Download Cause. - Cleveland Clinic

 Cause
The key to understanding SS is to appreciate the concept of “Autoimmune Endotheliopathy.”
“Endotheliopathy” means that the endothelial cells (EC) are sick (see Figures 6-8). “Autoimmune” means
that the endothelial cells are sick because the person’s own immune system is mistakenly waging an attack
on those cells---thereby injuring them.
In SS the endothelial cells that are being attacked are the endothelial cells that line the inner walls of the
microvasculature (the tiniest arteries and capillaries). This is happening almost exclusively in the
microvasculature of the brain, retina, and inner ear. The microvasculature elsewhere in the body (in the
lungs, heart, kidney, etc.) is unaffected---though, in an apparently harmless way, the microvasculature in the
muscle and skin may sometimes be affected. The endothelial cells that line the large and medium sized
arteries are not apparently affected.
Figure 6 depicts a magnified version of the cross-section of a tiny
artery or capillary. The yellow ovals represent the endothelial cells
that line the inner wall of the blood vessel. (For simplicity, only the
endothelial cells that are at the edge of the cross-cut blood vessel
are shown. The endothelial cells that line the rest of the inner wall of
the blood vessel are not shown.) Note that the endothelial cells fit
snugly together. There are “tight junctions” between them.
Figure 7 depicts early, moderately severe “autoimmune
endotheliopathy.” The endothelial cells have been injured and have
become swollen. Since they are swollen, they take up more space.
This endothelial cell swelling narrows the channel (the opening, the
lumen, the passageway) of the blood vessel. This narrowing makes it
harder for blood to flow through the vessel. The less blood that flows
through the vessel, the less oxygen and nutrients are delivered to the
tissues (brain, retina, and inner ear) that are served by those blood
vessels.
Figure 8 depicts extremely severe “autoimmune endotheliopathy.” The
endothelial cells have become markedly swollen, and they have
swollen the channel completely shut. No blood can flow through a
channel that has been swollen shut. As a result, the tissues (brain,
retina, inner ear) normally served by these blood vessels no longer
receive adequate oxygenation and nutrients. Consequently, those
tissues suffer from lack of oxygen and nutrients. They suffer from
“ischemic injury.” (“Ischemia” means lack of oxygen.)
Cause (PDF #2)
Page 1
If the ischemia is only mild-moderate (due to narrowing as depicted in Figure 7, for example) and of relatively
short duration, the tissues (brain cells, for example) become sick, but do not become permanently injured. If
the ischemia is severe (as in Figure 8) and/or prolonged, the ischemically injured cells (in the brain, retina, or
inner ear) may become so sick that they are irreversibly damaged.
The purpose and the urgency of medical treatment is to suppress the immune system’s attack on the
endothelial cells as quickly and completely as is safely possible----so that the endothelial cells do not become
increasingly swollen and so that the brain, retina, and inner ear do not become irreversibly damaged.
Treatment can suppress the mistaken autoimmune attack, normalize the health of the sick endothelial cells,
reverse the swelling, open up the channel, improve blood flow to the sick tissues (brain cells, retinal cells,
cochlea cells), and help these ischemically injured tissues to recover---assuming it is not too late.
The above understanding of “autoimmune endotheliopathy” makes it much easier to understand the
ophthalmologic findings, MRI findings, audiological findings and the variety of symptoms of SS.
But, before we proceed, let’s address two fundamental questions:
• Why does the immune system make this Susac’s Syndrome mistake in the first place?
• Can this mistake be corrected?
These questions are addressed in the section below.
The Immune System, Autoimmune Mistakes, and the Concept of Immunologic Self-Correction
The Immune System
By the “immune system” we mean that part of our body that is responsible for protecting us from infection.
Specifically, we primarily mean the white blood cells (their actions and the actions of the products they
produce) that circulate within our blood stream and that also reside in our lymph nodes and other tissues.
These white blood cells (WBC) include T lymphocytes, B lymphocytes, macrophages and polymorphonuclear
WBC, and the products they produce include cytokines, chemokines, and antibodies.
Autoimmune Mistakes
We want our immune system to go into action and use its products to attack invading organisms, like
bacteria and viruses. But, we do not want our immune system to attack parts of our own body, as if the
immune system thinks (erroneously) that it sees bacteria or virus in those parts, or otherwise thinks these
parts are foreign or dangerous and need to be attacked.
When the immune system does attack a part or parts of our own body, we call that an “autoimmune” attack.
Rheumatoid arthritis is probably the autoimmune disease that is best known to people. In rheumatoid
arthritis, the person’s immune system is mistakenly attacking that person’s joints, as if their immune system
Cause (PDF #2)
Page 2
has decided, quite erroneously, that there is infection in the joint that must be attacked. Their immune
system is well-meaning, but is making an unfortunate mistake, and chronically so.
In Susac’s Syndrome the immune system is making the unfortunate mistake of attacking the endothelial cells
that line the inner walls of the microvasculature that feeds the retina, inner ear, and certain parts of the brain.
Why does the immune system make such a mistake?
As is the case with rheumatoid arthritis, the mistake is usually a spontaneous one---meaning that it is not
triggered by anything specific or determinable. It just happens, out of the blue, for no apparent reason. Most
autoimmune diseases (rheumatoid arthritis, lupus, dermatomyositis, Susac’s Syndrome, etc.) occur
spontaneously.
These spontaneous mistakes probably happen, however, because of an underlying “programming error” in
the person’s “immune computer.” Our immune systems are, indeed, much like computers. They are
“programmed “ to know when to go into an attack mode, and when to leave things alone. This
“programming” is done by our “immune response genes.” Some people have immune response genes that,
unfortunately, mal-programed their immune computers, such that their immune system is prone to make
autoimmune mistakes, like rheumatoid arthritis (a common autoimmune mistake) or Susac’s Syndrome (a
rare autoimmune mistake).
Immunologic Self-Correction
Fortunately, our immune systems are often able to correct their mistakes---though it is apparently harder to
self-correct some mistakes than others, and children appear to have better capacity for self-correction than
do adults. For example, the immune systems of children usually are eventually able to correct the juvenile
rheumatoid arthritis mistake, the juvenile dermatomyositis mistake, and even the lupus mistake; but, the
immune system of adults usually has little success in correcting the rheumatoid arthritis mistake.
Fortunately, the immune systems of adults and children seem to be able to self-correct the Susac’s
Syndrome mistake, often within 1-3 years---though not always.
Limitations of Current Treatments
Unfortunately, we do not currently have treatments that can specifically and directly correct the immune
mistake that an immune system is making. If we did, we would have a “cure” for that particular autoimmune
disease. However, we do have treatments (immunosuppressive/anti-inflammatory treatments) that either
suppress the extent to which the immune system is making the mistake (by suppressing part or all of the
immune system), or at least “throw water” on the fires that the immune system is mistakenly setting.
Until we have true “cures” for these autoimmune diseases, the main approach is to use
immunosuppressive/anti-inflammatory medications to control the “autoimmune fires” (slow down the firesetting and throw water on the already set fires) until the person’s immune system is able to self-correct. If it
is going to take the individual’s immune system 2 years to self-correct, that individual will need
immunosuppressive treatment throughout those 2 years. Usually, self-correction occurs gradually, such that
doses of immunosuppressive drugs can gradually be reduced after initial control has been achieved. But,
the gradual reduction of immunosuppression needs to be done at a pace that is about equal to the pace of
Cause (PDF #2)
Page 3
self-correction. If immunosuppressive treatment is reduced at a pace faster than the pace of self correction,
a flare-up of disease is likely to occur.
Sometimes a person’s self-correction is interrupted by a return of loss of control (i.e. a relapse). In such an
instance, the immunosuppressive doses that were working well, may no longer be sufficient and may need to
be increased, at least temporarily.
Cause (PDF #2)
Page 4