I
Group B
Systemic sclerosis
Dr.fakhier
Definition:-
Is autoimmune and chronic connective tissue disease affect mainly middle aged
female in a proportion 4:1… usually male affected at older age .
Essentially it is a condition in which the body immune system (which normally
provides protection) is compromised and attack its own tissue this result into
inflammation and damage.
Etiology:-
❖ Unknown
❖ Environmental Exposures
✓ Silica exposure.
✓ Silicone breast implants.
✓ Aniline laced contaminated rapeseed oil.
✓ Vinyl chloride exposure.
✓ Bleomycin.
✓ L-tryptophan.
❖ Genetic factor
The pathogenesis still unclear but some unknown factors triggers the production
of collagen ( which normally keep the skin soft) when there is over production of
type 1 and 3 there will be thickening hardening and scarring of the skin and in
sever cases internal organ will be affected .
How it occur?
It begin when CD4 -T- helper lymphocytes react against some antigen in patient's
body… this result in accumulation of many cytokines which eventually lead to
vascular injury especially in small finger vessels…
The damaged endothelium produce
less vasodilator
as nitrous oxide and
more
vasoconstrictor
as endotheline 1… this result in vasoconstriction and tissue
hypoxia… the damaged endothelium also release PDF and TGF beta… these with
tissue hypoxia attract and activate fibroblast which will inevitably cause
fibrosis
.
So in the skin there will be thinning of epidermis and thickening of dermis and loss
II
of skin appendages (hair, sweat gland and sebaceous gland) resulting in dry stiff
skin.
Types:-
Systemic sclerosis (which previously known as scleroderma) in fact, it is part of it.
Scleroderma is a Greek word means hardening of skin and it is two types either
localized or systemic.
-Localized form: -
mainly affect skin (not internal organ) it is less in severity
and it is the only type that progression could be stopped, it’s of two types:
1-Morphea
:
is described as FIRM REDDISH OVAL SHAPE PATCH on skin which
may be single or multiple mainly on the chest and the back, the lesion also has
little sweat glands and hair.
2
-
Linear:
this type is charecterised by single line or band of thickened colored
skin ,typically the line runs down on arm ,legs and forehead, in some rare cases
it’s called (coup de sabre) a French word means sword stroke.
-Systemic form:-
also can affect the internal organ and its two types… diffuse
and limited.
*Limited type
affect skin areas over face, below elbow and the knee (distal
parts), progress to visceral organ and cause
slow
damage to organs that extend to
decades, it’s called
CREST syndrome
…
….
C
for calcinosis which are white lumps made of calcium found under the skin
can occur anywhere on the body but mainly on fingers , these lumps may ruptured
and produce whitish material, we should keep in mind that its not affected by
calcium intake.
….
R
for Raynaud's phenomena which is universal in all patients with SS and it
may proceed other clinical features by many years, it’s a condition where blood
vessels constrict by exposure to cold enviroment and stress which leads to
ischemia and color changes. If it’s not reversed, may end with gangrene and
amputation.
…
. E
for esophageal immobility (Barrett’s esophagus).
III
….
S
for sclerodactyly, localized thickening and tightness of the skin in the fingers
and toes, the fingers tend to be in a bend position and this could lead to ulceration
.... T
for telangiectasia also known as spider veins, a small red spots appear on
the skin caused by enlargement and damage of small blood capillary, these are
usually found on the fingers, palm, face, lips and tongue.
*Diffuse SS
(about30%of patient) have a
rapid
progression that occurs over
few years 3-5 years, it is diffuse, generalized skin thickening (proximal parts).
Clinical picture:-
1-skin:
the initial phase of skin manifestation is
non-pitting edema
of fingers and
flexor tendon sheaths, the skin become shiny, taut and the distal creases
disappear.
In the face the skin become tight (mask face) with radial furrowing around the lips
which limit mouth opening, telangiectasia, peaked nose and tight neck band.
2-musculoskeletal features:
arthralgia, morning stiffness and the flexor
tenosynovitis are common, restricted hand function is due to skin tightening rather
than joint problem, erosive arthropathy uncommon, myopathy, muscle weakness
and wasting can occur due to myositis.
3- Internal organ:
1-digestive tract:
it’s the 2
nd
system affected after the skin, collagen
deposition and fibrosis affect mainly the lower two third of esophagus lead to
absence peristalsis… hypomotility, the lower esophagus sphincter may lose its
function so acid reflux esophagitis, mucosal ulceration and stricture can occur.
The exposure to acidity could lead to metaplasia (barrette’s esophagus) which is
premalignant condition of esophageal adenocarcinoma.
The patient will suffer of dysphagia, odynophagia and heartburn sensation.
The collagen deposition in the stomach will cause stomach hypomotility which will
cause post prandial bloating.
Recurrent occult UGIB indicate watermelon stomach, antral vascular ectasia occur
in 20% of patients.
IV
Deposition of collagen in the small intestine will cause hypomotility malabsorption
and bacterial overgrowth so the patient will suffer from intermittent bloating pain
and constipation.
Wide mouth diverticula leak peritonitis.
Dilatation of small and large intestine due to autonomic neuropathy cause pseudo
obstruction (nausea vomiting and abdominal distention especially after meal).
2-cardiopulmonary system:
-Pulmonary involvement: is a major cause of morbidity and mortality, two forms
-interstitial lung fibrosis and fibrosing alveolitis mainly affect patient with diffuse
diseases particularly those with AB to topoisomerase 1.
-pulmonary HTN which is the complication of long standing diseases ,its six times
more prevalent in limited than in diffuse, it's presented with exertional shortness
of breath, leg edema due to right sided heart failure.
Pulmonary involvement could be recognized before symptom appear by high
resolution CT scan
-Cardiac involvement: collagen deposition will cause myocardial fibrosis,
myocarditis, pericarditis, pericardial effusion and conduction abnormalities
Presented by arrhythmia or even heart failure.
3-renal involvement:
one of the most common causes of death is
hypertensive renal crisis by rapid developing malignant HTN and acute renal
failure; it is more common in diffuse type and with AB to topoisomerase 1.
Investigation:-
Laboratory finding:-
1-raised inflammatory marker (ESR).
2-anemia of chronic illness (normochromic normocytic)
3-microangiopathic hemolytic anemia (hemolysis is caused by factors in the small
blood vessels).
4-complication related e.g. elevated urea and creatinine (renal failure) and
restrictive pulmonary function tests (pulmonary fibrosis).
Immunology (serology):-
V
The presences of serum autoantibodies directed to multiple intercellular is a
serological hallmark of SS .IN SS these autoantibodies present in 95% of patient
and are helpful biomarkers for establishing an early and accurate diagnosis.
It is important that they are also associated with distinctive clinical subset, specific
patterns of organ involvement, and different prognostic feature.
-Anti-topoisomerase 1 AB: where initially named anti -Scl-70, have been reported
in 15-42% of SS patient, with specificity ranging from 90-100%.
ATA are strongly associated with
dcSS
and a
poor
prognosis, SSc patient with ATA
have a higher risk of having sever pulmonary fibrosis and cardiac involvement.
Also the presence of ATA abs in patient with Raynaud's phenomenon is predictive
in that they are associated with a high risk of developing of SSc.
-Anti-centromere AB: is the most common autoantibody detected in SSC with
frequencies that range from 20 to 38%, although these antibodies are relatively
specific for SSc, they have been reported in SLE and other connective tissue
disease.
As with ATA, Anti-centromere AB is highly predictive of impending SSc in patient
with Reynaud's phenomenon .
This AB is classically associated with
lcss
and a
better
prognosis compared to
other SSc related abs.
Also this abs is associated with a higher risk of pulmonary hypertension and
mortality among this particular clinical subset.
Management:-
Treatments depend on:
✓ Type
✓ Severity
✓ Disease progression
✓ Patient's age
Mx of Raynaud’s:-
A) Advices like stop smoking (smoking cause narrowing of blood vessels even
more and make it worse), wearing warm clothes especially protecting hands and
feet from the cold and staying indoor during cold weather, exercise increase blood
supply.
VI
B) medical management: calcium channel blocker like nifidipine, intermittent
infusion of prostaglandin PGI2 (VD) called epoprostenol, affective in severe digital
ischemia and endothelin 1 antagonist (bosentan) can be of value in promoting
healing of digital ulcers, if these became infected, antibiotics should be given (they
are poorly infiltrate scleroderma) so we give them at higher doses, for longer
duration than usual.
MX of GIT system:-
Advices like:
A) Avoid lying down after meal for at least on hour.
B) Avoid late night meals, spicy and fatty food.
C) Eat moist soft food with little amount and chewing well.
D) Stop drinking alcohol.
Medical management:
A) Proton pump inhibitor,
B) Periodic dilatation of esophageal stricture.
C) Increase gastric emptying by metoclopramide, erythromycin and domperidone
D) Suppression of intestinal flora which causing malabsorption by antibiotic
…tetracycline
Mx of renal involvement:-
ACEI which made the disease less dangerous, you have to measure blood pressure
frequently to detect any sudden changes.
Mx of respiratory involvement:-
A) For pulmonary fibrosing alveolitis and interstitial fibrosis give
immunosuppressant like MTX, azathioprine or cyclophosphamide
B) For pulmonary HTN epoprostenol and bosentan.
C) Cardiopulmonary transplantation in selected cases.
PROGNOSIS:-
5 year’s survival is about 70%...
Bad prognostic features include:
✓ Diffuse cutaneous form
VII
✓ Onset at older age
✓ Male gender
✓ Renal involvement
✓ Pulmonary hypertension