SCLERODERMA Flashcards
DEFINITION
Autoimmune disorder characterized by 3 main manifestations:
1. Sclerosis of skin and visceral organs causing the hardening of the involved tissues
2. Microcirculation vasculopathy
3. Small arteries hypertrophy
EPIDEMIOLOGY
o Prevalence- 40-400/1.000.000
o Incidence- 10-20/1.000.000
o Sex- F/M- 3:1 (up to 7:1 in younger age)
o Age- at onset 45-65 years (35-50 if pre-clinical phase is considered)
o Classically presents in middle‐aged females (30‐60 years)- older than those seen in lupus or Sjogren.
PATHOGENESIS
This is an autoimmune disease but is not based on inflammation (like other the connective tissue disease that we saw), it is more associated with a fibrotic change and endothelial damage. These occur as a result of:
1. Small vessel vasculopathy with a hyperactive endothelium
2. Presence of autoantibodies
3. Fibroblasts dysfunction- leading to collagen deposition
SUMMARY PATHOGENESIS
Initially, mild perivascular fibrosis together with the vasoconstriction causes local ischemia, that will progressively cause even more fibrosis until eventually systemic sclerosis and organ damage will take place.
CLASSIFICATION
2 TYPES
- Limited type- Skin involvement is limited (hands and face) with late visceral involvement. The overall prognosis is good!
o Involvement of the skin can be either
o Linear scleroderma
o Morphea (annular fibrotic change)- the infiltration of sclerotic tissue is very deep (even in the image on the right).
These manifestations are very hard to treat, since we don’t know how to stop fibroblast dysfunction
* Diffuse type- Skin involvement is diffuse with early visceral involvement.
LIMITED
*Isolated Raynaud for many years
*skin sclerosis limited to face and distal area
*late organ involvement
*pulmonary hypertension
*auto antibodies : ACA(Anti-centromeric)
*megacapillaries
DIFFUSE
*Raynaud closer to the onset of the skin disease (<1 year)
*diffuse skin sclerori
*early organ involvement
*lung fibrosis
*auto antibodies anti-ENA
*megacapillaries + avascular area
!!!
All these features are important (and were repeated several times by the prof) but note especially the pulmonary hypertension in the limited form that is responsible for the reduction of life expectancy of these patients.
ANTIBODIES
o Limited type anti‐Centromere antibodies
o Diffuse type anti - DNA topoisomerase I antibodies (anti‐Scl‐70)
The old classification criteria:
MAJOR CRITERION Skin sclerosis proximal to MCP
MINOR CRITERIA:
1. Sclerodactyly
2. Necrosis or scars of the finger
3. Bilateral lung fibrosis
According to this classification criteria a patient can be classified as having Systemic Sclerosis in presence of either the major or 2 minor criteria.
The currently used criteria (2013) involves different manifestations- each with a weighted score where a total score >9 allows to classify a patient as having systemic sclerosis:
The purpose of this new classification (and the addition of detection of antibodies in the serum) is to catch the disease at an earlier stage in order to try to slow down the progression and fibrosis of major organs.
CLINICAL SIGNS
Raynaud phenomenon- vasospasms of small arteries that occur upon cold exposure or stress in the tips of the fingers, nose and earlobes. It is characterized by 3 phases:
* Ischemic phase white
* Cyanotic phase blue
* Hyperemic phase red
The different colors mark different levels of hemoglobin oxidation.
This is the earliest sign of SS- can appear years before other symptoms, but it is not very specific- and can be seen in lupus patients and healthy individuals.
How do we study Raynaud phenomenon?
capillaroscopy. The fingers are put under the microscope (non-invasive) and alteration of the capillaries are examined in terms of: distribution, number or shape.
Shape- the common alteration in SS is called ‘mega-capillaries’- the capillaries are enlarged at their tip.
Number- a gradual reduction in the number of capillaries. The capillaries themselves have an abnormal shape, because as more capillaries are lost, the existing ones attempt to branch in order to maintain the local blood supply.
A Raynaud’s phenomenon without the giant capillaries NOT SCLERODERMA!! This is a diagnostic feature and cannot be found in lupus, Sjogren syndrome.
This is treated with IV vasodilators (prostaglandin analogs) that are meant to maintain the blood supply at a systemic level (not just to the tips of the finger).
This reduction in blood flow can result in Acral ulcers that occur on the fingertips or on bony prominence.
Skin manifestations:
- Sclerodactyly- fibrosis of the skin of the hands. The skin becomes tight with loss of wrinkled surface. Eventually it can result in restriction of blood flow which results in necrosis and ulcerations.
This occurs in phases: Edematous phase («puffy fingers») Sclerotic phase Atrophic phase - Face- Another characteristic of the skin involvement is the amimic face, with thin lips, and reduced oral fissure. These patients are having trouble opening the mouth because the skin is completely fibrotic.
- Pigmentation modification- can be either Hyperpigmentation or Hypopigmentation
- Teleangectasias- dilated capillaries resulting in red spots. May occur on the face, neck and trunk, hands
- Calcinosis- Intra or subcutaneous calcifications (gross deposits of calcium phosphate or carbonate). These are VERY PAINFUL
