Scleroderma

Question 1

systemic sclerosis (scleroderma) - defined

Answer 1

*characterized by abnormal collagen deposition
*involves almost all organ systems
*tissue fibrosis
*microvascular changes (vasculopathy)
*classically, fibrosis of the skin but fibrosis can occur in any tissue
*dysregulation of fibroblasts and endothelial cells

Question 2

systemic sclerosis (scleroderma) - epidemiology

Answer 2

*female > male (10:1)
*equal prevalence across races, worse prognosis in African Americans
*onset: 30-50 yo
*less common in children and elderly
*possible environmental links (vinyl chloride, silica)

Question 3

classification of scleroderma - systemic vs. localized

Answer 3

1. systemic sclerosis:
   -differentiated by degree of skin involvement (diffuse cutaneous, limited cutaneous, sine scleroderma)
2. localized = no internal organ involvement
   -morphea
   -linear scleroderma

Question 4

classifications of systemic sclerosis - LIMITED cutaneous

Answer 4

*sclerodactyly
*skin affected: distal to elbows & knees, plus face
*previously called CREST syndrome:
-Calcinosis
-Raynaud’s phenomenon
-Esophageal dysfunction
-Sclerodactyly
-Telangiectasias

Question 5

classifications of systemic sclerosis - DIFFUSE cutaneous

Answer 5

*involves all that limited does PLUS: face, chest, abdomen, proximal skin
*characterized by: widespread skin involvement, rapid progression, early visceral involvement

Question 6

natural history of skin disease in systemic sclerosis (scleroderma)

Answer 6

*progression from inflammatory, puffy phase → fibrosis → atrophy, softening
*present in > 95% of pts
*no good treatment

Question 7

skin manifestations of systemic sclerosis (scleroderma)

Answer 7

*sclerodactyly (induration of the fingers and toes)
*salt and pepper skin
*“bird-like” facies

Question 8

Raynaud’s phenomenon in systemic sclerosis (scleroderma)

Answer 8

*vasospasm of small arteries in fingers/toes due to cold temperatures
*secondary, not primary
*more severe than in lupus or other autoimmune disease
*present in > 95%
*seen in both limited and diffuse cutaneous pts
1. limited cutaneous pts: onset is many years before other visceral involvement (10-20 years)
2. diffuse cutaneous pts: onset is close to time of onset of visceral disease

Question 9

sequela of Raynaud’s phenomenon

Answer 9

*digital ulcerations
*digital pits
*ischemia: gangrene, loss of digits, loss of bone
*vascular abnormalities: loss of collateral circulation, caution with A-lines

Question 10

treatment of Raynaud’s phenomenon - lifestyle modifications

Answer 10

1. protection = first line: GLOVES, CORE WARMTH
2. avoidance of cold: may need to change jobs or duties

Question 11

treatment of Raynaud’s phenomenon - medications

Answer 11

*dihydropyridine calcium channel blockers: amlodipine, (dilate smooth muscle)
*topical nitrates (apply to the web spaces)
*phosphodiesterase inhibitors (viagra)

Question 12

telangiectasias & calcinosis in systemic sclerosis (scleroderma)

Answer 12

*telangiectasias: a vascular lesion formed by dilation of a group of small blood vessels, commonly on the face, fingers, hands, mouth
*calcinosis: deposition of calcium

Question 13

systemic sclerosis (scleroderma) - GI involvement

Answer 13

*present in 75% of pts
*esophageal involvement most common: dysmotility of lower esophageal sphincter → hypotonia, dysphagia, GERD, Barrett’s metaplasia
*other manifestations include:
-primary biliary cirrhosis
-stomach involvement: GAVE, watermelon stomach
-small bowel bacterial overgrowth

Question 14

systemic sclerosis (scleroderma) - pulmonary involvement

Answer 14

*present in about 40% of pts
*leading cause of death in pts with scleroderma
1. diffuse SSc = interstitial lung disease (NSIP pattern)
2. limited SSc = pulmonary arterial hypertension
*aspiration pneumonia

Question 15

treatment of interstitial lung disease in pts with systemic sclerosis (scleroderma)

Answer 15

*meds: mycophenolate, cyclophosphamide, tocilizumab, anti-fibrotics
*lung transplant (low transplantation rate secondary to GERD, concern for higher failure rate)

recall - interstitial lung disease is more common in diffuse scleroderma pts

Question 16

treatment of pulmonary artery hypertension in pts with systemic sclerosis (scleroderma)

Answer 16

*primary vasculopathy
*monitor PFTs: looking for drop in DLCO, periodic echos
*treat with standard PAH meds

recall - pulmonary artery hypertension is more common in limited scleroderma pts

Question 17

systemic sclerosis (scleroderma) - cardiac involvement

Answer 17

*under-recognized
*conduction defects
*left or right ventricular dysfunction
*pericardial:
-pericarditis is rare
-pericardial effusion: can be large; exudative; risk of development of renal disease/crisis

Question 18

scleroderma renal crisis - overview

Answer 18

*this is an EMERGENCY!! (previously, was the greatest cause of mortality in pts with scleroderma)
*associated with diffuse scleroderma (15% of diffuse pts), usually in first 3 years
*associated factors:
-early diffuse disease
-RNA polymerase III antibody positive
-prednisone use > 20 mg is a risk factor

Question 19

scleroderma renal crisis - clinical symptoms

Answer 19

*new onset hypertension
*renal insufficiency/failure → proteinuria
*microangiopathic anemia
*thrombocytopenia

Question 20

scleroderma renal crisis - treatment

Answer 20

*ACE inhibitor
*improved 1 year survival rate from 10% to over 80%
*never stop the ACE inhibitor: even if renal function worsens, even if pregnant

Question 21

systemic sclerosis (scleroderma) - musculoskeletal involvement

Answer 21

*tendon friction rubs
*joint contractures
*arthralgias
*arthritis
*myopathy

Question 22

systemic sclerosis (scleroderma) - lab findings (overview)

Answer 22

*positive ANA
*anti-centromere [limited]
*Scl-70 (anti-topoisomerase) [diffuse]
*RNA polymerase III [diffuse; increased risk of scleroderma renal crisis]
*again, labs only support a clinical diagnosis

Question 23

limited cutaneous systemic sclerosis - summary

Answer 23

* CREST syndrome (calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, telangiectasias)
*anti-centromere positive
*skin involvement distal to elbows and knees
*Raynaud’s phenomenon precedes symptoms for years
*higher incidence of PAH (pulmonary arterial hypertension)

Question 24

diffuse cutaneous systemic sclerosis - summary

Answer 24

*widespread skin involvement, rapid progression, early visceral involvement
*anti-Scl-70 positive
*anti-RNA polymerase III
*skin involvement is diffuse
*Raynaud’s phenomenon starts around time of disease
*higher incidence of ILD (interstitial lung disease)
*at risk for SCLERODERMA RENAL CRISIS

Question 25

localized scleroderma

Answer 25

*no organ involvement
*varied skin involvement:
1. circumscribed plaques (classically called morphea)
2. linear (termed linear scleroderma)
3. diffuse (termed diffuse morphea)
*positive ANA, positive RD
*pathology looks like scleroderma

Question 26

mimics of systemic sclerosis (scleroderma)

Answer 26

*eosinophilic fasciitis
*nephrogenic systemic fibrosis
*graft vs host disease
*environmental exposure
*radiation exposure
*scleredema
*scleromyxedema

Question 27

mixed connective tissue disease - defined

Answer 27

*features of SLE, scleroderma, and polymyositis/dermatomyositis (seldom present all at once; may take years to see enough overlap)
*high titer ANA
*positive anti-RNP antibodies
*common features:
-arthritis
-Raynaud’s phenomenon
-inflammatory muscle disease
-sclerodactyly

Question 28

antibodies associated with diffuse cutaneous systemic sclerosis

Answer 28

1. anti-Scl-70 (aka anti-topoisomerase I)
2. anti-RNA polymerase III

Question 29

antibody associated with limited cutaneous systemic sclerosis

Answer 29

*anti-centromere

Question 30

limited cutaneous systemic sclerosis - CREST symptoms

Answer 30

*calcinosis
*Raynaud’s phenomenon
*esophageal dysfunction
*sclerodactyly
*telangiectasias