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