Systemic Sclerosis (Scleroderma) By Dr. Zahoor

Systemic Sclerosis Systemic Sclerosis (Scleroderma) is auto immune or connective tissue disorder Systemic Sclerosis is called connective tissue disease but now word Auto immune Rheumatic disease (ARD) is used. Why ? Because clinical effects of ARD are not limited to connective tissue only

Mixed Connective Tissue Disorder (MCTD) Mixed connective tissue disorders is old term, now we call Auto Immune Rheumatic Diseases This term is used when there is overlap condition, where there are clinical features of SLE (Systemic Lupus Erythematosis), Systemic Sclerosis, Myositis It commonly presents with synovitis and oedema of hands in combination of Raynaud's phenomenon and muscle pain/weakness

We will discuss Systemic Sclerosis or Scleroderma

Systemic Sclerosis Systemic Sclerosis is chronic, multi system disease characterized by fibrosis and vasculopathy of skin and visceral organs

Systemic Sclerosis There are two overlapping forms: 1. Limited cutaneous Systemic Sclerosis (LcSSc) It is limited to the skin of face, hands and feet. Pulmonary hypertension occurs late in disease. It is associated with CREST syndrome. CREST (Calcinosis, Raynaud’s phenomenon, Esophageal dysfunction, Sclerodactyly, Telangiestasias). 2. Diffuse cutaneous Systemic Sclerosis (DcSSc) Affects more skin and there is risk of visceral organ involvement – kidneys, heart, lungs, and GIT

Systemic Sclerosis (SSC) The incidence of SSC is 10/million population per year with 3.1 female to male ratio Peak age of SSC is 30 – 50 years Aetiology Familial cases are reported, genetic factors might be responsible Environmental risk factors - Exposure to silica, dust, vinyl chloride, trichloroethylene - Drugs e.g. Bleomycin

Systemic Sclerosis (Scleroderma) Pathology and Pathogenesis An early lesion is wide spread vascular damage involving small arteries, arterioles and capillaries There is endothelial damage with release of cytokines, Endothelin 1 which causes vasoconstriction Release of interleukin, platelet growth factor increased fibroblast activity resulting in abnormal growth of connective tissue

Systemic Sclerosis (Scleroderma) Pathology and Pathogenesis (cont) This causes vascular damage and fibrosis Fibrosis occurs in skin, GIT and other internal organs Damage to small blood vessels produces ischemia

Systemic Sclerosis (Scleroderma) Clinical Features - Raynaud's Phenomenon – seen in almost 100% of cases and can present before onset of disease by many years Limited Cutaneous Scleroderma (LcSSc) - 70% of the cases This usually starts with Raynaud’s phenomenon many years before Skin involvement is limited to hands, forearm, face, and feet Skin is tight over the fingers and often produces flexion deformities of the fingers

Systemic Sclerosis – Hands showing tight shiny skin, flexion contractures of the fingers (sclerodactyly)

Scleroderma: Raynaud's Phenomenon, Cyanosis of the Hands

Calcinosis in long standing systemic sclerosis. 

Systemic Sclerosis (Scleroderma) Limited Cutaneous Scleroderma (LcSSc) (cont) Involvement of skin of face produces “beak like nose” and small mouth (microstomia) Painful digital ulcers and telangiectasia are seen Digital ischemia may lead to gangrene GIT involvement is common Pulmonary hypertension develops in 21% of people Pulmonary interstial disease also occurs

Typical facial appearance in CREST syndrome

Facial appearance in Systemic Sclerosis - drawn pursed lips, shiny skin over the cheeks and forehead

Systemic Sclerosis (Scleroderma) Diffuse cutaneous Systemic Sclerosis (DcSSc) – 30% of cases Raynaud's phenomenon Diffused swelling and stiffness of fingers is rapidly followed by more extensive skin thickening which can involve most of the body Later, skin becomes atrophic Other organs are involved with general symptoms of lethargy, anorexia and weight loss

Systemic Sclerosis (Scleroderma) Diffuse cutaneous Systemic Sclerosis (cont) GIT symptoms - Heart burn, reflux, or dysphagie due to oesophageal involvement is almost present - Malabsorption from bacterial over growth due to dilatation and atony of small bowel Pseudo obstruction is known complication - Rarely dilatation and atony of colon - Anal incontinence occurs in many patients

Systemic Sclerosis (Scleroderma) Renal Involvement May be acute or chronic Acute hypertensive renal crisis used to be common cause of death, but ACE inhibitors and Dialysis and Renal transplantation has changed this

Systemic Sclerosis (Scleroderma) Lung involvement Lung fibrosis Pulmonary hypertension Myocardial involvement Myocardial fibrosis occurs and causes arrhythmias, conduction defects, pericarditis (occasionally)

Systemic Sclerosis (Scleroderma) Clinical Features

Systemic Sclerosis (Scleroderma) Investigation Full blood count - Normocytic, Normochromic anemia - Microangiopathic haemolytic anemia in some people Urea and electrolyte rise in acute kidney injury - Urine microscopy, proteinurea, urine/creatinine ratio should be measured

Systemic Sclerosis (Scleroderma) Investigations Antibodies a- Anti centromere anti bodies (ACAs) occur in 80% of cases in LcSSc b- Anti topoisomerase-1 (called Anti-ScL-70) in 30% of cases in DcSSc and Anti RNA Polymerase is associated with pulmonary fibrosis c- ANA is positive in 95% d- Rheumatoid factor is positive in 30%

Systemic Sclerosis (Scleroderma) Imaging CXR – to see cardiac size and lung disease High resolution CT – to demonstrate fibrotic lung involvement X-ray hands – look for deposits of calcium around fingers, in severe cases erosion and absorption of tufts of distal phalanges Barium swallow - impaired oesophageal motility - upper GI endoscopy

Systemic Sclerosis (Scleroderma) Treatment Currently there is no cure Treatment should be symptametic – organ based Corticosteroids and Immuno suppressants are rarely used except SSC related pulmonary fibrosis Counseling and family support are essential

Systemic Sclerosis (Scleroderma) Treatment (cont) Regular exercises and skin lubricants may limit contractures Raynaud’s – oral vasodilators (calcium channel blockers, ACE inhibitors) Esophageal symptoms are improved by proton pump inhibitors

Systemic Sclerosis (Scleroderma) Treatment (cont) Malabsorption symptoms require nutritional supplements and anti biotic to treat small intestinal bacterial over growth Renal involvement – control of hypertension, first drug of choice is ACE inhibitors Pulmonary hypertension is treated with oral vasodilator, oxygen, and warfarin

Systemic Sclerosis (Scleroderma) Treatment (cont) Pulmonary fibrosis is currently treated with Immuno suppression, cyclophosphamide or Azathioprine combined with low dose oral predinisolone Prognosis – Patient with limited cutaneous scleroderma have good prognosis 70% survive for 10 years . Patient with diffuse cutaneous scleroderma have 10 year survival of 55%. Death most often from pulmonary, heart or kidney involvement.

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