Scleroderma Flashcards
systemic sclerosis (scleroderma) - defined
*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
systemic sclerosis (scleroderma) - epidemiology
*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)
classification of scleroderma - systemic vs. localized
- systemic sclerosis:
-differentiated by degree of skin involvement (diffuse cutaneous, limited cutaneous, sine scleroderma) - localized = no internal organ involvement
-morphea
-linear scleroderma
classifications of systemic sclerosis - LIMITED cutaneous
*sclerodactyly
*skin affected: distal to elbows & knees, plus face
*previously called CREST syndrome:
-Calcinosis
-Raynaud’s phenomenon
-Esophageal dysfunction
-Sclerodactyly
-Telangiectasias
classifications of systemic sclerosis - DIFFUSE cutaneous
*involves all that limited does PLUS: face, chest, abdomen, proximal skin
*characterized by: widespread skin involvement, rapid progression, early visceral involvement
natural history of skin disease in systemic sclerosis (scleroderma)
*progression from inflammatory, puffy phase → fibrosis → atrophy, softening
*present in > 95% of pts
*no good treatment
skin manifestations of systemic sclerosis (scleroderma)
*sclerodactyly (induration of the fingers and toes)
*salt and pepper skin
*“bird-like” facies
Raynaud’s phenomenon in systemic sclerosis (scleroderma)
*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
sequela of Raynaud’s phenomenon
*digital ulcerations
*digital pits
*ischemia: gangrene, loss of digits, loss of bone
*vascular abnormalities: loss of collateral circulation, caution with A-lines
treatment of Raynaud’s phenomenon - lifestyle modifications
- protection = first line: GLOVES, CORE WARMTH
- avoidance of cold: may need to change jobs or duties
treatment of Raynaud’s phenomenon - medications
*dihydropyridine calcium channel blockers: amlodipine, (dilate smooth muscle)
*topical nitrates (apply to the web spaces)
*phosphodiesterase inhibitors (viagra)
telangiectasias & calcinosis in systemic sclerosis (scleroderma)
*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
systemic sclerosis (scleroderma) - GI involvement
*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
systemic sclerosis (scleroderma) - pulmonary involvement
*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
treatment of interstitial lung disease in pts with systemic sclerosis (scleroderma)
*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
treatment of pulmonary artery hypertension in pts with systemic sclerosis (scleroderma)
*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
systemic sclerosis (scleroderma) - cardiac involvement
*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
scleroderma renal crisis - overview
*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
scleroderma renal crisis - clinical symptoms
*new onset hypertension
*renal insufficiency/failure → proteinuria
*microangiopathic anemia
*thrombocytopenia
scleroderma renal crisis - treatment
*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
systemic sclerosis (scleroderma) - musculoskeletal involvement
*tendon friction rubs
*joint contractures
*arthralgias
*arthritis
*myopathy
systemic sclerosis (scleroderma) - lab findings (overview)
*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
limited cutaneous systemic sclerosis - summary
* 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)
diffuse cutaneous systemic sclerosis - summary
*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
localized scleroderma
*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
mimics of systemic sclerosis (scleroderma)
*eosinophilic fasciitis
*nephrogenic systemic fibrosis
*graft vs host disease
*environmental exposure
*radiation exposure
*scleredema
*scleromyxedema
mixed connective tissue disease - defined
*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
antibodies associated with diffuse cutaneous systemic sclerosis
- anti-Scl-70 (aka anti-topoisomerase I)
- anti-RNA polymerase III
antibody associated with limited cutaneous systemic sclerosis
*anti-centromere
limited cutaneous systemic sclerosis - CREST symptoms
*calcinosis
*Raynaud’s phenomenon
*esophageal dysfunction
*sclerodactyly
*telangiectasias
