C.

T disorder characterized by degenerative and inflammatory

changes with subsequent intense fibrosis; affecting skin,
synovium, blood vessels, skeletal muscles, GIT, heart, lung,
kidney.
 Vibration injury
Similar vascular
Aliphatic changes
hydrocarbons Silica
trichloroethylene

Organic solvents
Pesticides
benzene
Enviromental
Triggering
factors
unknown
Aminoacids
Epoxy resin
L-5-hydroxytryptopha

Drugs
Appetite suppressants Bleomycin,cocaine
phenylethylamine Carpidopa,vit-K
COSMETIC PENICILLAMINE
Silicone implants
 Etiopathogensis
Unknown triggering

Fibroblasts Mononuclear cells platelet

endothelial cell
Overproduction of collagen Obliteration of nutritional
vessels

Fibrosis Ischaemia
 Genetic predisposed
HLA B8,DR3,DR5,DR52,DQB2
&
Enviromental Triggers &Microchimeric and Vascular Factors
MACROPHAGES
T-LYMPHOCYTES
VASCLAR DYSFUNCTION
MAST CELL
&
FIBROBLASTS
PERMANENT SCARRING
Vascular endothelial cells
B-LYMPHOCYTES

Antiendotheliall cell antibodies

& The activated cells secrete
VEGF Avariety of substances
& .Cytokines and their soluble receptor
ADHESION MOLECULES Enzymes and their inhibitors
EXPRESSION

PROFIBROTIC
:CYTOKINES
APPOPTOSIS
TGF-BETA
&
PDGF
FREE RADICAL RELEASE
CHANGE IN THE IL-4
EXTRA-CELLULAR CTGF
MATRIX COMPONENT
COLLAGEN I,III,V,VII
FIBRONECTIN
PROTEOGLYCAN
 According to the American Rheumatism Association
(ARA), features characteristic for scleroderma are
divided into 2 groups:
 Major features include centrally located skin sclerosis
that affects the arms, face, and/or neck.
 Minor features include sclerodactyly, erosions,
atrophia of the fingertips, and bilateral lung fibrosis.
 SSc is diagnosed when a patient has 1 major and 2
minor criteria.
 Malignant scleroderma most often occurs in men,
usually in elderly men. An accelerated course of
malignant scleroderma leads to death.
 Classification
I. Systemic sclerosis
A. With diffuse cutaneous scleroderma
 Symetric widespread thickening of the skin
affecting distal, proximal extremities, trunk and
face. Areas
Areas of
of skin
skin hyperpigmentation
hyperpigmentation and
and hypopigmentation
hypopigmentation
 Rapid progression of skin changes
 Early appearance of visceral changes lungs, lungs, kidneys,
kidneys,
digestive
digestive system,
system, and
and heart
heart
 Tendon
Tendon friction
friction rubs
rubs
 Raynaudes (75%) precedes
precedes the
the development
development of
of skin
skin changes
changes by
by
approximately
approximately 11 year:
year:
 Antiscleroderma 70 (+ve)

 Nail-fold
Nail-fold capillary
capillary dilatation
dilatation and
and capillary
capillary destruction
destruction
B. with limited cutaneous scleroderma
•• Symetric
Symetric skin
skin involvement
involvement restricted
restricted to to distal
distal
extremities
extremities and
and face.
face. Atrophic
Atrophic changes
changes of
of the
the ala
ala nasi
nasi and
and lips,
lips,
facial
facial amimia
amimia .Telangiectasia
.Telangiectasia of
of the
the skin
skin ..
••Slow
Slow progression
progression of
of skin
skin affection
affection
••Late
Late appearance
appearance of
of visceral
visceral involvement
involvement .. Late
Late involvement
involvement
of
of the
the lungs
lungs and
and late
late development
development of
of pulmonary
pulmonary hypertension
hypertension ..
••Raynaud's
Raynaud's (universal,
(universal, may
may preceed
preceed skin
skin lesion
lesion by
by
several
several years).
years).
••Dilated
Dilated capillary
capillary loops
loops in
in nail
nail folds
folds .Cutaneous
.Cutaneous calcification
calcification ..
••Anti-centromere
Anti-centromere AbAb (+ve)
(+ve)
••Subtypes
Subtypes
1.
1. Pb-pulmonary
Pb-pulmonary hypertension
hypertension ++ biliary
biliary cirrhosis.
cirrhosis.
2.
2. CREST-cutaenous
CREST-cutaenous calcinosis,
calcinosis, raynaud's
raynaud's ++
esophagus
esophagus lesion
lesion ++ sclerodactyly
sclerodactyly ++ telangiectasia.
telangiectasia.
II. Localized scleroderma
- Skin without visceral lesion
1. Morphea-plaque like or generalized.
2. Linear scleroderma.
 Clinical features
Race
No apparent racial predominance exists. However, SSc is rare in
the resident population of Japan and China. Diffuse SSc
(dSSc) occurs more often in black women than in white
women.
Sex
Overall, a substantial female predominance exists, with a
female-to-male ratio of 3-6:1. However, dSSc occurs equally
in males and females. The limited form of SSc (lSSc) has a
strong female predominance, with a female-to-male ratio of
10:1.
Age
SSc usually appears in women aged 30-40 years, and it occurs
in slightly older men. In approximately 85% of cases, SSc
develops in individuals aged 20-60 years. Cases also are
observed in children and in the elderly population.
 A. Initial: Raynauds, puffiness of fingers
and hands, polyarthralgias , myositis or
GIT. Cutaneous
Cutaneous involvement
involvement has
has 33 phases:
phases: (1)
(1) edematous,
edematous, (2)
(2)
indurative,
indurative, and
and (3)
(3) atrophic.
atrophic.

B. Skin-thick, hard, loss of folds, shiny,

hypo or hyperpigmentation, ulcers at
finger tips or joints, telengiectasia,
calcinosis.
- Skin softness may occur later on (years)
- 5% of cases may occur without skin
thickening, (sine scleroderma). Systemic
Systemic
scleroderma
scleroderma sine
sine scleroderma
scleroderma is is difficult
difficult to
to diagnose
diagnose because
because only
only
internal
internal organs
organs are
are involved.
involved. Systemic
Systemic scleroderma
scleroderma sinesine scleroderma
scleroderma
usually
usually is
is diagnosed
diagnosed after
after the
the patient's
patient's death.
death.
C.Musculoskeletal
Polyarthralgias ,polyarthritis .Small and
Large joints. R A like picture .Arthritis
mutilans
Tenosynovitis . Carpal tunnel syndrome
palpable crepitus over tendons.
Skeletal muscle. Disuse atrophy,myopathy
contracture
 BONE RESORPTION
 Bone radiography reveals generalized
osteopenia, which most commonly affects the
hands. Intra-articular calcifications often are
observed
Calcinosis
 D.
D. Visceral
Visceral
1.
1. GIT
GIT (hypomotility,
(hypomotility, fibrosis)
fibrosis)
-- esophegous
esophegous –– Dysphagia,
Dysphagia, GERD).
GERD).
-- Stomach
Stomach –– rarely
rarely affected
affected or
or drugs
drugs induced
induced
dyspepsia.
dyspepsia.
-- Duodenum
Duodenum –– duodenitis,
duodenitis, iron
iron malabsorption.
malabsorption.
-- Distal
Distal small
small intestine
intestine –– malabsoprtion
malabsoprtion
-- Colon
Colon –malasoprtion,
–malasoprtion, pseudo
pseudo obstruction
obstruction
incontinence,
incontinence, diarrhea,
diarrhea, rectal
rectal prolapse.
prolapse.
 2. Lung
- Interstitial fibrosis (basal).
- Pleurisy (dry rare effusion)
- Pulmonary hypertension (vasculitis) and
core pulmonal.

3. Heart
- Left ventricular dysfunction
- Dysrrhythmia.
- Restrictive cardiomyopathy
- Coronary HD (vasculitis)
- Pericarditis (rare).
 Chest radiographs may show normal findings in
5-10% of the patients, even when the patients
have respiratory tract symptoms.
 In approximately 30-60% of patients, fibrosis of
the basal parts of the lungs is observed.
 4.
4. Kidney
Kidney
-- Renovascular
Renovascular hypertension.
hypertension.
-- Proteinuria,
Proteinuria, haematuria
haematuria
-- Renal
Renal failure.
failure. (Scleroderma
(Scleroderma renal
renal crisis).
crisis).
-- How
How is
is renal
renal vascular
vascular disease
disease diagnosed?
diagnosed?
-- arteriogram
arteriogram (Also
(Alsocalled
calledan
anangiogram.)
angiogram.)--an
anx-ray
x-rayimage
imageof
ofthe
theblood
bloodvessels
vesselsused
usedto
toevaluate
evaluate
various
various conditions,
conditions,such
suchas
as aneurysm,
aneurysm,stenosis
stenosis (narrowing
(narrowingof of the
theblood
bloodvessel),
vessel),or
orblockages.
blockages. AAdye
dye
(contrast)
(contrast)will
willbe
be injected
injectedthrough
through aathin
thin flexible
flexibletube
tube placed
placedinin an
an artery.
artery. This
Thisdye
dye makes
makes the
the blood
bloodvessels
vessels
visible
visible on
onx-ray.
x-ray.
-- duplex
duplex ultrasound
ultrasound --aatype
type of
ofvascular
vascularultrasound
ultrasound procedure
procedure done
done to
to assess
assessblood
bloodflow
flowand
and the
thestructure
structure
of
ofthe
the leg
legveins.
veins. The
The term
term"duplex"
"duplex"refers
refers totothe
the fact
fact that
that two
two modes
modes of of ultrasound
ultrasoundareare used
used --Doppler
Dopplerand
andB-mode.
B-mode.
The
The B-mode transducer (like a microphone) obtains an image of the carotid artery being studied. The Dopplerprobe
B-mode transducer (like a microphone) obtains an image of the carotid artery being studied. The Doppler probe
within
withinthe
the transducer
transducer evaluates
evaluates thethe velocity
velocity and
and direction
direction of
of blood
blood flow
flowin
in the
the vessel
vessel
-- renography
renography --aaspecialized
specialized radiology
radiology procedure
procedure used
used to
toassess
assessthe
the function
function and
and structure
structure of
ofthe
the kidneys.
kidneys.
Renography
Renography isis aatype
type of
of nuclear
nuclearradiology
radiology procedure.
procedure. This
This means
means that
that aa tiny
tinyamount
amount of of aa radioactive
radioactive substance
substance isis
used
usedduring
during the
theprocedure
procedureto to assist
assist in
in the
theexamination
examination of of the
the kidneys.
kidneys.

-- magnetic
magnetic resonance
resonance angiography
angiography (MRA
(MRA))--aanoninvasive
noninvasive diagnostic
diagnostic procedure
procedure that
that uses
usesaa
combination
combination of
of magnetic
magneticresonance
resonance technology
technology(MRI)
(MRI)and
and intravenous
intravenous(IV)
(IV)contrast
contrast dye
dyeto
to visualize
visualize blood
blood vessels.
vessels.
Contrast
Contrast dye
dyecauses
causes blood
blood vessels
vessels to
toappear
appearopaque
opaque on
onthe
the MRI
MRI image,
image, allowing
allowing the
thephysician
physician to
to visualize
visualize the
the blood
blood
vessels
vesselsbeing evaluated..
beingevaluated
  Investigations
A. Lab:
-- ↑ESR
↑ESR (rare
(rare or
or mild).
mild).
-- CBC-anaemia
CBC-anaemia (↓
(↓ iron,
iron, autoimmune,
autoimmune, traumatic
traumatic
microangiopathic).
microangiopathic). Thrombocytopenia
Thrombocytopenia ..
-- Increased
Increased creatine
creatine phosphokinase
phosphokinase levels
levels in
in patients
patients with
with muscle
muscle
involvement
involvement .. Increased
Increased urea
urea and
and creatinine
creatinine levels
levels in
in patients
patients with
with kidney
kidney
involvement
involvement ..
-- Serology
Serology
1.
1.Anticentromere
Anticentromere (limited
(limited type)
type)
2.
2.Anti-scl
Anti-scl 70
70 (Diffuse
(Diffuse type)
type)
3.
3.Antinucleolar
Antinucleolar (Diffuse
(Diffuse type)
type)
4.
4.Anti
Anti PM-Scl
PM-Scl (overlap)
(overlap)
5.
5.Hypocomplementaemia,
Hypocomplementaemia, anti
anti dsDNA
dsDNA rare
rare (overlap)
(overlap)
6.
6.++ ve
ve Rf
Rf (overlap).
(overlap). 7. ↑↑  globulin.
7. globulin.
 C. Synovial fluid
- ↑ WBCs (less than 10,000), ↑ plasma cells, ↑
lymphocytes, fibrin deposits, ↓ mucin, ↓
viscosity.

D. Wide field nailfold capillary microscope.

→ loss of capillaries, dilatation & tortusity .
Capillary
Capillary microscopy:
microscopy: enlarged
enlarged capillaries
capillaries are
are observed
observed in
in all
all 33
portions
portions of
of the
the capillary
capillary nail
nail fold–arterial,
fold–arterial, apical,
apical, and
and venous–
venous–
and
and especially
especially at
at the
the edge
edge ofof the
the nail
nail fold.
fold. Adjacent
Adjacent areas
areas are
are
avascular.
avascular.
 Treatment
A.
A. ↓↓ or
or inhibit
inhibit fibrosis
fibrosis
1.
1. Penicllamine
Penicllamine (↓
(↓ cross
cross linking
linking of
of collagen).
collagen).
2.
2. Colchicine.
Colchicine.
3.
3. Steroides.
Steroides.
4.Interferon
4.Interferon alpha.
alpha.
B.
B. ↑Circulation
↑Circulation

 Salicylates
Salicylates (↓
(↓ platelet
platelet aggregation).
aggregation).

 Vasodilators.
Vasodilators.

 ACEI
ACEI (captopril).
(captopril).
C.
C. Immunosupressives.
Immunosupressives.

 Methoterxate.
Methoterxate.

 Azathioprine.
Azathioprine.

 Cyclophosphamide.
Cyclophosphamide.
D.
D. Biological
Biological therapies
therapies e.g.
e.g. antiTNF
antiTNF (undertriales).
(undertriales).
E.
E. Symptomatic
Symptomatic and
and supportive
supportive care
care of
of skin,
skin, Rx
Rx of
of ulcers,
ulcers,
antiinflammatory,
antiinflammatory, Rx
Rx of
of viseral
viseral manifestation.
manifestation.
In
In pruritus,
pruritus, the
the following
following agents
agents are
are sometimes
sometimes helpful:
helpful:
Camphor
Camphor and and menthol
menthol
Topical
Topical emollients
emollients
Psoralen
Psoralen UV-A
UV-A (PUVA)
(PUVA) treatment
treatment
When
When Raynaud
Raynaud phenomenon
phenomenon is is present,
present, the
the most
most effective
effective
nonpharmacologic
nonpharmacologic methodmethod of of preventing
preventing Raynaud
Raynaud episodes
episodes isis avoiding
avoiding
exposure
exposure to to cold
cold temperature
temperature and and wearing
wearing layers
layers of
of warm,
warm, loose-fitting
loose-fitting
clothing,
clothing, including
including socks
socks andand gloves.
gloves. Also,
Also, smoking
smoking cessation
cessation is
is advised.
advised. In
In
the
the pharmacologic
pharmacologic regimen,
regimen, consider
consider the the use
use of
of agents
agents such
such asas calcium-
calcium-
channel
channel blockers,
blockers, vasodilating
vasodilating drugs,
drugs, intravenous
intravenous prostaglandins,
prostaglandins,
prostacyclin
prostacyclin analogs,
analogs, or or aspirin.
aspirin.