Part II

Dr. Samir Ayad

Scleroderma/Progressive Systemic Sclerosis

Definition:
Autoimmune disease characterized by vasculitis and
excessive deposition of collagen throughout the body,
mainly in the skin ending in fibrosis & atrophy
Incidence:
Sex: females (3:1)
Age: 30-50 years at onset

Dr. Samir Ayad

Possible mechanisms
leading to systemic
sclerosis.
PDGF =
platelet-derived
growth factor
FGF =
fibroblast growth factor

Dr. Samir Ayad

Pathological changes:
(1) Vasculitis
- perivascular lymphocytic infiltration
- thickened wall
- partial occlusion

(2) Marked fibrosis and atrophy

(3) Restricted to the skin first, later on viscera
Dr. Samir Ayad

Scleroderma with characteristic renal vascular

involvement.
The interlobular artery shows marked intimal
thickening, with virtual obliteration of the lumen.

Dr. Samir Ayad

Scleroderma, skin, low power microscope

At low magnification, the collagen of the dermis is
increased. Chronic inflammatory cells are sparse with
systemic sclerosis, unlike SLE.

Dr. Samir Ayad

Clinical features:
(1) skin
- starts by fingers, then extends proximally to
arms, shoulders, neck and face
- initially, skin is edematous with petechial
hemorrhages (vasculitis), followed by
progressive fibrosis:

fingers: - tapered
- range of motion
- blood supply
ulceration and
gangrene
face:
restricted
movements
Dr. Samir Ayad

Scleroderma: Typical rat bite necroses and ulcerations of

fingertips.

Dr. Samir Ayad

Scleroderma
Masklike face (stone facies)
with stretched, shiny skin
and loss of normal facial
lines giving a younger
appearance than actual age;
the hair and eyebrows are
dyed black. Thinning of the
lips and perioral sclerosis
result in small mouth, which
is asymmetric.
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(2) Gastrointestinal tract

- mucosa: thin, ulcers, loss of villi
- submucosa: collagenized
- muscle layer: atrophies, replaced by collagen,
deficient peristalsis
- esophagus: in 50%, dysphagia due to narrowing
of lower portion (rubber hose appearance)
- intestines: malabsorbtion

(3) Joints
- synovitis: proliferation of synovial membrane,
later fibrosis & movement
- resembles rheumatoid arthritis, but destruction
of articular cartilage is rare
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Scleroderma, Gastrointestinal fibrosis, trichrome stain

This trichrome stain of the stomach demonstrates intense blue
staining in the submucosa from the collagen deposition. Such
fibrosis can occur anywhere in the gastrointestinal tract, but is
most common in the lower esophagus, leading to the
esophageal dysmotility with systemic sclerosis.

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(4) Muscles
- focal inflammatory infiltrates & edema,
followed by fibrosis & atrophy

(5) Kidneys
- small arterioles: vasculitis, fibrosis,
ischemia
-

malignant hypertension

glomerular filtration rate and renal failure

- glomerular lesion: depositon of immune

complexes

hypercellularity and basement

membrane thickening
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(6) Lungs
- diffuse interstitial pneumonitis and fibrosis
- progressive thickening of the walls of small
vessels

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Sjogrens disease
Definition:
Autoimmune disease characterized by immunemediated destruction of salivary glands and lacrimal
glands.
Incidence:
- Sex: females (9:1)
- Age: 40-60 years
- Either primary (40%) or secondary (60%)
associated with other autoimmune diseases
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Pathological lesions:
- involve the salivary & lacrimal glands, mucous
secreting glands of respiratory tract
- marked infiltration with lymphocytes & plasma
cells replacing the normal acinar cells

- hyperplasia of duct epithlium

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lumen obstruction
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Sjogren's disease, microscopic

Notice all the lymphocytes which have destroyed this
salivary gland but spared the ducts (arrow).

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Clinical findings:
(1) Dry eye (keratoconjunctivitis sicca):
- tears
- blurring of vision
- itchy eyes
- corneal ulceration
(2) Dry mouth (xerostomia):
- salivary secretion
- atrophy and ulceration of oral mucosa
- taste
- dysphagia
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(3) Respiratory tract:

- dryness and crusting of nasal mucosa
- laryngitis, bronchitis, pneumonia
(4) Lymphadenopathy:
(5) Arthritis (60%)

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Polymyositis/Dermatomyositis
Definition:
Autoimmune disease that affects primarily the
skeletal muscles and skin
Incidence:
Sex: females (2:1)
Age: two peaks, 5-15 and 50-60 years

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Pathological lesions:
(1) Skeletal muscle

- symmetrical, proximal muscle groups:

- shoulder and pelvic girdle
- neck and pharynx
- intercostals and diaphragm

- in early stage, muscle fibers show edema,

lymphocytes, fatty change & necrosis
- later atrophy & fibrosis
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(2) Skin
- 50% of cases
- vasculitis with edema and cellular infiltration
- later on, atrophy, fibrosis and calcification

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Dermatomyositis
Violaceous erythema of the dorsum of the hands and fingers,
especially over the metacarpophalangeal and interphalangeal
joints; the light-protected areas of the forearms are not
involved.

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Clinical features:
(1) Muscles
- symmetrical weakness, pain and
tenderness
- stiff fingers
- dysphagia due to affection of pharyngeal
muscles
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(2) Skin
- erythematous rash on:
- malar area of face (butterfly rash)
- V area of neck
- forhead
- shoulders
- chest
- heliotrope rash of upper eyelids
- atrophy
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Dermatomyositis: Violaceous erythema on the upper

chest, neck, and face; with periorbital edema.

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(3) Visceral involvement (uncommon)

constipation and abdominal pain

(4) Raynauds phenomenon (30%)

(5) risk of malignancy (25%)
particularly in adults

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Amyloidosis
Definition:
- Extracellular accumulation of fibrillar proteins
pressure atrophy of adjacent parenchyma
Etiology:
- production or

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utilization

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Clinical forms:
I Systemic amyloidosis:
(i) Primary amyloidosis
- associated with multiple myeloma, the most
common form in the US (3000 new cases/y.)
- malignant plasma cells synthesize excessive
light immunoglobulin chains
- amyloid proteins: type AL (amyloid light
chain) accumulate in the tissue (amyloidosis)
and pass in urine (Bence Jones protein)
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Multiple myeloma
A smear of a bone marrow aspirate illustrates a cluster
of neoplastic plasma cells with eccentric nuclei and a
perinuclear halo of clearer cytoplasm.

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(ii) Secondary (reactive) amyloidosis associated

with (secondary to):
a - Chronic inflammatory diseases:
- tuberculosis
- leprosy
- bronchiectasis
- chronic osteomyelitis
- chronic pyelonephritis
b - Autoimmune diseases:
- Crohns disease
- ulcerative colitis
- scleroderma
rheumatoid
arthritis
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c - Neoplasms:
- Hodgkins lymphoma
- renal cell carcinoma
In secondary amyloidosis there is systemic
distribution of amyloid protein, type AA protein
(amyloid associated protein) which accumulates in
the tissues of
*liver
*kidneys
*spleen
*lymph nodes
*thyroid
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Dr. Samir Ayad

(iii) Hemodialysis - related amyloidosis:

- associated with renal failure affects 70% of
patients maintained on hemodialysis
- amyloid protein (2-microglobulin):
accumulates mainly in joints & synovium

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(iv) Hereditary amyloidosis:

- present in certain geographical locations (e.g.

Familial Mediterranean Fever: recurrent

inflammation of serosal linings and fever

- amyloid protein: type AA (amyloid associated

protein)

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II Localized amyloidosis
(i) Senile amyloidosis (amyloid of aging):
- occurs in old age (80-90 years)
- amyloid protein: accumulates in
heart (senile cardiac amyloidosis) and

brain (senile cerebral amyloidosis), as in

Alzheimers disease

(ii) Amyloid in neoplasms (endocrine amyloid):

- local deposits within the stroma of neoplasms of
endocrines
- amyloid protein derived from precursors molecules
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Dr. Samir Ayad of polypeptide hormone

General morphology
Gross:
- the organ is enlarged, tissue appears pale,
waxy, gray and firm in consistency
Microscopic:
- pressure atrophy of neighboring cells

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Morphology of affected organs:

(1) Liver
Gross:
- normal or enlarged in size
- pale, waxy, gray and firm in consistency
Microscopic:
- amyloid deposit begins in the space of
Disse enlarge to encroach on sinusoids
& liver cells are compressed
- pressure atrophy and replacement of
hepatocytes by sheets of amyloid
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(2) Kidneys
Gross:
- larger in size

- gray in color and firm in consistency

- involvement of renal artery ischemia,
atrophy and in size (in long-standing
cases)
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Microscopic:
- glomeruli: amyloid deposit in mesangial
matrix and basement membrane of capillaries
narrowed or obliterated lumen

- renal tubules: peritubular deposit compressing

the lumen
- renal artery and arterioles: thickened walls and
narrowed lumen ischemia, fibrosis, and
atrophy
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Amyloid nephropathy.
The mesangial areas are
expanded
and
the
glomerular capillaries are
obstructed by amorphous
acellular material. The
deposits of amyloid may
take on a nodular
appearance.

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(3) Heart
Gross:
- normal or enlarged
- subendocardial deposits localized
elevation
Microscopic:
- amyloid deposits in all layers
- separation of muscle fibers, pressure
atrophy
- subendocardial deposits affect the
conducting system arrhythmias
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Amyloid deposition, myocardium, microscopic

Amyloidosis is characterized by slow deposition over years of
increasing amounts of an amorphous proteinaceous material in
one or more tissues. Seen here in the heart between the darker
red myofibers are pale pink amyloid deposits.

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Clinical features
General
- weight loss, weakness, fatigue (non-specific)

Local
- related to affected organ (e.g. hepatomegaly,

cardiac abnormalities, proteinuria)

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