What is Scleroderma?
Systemic Sclerosis
A systemic autoimmune disease that is mediated by vascular damage and fibrosis within the skin and visceral organs. The term scleroderma includes localized skin fibrosis (previously termed morphoea) and generalized forms with inflammatory, vascular and fibrotic pathology
Which sex is systemic sclerosis more common in?
Women - 4 times more likely
What are the 2 main forms of systemic sclerosis?
- Limited cutaneous SS
- Diffuse cutaneous SS
What age does systemic sclerosis most commonly present/
30-50
What vascular changes occur in Scleroderma?
- Widespread vascular damage of small arteries, arterioles and capillaries
- Widespread obliterative arterial lesions and subsequent chronic ischaemia
What are fibrotic features of the pathophysiology of Scleroderma?
Increased collagen, fibronectin and glycosaminoglycan synthesis - fibrosis in lower dermis of skin as well as internal organs
Thought to be caused by antibodies to platelet derived growth factor
What are the features of limited cuatneous systemic sclerosis?
Skin involvement limited to face, hands and feet
- Flexion deformities
- Beak-like nose
- Small mouth (microstomia)
- CREST syndrome
- Pulmonary hypertension
What is CREST syndrome?
- Calcinosis
- Raynaud’s Phenomenon
- Esophageal and gut dysmotility
- Sclerodactyly
- Telangiectasia
What is calcinosis?
Calcinosis refers to the formation or deposition of calcium in soft tissue. Calcinosis cutis more specifically refers to calcium deposits in the skin. The type of calcinosis that occurs in scleroderma is dystrophic calcinosis
What is the mechanism of calcinosis seen in scleroderma?
Dystrophic calcinosis - occurs when crystals of calcium phosphate or hydroxyapatite are deposited in the skin secondary to inflammation, tissue damage and degeneration. Proposed mechanisms include:
- High local levels of alkaline phosphatase break down a pyrophosphate that normally inhibits calcification
- Tissue breakdown may lead to denatured proteins that bind to phosphate. These phosphate–protein compounds may react with calcium and thus provide a nidus for calcification
What is the following?
Calcinosis
What is telangiectasia?
Permanent dilatation of superficial peripheral vessels resulting in blanching red lesions on the skin. Telangiectasia may present as a fine red line or a punctum (dot) with radiating lines
What is the following?
Telangiectasia
What is sclerodactyly?
Thickening and tightening of the skin covering the digits.
What is the following?
Sclerodactyly
What is thought to be the mechanism behind sclerodactyly?
T cells infiltrate the skin and set in motion a cascade of events including abnormal fibroblast and growth factor stimulation. This in turn leads to increased production of extracellular matrix, fibrillin and type 1 collagen and other factors. Ultimately this results in fibrosis and thickening of the skin.
What are features of Diffuse cutaneous systemic sclerosis?
- Oedematous +/- raynauds
- Whole skin involvement
- Dysphagia, heartburn or reflux
- Renal symptoms
- Pulmonary fibrosis and PHTN
- Arrhythmias - Myocardial fibrosis
What is raynaud’s phenomenon?
Raynaud’s syndrome/phenomenon occurs in the digits from various stimuli, resulting in peripheral hypoperfusion followed by hyperaemia.
What are the 3 stages of Raynaud’s phenomenon?
Episodes are often painful
- White – blanching associated with vasoconstriction of the blood vessels
- Blue – cyanosis
- Red – when blood flow is restored and hyperaemia results.
What is the mechanism behind raynauds phenomenon in scleroderma?
Occurs due to an exaggerated vasoconstrictive response causing transient cessation of blood flow to the digits which is thought to be multifactorial.
In scleroderma, abnormal proliferation of intimal cells results in endothelial cell damage. Abnormal endothelial cells then exacerbate vasospasm by:
- Perturbing smooth muscle cells, causing them to proliferate and contract
- Enhancing pro-coagulant activity and inhibitors of fibrinolysis -> microthrombi
- Promoting inflammation through release of adhesion factors.
- Raised levels of angiotensin II – a vasoconstrictor
- Lack of compensatory angiogenesis to meet the demands of proliferated intima – leading to ischaemia.
In terms of cutaneous distribution, how is diffuse cutaneous scleroderma distributed?
More widespread skin involvement proximal to the elbows
In terms of distribution, how is local cutaneous Scleroderma distributed on the skin?
Distal to the Elbows
How would you investigate someone for suspected scleroderma?
- Bloods - U+E’s, FBC, Autoantibodies
- Urinalysis
- CXR
- Barium Swallow
Why would you do FBC and U+E’s for someone with suspected Scleroderma?
Check for anaemia and AKI
-
Rheumatoid Arthritis51
-
Osteomalacia, Rickets, Osteogenesis Imperfecta and Pagets Disease35
-
Juvenile Idiopathic Arthritis24
-
Seronegative Arthropathies28
-
Polmyalgia Rheumatica and GCA15
-
Crystal Disease27
-
Immunological Testing0
-
SLE50
-
GCA11
-
Scleroderma/Systemic Sclerosis37
-
Sjogren's Syndrome20
-
Polymyositis/Dermatomyositis27
-
Granulomatosis with Polyangitis (Wegner's Granulomatosis)13
-
Microscopic Polyangitis5
-
Eosinophilic granulomatosis with polyangitis (EGPA)4
-
Fibromyalgia3
-
Polyarteritis Nodosa0
-
Clinical Signs/Symptoms - Systemic Disease0
-
Vasculitis26
-
investigations and Management30
