Scleroderma
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Transcript of Scleroderma
SCLERODERMA
Systemic sclerosis is a rare, heterogeneous, slow-motion disease, with (allegedly) a small window of opportunity to fundamentally change the course
of the disease.
derived from greek and means hard skin
Affects about 250/million = 7500 Canadians
Affects mainly women in the prime of their life women: men ratio 3-5:1, onset between 30-50 years
Systemic sclerosis (scleroderma)
a multisystem disorder characterized by functional and structural abnormalities of
blood vessels
fibrosis of the skin and internal organs
immune system activation
autoimmunity
Localized scleroderma morphea, linear scleroderma
LOCALIZED FORMS Morphea Generalized / pansclerotic morphea Linear scleroderma - En coup de
saber Progressive hemifacial atrophy
MORPHEA A rare skin condition that causes
reddish or purplish patches on your skin.
Tends to affect only the outermost layers of your skin — the dermis and the fatty tissue just beneath the dermis.
Location – Abdomen, chest and back - % Face, Arms and legs
Signs of morphea - Hardening and thickening of the
skin. Discoloration of the affected skin to
look lighter or darker than the surrounding area.
Oval-shaped patches that may change colors and gradually develop a whitish center.
Linear patches, especially when on arms and legs
Loss of hair and sweat glands in the affected area over time.
Generalized
Linear variety
Epidemiology Prevalence: 19-75 cases per 100,000
Susceptibility: host factor
age - peak occurrence: age 35-65 years
gender - female : male = 7-12 : 1
genetic background
Environmental factors
infection
occupational exposures: silica dust
Pathogenesis Vasculopathy of small artery and capillary
endothelial cell injury adhesion and activation of platelet PDGF, thromboxane A2 release vasoconstriction & growth of endothelial cell and
fibroblast narrowing or obliteration, increased permeability
Fibrosis aberrant regulation of fibroblast cell growth increased production of extracellular matrix
(collagen, fibronectin, and glycosaminoglycan) thickening of the skin & fibrosis of internal
organs
Immunologic mechanism cell mediated immunity
skin: cellular infiltrates in perivascular region and dermis (T cell, Langerhans cell, plasma cell, macrophage)
Humoral immunity hypergammaglobulinemia autoantibody production
antinuclear antibody (+) > 95%
•Environmental factors 1) silica dust 2) organic solvents 3) biogenic amines 4) urea formaldehyde 5) polyvinyl chloride 6) rapeseed oil 7) bleomycin 8) L-tryptophan 9) silicone implant (?)
•Environmental factors 1) silica dust 2) organic solvents 3) biogenic amines 4) urea formaldehyde 5) polyvinyl chloride 6) rapeseed oil 7) bleomycin 8) L-tryptophan 9) silicone implant (?)
Classification of systemic sclerosis
Diffuse cutaneous systemic sclerosis
proximal skin thickening
- distal and proximal extremity and often the trunk
and face
tendency to rapid progression of skin change
rapid onset of disease following Raynaud’s
phenomenon
early appearance of visceral involvement
poor prognosis
Limited cutaneous systemic sclerosis 1) symmetric restricted fibrosis - affecting the distal extremities and face/neck 2) prolonged delay in appearance of distinctive internal manifestation 3) prominence of calcinosis and telangiectasia 4) good prognosis
* CREST syndrome
Limited cutaneous systemic sclerosis 1) symmetric restricted fibrosis - affecting the distal extremities and face/neck 2) prolonged delay in appearance of distinctive internal manifestation 3) prominence of calcinosis and telangiectasia 4) good prognosis
* CREST syndrome
Clinical features Vascular abnormalities Raynaud's phenomenon
cold hands and feet with reversible skin color change (white to blue to red)
induced by cold temperature or emotional stress
initial complaint in 3/4 of patients 90% in patients with skin change (prevalence in the general population: 4-
15%) Digital ischemic injury
Raynaud’s phenomenon
telangiectasia
Terminal digit resorption
Digital ulcers – evidence of vascular disease
Digital necrosis
Skin involvement 1) stage - edematous phase - indurative phase - atrophic phase
2) firm, thickened bound to underlying soft tissue
3) decrease in range of motion, loss of facial expression, inability to open mouth fully
Skin involvement 1) stage - edematous phase - indurative phase - atrophic phase
2) firm, thickened bound to underlying soft tissue
3) decrease in range of motion, loss of facial expression, inability to open mouth fully
Skin thickening of systemic sclerosis begins on the fingers and hands in nearly all cases. The skin initially appears shiny and taut and may be erythematous at early stages.
Phases of skin thickening Edematous
Causes of this swelling
Basically this is water in the tissues = edema
Binding of water to increased extracellular connective tissue matrix
Inflammation Poor lymphatic return Microvascular injury with fluid
extravasation
Indurative Phase
Thick Shiny Taught Tightly adheres to underlying tissue
so cannot be easily picked up Creases disappear May become hyper- or hypo-
pigmented Hair loss Decreased sweating
Acrosclerosis (flexion contractures secondary to skin tightening) (sclerodactyly)
Facial changes
Pinched nose (“mauskopf”)
Pursed lips Cannot evert
eyelids Lip thinning and
retraction Immobile facies
•Atrophic phase
Thick dermis reverts to normal or even becomes thinner (atrophy)
Skin involvement 4) ulceration, loss of soft tissue of finger tip, pigmentation, calcific deposit, capillary change5) pathology - atrophy of dermal appendages - loss of rete pegs - compact bundles of collagen
Skin involvement 4) ulceration, loss of soft tissue of finger tip, pigmentation, calcific deposit, capillary change5) pathology - atrophy of dermal appendages - loss of rete pegs - compact bundles of collagen
Digital pitting scars
calcinosis
Telangiectasia
Face / mucous
membrane
blanched by
pressure
Musculoskeletal Generalized arthralgia and morning
stiffness Erosive arthropathy has been
demonstrated to occur in some series in as many as 29 percent of patients.
An inexorable loss of hand function is the rule as skin thickening worsens and the underlying joints become tethered and restricted in motion.
Insidious muscle weakness, both proximal and distal, occurs in many patients with systemic sclerosis secondary to disuse atrophy
Subcutaneous calcinosis occurs in around 40 percent of patients with long-standing limited scleroderma and less frequently in diffuse disease
Calcinosis and acrolysis
Intestinal involvement 1) esophagus: hypomotility and retrosternal pain,
reflux esophagitis, stricture
2) stomach: delayed emptying
3) small intestine: pseudo-obstruction, paralytic ileus,
malabsorption
4) large intestine: chronic constipation and fecal impaction
diverticula
Intestinal involvement 1) esophagus: hypomotility and retrosternal pain,
reflux esophagitis, stricture
2) stomach: delayed emptying
3) small intestine: pseudo-obstruction, paralytic ileus,
malabsorption
4) large intestine: chronic constipation and fecal impaction
diverticula
Gastrointestinal Disordered peristalsis of the lower two thirds
of the esophagus presents as dysphagia Impaired function of the lower esophageal
sphincter chronic esophageal reflux include erosive
esophagitis with bleeding, Barrett's esophagus, and lower esophageal stricture
Involvement of the stomach occurs in systemic sclerosis and presents clinically as ease of satiety and on occasion as either functional gastric outlet obstruction or acute gastric dilatation.
Small bowel involvement Intermittent bloating with
abdominal cramps, intermittent or chronic diarrhea, and presentations suggestive of intestinal obstruction.
Malabsorption occurs Bacterial overgrowth in areas of
intestinal stasis occurs frequently
Diverticula
Colonic involvement… is present in the majority of patients with systemic sclerosis
is infrequently a prominent cause of clinical symptoms.
and constipation, obstipation, and pseudo-obstruction may occur and are related to abnormal colonic motility
Lungs 1) 2/3 of patients affected
- leading cause of mortality and morbidity in
later stage of systemic sclerosis
2) pathology
- interstitial fibrosis
- intimal thickening of pulmonary arterioles
(pulmonary hypertension)
Lungs 1) 2/3 of patients affected
- leading cause of mortality and morbidity in
later stage of systemic sclerosis
2) pathology
- interstitial fibrosis
- intimal thickening of pulmonary arterioles
(pulmonary hypertension)
Pulmonary manifestations Progressive dyspnea on exertion,
limited effort tolerance, and a nonproductive cough
Interstitial thickening and fibrosis and continuing evidence of interstitial
inflammation.
Pulmonary Hypertension Individuals with limited systemic sclerosis may also develop interstitial disease but are also at risk for progressive pulmonary hypertension in the absence of interstitial change, a complication most typical of long-standing disease
Heart (10%)
1) pericarditis
2) heart failure
3) arrhythmia
4) myocardial fibrosis
Heart (10%)
1) pericarditis
2) heart failure
3) arrhythmia
4) myocardial fibrosis
Kidney 1) diffuse scleroderma in association with rapid
progression of skin involvement
2) pathology
- intimal hyperplasia of the interlobular artery
- fibrinoid necrosis of afferent arterioles
- glomerulosclerosis
3) proteinuria, abnormal sediment, azotemia,
microangiopathic hemolytic anemia (scleroderma renal
crisis), renal failure
Kidney 1) diffuse scleroderma in association with rapid
progression of skin involvement
2) pathology
- intimal hyperplasia of the interlobular artery
- fibrinoid necrosis of afferent arterioles
- glomerulosclerosis
3) proteinuria, abnormal sediment, azotemia,
microangiopathic hemolytic anemia (scleroderma renal
crisis), renal failure
Diagnosis major criteria: proximal scleroderma
minor criteria: sclerodactyly
digital pitting scar or loss of substance from the finger pads
bibasilar pulmonary fibrosis
* one major or 2 or more minor criteria for diagnosis
Prognosis Quite variable and difficult to predict Cumulative survival diffuse limited 5 yr 70% 90% 10 yr 50% 70% Major cause of death
renal involvement cardiac involvement pulmonary involvement