Part I - SLE

Dr. Samir Ayad

Systemic Lupus Erythematosus

(SLE)
Definition:
Autoimmune disease of connective tissue that
involves multiple systems.
Incidence:
- 1:2500
- Sex: females to males (9:1)
- Age: 20-40 years at onset (mostly)
Dr. Samir Ayad

Etiology:
(1) Genetic factors:

- familial incidence
- HLA-DR2 and DR3

(2) Immunological factors:

- deficiency of suppresor T-cells
- hyperactive helper T-cells
- abnormal B-cells
(3) Drugs - induced (e.g. hydralazine, procainamide)
(4) Viral infection
(5) Sex hormones (exacerbations in pregnancy)
Dr. Samir Ayad

Mechanism:
(a) Autoimmune disease: antinuclear antibodies
(ANAs) against several nuclear antigens (DNA,
RNA, nucleoproteins) react with nuclei of
damaged cells (cannot penetrate intact cells)
(b) Formation of immune complexes and their
deposition in different tissues

(c) Activation of complement inflammatory lesions

(type III hypersensitivity)
Dr. Samir Ayad

Antinuclear antibody test, homogenous pattern,

fluorescence microscopy
Here is a positive ANA, homogenous or diffuse staining
reflecting antibodies to chromatin, histones, and doublestranded DNA.

Dr. Samir Ayad

Antinuclear antibody test, rim pattern, fluorescence

microscopy
Sometimes when performing the ANA test, the cells
demonstrate particular patterns of staining rim or peripheral
staining, indicative of AB to double stranded DNA. This is the
so-called "rim" pattern that is more characteristic of SLE.

Dr. Samir Ayad

Antinuclear antibody test, nucleolar pattern, fluorescence

microscopy
This is the so-called "nucleolar pattern" of staining in which
the bright fluorescence is seen within the nucleoli of the cells.
This pattern is more suggestive of progressive systemic
sclerosis.

Dr. Samir Ayad

Pathological changes:
(1) Blood vessels:(acute necrotizing vasculitis)
- acute vasculitis of small arteries and arterioles
due to deposition of immune complexes
- necrosis & fibrinoid deposits within vessel wall
- later, fibrous thickening with luminal narrowing
- perivascular lymphocytic infilterate

(2) Heart:
- pericarditis
- myocarditis
- endocarditis (Libman-Sacks):
multiple, small, sterile, flat vegetations,
detachable
embolization
Dr. Samir Ayad

Libman-Sacks endocarditis, gross

Here are flat, pale tan, spreading vegetations over the mitral
valve surface and even on the chordae tendineae. This patient
has SLE. Thus, these vegetations that can be on any valve or
even on endocardial surfaces are consistent with LibmanSacks endocarditis. These vegetations appear in about 4% of
SLE patients.

Dr. Samir Ayad

(3) Kidneys:Normal (in few cases):

(i) Mesangial glomerulonephritis (10%):
increased cellularity of mesangial matrix
(ii) Focal proliferative glomerulonephritis (30%):
hypercellularity, but not all (focal) glomeruli, due to
proliferation of endothelial and mesangial cells. Present
with hematuria, proteinuria, mild renal insufficiency.

(iii) Diffuse proliferative glomerulonephritis(45-50%):

Most serious, all glomeruli involved. Hematuria,
proteinuria, hypertension, & renal insufficiency
(iv) Membranous glomerulonephritis (10%):
Thickening of capillary wall
massive proteinuria 10
Dr. Samir Ayad

lupus nephritis. The mesangial component of the

glomerulus is more prominent because of an increase
in both cells and matrix.

Dr. Samir Ayad

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Rapidly progressive glomerulonephritis with crescents, microscopic

Seen here within the glomeruli are crescents composed of proliferating
epithelial cells. Crescentic glomerulonephritis is known as rapidly
progressive glomerulonephritis (RPGN) because this disease is very
progressive. There are several causes, and in this case is due to SLE.
Note in the lower left glomerulus that the capillary loops are markedly
thickened (the so-called "wire loop" lesion of lupus nephritis).

Dr. Samir Ayad

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Lupus nephritis, kidney, microscopic

Here is a glomerulus with thickened pink capillary
loops, the so-called wire loops", in a patient with
lupus nephritis. The surrounding renal tubules are
unremarkable.

Dr. Samir Ayad

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Lupus nephritis, electron micrograph

The thickened basement membrane (arrow) that
results from immune complex deposition in the
glomerular capillary loop is prominent in this electron
micrograph. The dark immune deposits are located
mainly in a subendothelial position.

Dr. Samir Ayad

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(4) Skin:
- deposition of immune complexes along the
dermo-epidermal junction
- activation of complement
skin rash

inflammation

- erythema, maculopapular rash

- malar regions of the face and bridge of nose
(butterfly rash, photosensitivity to UVR)
Dr. Samir Ayad

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Malar (butterfly) rash, patient

with SLE, gross
The young woman has a malar
rash (the so-called "butterfly"
rash because of the shape
across the cheeks). Such a rash
suggests
lupus.
Sunlight
exposure accentuates this
erythematous rash.

Dr. Samir Ayad

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Vasculitis with marked inflammation, skin, patient with SLE,

microscopic
Here is a more severe inflammatory skin infiltrate in the upper
dermis of a patient with SLE in which the basal layer is
undergoing vacuolization, and there is purpura with RBC's in
the upper dermis (which are the reason for the rash).

Dr. Samir Ayad

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(5) Joints:
- arthritis (most common presenting symptom)
resembles rheumatoid arthritis but:
- involves large and small joints
- mild (rarely causes destruction of cartilage)

(6) C.N.S:
- vasculitis

hemorrhages, ischemia, infarcts

(7) Lung:
- pleurisy with pleural effusion
- alveolitis and fibrosis
Dr. Samir Ayad

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(8) Serosal cavities:

- Inflammation (pleurisy, pericarditis, peritonitis)
with serous effusion or fibrinous exudation in
acute cases to fibrous opacification in chronic
cases.

(8) Spleen:
- enlarged slightly
- capsule is thickened
- follicular hyperplasia
Dr. Samir Ayad

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Complications of systemic lupus erythematosus.

Dr. Samir Ayad

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Discoid lupus erythematosus

Dr. Samir Ayad

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Discoid lupus erythematosus

Dr. Samir Ayad

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Clinical features:
- females
- arthritis (larger joints)
- fever
- skin eruption (butterfly rash over face)
- hypertension
- hematuria, albuminuria, nephrotic syndrome

Dr. Samir Ayad

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Diagnosis :
- antinuclear antibodies (ANAs) in the serum
- presence of LE cells (nuclear debris ingested by
blood neutrophils)

Prognosis:
- chronic course with repeated exacerbations and
remissions
- survival rate is 90% at 10 years (death mostly due
to renal failure)
Dr. Samir Ayad

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LE cell preparation, microscopic

Here is the famous "LE cell" test which has value only in
demonstrating how the concept of autoantibodies work. The
pink blobs are denatured nuclei. Here are two, with one seen
being phagocytozed in the center by a PMN.

Dr. Samir Ayad

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