Systemic sclerosis

Question 1

Systemic sclerosis

Answer 1

• Scleroderma: thickened hardened skin (may be diffuse or limited)
• Localized (morphoea and linear scleroderma) and systemic scleoderma (limited systemic sclerosis, diffuse systemic sclerosis, systemic sclerosis w/o scleroderma)
• Diffuse scleroderma is the same as systemic sclerosis, except there is skin involvement as well

Question 2

Limited systemic scleroderma 1

Answer 2

• Limited to hands, distal forearms, face, chest (visceral involvement delayed) usually symmetrical
• Assciated w/ pulmonary HTN
• CREST are main defining Sx
• Calcinosis: usually not painless/dangerous
• Raynauds: change in color of skin due to vasospasm (white-> blue-> red)

Question 3

Limited systemic scleroderma 2

Answer 3

• Esophageal dysfunction: dysfunction of the lower esophageal sphincter, causes esophageal reflux
• Sclerodactyly: deformities due to tightening/fibrosis of soft tissues of the feet/hands (contractures, ulcerations, ischemia)
• Telangiectasia: small dilated blood vessels
• More slowly progressing than diffuse, limited is associated w/ anti-centromere

Question 4

Diffuse systemic sclerosis

Answer 4

• Diffuse skin thickening: face, neck, chest, hands, arms, legs
• Significant early extra-cutaneous manifestations
• Major face involvement: mask like facies, thinned and/or retracted lips, decreased oral aperture, tight skin w/ waxy texture
• Stages of skin involvement: edema, induration, atrophy
• Dermis gets very thick w/ collagen, salt and pepper appearance (advanced changes of sclerodactyly)
• Rapidly progressing, associated w/ anti-topoisomerace (SCL70)

Question 5

Systemic sclerosis sine scleroderma

Answer 5

• Systemic sclerosis w/o significant skin involvement
• Extra-cutaneous features: musculoskeletal, GI, pulmonary, CV, renal
• MSK: symmetric polyarticular arthritis, tendon rubs (squeaky tendons, muscle atrophy and/or myositis, associated w/ more severe disease)

Question 6

Systemic sclerosis sine scleroderma: GI involvement

Answer 6

• Entire extent of GI tract affected
• Esophagus: dilation, impaired mobility, lower esophageal sphincter dysfunction, esophageal reflux w/ mucosal ulcerations
• Stomach: delayed gastric emptying, watermelon stomach (gastric antral vascular ectasia)
• Small intestine: atony w/ obstruction, stasis w/ malabsorption
• Large intestine: pseudo-diverticula, infarction

Question 7

Systemic sclerosis sine scleroderma: pathophysiology of GI Sx

Answer 7

• Atrophy of smooth muscle and replacement w/ collagen (fibrosis)
• Atrophy and fibrosis of submucosa and mucosa
• Degenerative and inflammatory changes in blood vessels

Question 8

Systemic sclerosis sine scleroderma: pulmonary involvement

Answer 8

• Pulmonary fibrosis
• Hyperplasia and sclerosis of pulmonary artery-> pulmonary HTN-> heart failure
• Superimposed infection
• Microaspirations (exacerbated by GERD)
• Lung CA

Question 9

Systemic sclerosis sine scleroderma: CV involvement

Answer 9

• Myocardial fibrosis
• Conduction deficits
• Pericarditis
• Pulm HTN-> heart failure

Question 10

Systemic sclerosis sine scleroderma: renal involvement

Answer 10

• Malignant HTN plus renal insufficiency can lead to scleroderma renal crisis
• Precipitated by steroid use, results in intimal hyperplasia and fibrinoid necrosis of medium size renal blood vessels (vascular issue due to fibrosis)
• Rx is ACE inhibitor, since angiotensin/renin is over activated you must block the converting nz for angiotensin (ACE)

Question 11

Localized scleroderma: morphoea

Answer 11

• Spectrum of diseases mainly affecting the skin
• Plaque-like lesion, most common
• Lesions usually oval and small, on 1 area of body
• Early phase of morphoea: erythematous
• Late phase of morphoea: sclerotic, white

Question 12

Localized scleroderma: linear scleroderma

Answer 12

• Most common type in children
• Longitudinal, line-band lesions usually on limbs
• Can lead to joint contractures and muscle atrophy

Question 13

Pathogenesis of systemic sclerosis

Answer 13

• Not understood completely
• Key elements: immune activation, vascular damage, fibrosis
• There is an increased number of activated fibroblasts in affected areas
• There are usually ANAs against topoisomerase (leading to diffuse) or centromeres (leading to limited)
• But these two are mutually exclusive
• Imbalance of cytokines due to/causing inflammation