Suzi’s story is the first in a series of blogs exploring the possibility that the autoimmune findings will open the door for IVIG (Intravenous Immunoglobulin) treatment in chronic fatigue syndrome (ME/CFS), fibromaylgia (FM) and postural orthostatic tachycardia syndrome (POTS).
IVIG is an immune treatment mostly used in autoimmune diseases and as something of a last gasp when nothing else is working. It’s expensive and hard to get, but if you’re lucky enough to be able to get a hold of it, it can, at times, make a major difference.
This is the tale of a very enterprising mother and her very sick daughter. Suzi’s mother kept up on the latest research findings and reached out to doctors and researchers and ultimately got Suzi a chance at IVIG. The fact that she was able to achieve this in the U.K., of all places, was astonishing – and hopeful. This is hers and Suzi’s story.
How healthy was Suzi before she got sick?
Suzi got sick very suddenly at the age of 18. She had some health problems, suggesting she may have had a weakened immune system growing up, but was very well immediately before this and regularly played sports and had competed at the national, county and school level.
How did she get sick and how sick did she get?
Suddenly Suzi had an alarming prolonged episode of dizziness and was hit with a feeling of nausea. Her stomach felt too full to eat more than a small amount; she had stomach pain, severe fatigue, headaches, dizziness, feeling flu-like and generally felt unwell.
This continued for several weeks and she visited the GP pretty much every week. First, she was told by her GP that she had a virus, then at another visit, that her symptoms must be due to exam stress. After five weeks she had a test for glandular fever, which was negative.
Shortly after that, she had a longer episode of worsened dizziness (she was unable to stand) and then her vision went. From that point on, all of her symptoms became much worse; she could barely get out of bed or off the sofa. We went back through our diaries and found that exactly two days before each of the episodes of dizziness she had received the first two vaccinations for HPV.
In the nine years since then, her symptoms remained the same but varied in severity. She has had times when she could do more but has also had three unplanned hospital admissions, periods when she’s needed to use a wheelchair, and years when she barely left the house. She spent a year bed-bound.
What were her experiences with doctors?
Initially, the GP said Suzi must be depressed, because she felt so unwell that she cried in the doctor’s office. When we resisted that diagnosis, she was told she had post-viral fatigue syndrome, which became chronic fatigue syndrome (ME/CFS) after six months of being symptomatic. She followed all the advice about pacing and graded exercise but nothing gave relief or resulted in any improvement.
During the years of her illness she has been seen in the following hospital clinics: Infectious Diseases (for chronic fatigue); Ophthalmology, Cardiology, Endocrinology, Immunology, Gastroenterology, Rheumatology, Migraine, Neurology, Neuro-physiology, Neuro-gastroenterology, Neuro-immunology, Sleep Neurology, Autonomic Neurology, Neuroscience, in addition to visits to the Emergency Room in no less than 6 different hospitals.
Suzi received many different diagnoses ranging from ME/CFS to hypermobility syndrome to delayed gastric emptying to encephalopathy to migraine with aura to POTS. We found that the various consultants we saw seemed only to look at their specialty and not the bigger picture, hence the various diagnoses and drug treatments that might improve an individual symptom but generally made other things worse.
Several drugs caused severe reactions that led to hospital admissions. We lost count of how many doctors said that her test results were fine, so there was nothing ‘actually wrong’ and those who said it was psychological and she just needed to push herself.
A 7-day ECG was the first indication of autonomic dysfunction, and autonomic function tests four years after becoming ill led to a diagnosis of POTS.
We were very lucky to find a local neurologist who knew about autonomic dysfunction and also about autoimmune disease. The discovery of some low level antibodies, usually linked to paraneoplastic encephalopathy, led to treatment with plasma exchange and steroids.
The plasma exchange on its own gave immediate improvement, but this only lasted for 6-8 weeks at best before symptoms rapidly returned. The steroids caused their own problems and were not well tolerated.
Over time, when the antibody levels returned to normal, it was decided that they were coincidental and not the cause of Suzi’s illness. No further treatment was offered.
How did Suzi get access to IVIG treatment?
At a particularly low point in early 2016, I was reading a paper about gastrointestinal dysmotility following HPV vaccination (Rebecca Chandler, Uppsala Monitoring Centre) whilst Suzi was in hospital with continuous vomiting and weight loss.
Gastrointestinal problems were early symptoms in Suzi’s illness and I was interested to read in this paper about antibodies to adrenergic and muscarinic receptors. A Google investigation showed that tests for these antibodies are not available in the UK.
More investigation led me to Professor Jeanne Hendrickson at Yale University and she was able to direct me to Berlincures who agreed to test Suzi’s blood as part of their research program.
(Berlincures is a German Life Science company that specializes in the research and testing of antibodies that it believes play a role autoimmune cardiovascular diseases. A drug to neutralize one of these autoantibodies is in clinical trials now.)
We had to get a private phlebotomist with a centrifuge to come to our house and send the sample by courier to Germany on dry ice. Suzi tested highly positive for beta-2 adrenergic and muscarinic-2 antibodies.
With that, we went back to see our local neurologist who rolled her eyes when we mentioned blood tests and Germany. However, once we explained that Berlincures is not a commercial lab and showed her research articles from Dr. David Kem, Dr. Artur Federowski, Professor Jeanne Hendrickson and Professor Carmen Scheibenbogen, she was more receptive.
After talking to colleagues, and taking into account Suzie’s previous response to immunotherapy, she suggested another course of plasma exchange initially to see if there was improvement, while monitoring her antibody levels to see if any correlation existed.
We were probably lucky that the plasma exchange machine was out of operation and there was already a long waiting list, so Suzi was offered a course of IVIG.
What effects did the IVIG treatment have?
From the first infusion Suzi could see improvement – her gastrointestinal symptoms, in particular, improved immediately. That first infusion was two years ago this month. Unfortunately she developed aseptic meningitis and had a short hospital stay to resolve that.
(Aseptic meningitis causes the tissues covering the brain and spinal cord to become inflamed. People with migraines have an increased risk of aseptic meningitis when given IVIG. A rare side effect of IVIG, aseptic meningitis can have serious consequences, but most people recover without issue over a week or two. Slower infusion rates are believed to reduce the risk of aseptic meningitis.)
The following infusions were given much more slowly, over two days. We saw improvements month after month and Suzi got stronger. The course finished in June 2017, and there was an initial dip in her condition after the last infusion; however the improvement is continuing and she is now able to work part-time, is driving, has ridden a bike for the first time in nearly 10 years and she walks for an hour every day.
Migraine with aura continues to cause problems and she’s had botox treatment to try to help this. She still has POTS symptoms and days when she is not able to do much, but the improvement really is significant.
We sent samples to Berlincures throughout the treatment and they found her antibody levels remained highly positive. Berlincures have never recommended IVIG and say that Immunoadsorption is the best treatment as it will remove the antibodies; however, that is not available in the UK. Speaking to researchers in Scandinavia and the USA, it seems that IVIG disrupts the activity of the antibodies but doesn’t remove them.
Unfortunately, we have met resistance in the UK to any suggestions that POTS can have an underlying autoimmune cause and recently Suzi has been told that her response to IVIG was probably the placebo effect. One neurologist wrote, “I have never personally seen a patient with these antibodies ...“ and another, “We don’t test for these antibodies because they are not diagnostic or helpful”. So we are grateful to the researchers who are working so hard on autoimmunity and how to treat it, and to Cort for keeping the patient and medical audience updated.
Suzi’s mother had reached out so much and was so proactive in her attempts to find help for her daughter that I asked if she had any background in the medical field. It turned out that she hadn’t! She reported:
I don’t have any experience in the medical field, I’m a mum of three who works in Finance. As you suggested, I have just plugged away, contacted people, read a lot and learned a lot – alongside other mums who have found themselves in a similar situation.
I found it hard to accept that someone could be so unwell, yet all tests, other than autonomic tests, came back negative – and I badly wanted my daughter to have her life back.
I’ve been in touch with some very helpful researchers and doctors in Germany, Scandinavia and the USA. It has amazed me that you can correspond by e-mail with some highly respected doctors in other parts of the world (and many reply). My questions have been answered with good suggestions and offers of help and they are always pleased to get an update. I have also met several of these doctors when they have come to London. They have really kept us going.
Will Suzi be able to keep up with the IVIG?
No, unfortunately not, so we really hope that she won’t relapse. We have moved recently and asked the neurologists here and they have said absolutely not because there are no NICE guidelines for the use of IVIG for dysautonomia and not enough published evidence that the antibodies cause the symptoms. So we need doctors in the UK to know more about the antibodies and the current research.
Suzi’s story suggests that IVIG presents an intriguing treatment possibility if you can get it. The good news is that with autoimmune and small fiber neuropathy findings showing up in ME/CFS, and with IVIG trials looming in small fiber polyneuropathy and POTS, it may be more possible in a few years to get a better shot at this expensive drug. With recent clinical trial findings, and with Dysautonomia International funding the first IVIG POTS trial, hopefully Suzi’s doctors will get he evidence they need to give her another round of IVIG should she need it in the future.
- Next Up – Part II: Big Picture Emerging? Are Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia Autoimmune Dysautonomias?