1
Fifth stage
Medicine
Lec-9
د.فاخر
17/4/2016
Systemic sclerosis
Definition:
Systemic sclerosis (previously called 'scleroderma') is a generalized disorder of connective
tissue affecting the skin, internal organs and vasculature. The clinical hallmark is the presence
of sclerodactyly in combination with Raynaud's phenomenon or digital ischemia. The peak
age of onset is in the fourth and fifth decades, and overall prevalence is 10-20 per 100 000
with a 4:1 female: male ratio
Etiological factors:
Environmental factors:-
increased frequency in coal & gold minors.
induced scleroderma like syndrome ; exposure to polyvinyl chloride, bleomycine therapy &
silicone breast implants.
scleroderma like lesions in GVHD.
Genetic factors:
.High risk in 1
st
degree relative.
Pathology:
Early in the disease there is skin infiltration by T lymphocytes and abnormal fibroblast
activation that leads to increased production of extracellular matrix in the dermis, primarily
type I collagen. This results in symmetrical thickening, tightening and induration of the skin
(sclerodactyly). There is arteriolar narrowing due to intimal proliferation and vessel wall
inflammation. Endothelial injury causes release of vasoconstrictors and platelet .activation,
resulting in ischemia
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The initial phase of skin disease is characterised by non-pitting oedema of the fingers and
flexor tendon sheaths. Subsequently, the skin becomes shiny and taut, and distal skin creases
disappear. There is usually erythema and tortuous dilatation of capillary loops in the nail-fold
bed, readily visible with an ophthalmoscope set to +20. The face and neck are usually involved
next, with thinning of the lips and radial furrowing.
Skin involvement restricted to sites distal to the elbow or knee (apart from the face) is
classified as 'limited cutaneous disease' or CREST syndrome … Involvement proximal to the
knee and elbow and on the trunk is classified as 'diffuse cutaneous disease'. fingertips.
Scleroderma:
Head and Neck Manifestations
o tight skin, thin lips, vertical perioral furrows
dermal and subcutaneous inflammatory process
edema preceeds epidermal atrophy, loss of appendages
o decreased mouth opening
o Peaked nose
o Tight neck bands
Facial changes: marked telangiectasia
Raynaud’s phenomenon, blanching of hands
Acrosclerosis
calcinosis cutis, fingers
calcinosis and acrolysis
esophageal dysmotility , sclerodactyly
Musculoskeletal features:
Arthralgia, morning stiffness and flexor tenosynovitis are common. Restricted hand function is
due to skin rather than joint disease and erosive arthropathy is uncommon. Muscle weakness
and wasting are usually due to myositis.
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Gastrointestinal features:
Gut involvement is common. Smooth muscle atrophy and fibrosis in the lower two-thirds of
the oesophagus lead to acid reflux with erosive oesophagitis. Since this may progress to
further fibrosis, adequate treatment of reflux (usually with proton pump inhibitors) is
important. Dysphagia and odynophagia (painful dysphagia) may also occur
Cardiorespiratory features:
Pulmonary involvement is a major cause of morbidity and mortality. Fibrosing alveolitis mainly
affects patients with diffuse disease, particularly those with antibodies to topoisomerase 1.
Pulmonary hypertension is a complication of long-standing disease and is six times more
prevalent in limited than in diffuse disease.
Renal features:
One of the main causes of death is hypertensive renal crisis characterized by rapidly
developing malignant hypertension and renal failure. Treatment is by angiotensin-converting
enzyme (ACE) inhibition even if renal impairment is present. Hypertensive renal crisis is much
more likely to occur in patients with diffuse rather than limited disease
Laboratory findings:
Raised inflammatory markers.
Anemia:
o of chronic illness.
o Microangiopathic hemolytic anemia (hemolysis is caused by factors in the small
blood vessels) .
o malabsorption.
Complication related e.g. renal failure findings and restrictive lung function tests.
Autoantibodies
o Anticentromere Abs:40-80% of cases with limited SSc or CREST. Rare (2-5%) in
diffuse SSc & in other connective tissue disorders.
o Antitopoisomerase 1 Abs: about 40% of cases of diffuse SSc specially with visceral
involvement. Rare in other disorders.
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o Antinucleolar Abs :near 20-30% of SSc. High speceficity.
o ANA in up to 90% of patients (poor specificity) .
Prognosis:
5-years survival is about 70%.
Bad prognostic features include:
o -diffuse cutaneous form.
o -onset at an older age.
o -male gender.
o -renal involvement.
o -pulmonary hypertension.
Management:
Five-year survival is approximately 70%. Risk factors at presentation that associate with a
poor prognosis include older age, diffuse skin disease, proteinuria, high ESR, a low gas
transfer factor for carbon monoxide (TLCO) and pulmonary hypertension. Self-
management to maintain core body temperature and avoid peripheral cold exposure is
important. Infection of ulcerated skin should be treated with prompt antibiotic therapy.
Antibiotics penetrate poorly into the skin lesions of systemic sclerosis and therefore
need to be given at higher dose for longer periods (e.g. flucloxacillin 500 mg 6-hourly for
14 days).
Calcium antagonists (e.g. nifedipine, amlodipine) or angiotensin II receptor antagonists
(e.g. valsartan) may be effective for Raynaud's symptoms. For severe digital ischaemia,
intermittent infusions of epoprostenol may be helpful. Corticosteroids and cytotoxic
drugs are indicated in patients with myositis or alveolitis. No agent has been shown to
arrest or improve skin changes