Systemic Sclerosis, Fibrosis

1. SCLERODERMA

2. Systemic sclerosis is a rare, heterogeneous, slow-
motion disease, with (allegedly) a small window of
opportunity to fundamentally change the course of the
disease.

5.  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

8.  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

10. LOCALIZED FORMS
 Morphea
 Generalized / pansclerotic morphea
 Linear scleroderma - En coup de saber
 Progressive hemifacial atrophy

11. 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

12.  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.

14. Generalized

16. Linear variety

18. 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

19. 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

20.  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%

21. •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 (?)

23. 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

24. 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

31. 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

32. Raynaud’s phenomenon

33. telangiectasia

35. Terminal digit resorption

36. Digital ulcers – evidence of
vascular disease

37. Digital necrosis

38. 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

39. 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.

40. Phases of skin thickening
 Edematous

41. 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

42.  Indurative Phase

44.  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

46. Acrosclerosis (flexion contractures
secondary to skin tightening)
(sclerodactyly)

47. Facial changes
 Pinched nose
(“mauskopf”)
 Pursed lips
 Cannot evert eyelids
 Lip thinning and
retraction
 Immobile facies

49. •Atrophic phase
 Thick dermis reverts to normal or
even becomes thinner (atrophy)

50. Skin involvement
4) ulceration, loss of soft tissue of finger
tip, pigmentation, calcific deposit,
capillary change
5) pathology
- atrophy of dermal appendages
- loss of rete pegs
- compact bundles of collagen

51. Digital pitting scars

52. calcinosis

53. Telangiectasia
 Face / mucous
membrane
 blanched by pressure

54. 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.

55.  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

56. Calcinosis and acrolysis

57. 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

58. 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.

60.  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

62. Diverticula

63.  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

64. 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)

65.  Pulmonary manifestations
 Progressive dyspnea on exertion, limited
effort tolerance, and a nonproductive
cough

66. Interstitial thickening and fibrosis and
continuing evidence of interstitial
inflammation.

67.  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

69. Heart (10%)
1) pericarditis
2) heart failure
3) arrhythmia
4) myocardial fibrosis

70. 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

71. 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

74. 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