~ The Sneddon’s Foundation: Healing Through the Flow of
Information ~
Frequently Asked Questions
(Please feel free to contact us with any questions we don't answer here!)
Note: The information provided on this website is not
intended for diagnostic purposes. It is provided for informational purposes
only. The Sneddon’s Foundation recommends that affected individuals seek the
advice or counsel of their own personal physicians.
Sneddon’s
Syndrome is a rare, though under-diagnosed, disease of the arteries that affects women
more often than men. Its primary
symptoms are “livedo reticularis” (a bluish-purple, net-like mottling on the
skin that often gets worse in the cold) and either strokes or transient neurological episodes that can
be very severe.
Sneddon's patients sometimes describe “episodes” or “spells”, during which they might have
confusion, speech difficulties, dizziness, collapse, weakness, numbness or
tingling on one side of the body, drooping on one side of the face, or vision
problems. Some Sneddon’s patients
have full strokes. Many Sneddon’s
patients have problems with memory or concentration and these sometimes (though not always) develop into dementia.
There are many
problems that can occur with Sneddon’s patients aside from episodes or strokes, though these are not all fundamental
to the diagnostic process and not all Sneddon’s patients will have them: high
blood pressure, autoimmune diseases like Systemic Lupus, dizziness (both during
and not during episodes), exercise intolerance, head pain, eye pain, severe fatigue, unusual muscle spasms, trembling, Raynaud’s (a sensitivity of fingers and toes to
cold, leading them to change colors), seizures, fetal loss,
character changes, anxiety and depression.
Very recent research suggests that it might be useful to think of Sneddon's not as a strictly a brain disease (or "cerebrovascular disease"), but rather as a systemic disease that can affect any part of the body. Cases of Sneddon's Syndrome have been confirmed in which patients suffer from only heart problems or only kidney problems, and these cases seem to be good evidence that the disease process in Sneddon's might be much more wide-reaching than previously thought.
How Does Sneddon's Develop?
There has not been enough research on Sneddon's to clarify the details of the disease process fully. It seems to be a progressive deterioration of the "arterial endothelium", that is, the linings of the arteries, the blood vessels carrying blood from the heart out to the body, and it is only in this sense that Sneddon's Syndrome is a progressive disease. The material just beneath the linings also tends to proliferate in abnormal ways and it is this dermatologists are looking for when they do skin biopsies to look for Sneddon's. (Unfortunately, 20% of Sneddon's patients will have normal results on these biopsies.)
Once the
vessels have deteriorated significantly, the patient will develop clotting
abnormalities in the blood, causing "micro-clots" even in those patients who never suffer full stroke from larger clots. This is Sneddon’s primary threat. Its primary treatment, "warfarin", thins the blood to protect the body, and especially the brain, from clots. Compromised arterial linings can also trigger the formation of plaque on the walls of the arteries, even in patents who do not have high cholesterol.
Some researchers believe that when the linings of the arteries are compromised this causes problems in the signaling pathways that tell the vessels when to dilate and when to constrict so that consistent blood flow to the brain (or other parts of the body) is maintained. As a result, vasospasm can occur without warning, resulting in the "severe but transient neurological episodes" so characteristic of Sneddon's. A similar process is thought to occur in the skin as "livedo reticularis" in Sneddon's patients.
Though there have not been studies on large enough numbers of Sneddon's patients to specify its course definitively, the general path often (but not always) seems to proceed something like this: As a child the
patient may develop livedo reticularis of the skin (though a great many
people with livedo reticularis do not have Sneddon’s Syndrome), and perhaps
also headaches, tremors, or Raynauds (color changes in the fingers and toes in
response to cold). At age 30-40 severe, though usually transient, neurological symptoms will begin to
occur, or stroke. Non-transient memory problems develop roughly ten years after the patient's first neurological episodes, and these can develop into early onset dementia (though dementia does not always occur). Sneddon’s
patients who have strokes may have them at any time, and of course the
potential lasting effects of stroke are wide-ranging and very well known.
Is Sneddon's Always a Progressive Disease?
Many Sneddon’s patients and their families are frightened by the “progressive” nature of Sneddon’s Syndrome. It is important to keep in mind that it's the deterioration of the arterial linings that progresses, while it does not seem to be the case that the actual symptoms of Sneddon’s will always get significantly worse as thepatient ages, especially with proper treatment. It is certainly not clear that all Sneddon’s patients will ultimately face dementia or stroke.
What kind of disease is Sneddon's Syndrome?
“Sneddon’s”
Syndrome was first described in 1965 by a doctor of that name, as a
combination of transient neurological episodes and livedo reticularis. It was
discovered not long thereafter that people with livedo reticularis are more likely to
have strokes. In this initial understanding, and for many years afterwards, it was thought that Sneddon’s Syndrome was a form of another disease called
“Antiphospholipid Antibody Syndrome” (“APS”) or
“Hughes Syndrome”.
Sneddon’s and
APS are very similar. They have
similar (though not identical) symptoms and, like APS patients, many Sneddon’s
patients have Systemic Lupus or other autoimmune disorders. There are decisive blood tests for APS and for many years only patients with positive
results on those tests were given a diagnosis of Sneddon’s Syndrome.
It has now been shown, however, that most Sneddon’s patients do not, in fact, have positive results on tests for APS. As a result, doctors
often use the terms “aPL-positive” and “aPL-negative” to clarify which sort
of Sneddon’s patient they’re working with (though as of yet, no clear
difference between them in terms of symptoms has been established).
While APS is itself an autoimmune disease (like Systemic Lupus), Sneddon’s Syndrome is not autoimmune. It is now classified as a “cerebrovascular disease” instead, one that is not "inflammatory". This difference has wide-reaching importance when it comes to diagnosis and treatment.
Because Sneddon's was originally misunderstood as autoimmune, it was treated by rheumatologists. Now that it is known not to be autoimmune, but to be cerebrovascular instead, it is treated by neurologists. Residents in training in neurology learn about Sneddon's Syndrome now, though many practicing rheumatologists are not aware of this important and decisive change in the way the disease is understood.
How is Sneddon’s Syndrome Diagnosed?
For someone with
Sneddon’s Syndrome the process of diagnosis can be extremely difficult. It is not uncommon for Sneddon’s
patients to spend many years in the diagnostic process and to struggle, even
long after the diagnosis has been clarified, with the trauma of their
diagnostic years. Even after diagnosis, Sneddon's patients often struggle to find doctors willing to read about the disease and offer treatment, wrongly assuming that "experts" must surely be available instead.
A great many Sneddon's patients with clear diagnoses struggle to receive treatment for severe but transient neurological episodes that have never been captured on brain scans. For many patients the combination of this unbearable, unpredictable symptom and the loss of hope for treatment is the greatest difficulty to face with this disease, and the area in which they need the greatest support.
There is no consensus among doctors and researchers as to how a diagnosis of Sneddon’s Syndrome should be made, though there do seem to be common assumptions. To begin, Sneddon’s Syndrome is considered in patients who have the combination of livedo reticular is and either stroke or transient, generally severe, neurological problems.
Once the two fundamental problems are seen to be present and in need of explanation and treatment, doctors will often begin assessing for Sneddon’s by doing blood tests for “antiphospholipid antibodies”. A positive result on one of these tests will often (in combination with livedo, strokes or episodes, and evidence of other typical Sneddon’s problems) lead a doctor to make a Sneddon’s diagnosis. Most people with Sneddon’s Syndrome will never have a positive result on these tests, however, so aPL tests can never be used to rule out a diagnosis of Sneddon's.
Some doctors
believe a skin biopsy is the best method for diagnosing Sneddon’s. Unfortunately, it is difficult to find
a dermatologist familiar enough with Sneddon’s to do the biopsy
confidently. Moreover, because 20% of Sneddon's patients will have a normal result on the biopsy even when it’s performed by an expert, a normal biopsy can never be used to rule out a diagnosis of Sneddon’s.
An MRI of the brain seems to be a useful neurological test when it comes to diagnosing Sneddon’s. In a patient who has livedo and stroke or transient neurological episodes, an MRI showing “infarcts” (areas of dead brain tissue caused by obstruction of blood supply) will be sufficient for confirming a diagnosis of Sneddon’s.
If a patient with Sneddon’s symptoms has an MRI that shows “lesions in the white matter” or “white matter disease”, and the patient is under age fifty, that is often considered sufficient for a diagnosis of Sneddon’s. A few white matter lesions can be perfectly normal, however, and doctors may dismiss an MRI as normal with this result. If you or your doctor suspect Sneddon’s Syndrome it is important to look carefully at the MRI report even if it is ultimately described as normal. It is also important to keep in mind that quite a few white matter lesions would be expected in the brain of an older patient. Moreover, there are some patients whose MRI results remain normal even through the development of severe disability due to Sneddon’s. Like the other tests, a normal MRI cannot be used to rule out Sneddon’s Syndrome.
If a patient is having memory or concentration problems it is often diagnostically useful to have cognitive testing to determine exactly what these problems are and how severe they may be. Not all Sneddon’s patients have cognitive problems, however, and those who do very often develop them only after many years of untreated episodes. That is to say, unfortunately, that normal cognitive tests cannot be used to rule out Sneddon’s either.
A Sneddon’s patient with a normal result on antiphospholipid antibody tests and without infarcts on the MRI is in a very difficult position, and so is her, or his, doctor. Many doctors will be reluctant to make a “clinical diagnosis” of Sneddon’s (that is, a diagnosis based primarily on symptoms) because they don’t feel they have the necessary expertise and they wrongly assume that doctors are available who do have this expertise.
Generally
speaking, a doctor faced with such a patient – i.e. someone who has livedo, who
suffers from stroke or severe, transient neurological problems, who also struggles with
dizziness, head or eye pain, exercise intolerance or other Sneddon’s symptoms – uses treatment for diagnostic purposes.
When symptoms are severe and there is strong suspicion of Sneddon’s
Syndrome, a trial period on anticoagulant medications (i.e. Warfarin) is typically offered to
the patient (assuming all relevant risk factors have been assessed and
carefully explained to the patient).
If the patient improves significantly after a month of adequately thinned blood, a diagnosis
of Sneddon’s Syndrome is generally considered to be confirmed.
How is Sneddon’s Syndrome Treated?
For many years
there was significant confusion among doctors as to how Sneddon’s Syndrome
should be treated. When it was
believed that Sneddon’s Syndrome is an autoimmune disease, doctors often treated
it with steroids (like Prednisone or SoluMedrol) or immunosuppressant
medications (like Azathioprine or Cytoxin).
Research has now shown that these
medications are not effective in treating Sneddon’s, even when the patient also
has an autoimmune disease like Lupus.
Doctors now believe that treatment with anticoagulant medications is necessary for all Sneddon’s patients. Generally speaking, it is thought that milder anticoagulants, like aspirin and clopidogrel (“Plavix”), are not sufficient to treat Sneddon’s, even though they are sometimes strong enough for patients with the very similar disease, Antiphospholipid Syndrome. Alternatively, some Sneddon’s patients are given “Heparin” (also known as “Lovenox”) through daily injections at home.
Most often, Sneddon’s patients are treated with Warfarin (also known as “Coumadin”). Because many other medications, and many foods, affect the way the body metabolizes Warfarin, this medication requires regular monitoring through blood tests or finger stick to make sure that the level of anticoagulation is maintained consistently.
Doctors and “Coumadin Clinics” keep track of the level of thinness of a patient’s blood through measuring the patients “INR” (for “International Normalized Ratio”). It is generally believed that a Sneddon’s patient needs to maintain an INR between 3-4 (while patients with Antiphospholipid Syndrome are maintained at a lower level, between 2-3). Research has suggested that neurological events occur when a Sneddon patient’s INR drops to 2 or below.
It is crucial
for Sneddon’s patients to be constantly aware of the risks involved in taking
this medication. Regular
monitoring is absolutely essential, as is avoidance of any activity that can
cause bleeding. Warfarin is an
anti-clotting medication and there are times, as with injury, when an inability
to clot can be extremely dangerous.
Unfortunately, it seems that general medical training has not typically included familiarizing new doctors with Sneddon’s Syndrome. Very few general practitioners would know to consider a Sneddon’s diagnosis even when a patient with constant severe livedo is disabled by unexplained neurological problems or stroke. If the MRI does not show any major abnormalities – which, unfortunately, it often doesn’t – the Sneddon’s patient is frequently ignored, often labeled as a “difficult patient”, and not uncommonly humiliated by the suggestion that her, or his, symptoms are caused by stress or anxiety. Because early treatment may be essential to effective management of Sneddon’s Syndrome, this problem is no small matter.
Sneddon’s has
been reported to occur with a frequency of four cases per million people. It is generally believed, however, that
this figure is not a real measure of how often the disease occurs, but rather
of how rare it is for doctors to be familiar enough with the disease to pursue
it as a diagnostic possibility. That
is to say that there are a great many people who currently suffer from
Sneddon’s Syndrome but have been given a diagnosis of “anxiety”, no diagnosis,
or an actual misdiagnosis.
Migraine
If the Sneddon’s
patient has severe head or eye pain often she, or he, is misdiagnosed with
migraine. When memory problems
develop, sometimes doctors will attribute those to migraine as well and do not pursue
further testing. Fortunately,
recent work in headache clinics has shown a strong correlation between headache
patients who have livedo reticularis and those who go on to have stroke. Hopefully, at some point all patients diagnosed with migraine who do not respond to treatment will be routinely evaluated for livedo
reticularis, and considered for Sneddon’s Syndrome when livedo is apparent.
Systemic Autoimmune Disease
If the Sneddon’s
patient also has an autoimmune disease, such as Systemic Lupus, Behcet’s, or
Mixed Connective Tissue Disease - as many Sneddon's patients do - a rheumatologist will often attribute both
livedo reticularis and transient neurological problems to the autoimmune
disease and not proceed with further testing or anticoagulant treatments. Unfortunately, even when
rheumatologists are aware of Sneddon’s Syndrome, many are unaware of recent
research showing that most Sneddon’s patients do not have a positive result on
blood tests for antiphospholipid antibodies. Similarly, sometimes they are not aware of research showing
that Sneddon’s will not respond to treatment for autoimmune disease even when
the patient does actually have an autoimmune disease in addition to
Sneddon’s. When rheumatologists
understand Sneddon’s as “secondary to” Lupus or another autoimmune disease
often they do not consider the treatment with warfarin that Sneddon’s patients desperately need.
Vasculitis
When neurological problems are severe in patients with autoimmune disease the patient is very often misdiagnosed with the autoimmune disorder “CNS Vasculitis” (also known as “Vasculitis of the Brain”) and treated with high doses of steroids and immunosuppressants. Some doctors believe that steroids make Sneddon’s symptoms more frequent and more severe.
Some research suggests that the overwhelming majority of patients diagnosed with Vasculitis are not actually suffering from autoimmune, or “inflammatory” problems of the brain, but rather from “vasculopathies” like Sneddon’s Syndrome, which must be treated with warfarin rather than immunosuppressant medications or steroids.
Finally, when
Sneddon’s patients do have a positive result on the antiphospholipid antibody
tests many doctors will understand them to have Antiphospholipid Syndrome
rather than Sneddon’s Syndrome.
Fortunately, most APS patients are treated with Warfarin just as
patients diagnosed with Sneddon’s would be. Lack of information about the differences between the two
diseases does continue to be a problem on two counts, however.
First, APS is an autoimmune disease and
Sneddon’s is not. That is to say
that, while Sneddon’s is generally treated by rheumatologists, Sneddon’s must
be treated by neurologists (or, when autoimmune disease is also present, by a
team of rheumatologists and neurologists). Second, patients with APS are generally understood to have
strokes, not TIA’s or “severe but transient neurological events”. Treating a Sneddon’s patient as an APS
patient can lead doctors to dismiss the severity and the importance of what
patients endure during these episodes.
Finally, APS patients will generally do well with a
relatively low level of anticoagulation (INR 2-3), while it is generally
believed that Sneddon’s patients need a higher level (INR 3-4). That small difference in treatment
protocol can make the difference between disability and ability for a patient
who actually has Sneddon’s Syndrome rather than APS.
Where Can Sneddon’s Patients and their Families Turn for Support?
Until very recently, there were few resources for the Sneddon’s patient, or the doctor working to diagnose or treat Sneddon’s. Both doctors and patients can search under Sneddon’s Syndrome at the National Library of Health website (at www.pubmed.com), but most of what’s there is difficult for the ordinary patient to understand, and there is too much of it for the doctor to wade through for the information needed. Unfortunately, neither the National Stroke Association nor the National Institute for Neurological Disorders even has a listing that defines Sneddon’s syndrome for doctors or patients looking for answers. (We at the Sneddon's Foundation find this atrocious and do our best to remedy the problem.)
Because of the enormous physical challenges patients with Sneddon’s face, because those challenges can sometimes affect the patient’s thinking and even her, or his, character, and because the process of being diagnosed with Sneddon’s Syndrome can be extremely traumatic, patients with Sneddon’s Syndrome need places to turn for support. They need to know that, yes, there are others who’ve endured the same suffering with stroke, the same indescribable episodes, the same fear about waning memory skills, and the same dismissive responses from doctors unfamiliar with this disease. Because of the enormous range of difficulties it poses, Sneddon’s Syndrome can be a formidable challenge for family members as well.
The National
Organization for Rare Disorders (NORD) has information about Sneddon’s, as well
as a networking process that puts patients with Sneddon’s Syndrome in touch
with each other.
The Sneddon’s Foundation is working to establish a complete listing of U.S. patients with Sneddon’s Syndrome, and hopes to create online discussion tools that allow patients and their family members to freely interact with others about all aspects of this difficult disease. In the meantime, The Foundation remains eager to respond to your questions and concerns through the “Contact Us” page at our website.
Please keep in
mind that all Sneddon’s patients benefit when even a single new Sneddon’s
patient contacts the organization.
Because so much of what is known about Sneddon’s was learned from very
small samplings of patients, the larger a group we can create, the
easier it will be for doctors and researchers to make progress in clarifying
and treating this difficult disease.
~ The Sneddon’s Foundation: Healing Through the Flow of
Information ~