Scleroderma lecture
Terms
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- scleroderma
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a disease manifested as inappropriate scar tissue formation (fibrosis) thorughout the entire body, including skin, arteries, kidneys, GI, lungs, and heart--significant organ dysfunction and characteristic skin changes
sclero = hard; derma = skin - epidemiology
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prevalence from 19/100,000 to 75/100,000
male to female from 1:7 to 1:12 - classification
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1. localized scleroderma
2. limited scleroderma (CREST)
3. diffuse systemic sclerosis - localized scleroderma
- morphea and linear scleroderma
- limted scleroderma
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C= calcinosis
R= raynaud's phenomenon
E=esophageal dysmotility
S= sclerodactyly
T= telangectasias
-skin tightening of hands, distal forearm, face, and feet - diffuse systemic sclerosis
- skin tightening of arm, forearm, hands, feet, and trunk
- mimic scleroderma
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Eosinophilic fascitis
Eosinophilic myalgia syndrome
Scleredema skin tightening (seen in Diabetes)--differentiated by deep skin and fascia biopsy - pathology
- immune system dysfunction (T cells, cytokines) may either injure or stimulate the endothelium or the fibroblasts; inappropriate fibroblast activation with collagen production and deposition which disrupts normal organ architecture and function
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Clinical manifestations:
Raynaud's phenomenon -
change in color of peripheral tissues due to stress induced vasospasm from cold temps (or emotional stress)
white to blue to red
white: blanching caused by vasospasm
blue: cyanosis- RBC deoxygenation
red: vasodilation and new oxygenated RBC's - Persistent or recurrent ischemia
- result in digital pitting ulcers, loss of digital pads (known as sclerodactyly), and gangrene and autoamputation; >90% of scleroderma patients have Raynaud's phenomenon
- stages of skin involvement
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earliest: edematous skin
fibrotic stage: thick hard skin
atrophic: skin is tight
-hypopigmentation, hyperpigmentation, subcutaneous calcinosis - extra-cutaneous involvement
- GI, Renal, pulmonary, cardiac, musculoskeletal
- GI
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entire tract potentially affected
-mouth: decreased oral aperature and purse string mouth
-esophagus: decreased LES tone leads to reflux esophagitis and stricture formation or Barrett's esophagus (premalignant); esophageal dysmotility (decreased peristalsis) of lower 1/3 of esophagus (smooth muscle portion) - GI ctd
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LI: thinning of muscular walls causes wide mouth diverticulum
liver: primary biliary cirhosis is an autoimmune liver disease associtated with limited PSS - Renal
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60-80% evidence of kidney involvement
50% have renal dysfnction such as mild proteuria and mild elevation of Cr and/or hypertension
-scleroderma renal crisis is a severe and life threatenting disease that occurs in 10-15% of patients and is manifested as accelerated hypertension and rapidly progressive renal failure - renal ctd
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worse prognosis if:
male, old, Cr> 3 mg/dl, new anemia, RNA - pulmonary
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in 70% of pts;
1. interstitial lung disease (fibrosing alveolitis or pulmonary fibrosis) - most common symptom is dyspnea
2. pulmonary vascular disease later leading to pulmonary hypertension- as many as 1/3 of patients are asymptomatic, but dyspnea is seen commonly - cardiac
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pericarditis and pericardial effusion in 40% of patients
-fibrosis can develop in myocardium (band necrosis), which contracts and disrupts conduction system
-conduction system abnormalities cause dysrrhymias and may even cause ventricular arrhythmias and sudden death - musculo
- arthralgia, mild arthritis (rarely destructive), tendon friction ribs, myositis, DIP tuft absorption
- lab findings
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antinuclear antibodies; anticentromere antibodies in 30-50% of pts with limited variant
antitopoisomerase 1 Ab (SCL 70) in 30-40% of pts with diffuse disease - radiographic findings
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GI:abnormal esophageal motility on barium swallow; stricture on barium swallow, wide mouth diverticulum
chest: basal reticulo nodular pattern and pulmonary reticular fibrosis on chest xray; HRCT with ground glass appearance and reticular pattern--active inflammation (alveolitis) or fibrosis - PET results
- restrictive lung disease with reduced DLCO
- BAL
- inflammatory cells- lymphocytes early on, neutrophils when 50% of lung affected
- nail fold capillary microscopy
- loss of capillary loops with dilation of both venular and arteriolar links
- treatment and management
- don't know what cuases it, can't treat it
- treatment of raynaud's
- avoid cold, gloves; topical vasodilators (nitroglycerine), oral vasodilators (angiotensin receptor blockers and calcium channel blockers), and parenteral vasodilators: iloprost if severe; finally, surgical digital sympathectomy
- D-penicillamine
- affects both collagen biosynthesis and immune system; dose ranges from 125 mg every other day to 1500 mg/day
- minocycline
- 11 pts used low dose and 4 had complete resolution
- GI treatment
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proton pump inhibitors and H2 blockers for GERD
esophageal dilattation of strictures
antibiotics
dysmotility treated with metoclopramide and or erythromycin - renal treatment
- ACE inhibitors- 60% 5 yr survival
- pulmonary treatment
- corticosteroids for interstitial lung disease; steroids have also caused renal crisis, so best when used in combo with cyclophosphamide, both IV and oral (ocassionally substitute azathioprine)
- pulmonary hypertension
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Epoprostenol (Iloprost)--prostacyclin analog delivered as continuous infusion via indwelling right atrial catheter and pump
-iloprost inhalation therapy
-bosentan (tracleer)--nonselevtive endothelin receptor antagonist appears to be safe and effective; viagra?! - investigational
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stem cell transplant (41 pts showed improvement, but 27% mortality
solid organ transplant: lung and heart transplant if severe enough