 25-year-old female gives birth to a baby with complete heart
block who subsequently requires pacemaker insertion. Which of
the following antibodies is most likely to be detected in the
maternal serum?
a. Anti-dsDNA antibodies
b.Anti-endomysial antibodies
c.Anti-Ro/SSA antibodies
d.Anti-SCL70 antibodies
e.Rheumatoid factor

96. 3.A 69-year-old woman taking hydralazine for
hypertension presents with joint pain and chest
pain. On cardiac examination, the patient has a
pericardial rub. What is the most likely diagnosis?
a.Dermatomyositis
b.SLE
c.Polymyalgia rheumatic
d.Felty syndrome

97. 4.A 25-year-old lady with known systemic lupus erythematosus (SLE)
presents with the nephrotic syndrome. A renal biopsy is performed
and this confirms diffuse proliferative glomeronephritis (WHO
Class IV). Which of the following treatment regimens would you
advise?
a.Azathioprine alone
b.Prednisolone alone
c.Azathioprine and prednisolone
d.Prednisolone and intravenous cyclophosphamide
e.Prednisolone and methotrexate

98. 5.Which of the following auto-antibodies may have a
role in monitoring disease activity?
a.Rheumatoid factor in RA
b.Antinuclear antibodies in SLE
c.Anti-Sm antibodies in SLE
d.Anti-dsDNA antibodies in SLE
e.Anti-Ro (SSA) antibodies in Sjogren’s
syndrome

99. 6. A 32-year-old woman with longstanding SLE presents with severe
headache. Her blood pressure is 200/110 mm Hg, the cardiac
examination is remarkable for a new heart murmur is noted at the
left sternal border. Her medical history includes 3 spontaneous
abortions and multiple episodes of pleurisy, arthritis, and
thrombocytopenia. Dipstick urinalysis is positive for protein and
trace blood.Microscopic examination shows 3 to 5 erythrocytes per
high power field and an occasional granular cast.PBF shows
presence of schistocytes.Serum creatinine level is 4.0 mg/dL. What
is a renal biopsy likely to show?
(A) Diffuse proliferative glomerulonephritis
(B) Focal segmental glomerulonephritis
(C) IgA deposits
(D) Mesangial deposits (seen by electron
microscopy only)
(E) Thrombotic microangiopathy

100. 7.A 20 - year - old man with SLE presents to the emer-gency
department with chest pain that started 10 days ago. He has become
increasingly dyspneic over the last 48 hours and has been too
exhausted to make meals. He will not lay flat on the examination table
and insists on leaning slightly forward Blood pressure is 94/50 mm Hg
and heart rate is 100 bpm. The heart sounds are quiet . JVP is raised
.There is 1+ peripheral edema. What is the lifesaving next step in this
patients management?
(A)Arterial blood gas
(B) Diuresis with intravenous furosemide
(C) Echocardiogram
(D) High-dose nonsteroidal medication

101. 8.A 23 year old girl with SLE (previous lupus nephritis, currently in
remission), and requests an urgent appointment as she is pregnant. Her
past medical history includes epilepsy, stroke, and TIA. On examination,
she has a photosensitive malar rash, patchy alopecia, and puffy MCPJs,
and wrists. Current medications include Mycophenolate 2gmod, Aspirin
75mgod,Prednisolone 2.5mg/day and Hydroxychloroquine 400 mg od.
What will you advice regarding her medications in view of the pregnancy?
a. Stop mycophenolate
b. Stop aspirin
c. Switch mycophenolate to azathioprine
d. Switch mycophenolate to ciclosporin
e. Switch mycophenolate to rituximab