Systemic Lupus

Erythematosus
 Autoimmune disease that
affects multisystems
 1.5 million cases of lupus
 Prevalence of 17 to 48 per
100,000 population
 Women > Men - 9:1 ratio
 90% cases are women
 African Americans > Whites
 Onset usually between ages of 15 and
45 years, but
 Can occur in childhood or later in life
 CLINICAL MANIFESTATIONS
• Disorder ranges from a relatively mild to
rapidly progressing, affecting many
body systems.
• Chronic with relapsing and remitting course.
• Most commonly affects the skin / muscles,
lining of lungs, heart, nervous tissue, and
kidneys
 ETIOLOGY
 Etiology is
unknown
 Most probable
causes
 Genetic influence
 Hormones
 Environmental
PATHOGENESIS OF
SLE
PATHOPHYSIOLOGY
 Autoimmune reactions
directed against
constituents of cell nucleus,
DNA
 Antibody response
related to B and T
cell hyperactivity
 1997 Update Of The 1982 American College Of
Rheumatology Revised Criteria For
Classification Of Systemic Lupus
Erythematosus

1. Malar (butterfly) rash

2. Discoid lesions
3. Photosensitivity
4. Oral or nasopharyngeal ulcers
5. Non-deforming arthritis in two or more joints
6. Serositis: pleuropericarditis, aseptic peritonitis
7. Renal: persistent proteinuria › 0.5 g/d or ›3+ or cellular casts

Definite SLE = 4 or more positive criteria

1997 Update Of The 1982 American College Of
Rheumatology Revised Criteria For
Classification Of Systemic Lupus
Erythematosus

8. Neurologic disorders: seizures, psychosis

9. Heme: hemolytic anemia; leucopenia, lymphopenia,
thrombocytopenia
10.Immune: anti-DNA, or anti-Sm, or APS (ACA IgG, IgM), or
lupus anticoagulant (standard) or false + VDRL
11.Positive ANA

Definite SLE = 4 or more positive criteria

 NEW SLICC* REVISION OF THE ACR
CLASSIFICATION CRITERIA - CLINICAL

1. Acute/subacute cutaneous lupus

2. Chronic cutaneous lupus
3. Oral/Nasal ulcers
4. Nonscarring alopecia
5. Inflammatory synovitis with physician-observed
swelling of two or more joints OR tender joints with
morning stiffness
6. Serositis

*Systemic Lupus International Collaborating Clinics (SLICC)

 NEW SLICC REVISION OF THE ACR
CLASSIFICATION CRITERIA - CLINICAL

7. Renal: Urine protein/creatinine (or 24 hr urine protein) representing at least

500 mg of protein/24 hours or red blood cell casts
8. Neurologic: seizures, psychosis, mononeuritis multiplex, myelitis,
peripheral or cranial neuropathy, cerebritis (acute confusional state)
9. Hemolytic anemia
10. Leukopenia (< 4000/mm3 at least once) OR Lymphopenia (< 1000/mm3
at least once)
11. Thrombocytopenia (<100,000/mm3) at least once
SLICC REVISION OF THE ACR CLASSIFICATION
CRITERIA – IMMUNOLOGIC

1. ANA (antinuclear antibody)

2. Anti-dsDNA
3. Anti-Sm (anti-Smith) antibody
4. APS abs: Lupus anticoagulant , false-positive test for
syphilis, anticardiolipin IgG, IgM, or IgA
5. Low complement: low C3, low C4, low CH50
6. Direct Coombs test in the absence of hemolytic
anemia
 LUPUS – SLICC NEW CLASSIFICATION
Criteria: 4 Needed

▪At least 1 clinical plus at least 1

immunologic criteria (for a total of 4)

or
▪Lupus nephritis by biopsy as the sole
clinical criterion plus SLE
autoantibodies: (+) ANA or (+) anti-
dsDNA
 GENERAL
SYMPTOMS

The most common symptoms

listed as initial complaints are
fatigue, fever, and weight
loss.
 Fever: fever secondary to active
disease was recorded from 50%
to 86%. No fever curve or pattern
is characteristic. It can be
difficult, but very important to
distinguish the fever of SLE from
Clinical Manifestations

 Infection
 Increased
susceptibility to
infections
 Fever should be
considered serious
 Infections such as
 Fatig is common patien
ue
with in ts
SLE,
periods ofespecially durin
disease activity.
It is also often the gonly
symptom that remains
after treatment of acute
flares.
Low grade fever, anemia,
or any source of
inflammation can result in
Clinical Manifestations

Dermatologic
 Cutaneous vascular
lesions
 Photosensitivity
 Butterfly rash (Malar
Rash)
 Oral/nasopharyngeal
MALAR RASH
DISCOID RASH
 Maculopap
ular
eruption
ORAL ULCERS
 Raynaud’s phenomenon is
commonly found in lupus. It lack
specificity.
(a triphasic reaction of distal digits to cold
or emotion, in which the skin colour
changes from white to blue to red)
 Vasculitic skin
lesion
 CLINICAL MANIFESTATIONS
Musculoskeletal
 (jaccoud arthropathy) ‘
is the term used to describe the nonerosive
hand deformities due to chronic arthritis and
tendonitis that develop in 10% of patients with
SLE.
 Polyarthralgia with
morning stiffness
 A vascular necrosis
 Arthritis bilateral – hands / wrists
/knees
◾Swan neck fingers
◾Ulnar deviation
 Avacular necrosis
of bone
Clinical
Manifestations

Cardiopulmonary
 Tachypnea
 Pleurisy
 Dysrhythmias
 Accelerated CAD
 Pericarditis
 PULMONARY
MANIFESTATIONS
 Pleurisy
it is the most common
manifestation of pulmonary
involvement of SLE. The volume
of pleural effusions usually is
small to moderate and maybe
unilateral or bilateral. Large
pleural effusion are uncommon.
It usually exudative in
character.
Pleural effusions may also occur in SLE
 Lung
1)acute lupus pneumonitis:
fever, dyspnea, cough with scanty
sputum, hemoptysis, tachypnea
and pleuritic chest pain.
2)pulmonary hemorrhage
3)chronic diffuse interstitial
lung disease.
the diagnosis should not be made
until infectious processes such as
viral pneumonia, tuberculosis, and
other bacterial, fungal and
 CARDIOVASCULAR
MANIFESTATIONS
 Pericarditis is the most
common cardiac
manifestation of SLE.
 Myocarditis (the clinical
features of lupus myocarditis
resembles that of viral
myocarditis)
 Libman-Sacks endocarditis
and valvular disease

 SLE can be
associated with
endocarditis.
 Shown here
is Libman-
Sacks
endocarditis in
which there
are many
flat, reddish-tan
vegetations
spreading over
the mitral valve
and chordae.
Clinical Manifestations

Renal
 Lupus nephritis
◾Ranging from mild
proteinuria to
glomerulonephritis
◾Primary goal in
treatment is slowing the
 Haematuria
 Proteinure (>0.5g protein/d or
3+ )
 Cast
 LUPUS
NEPHRITIS
 CLINICAL
MANIFESTATIONS
Nervous system
 Generalized/focal seizures
 Peripheral neuropathy
 Cognitive dysfunction
◾Disorientation
◾Memory and reasoning deficits
◾Psychiatric symptoms –
severe depression / psychosis
 CLINICAL MANIFESTATIONS

 Red blood cells

a normochromic, normocytic anemia
is frequently found in SLE. They
appears to be related to chronic
inflammation, drug-related
haemorrhage.
haemolytic anemia as detected by
the Coombs’ test is the feature of
SLE.
on rare occasion, a serum antibody
may be produced which impairs
red cell production.
 Platelets
thrombocytopenia (<100*109/L)
appears to be mediated by anti-
platelet antibodies or/and anti-
phospholipid antibodies.
 White blood cell
leucopenia (<4.0*109/L), its cause
is probably a combination of
destruction of white cells by
autoantibodies, decreased
marrow production, increased or
marginal
it should splenic note
pooling,
that and
complement
immunosuppre
also activation.
d use the
ssive
treatment of SLE d cause
drugmay in
a marked s leucopenia.
the
Gastrointestinal and
hepatic manifestation
• Esophagitis,dysphagia,
nausea, vomiting:(drug related
in most cases)
• Chronic intestinal pseudo
obstruction
• Mesenteric vasculitis, protein-
losing enteropathy
• Pancreatitis
• Lupus hepatitis
 DIAGNOSTIC
STUDIES
 No specific test
 SLE is diagnosed
primarily on criteria
relating to
 patient history,
 physical examination,
and
 laboratory findings
 ON EXAMINATION
 Constitutional –
lymphadenopathy,
hepatosplenomegaly
 Musculoskeletal – Jaccoud
arthropathy
 Dermatologic -
capillaroscopy
 Renal
 Neuropsychiatric
 Cardiopulmonary – friction rubs,
pulmonary embolism, Libman-
DIAGNOSTIC STUDIES

 Antinuclear antibodies
 ANA and other antibodies
indicate autoimmune
disease
 Anti-DNA and anti-Smith antibody
tests most specific for SLE
 LE prep can be positive with other
rheumatoid diseases
 ESR & CRP are indicative of
inflammatory activity
RADIOLOGICAL STUDIES

 Joint x-rays: no erosions, periarticular

osteopenia
+ soft tissue swelling
 CXR/CT chest: interstitial lung
disease, pneumonitis, pulmonary
emboli, alveolar hemorrhage
 CTBrain or Brain MRI ± angiography:
lupus white matter changes, vasculitis
or stroke
 Echo: pericardial effusion,
pulmonary hypertension or
ADDITIONAL WORK-UP

- Serum cr. and

albumin
- CBC w/ diff
- U/A
- ESR
- Complement levels
- Renal profile if
warranted
INVASIVE PROCEDURES

 LP – nonspecific ↑cells +
protein, ↓
glucose
 Renal biopsy – prognosis
and Rx
 Skin biopsy
DIAGNOSTIC CRITERIA

American College of
Rheumatology 4/11 criteria
(sens 85%, specif 95%)
“SOAP BRAIN MD”
 Serositis – heart, lung,
peritoneum
 Oral ulcers – painless esp
palate
 DIAGNOSTIC CRITERIA
 Blood disorders - ↓RBC (Coombs +),
PLT, WCC, Lymphocytes
 Renal involvement – proteinuria /±
casts
 ANA – titer > 1:160
 Immunologic phenomena – LE cells,
anti- dsDNA Ab, anti-Sm Ab,
antiphospholipid Ab, false WR +
 Neurological disorders – seizures/
psychosis
 Malar rash – cheeks + nasal bridge

 TREATMEN
T based on patient
 Treatment plans are
age, sex, health, symptoms, and
lifestyle and on disease severity
 Fever, skin, musculoskeletal and
serositis = milder disease
 CNS and renal involvement – aggressive
Rx

 Goals of treatment are to:

-prevent flares
-treat flares when they occur
-minimize organ damage and
COLLABORATIVE CARE

 Drug therapy
 NSAIDs
 Antimalarial drugs
 Steroid-sparing drugs
 Corticosteroids
 Immunosuppressive
drugs
 CONSERVATIVE MANAGEMENT

 For those w/out major organ

involvement.
 NSAIDs: to control pain, swelling,
and fever
 Caution w/ NSAIDS though. SLE pts
are at increased risk for aseptic
meningitis
 Antimalarials: Generally to treat
fatigue joint pain, skin rashes, and
inflammation of the lungs
 Commonly used:
 Corticosteroids (Mainstay of SLE
treatment)
 To rapidly suppress inflammation
 Usually start with high-dose IV
pulse and convert to PO
steroids with goal of tapering
and converting to something
else.
 Commonly used:
prednisone, hydrocortisone,
methylprednisolone, and
dexamethasone
IMMUNOSUPPRESSIVES
 Primarily for CNS/renal involvement
 Mycophenolate mofetil (cellcept)
 Azathioprine (imuran): requires several
months to be effective, effective in
smaller percentage of patients
 MTX: for treatment of dermatitis and
arthritis, not life-threatening disease
 Cyclosporine: used in steroid-resistant
SLE, risk of nephrotoxicity
 Cyclophosphamide (cytoxan) Almost all
trials performed on patients with
nephritis
 OTHER THERAPY

 Plasma exchange
 Intravenous Immunoglobulin
 Stem cell transplantation
 Immune therapy ( anti-IL10,
anti-CD20, and immune
tolerance therapy)
PROGNOSIS

 Benign to rapidly progressive

 Better for isolated skin + musculoskeletal
disease vs renal and CNS
 Death rate 3X age-comparable general
population

Mortality

 Nephritis (most within 5 yrs of symptoms)

 Infectious (active SLE + Rx – most common)
 CVS disease (50X more MI than other woman)
 Malignancy (chronic inflammation + Rx)
 SLE DISEASE ACTIVITY INDEX
Clinical feature
(SLEDAI)
score
seizure , psychosis , organ brain 8
syndrome visual disturbance, 8
cranial nerve disorder lupus 8
headache, cerebrovascular 8
accidents, vasculitis 4
arthrit 4
is 4
myosi 2
tis 2
urinary casts, hematuria, 2
proteinure, pyuria rash, 1
alopecia, mucosal ulcers, 1
pleurisy, pericarditis
low complement, increased
 SLE DISEASE ACTIVITY INDEX
(SLEDAI)
Interpretation:

The most appropriate SLEDAI-2K cut-off

score for definition of active disease which
links to the need to increase therapy is 3 or
4, and trending changes over time in order
to help with decision-making is
recommended (Yee 2011).
Thank you