A Lecture on the basics of SLE for Interns, General Practioners and Nurses

1. Lupus
Allan D. Corpuz, MD, FPCP, DPRA
Section of Rheumatology
Department of Medicine
Philippine GENERAL HOSPITAL

2. Objectives
• Recognize the clinical manifestations of SLE
• Order the important diagnostic tests
• Enumerate the treatment modalities
• Know when and where to refer
• Counsel patients with the disease

3. What is SLE: Systemic

4. What is SLE: Autoimmune
pDCs
Res(ng
epithelium
Dysregulated
(ssue
Chemokine
BAFF/BlyS
ANA
Type
I
IFNs
virus
AutoAb
IC
1.
Voulgarelis
M,
et
al.
Nat
Rev
Rheumatol.2010;101:529-­‐537.
2.
Jonsson
R,
et
al.
Immunol
LeQ.
2011;141:1-­‐9.
3.
Nocturne
G,et
al.
Nat
Rev
Rheumatol.
2013
Jul
16.
doi:
10.1038
IL-­‐1β,
IFN-­‐γ,TNF-­‐α

5. What is SLE: Autoimmune

6. What is SLE: Autoimmune

7. What is SLE: Chronic, Relapsing,
Inflammatory

8. What is SLE: Primarily Female
9
1

9. The Impaired Immune System in SLE

10. Pathogenesis
T
cells
B
cells
Comple
ment

11. Pathogenesis: Panoramic View

12. APOPTOSIS:
Programmed
Cell Death

13. But some things don’t go
as programmed…

14. Complement in the Pathogenesis of SLE

15. What it is NOT

16. In Summary
• What it Is
– Systemic
– Autoimmune
– Chronic
– Relapsing
– Inflammatory
– Often febrile
– Female
– Impaired Immune System
– Can be controlled
• What It is Not
– Uniformly fatal
– Hopeless
– Curable

17. DIAGNOSIS

18. 1997 update of the 1982 ACR
Classification Criteria
Malar rash
Discoid Rash

19. Discoid Rash

20. Oral Ulcer
Photosensitive Rash

21. Serositis
Non-erosive arthritis

22. Nephritis
Seizures Psychosis

23. WBC < 4000/mm3
Platelet <100,000/mm3
Hemolytic Anemia

24. Positive Antinuclear Antibody

25. Immunologic Disorder
• Anti-dsDNA
• Anti-Smith
• Positive finding of aPL Abs
– Abnormal serum concentration of IgG/IgM
Anticardiolipin Abs
– (+) test result for lupus anticoagulant
– False (+) serologic test for syphilis known to be (+) for
6mos and confirmed by T.pallidum immobilization or
FTA-Abs test

26. Frequency of Manifestations of SLE

27. 2012 SLICC Criteria

28. In Summary: SOAP BRAIN MD
• Serositis
• Oral Ulcer
• Arthritis
• Photosensitivity
• Blood disorder
• Renal Disorder
• ANA
• Immunologic Disorder
• Neurologic Disroder
• Malar rash
• Discoid Rash
At least
4 of the11
Fulfillment of these
criteria is NOT an
absolute requirement
for Dx

29. DIAGNOSTIC
TESTING

30. • Noclinical manifestation or lab testcan serve as
a definitivediagnostic test
• SLE is diagnosed based on a constellation of
characteristic signs and symptoms and lab
findingsin the appropriate clinical
context

31. Serologic Tests790 PART 7 | DIAGNOSTIC TESTS AND PROCEDURES IN RHEUMATIC DISEASES
Because of the character
ies among the ANA dis
lated to play a role in
antibodies, for instance
inflammation in SLE ne
tion, direct binding to
and/or intracellular pen
toxicity.6
Similarly, rib
anti-Ro/SSA, anti-La/S
cated in the pathogenes
tions by penetrating liv
antigens in the skin an
anti-Scl-70 (topoisome
levels of interferon (IFN
ous scleroderma and
anti-Ro/SSA-positive se
demonstrated to induc
adhesion molecule (ICA
However, autoantibo
account for disease path
activity by anti-Ro/SS
appears restricted to pa
tomatic individuals,12
an
I may be required for
antibodies.13
This may
among or effects of the
novel conformations or
cally sensitive conforma
thetase (HisRS), the targ
Jo-1–specific antibody, h
an apoptope (epitope e
SSA may be specific to
Table 55-1 Antinuclear Antibody (ANA)-
Associated Diseases and Related Conditions
Condition
Patients with
ANAs (%)
Diseases for Which ANA Testing Is Helpful for Diagnosis
Systemic lupus erythematosus 99-100
Systemic sclerosis 97
Polymyositis/Dermatomyositis 40-80
Sjögren’s syndrome 48-96
Diseases in Which ANA Is Required for Diagnosis
Drug-induced lupus 100
Mixed connective tissue disease 100
Autoimmune hepatitis 100
Diseases in Which ANA May Be Useful for Prognosis
Juvenile idiopathic arthritis 20-50
Antiphospholipid antibody syndrome 40-50
Raynaud’s phenomenon 20-60
Some Diseases for Which ANA Typically Is Not Useful
Discoid lupus erythematosus 5-25
Fibromyalgia 15-25
Rheumatoid arthritis 30-50
Relatives of patients with autoimmune disease 5-25
Multiple sclerosis 25
Idiopathic thrombocytopenic purpura 10-30
Thyroid disease 30-50
Patients with silicone breast implants 15-25
Infectious disease Varies widely
Malignancies Varies widely
Healthy (“Normal”) Individuals
≥1:40 20-30
≥1:80 10-12
≥1:160 5
≥1:320 3

32. Antinuclear Antibodies
• Anti-nuclear (or anticytoplasmic) Abs bind to cells fixed on a
slide
• Addition of a secondary Ab (with an attached fluorescent
dye)
• Dilution at 1:40 and 1:160 buffered solution
• The titer is a measure of the amount of ANA in the blood
(higher titer – more autoABs)
• Standardization: 30% of normal individuals will have a
positive test at 1:40 (sensitive)
• At 1:160, only 5% of normal individuals will have a positive
test (specific)

33. False Positives
• 32% in normal individuals (>1:40)
• 13% (>1:80)
• 3% (>1:320)
• Relatively constant over time
Tan
EM,
Feltkamp
TE,
Smolen
JS,
et
al.
Range
of
an(nuclear
an(bodies
in
"healthy"
individuals.
Arthri(s
Rheum
1997;
40:1601.

34. False Negatives
• From technical and physical nuances
• Method of substrate fixation, the solubility of the
antigen (eg, Ro, La, PCNA, and Ku), and the
localization of the antigen outside the nucleus (ie,
Jo-1 and single stranded DNA)
• There is rarely any need to request testing for
antibodies to DNA, Sm, RNP, Ro/SSa, or La/SSb
unless the ANA is known to be positive
• Elderly (<1:80 titer)
Tan
EM,
Feltkamp
TE,
Smolen
JS,
et
al.
Range
of
an(nuclear
an(bodies
in
"healthy"
individuals.
Arthri(s
Rheum
1997;
40:1601.

35. IF (1:160) vs ELIA
• ELIA: recombinant technology (using kits); faster,
no training needed
• Agreement: 87-95%
• Sensitivity: 69-98%
• Specificity: 81-98%
• Still with high # of false +
Jaskowski
TD,
Schroder
C,
Mar(ns
TB,
Mouritsen
CL,
Litwin
CM,
Hill
HR:
Screening
for
an(nuclear
an(bodies
by
enzyme
immu-­‐
noassay.
Am
J
Clin
Pathol
1996,
105:468-­‐473.
Bizzaro
N,
Tozzoli
R,
Tonu^
E,
Piazza
A,
Manoni
F,
Ghirardello
A,
Basse^
D,
Villalta
D,
Pradella
M,
Rizzo^
P:
Variability
between
methods
to
determine
ANA,
an;-­‐dsDNA
and
an;-­‐ENA
auto
an;bodies:
a
collabora;ve
study
with
the
biomedical
industry.
J
Immunol
Methods
1998,
219:99-­‐107.

36. Interpretation
A negative or low titer ANA-IF in the
setting of low clinical suspicion of
rheumatic disease usually indicates the
absence of significant ANAs and
argues against the diagnosisof one of
the ANA diseases

37. When to treat
Although the ANA-IF pattern and titer may provide
insight into the specific auto-Ag(s) targeted,
as well as the potential likelihood of CTD,
such correlations should ONLY guide,
NOT absolutely determine, clinical
decisions

38. Some specific ANAs possess diagnostic significance
and would need follow-up with specialized assays
BUT ONLY IN THE SETTING OF STRONG
CLINICAL SUSPICION because:
1. the PPV of an ANA in the absence of other clinical
signs of CTD is low, in part because it may
precede clinical disease by many years
2. because of the relatively high incidence of ANA in
normal individuals

39. If specific testing is negativein the setting of
high clinical suspicion, repeat testing at a later
date may be warranted, because titers of such
autoantibodies can fluctuateover time,
irrespective of disease course.

40. General Guidelines
• -ANA testing is not helpful in confirming a
diagnosis of rheumatoid arthritis or osteoarthritis
therefore should not be used in such conditions.
• - ANA testing is not recommended to evaluate
fatigue, back pain or other musculoskeletal pain
unless accompanied by one or more of the clinical
features in favor of a CTD.
• - ANA testing should usually be ordered only once.
• - Positive ANA tests do not need to be repeated.

41. • - Negative tests need to be repeated only if there is a
strong suspicion of an evolving CTD or a change in
the patient's illness suggesting the diagnosis should
be revised.
• - A positive ANA test is important only in conjunction
with clinical evaluation and in the absence of
symptoms and signs of a CTD; a positive ANA test
only confounds the diagnosis.A positive ANA test can
also be seen in healthy individuals, particularly the
elderly or in a wide range of diseases other than CTD,
where it has no diagnostic or prognostic value.
Kavanaugh
A,
Tomar
R,
Reveille
J,
Solomon
DH,
Homburger
HA:
Guidelines
for
Clinical
Use
of
the
An;nuclear
An;body
Test
and
Tests
for
Specific
Auto
an;bodies
to
Nuclear
An;gens.
Arch
Pathol
Lab
Med
2000,
124:71-­‐81.
Guidelines
and
Protocols
Advisory
CommiOee.
BCGuide-­‐
lines.ca
2007.

42. Other Serologic Tests

43. Other Tests
• CBC with platelet count
• U/A, 24 hour urine studies (TV,TP, Crea)
• BUN, Creatinine
• Electrolytes
• LFTs
• CXR
• 2D Echo
• Kidney Biopsy
• Complement (C3, C4, CH50)

44. IMPACT on LIFE
• Chronically fatigued: vicious cycle
• Inability to finish school and find jobs
• Inability to sustain jobs
• Depression and Anxiety
• Family Support

45. SUMMARY
• Systemic autoimmune chronic relapsing
inflammatory disease
• Protean Manifestations (SOAP BRAIN MD)
• No definitive diagnostic test
• Use and Interpret S/Sx and tests based on a
clinical context
• Poor HRQoL