SCLERODERMA DR MAGDI AWAD SASI 2016 LMB

SCLERODERMA 2016 DR MAGDI AWAD SASI LIBYAN MEDICAL BOARD 7
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SCLERODERMA
DEFINITION:
It is a chronic autoimmune disease condition of unknown aetiology characterised by
increased fibroblast activity and fibrosis in a number of different organ systems in the
form of hardened, sclerotic skin and other connective tissues.
Scleroderma = hard skin = skin fibrosis
2
Types of Scleroderma
Scleroderma
Localized
Scleroderma
Systemic
Scleroderma
(Systemic Sclerosis)
Morphea
Linear
Scleroderma
Limited
Scleroderma
Diffuse
Scleroderma
Sine
Scleroderma
PATHOPHYSIOLOGY:
TISSUE FIBROSIS OBLITERATION OF PRODUCTION OF AUTO- CELLULAR
ARTERIOLES/SMALL ARTERIES ANTIBODIES IFILTRATION

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PREVALENCE:
 Incidence in US of 9-19 cases per million per year
 Prevalence in US of ~286 cases per million
 250 patients / million / in USA
 New cases 20 /million /year
SEX: Female to male ---- 4 to 5 times in female
AGE: Average at time of diagnosis 50 years
The prevalence and manifestation of scleroderma vary among racial and ethinic groups!
ex; scleroderma is 100 times more common among the choctan native Americans in
Oklahoma ; the disease is characterized by diffuse skin disease and pulmonary fibrosis.
Milder limited disease is more common among white women and African American are
more likely to have sever disease.
The disease expression is influenced by:
1. Ethinic and racial groups
2. Family clustering
3. Specific autoantibodies with specific HLA
4. Environmental factors
CLINICAL FEATURES:
The most frequent symptoms (( in descending order )) are:
A. Raynauds phenomena
B. Gastro-esophageal reflux
C. Swollen fingers
D. Musculoskeletal pain /Arthralgias
You have to be aware of scleroderma ;WHY?
Because early intervention can reduce morbidity and prevent life threatening complications.
The diagnostic criteria for scleroderma :
1. Thickened skin changes proximal to MCP joints. OR
2. Two of the following:
i. Sclerodactaly
ii. Digital pitting ---loss of tissue on finger pads
iii. Bibasilar pulmonary fibrosis

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The diagnosis of limited scleroderma can be made if the patient has 3/5 of CREST:
1. Calcinosis
2. Raynaud phenomena
3. Esophageal dysmotility
4. Sclerodactly
5. telangiectasia
Early presentation of scleroderma:-
A. musculoskeletal discomfort
B. fatigue
C. weight loss
D. heart burn due to GERD
when the symptoms are accompanied by raynauds or new onset of cold
sensitivity ,scleroderma is more likely.
Classical presentation:
There are three patterns of disease:
A.LIMITED CUTANEOUS SYSTEMIC SCLEROSIS : -----
 Long H/O Raynauds phenomena ---Raynaud's may be first sign
 Scleroderma affects face and distal limbs predominately
 Swelling or skin thickening of the fingers.
 Gastroesophageal reflux and dysphagia.
 Systemic --- weight loss ,dyspnea ,arthralgia
 Associated with anti-centromere antibodies
 CREST syndrome is an older term for the limited
cutaneous form. CREST syndrome is a subtype of
limited cutaneous systemic sclerosis: Calcinosis,
Raynaud's phenomenon, Esophageal dysmotility,
Sclerodactyly, Telangiectasia
Complications of CREST syndrome: Malabsorption
can develop in these patients secondary to bacterial
overgrowth of the sclerosed small intestine
(dysmotility secondary to infiltration of the intestinal
wall with fibrous tissue).
 Also, unfortunately pulmonary hypertension is one
of the more common late complications seen in such
patients.
EX: Female pt. with SOB, lung fibrosis, GERD, Raynaud’s, +ve ANA >> Systemic
sclerosis as CREST develop pulmonary HTN NOT ILF.

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B.DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS ------
 New onset of Raynauds phenomena
 Rapid change of skin texture and edema ,pain ,pruritis
 Significant systemic symptoms with arthralgia ,weight loss ,tendon friction rubs
 Internal organ involvement –lung ((dyspnea)) ,Kidney
((HTN)) , GIT ((malabsorption)).
 Scleroderma affects trunk and proximal limbs
predominately ((ALL THE BODY)).
 Associated with scl-70 antibodies
 Poor prognosis
 Whilst diffuse systemic sclerosis is associated with more
severe and rapid internal organ involvement ,it is also
seen in the limited form.
C. Morphea (Localized Scleroderma) (without internal organ involvement)
Tightening and fibrosis of skin.
May manifest as plaques (morphoea) or linear.
This is a well-defined oval to round plaque. (Like a painless lesion to his left
subcostal region, dry, indurated and slightly coarse to palpation).
The pathogenesis is poorly defined.
An autoimmune component is suggested by enhanced T helper 2 (Th2) dependent
interleukin 4 (IL-4) activity, which in turn up regulates transforming growth factor
beta (TGF -beta). TGF-beta stimulates fibroblast production of collagen and other
extracellular matrix proteins.
SYMPTOMS AND SIGNS:
A. SKIN:
The skin is one of the most universally and prominently involved organs in both
diffuse and limited cutaneous disease. Initially may manifest as diffuse swelling,
especially in the hands and fingers. This is followed by progressive skin tightening
from excess collagen deposition. A notable difference in diffuse vs limited disease
(and one that largely defines the different subsets) is that the skin changes in
limited disease are confined to areas below the elbows and knees. Skin
involvement in diffuse disease is more widespread, involving the entire arm
and/or leg as well as skin on the trunk. Be aware that the skin on the face is
typically involved in both disease subsets.
Other skin findings may include hard calcium deposits under the skin, known as
calcinosis cutis (seen more often in limited cutaneous systemic sclerosis). Small,
spider-like, visible, dilated blood vessels called telangiectasias can be seen (often
on the face and chest). Skin ulcers and pigment changes are not uncommon.

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a. Thickening of the skin:
- Most easily recognizable manifestation
- Not prominent in all patients
- Scleroderma classified according to the amount and location of
involvement.
Patient with limited disease:---
Skin changes on the face and distal to knees and elbows ex; CREST
1. Typically only involves the skin of fingers distal to the MCPJ –Sclerodactly.
2. Marked Telengectasias ((dilatated capillaries ))that occur on the skin of face ,the
palmer surface of the hands and the mucous membranes.
3. Subcutaneous calcinosis ---fingers ,extensor surface of forearm.
Patient with diffuse disease----
Patient with proximal extremity or truncal skin involvement
The amount of skin thickening can be quantified by skin score .
The skin is pinched between the examiners thumbs in 17
specified areas of the patients body .
0 (( Normal )) --- ------------ 3 (( Very thick))
Higher skin scores correlates with greater degree of internal
organ involvement.
The early stage----- inflammatory face:
Skin edematous and inflamed
Skin erythema
Pigmentary changes ---hyperpigmented areas with
depigemntation—salt&pepper appearance.
Pruritis and discomfort
Lasts weeks –months
Fibroblasts ---over produce
extracellular matrix that
leads to increased collagen
deposition in the skin
leading to collagen cross
linking –skin tighting
The later stages----
Skin become thickening , dry ,scaly because of the loss of its natural oily due to sebaceous
gland damage.
Dry skin are intensly pruritic causing excoriation.

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B. Vascular disease:
A diffuse vasculopathy of peripheral arteries is manifested by :
1. Intimal proliferation
2. Activation of arterial smooth muscles.
3. Narrowing of the vessel lumen.
Critical ischemia occurs in the tissues when vasoconstriction occlude these vessels.
Evidence suggested that this vascular disease is fundamental to organ damage.
 Heart----------CMP
 Lung -----------PHTN
 Kidney --------- scleroderma renal crisis ((SRC))
Table 1: ACR/EULAR Revised Systemic Sclerosis Classification Criteria
Item Sub-item(s) Score
Skin thickening of the fingers of both hands extending
proximally to the metacarpophalangeal joints (presence
of this criterion is sufficient criterion for SSc
classification)
None 9
Skin thickening of the fingers (count the higher score
only)
Puffy fingers 2
Sclerodactyly (distal to the
metacarpophalangeal joints but
proximal to the proximal
interphalangeal joints)
4
Fingertip lesions (count the higher score only) Digital tip ulcers 2
Fingertip pitting scars 3
Telangiectasia None 2
Abnormal nailfold capillaries None 2
Pulmonary arterial hypertension and/or interstitial lung
disease (maximum score is 2)
Pulmonary arterial hypertension 2
Interstitial lung disease 2
Raynaud phenomenon None 3
Systemic sclerosis–related autoantibodies (maximum
score is 3)
Anticentromere 3
Anti–topoisomerase I 3
Anti–RNA polymerase III 3
The total score is determined by adding the maximum score in each category. Patients
with a total score equal to or greater than 9 are classified as having definite systemic
sclerosis (modified from van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification
criteria for systemic sclerosis: an American College of Rheumatology/European League
against Rheumatism collaborative initiative.

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C/F---
A) Raynauds phenomenon:
Is the first manifestation of the disease in almost every patient.
RP is an episodic self limited and reversible vasomotor disturbance manifested as a
color changes bilaterally in the fingers ,toes sometimes ears ,nose and lips.
The color changes are pallor ,cyanosis and then erythema((white ,blue ,then red)).
There is triad of colours: initial whitening of the fingers resulting from vasospasm,
followed by blue discolouration and then reddening and pain.
Raynaud's phenomena may be:
Primary (Raynaud's disease) or Secondary (Raynaud's phenomenon)
Raynaud's disease typically presents in young women (e.g. 30 years old) with
symmetrical attacks.
There is no need for the three color for diagnosis.
Episodic pallor or cyanosis that reverses to erythema or normal skin color may be
all that is seen.
Patient may describe symptoms of numbness ;tingling or pain on recovery.
Stress and cold temperature induce an exaggerated vasoconstriction of the small
arteries ,arterioles and AV shunts of the skin of the digits.
This is manifested clinically as PALLOR & CYANOSIS of the digits followed by
reactive hyperemia after rewarming.
The attacks are often painful and lead to digital ulceration ,gangrene or
amputation.
In patient with Raynauds phenomena ,to suggest early SS:
a) Positive ANA ,Antitopoisomerase ( SCL 70) ,Anticentromer AB
b) Nail fold capillary abnormality
c) GERD
d) Puffy swollen fingers or legs
e) Tendon friction rubs
Raynauds phenomena occur in limited and diffuse scleroderma.
 If RP precedes skin changes by a year === LIMITED
 If RP occur simultaneously with skin changes ==DIFFUSE
For treatment;
i. Calcium channel blocker---Nifedipine ,Diltiazem
ii. Antiadrenergic agents ----Prazosin ,Methyldopa
iii. ACE-I ,AGB II
iv. Aspirin ,Niacin
NOTE:
 Patient > 30 years in whom RP develops should be screened with an ANA test and
nail fold examination if they have sever painful episodes and signs of digital
ischemia.
 Patient with scleroderma almost always have positive ANA.

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 A negative ANA makes diagnosis of scleroderma unlikely.
HOW TO DIFFERENTIATE BETWEEN PRIMARY AND SECONDARY RAYNAUDS PHENOMENA?
For primary ,
- Symmetrical episodes ,intermittent attacks.
- Affecting both hands, but not necessarily all fingers
- No evidence of peripheral vascular disease
- No evidence of tissue gangrene/digital
pitting/ulceration/severe ischaemia
- No suspicion of underlying disease
- Normal nail-fold capillary microscopy
- Negative ANA with normal ESR
For secondary,
- Male sex
- Onset > 40 years
- Unilateral symptoms
- Asymmetry of digits affected
- Painful attacks
- Digital ulcers
- Tissue ischemia-- gangrene or severe ischaemia of one
or more digits.
- Very rarely: chilblains (pernio) are itchy, painful purple
swellings which occur on the fingers and toes after
exposure to the cold.
- Symptoms and signs of CTD
- Rashes Features which may suggest RA or SLE, e.g. arthritis or recurrent
miscarriages ,calcinosis
- Presence of autoantibodies--- Positive ANA
The most useful initial assessment to determine whether the Raynaud’s is related to
vasculitis or not >>>(( must include nail fold capillary loop examination, ideally by
capillaroscopy or, if not available, by ophthalmoscopy using magnification ))>>> In CTD
such as systemic sclerosis: dilated, distorted, missed nail fold capillary loops.
Secondary causes:
1) Connective tissue diseases (CTD): scleroderma (most common), RA, SLE, PAN,
Sjogren’s syndrome.
2) Type I cryoglobulinaemia, cold agglutinins.
3) Leukaemia , Polycythaemia , Thrombangitis obliterans (Buerger’s disease)
4) Use of vibrating tools , Drugs: oral contraceptive pill, ergot (NB: Ergotamine is
associated with Raynaud's phenomenon), βB, Vinblastine, Bleomycin.
5) Cervical rib.

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Differential diagnosis of Raynaud's phenomenon includes:
A. Chilblains (perniosis): erythematous itchy swellings on fingers and toes in response
to cold.
B. Acrocyanosis: continuous blueness of the extremities aggravated by cold.
C. Erythromelalgia: painful erythema caused by paroxysmal dilatation of blood
vessels.
D. Vascular embolism.
E. Livedo reticularis.
F. Mottled, cyanotic discolouration of skin.
B) Lung involvement:
2 forms pulmonary HTN and inflammatory alveolitis –ILF
ILF PULMONARY HTN
Limited SS Bibasilar and non progressive
((20%))
(( 8----28%))
Poor prognosis
Diffuse SS More common and progressive
((30-60%))
Very rare
Over lap Common and can progress (( 85%)) 21----30%
1. INTERSTITIAL LUNG DISEASE:
Many patient are asymptomatic
Clinical symptoms can be insidious and include exertional dyspnea ,easy
fatigability and exertional dry cough.
Later ,it may progress to dyspnea at rest.
Clinical signs are typically early inspiratory fine crackles.
PFT or HR CT scanning can detect very mild and early disease.
Routine PFT is mandatory because early intervention may prevent progression.
80% of patients have restrictive ventilator defects on PFT
Only 10—20% suffer from progressive ILD.
Treatment:
Patient with disease restricted to bases ----no treatment
Patient with progressive disease ---treatment with progression to middle
&upper lobes.
Patient who respond to immunosuppressive have active alveolitis
a. Bronchoalveolar lavage ---- Neutrophils / Eosinophils > 5%
b. HR CT scan ---nonspecific interstitial pneumonitis ---ground glass
c. Lung biopsy
These patients may respond to prednisolone and cyclophosphamide.
Patients with progressive lung disease without alveolitis /UIP-usual interstitial
pneumonitis on HRCT scan /Lung biopsy do not respond to treatment.

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WHY? Because fibrosis due to fibroblastic foci.
Treatment ---- antifibrotic therapy , alpha interferon
2. Pulmonary HTN:
Risk Factors for PAH in Scleroderma—
1) Long disease duration (usually >8 yr)
2) Limited scleroderma > diffuse scleroderma
3) Abnormal pulmonary function tests
a. low DLCO <55% predicted and FVC %/DLCO % >1.6
4) Autoantibody profile
a. anticentromere antibody
b. antinucleolar pattern on ANA (anti-U3 antibody, which is not clinically
available)
Due to pulmonary vascular disease.
Patient usually have an insidious onset of exertional dyspnea which can
become at rest with fatigue and loss of effort.
Physical exam ; loud P2 ,S3 RV ,TR ,PULMONARY REGURGITATION
Raised JVP ,pedal edema
Isolated pulmonary HTN occurs more commonly in limited SCL which have long
duration of disease.
Pulmonary HTN complicates the course in 10% CREST.
Treatment :
Initially ;patients are placed on nasal O2.
Ca channel blocker can be tried.
Full anticoagulation is often administered.
For sever pulmonary HTN ,
A. Continous I.V. epoprostenol ((PGI2))
B. Oral non specific endothelin antagonist ((bosentan))125mgBID
It is Contraindicated in:
1. Pregnancy
2. Cyclosporine
3. Glyburide
4. Hepatotoxic
C. Lung transplantation
D. Silendafil
C) GIT:
Both upper and lower GIT are involved.
Highly variable in its clinical expression.
It can be asymptomatic ((mild constipation)) or profound
dysfunction((malnutrition)). The gastrointestinal tract is involved in almost all
cases of systemic sclerosis. Fibrotic and vascular changes all along the GI tract
interfere with normal motility, resulting in a host of problems including
gastroesophageal reflux disease (GERD), intestinal dilatation with abdominal pain,
bacterial overgrowth with diarrhea, and malabsorption. An increasingly recognized
problem in both diffuse and limited cutaneous forms of disease is gastric antral
vascular ectasia (GAVE). Analagous to dilated blood vessels seen on the skin, blood

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vessels in the stomach can dilate and then rupture, with the
potential for massive blood loss. This photo shows the appearance
of the dilated blood vessels on endoscopy.
1. GERD:
The majority are symptomatic with dysphagia.
The patient is complaining of sensation of the food getting stuck in the mid
esophagus ,atypical chest pain ,or cough.
The patient often complain that they must drink liquids to swallow solid food
,meat or bread.
Reflux and dysphagia occur because of dysmotility of esophagus and stomach
((gastroparesis)).
This type of organ dysfunction results from atrophy of the esophageal smooth
muscle.
Complication:
1. Esophagitis
2. Esophageal ulceration with bleeding
3. Esophageal stricture
4. Barret esophagus
5. Candidiasis
GIT dysfunction is due to:
1. There is neural dysfunction thought to be due to arteriolar changes of vasa
nervourum leading to dysmotility.
2. Smooth muscle atrophy

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Esophagealdysmotility is assesd by:
 Manometry
 Cine –esophagography
 Endoscopy
 Barium swallow
WHAT IS WATER-MELON STOMACH?
Gastric antral venous ectasia
It causes upper GIT bleeding in SS.
Treatment:
patient should not eat for 2—3 hours before bed time
 The head of the bed should be elevated 4 inche.
 Decrease the acidity of stomach by antacids.
 Proton pump inhibitors can be used ---Esmoprazole ,Lansoprazole
 Motility agents ((metoclopramide))before meals are helpful early in
the diagnosis.
Bowel involvement
Diminished peristalsis with stasis and dilatation
Bacterial over growth –H breathtest ,High folate
Malabsorption
Low albumin
Low fat content
Low B6/B12/folate/ vitD
Low D xylose absorption test
Low carotene
 Patient may complain of abdominal distention ,obstructive symptoms ,diarrhea
,vitamin deficiencies.
 Patient with large bowel involvement ---wide mouth diverticular on barium
enema.
 Barium enema is contraindicated in patient with scleroderma.
Treatment:
 Stimulation of gut motility ---metoclopramide ,erythromycin ,motilin agonist ,daily
injection octreotide 50microgm /6hr S/C ,fibers.
 Diarrhea --bacterial overgrowth --metoclopramide ,tetracycline ,ciprofloxacin-10/d
 Avoid loperamide ,paregoric
Smooth muscle atrophy of the bowel wall
Affect small and large intestine
Abnormal motility of the gut

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Symptoms ----
 Combination of constipation and diarrhea
 Recurrent bouts of pseudo-obstruction
 Bowel distention with leakage of air into the intestine—
pneumatosis coli intestinalis
 Bowel rupture
 Lower bowel dys-motility can lead to bacterial overgrowth,
diarrhea ,mal-absorption.
D) CVS:
Symptomatic cardiac disease is relatively rare. The lining
around the heart may become inflamed, a condition called pericarditis. Fluid can
build up around the heart (pericardial effusion) – the presence of this fluid may
herald scleroderma renal crisis. The heart muscle itself may be affected causing a
cardiomyopathy and the conduction system that carries electrical signals through
the heart may become damaged.
 Usually subclinical
 Cardiopulmonary morbidity
 Ischemia ----reperfusion secondary to small arterial disease of myocardium
leads to necrosis and tissue fibrosis.
This leads to:
1. Cardiomyopathy
2. Arrhythmia
3. Heart failure
4. Pericarditis
5. Pericardial effusion
Pericardial effusion—
Detected by ECHO
Large PE associated with poor prognosis
It is usually clinically silent.
E) RENAL:
occurs almost exclusively in patients with diffuse cutaneous systemic sclerosis.
It is characterized by HTN, anemia secondary to destruction of RBC (hemolytic
anemia), and evidence of kidney damage (PROTEINURIA and HIGH creatinine).
Patients at greatest risk for SRC include :
1. Rapid progression of skin involvement
2. Positive for anti-RNA polymerase III antibodies
3. Who have taken moderate or high doses of steroids in the preceding
weeks or months.
This complication is usually seen within the first 4 years of disease onset. It is
almost universally fatal if not treated early and aggressively. The treatment is ACEI
Clinically important kidney disease occur in minority of patients.
SCR develops in 10% of patients.
SCR occurs early in the course of diffuse scleroderma 2—3 years of onset
,more often in the fall and winter months.

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SYMPTOMS:--
Symptoms are HEADACHE ,VISUAL CHANGES AND SEIZURES.
The clinical presentation is typically with the symptoms of malignant
hypertension: Headaches, Hypertensive retinopathy associated with visual
disturbances, Seizures, Heart failure and pulmonary oedema.
Renal failure may present as acute renal crisis , after prolonged HTN ,less
commonly as normotensive renal failure.
SCR is the abrupt onset of HTN ,appearance of flame shaped haemorrhage
,cotton wall exudates , grade III/IV retinopathy –papillodema and rapid
deterioration of renal function over a month.
The hypertension is almost always severe with a diastolic BP over 100
mmHg in 90% of patients.
There is hypertensive retinopathy in about 85% of patients with exudates
and haemorrhages and if severe, papilledema.
If malignant HTN left untreated ,it can lead to renal failure
Some are asymptomatic and normotensive with aprupt rise of creatinine.
There may also be microangiopathic haemolytic anaemia (↓ Hb with
blood film shows schistocytes and helmet cells), thrombocytopenia and
raised renin levels. Renal function is impaired and usually deteriorates.
TREATMENT:
Scleroderma renal crisis is a medical emergency. Aggressive treatment is
required to prevent the occurrence of irreversible vascular injury.
ACE-I is the treatment of choice
First line treatment is a gradual reduction in blood pressure (10-15 mmHg
per day) with an oral ACEIs until the diastolic pressure reaches 85-90
mmHg. Upto to 400mg doses can be given to control BP.
ACEI will improve hypertension and slow further renal impairment.
This approach leads to a response in 90% of patients by reversing the
angiotensin II mediated vasoconstriction.
An abrupt fall in BP should be avoided as it can further diminish renal
perfusion and increase the risk of ATN. Therefore, parenteral
antihypertensive agents (for example, IV nitroprusside or IV labetalol)
should be avoided.
CCBs, usually nifedipine, may be added where there is inadequate
reduction of BP with ACEI alone.
Additional oral hypotensive agents (for example, labetalol) can be used if
required, and if pulmonary oedema is present a nitrate infusion may be
indicated.
High dose of steroids increased the risk of renal failure in SS.
There is anecdotal evidence that IV prostacyclin helps the microvascular
lesion without precipitating hypotension, and this is used in some UK
centres.
LABRATORY ----- Renal crisis is linked with a positive ANA speckled pattern,
anti-RNA polymerase I and II antibodies and absence of anti-centromere
antibodies.

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 Increased RFT & RENIN ,microangiopathic hemolysis ,low platelets .
 Renal biopsy is not necessary in patients presenting with classical features
of renal crisis
 Renal biopsy specimen –intestinal hyperplasia ,vasospasm of cortical
arteries.
F) MUSCULOSKELETAL INVOLVEMENT:
Signs and symptoms related to involvement of the musculoskeletal system are
found in systemic sclerosis. Many patients have joint and/or muscle pain. In
diffuse cutaneous systemic sclerosis, tendon inflammation can result in an audible
sound upon movement of involved structures (most commonly the fingers and
wrists) known as a tendon friction rub. This finding is a
marker of aggressive disease and puts patients at higher risk
of serious organ involvement. Resorption of the most distal
aspects of bones is a result of severe ischemia-osteolysis.
Mild arthralgia
Non erosive arthritis with synovitis
Morning stiffness
Deep tissue fibrosis ((tendon sheaths inflamed))
Areas around the tendons
Active and passive range of joints motions are limited &painful
Tendon friction rub over the wrists ,ankles and knees.
DSS patients develop tendon friction rubs.
Hand deformities and ankylosis are seen
Bone ---resorption of bone---acrosclerosis and osteolysis
Resoprption of ribs ,mandible ,radius ,ulna.
G) MUSCLE:
1. Mild proximal weakness---fiber 2 myopathy
2. Mild elevation of muscle enzymes with waxing & waning of symptoms
3. Inflammatory type of myopathy with CPK increased(( overlap))—polymyositis.
INVESTIGATION:
Let’s look at a typical case of someone presenting with fairly early systemic sclerosis. The
patient would statistically more likely be a female between the ages of 30-50 years old.
She might complain of diffuse joint pain, fatigue and swollen hands and fingers. She might
admit to new acid reflux and also to frequent episodes of her fingers turning colors when
exposed to cold and pain in the fingers when they warm up. This is the Raynaud’s
phenomenon already mentioned.
 Physical Exam:
o Diffusely swollen hands/fingers
o Early skin tightening in most distal

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o aspects of extremities and around face
o Changes in nail fold capillaries
 An important part of the physical exam is nail-fold microscopy (or nail-fold
capillaroscopy). This is accomplished by looking closely with an ophthalmoscope at
the capillaries near the cuticles. The picture on DOWN demonstrates possible
findings.
 Panel a: normal nailfold capillaries
 Panel b: mild abnormalities (dilation of capillary loops)
 Panel c: dilation of capillaries and “dropout”
 Panel d: grossly abnormal
 Nailfold capillaroscopy is very important because many people, especially young
women, experience Raynaud’s, but most of them never go on to develop systemic
sclerosis or any other disease related to the Raynaud’s. This is called primary
Raynaud’s (as opposed to secondary Raynaud’s when it is related to an underlying
condition). Patients with primary Raynaud’s will have normal nailfold capillaries. If
the nailfold capillaries are abnormal, the risk of going on to develop systemic
sclerosis or another connective tissue disease is much greater.

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LABORATORY:
1. ANA:
 Are the most frequently detected
 Not specific for SCL.
 Seen in up to 10% normal people.
 >95% of SCL patients
Anticentromere –
o 20—40% of patients with SCL.
o Associated specifically with CREST ,sever
digital ischemia and ulceration ,digital loss
o Can be found in patient with PBC and sjogrens syndrome.
Antitopoisomerase I (( antiSCL 70 ))
 20---40% of patient with SCL
 Typically have diffuse skin changes ,ILD ,and worse prognosis
 Africans Americans
 Highly specific for SCL.
Anti –RNP I II III (( RNA polymerase ))
Associated with diffuse skin changes ,cardiac ,renal involvement and increased mortality.
Anti U3 RNP ---antifibrillarian ----8% lung disease ,diffuse
Anti U1 RNP ---------------------------5% MCTD
Anti TH/TO ---------------------------- 1—5% limited cutaneous ,lung
2. Baseline kidney and liver function, CBC, ESR and CRP
3. LUNG INVOLVEMENT:
Recommendations for Screening and Detection of
SSc-Associated PAH---
A. Initial SSc Screening Evaluation:
 FT with DLCO (high)
 Transthoracic echocardiogram (TTE) (high)
 NT- Pro BNP (mod)
 DETECT algorithm if DLCO% < 60% and >3 yrs
disease duration (mod)
B. Frequency of Noninvasive Tests
TTE annually as screening (low); if new signs or
symptoms develop (high)
PFT with DLCO annually as screening (low qual); if
new signs or symptoms develop (low)
NT-Pro BNP if new signs of symptoms develop (low)
ECHO OR RIGHT HEART CATHETERIZATION---
Recommendations for Screening and Detection of SSC-Associated PAH
General Evidence-based Guidelines:
1) All patients with SSc should be screened for PAH .
2) All SSc and scleroderma-spectrum patients with a positive non-invasive screen
should be referred for RHC .
3) RHC is mandatory for diagnosis of PAH.

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TREATMENT:
There is no cure for systemic sclerosis. However, there are treatments that ameliorate
symptoms and prolong organ and patient survival. These treatments are instituted on a
case-by-case basis, depending on the specific disease manifestations in an individual
patient. Care of patients with systemic sclerosis requires an understanding of the potential
complications of the disease and close monitoring, so treatment can be started early.
BASICS IN TREATMENT---
 No effective therapy for underlying disease process
 Treatment is targeted to specific organs involved
 Early recognition of internal organ involvement and aggressive treatment improve
quality of life and increases survival time.
Successful management of patients with SSc requires an understanding of the potential
complications of the disease, close monitoring, and early institution of targeted therapies .
Treatment of Raynaud’s Phenomenon:
A cornerstone of management of Raynaud’s is patient education to achieve behavioral
modification. All patients with Raynaud’s should be instructed to maintain a warm core body
temperature and to avoid extreme temperature changes. They also should be counseled to avoid
certain factors that can aggravate Raynaud’s, particularly smoking. Use of certain drugs like
decongestants and repeated trauma should also be avoided.
If pharmacologic intervention is necessary, the first line class of drugs is calcium channel blockers.
This class of drugs is by far the most commonly used in the treatment of Raynaud’s, although their
effectiveness is variable. If calcium channel blockers are ineffective or not tolerated, there are
other classes of drugs frequently used, also with varying effectiveness.
 Behavioral
 Maintain warm core body temperature
 Avoidance of smoking, sympathomimetic drugs (decongestants), and repeated
trauma/vibration of the hands and fingers
 Pharmacologic
 First line: Long-acting calcium channel blockers (amlodipine, nifedipine)
 Selective serotonin reuptake inhibitors (fluoxetine)
 Phosphodiesterase-5 inhibitors (sildenafil)
 Angiotensin II receptor blockers (losartan)
 Topical nitrates
 α 1-adrenergic receptor antagonists (prazosin)
• Raynaud’s
• Pulmonary arterial hypertension
• Scleroderma renal crisis
Vascular
• Interstitial lung disease
• Cutaneous/Musculoskeletal
Immune suppressors/anti-
inflammatories
• Gastroesophageal reflux
• GI dysmotilitySymptomatic

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OCTOPER HOSPITAL
Treatment of Severe Raynaud’s and Digital Ulcers:
Severe, digit-threatening Raynaud’s requires the use of potent vasodilating drugs. Most of these
medications require intravenous or injection administration and carry significant side effects.
They are also quite costly.
 Potent vasodilators
 Intravenous prostaglandin (iloprost, epoprostenol)
 Endothelin antagonist (bosentan)
Treatment of Pulmonary Arterial Hypertension:
cGMP
cAMP
Vasoconstriction and
proliferation
Endothelin receptor A
Exogenous
nitric oxideEndothelin-receptor
antagonists
Endothelin
receptor B
Phosphodiesterase
type 5 inhibitor
Vasodilation
and antiproliferation
Phosphodi
esterase
type 5 Vasodilation
and antiproliferation
Prostacyclin
derivatives
Nitric Oxide
Endothelin-1
Pre-proendothelin
L-arginine
Prostaglandin I2
L-citrulline
Nitric Oxide
Pathway
Endothelin
Pathway
Prostacyclin
Pathway
Endothelial
cells
Proendothelin
Endothelial
cells
Arachidonic
acid
Smooth muscle cells
Prostacyclin (prostaglandin I2)
Smooth muscle cells
Prostacyclins
Epoprostenol, Treprostinil
Iloprost (inhaled)
PDE-5 Inhibitors
Sildenafil, Tadalafil
SGC Stimulator
Riociguat
Endothelin Receptor Antagonists
Bosentan, Ambrisentan ,
Macitentan
Adapted from Humbert M et al. N Engl J Med. 2004;351:1425-1436.
Many of the same vasodilating drugs that are used in severe Raynaud’s are also used to treat pulmonary
arterial hypertension. Typically the prostaglandin analogues are used as first line treatment in PAH and
carry the burden of requiring continuous IV or subcutaneous infusion. An inhaled prostacyclin (iloprost) is
available – this requires administration up to 9 times daily.
 Potent vasodilators
 Parenteral prostaglandins (epoprostenol)
 Inhaled prostacyclin (iloprost)
 Endothelin receptor antagonist (bosentan)
 Phosphodiesterase inhibitors (sildenafil)
Treatment of Scleroderma Renal Crisis
 It is important for you to be familiar with the management of scleroderma renal crisis.
Remember, early recognition is critical. Patients at high risk for SRC require home blood
pressure monitoring. Evaluation of kidney function and red blood count should be done at
any sign concerning for development of SRC. If SRC does develop, an ACE-inhibitor should
be started immediately and titrated up to the maximum dose as tolerated. The ACE-
inhibitor should be continued even if the patient goes on to require dialysis. ACE-inhibitors
have revolutioned care of SRC – what used to be a fatal complication now carries 1- and 5-
year survival rates of >70% and 60%, respectively.

TH
OCTOPER HOSPITAL
 Close Monitoring!
Home blood pressure readings daily
If BP rises, evaluate for evidence of kidney damage/dysfunction (blood in urine and rise in
creatinine) and new anemia
 Treatment
ACE-INHIBITORS (Treat aggressively to maximum dose as tolerated)
Dialysis if necessary (with continued Ace-inhibitor)
Use of Ace-inhibitors has changed what used to be an almost universally fatal complication
of SSc to one with 1-year survival >70%, 5-year survival 60% (and long-term renal survival is
50-80%)
Treatment of Inflammatory Manifestations----
Interstitial lung disease is largely mediated by an intense inflammatory reaction and is
treated with strong immunosuppressive drugs. Typically the initial treatment of ILD is
cyclophosphamide in combination with glucocorticoids. If the lungs improve, then less
potent agents can be substituted (such as azathioprine and mycophenolate mofetil). The
treatment of ILD is suboptimal – some patients do not respond and treatments are
potentially very toxic. Therefore, researchers are actively looking at more effective and less
toxic approaches. Some of the investigational therapies include stem cell transplant and
antibody-based therapies such as imatinib and rituximab.
 Interstitial Lung Disease
 Cyclophosphamide (+/- low-dose glucocorticoids)
 Azathioprine
 Mycophenolate mofetil
 Investigational approaches: hematopoetic stem cell transplant, imatinib,
rituximab, tadalafil
 Cutaneous/Musculoskeletal
 Physical therapy
 Methotrexate
 Azathioprine
 Low-dose glucocorticoids – with caution because of risk of SRC
Monitoring for Complications---
Treatment of patients with systemic sclerosis requires “anticipatory management” (ie close
monitoring for early detection of disease complications). It is reasonable to perform
transthoracic echocardiograms and pulmonary function tests up to once every year in
these patients to screen for pulmonary arterial hypertension, even if they don’t complain
of cardiopulmonary symptoms (as their functional status may be quite compromised).
Likewise, pulmonary function tests in combination with chest CT scan should be done at
regular intervals to assess for the presence of interstitial lung disease. In patients at risk of
scleroderma renal crisis, home blood pressure monitoring is indicated as is regular testing
of urine and blood.
 Consider annual transthoracic echocardiography and pulmonary function tests to
screen for pulmonary arterial hypertension (more frequent screening if symptoms
develop)
 Pulmonary function tests and high resolution chest CT to assess for interstitial lung
disease
 In patients at high risk for scleroderma renal crisis - home blood pressure readings
daily and regular testing of kidney function and urine

TH
OCTOPER HOSPITAL
PROGNOSIS:
The prognosis for patients diagnosed with systemic sclerosis is better now than it was 25
years ago, but the potential for significant morbidity and early mortality is still substantial.
Several factors are associated with a poor prognosis
Highlights ((summary of the talk)):
Systemic sclerosis is a multisystem autoimmune disease characterized by inflammation, disordered
connective tissue metabolism and functional and structural abnormalities in blood vessels, all
contributing to progressive fibrosis of the skin and visceral organs. The primary target organs are
skin, lungs, kidney, and gastrointestinal tract. The symptoms are quite varied but the most
characteristic clinical features are Raynaud’s, skin tightening/fibrosis, interstitial lung disease,
pulmonary arterial hypertension, scleroderma renal crisis, and GI tract dysmotility.
 Systemic sclerosis is a multisystem autoimmune disease characterized by inflammation,
disordered connective tissue metabolism and functional and structural abnormalities in
blood vessels, all contributing to progressive fibrosis of the skin and visceral organs
 Primary target organs: skin, lungs, kidney, GI tract
 Cardinal clinical features: Raynaud’s, skin tightening, interstitial lung disease, pulmonary
arterial hypertension, scleroderma renal crisis, GI tract dysmotility
 Important aspects of management include:
 Close monitoring for complications (including home BP and close monitoring for
lung involvement)
 Calcium channel blockers for Raynaud’s
•dcSSc 40-60% at 10 years
•lcSSc >70% at 10 years
Overall survival:
•Rapidly progressive skin involvement
•Older age at disease onset
•African- or Native-American race
•Severe lung involvement
•Large pericardial effusion
•Proteinuria, hematuria, renal failure
•Anemia
•Elevated ESR
•Abnormal ECG
•Anti-Scl 70 (anti-topoisomerase) antibodies – increased risk of severe
pulmonary fibrosis
•Anti-RNA-polymerase antibodies – increased risk of scleroderma renal crisis
Poor prognosis associated with:

TH
OCTOPER HOSPITAL
 Ace-inhibitors for scleroderma renal crisis
 Vasodilators for pulmonary arterial hypertension
 Immunosuppression for interstitial lung disease

SCLERODERMA DR MAGDI AWAD SASI 2016 LMB

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