Oct 12, 2011

How could IVIG help POTS?

IVIG is shorthand for Intravenous Immunoglobulin.  Immunoglobulins are proteins within your body that help protect you against infections and play many other important roles in your immune system.  There are different types of Immuglobulins, such as IgG, IgM, IgE, IgD, IgA, etc.  IVIG is mostly comprised of IgG proteins, although it does contain other classes of immunoglobulin in smaller quantities.

IVIG is collected from the blood of over 1000 donors, and screened for infectious diseases like HIV and Hepatitis.  It also undergoes heat treatment, acid bathing and other measures to rid it of any pathogens.  Even with all of these precautions, there is still a possibility that you could contract an infectious disease from receiving an infusion of IVIG - however this is very, very rare.

IVIG is used to treat a growing number of medical conditions, but it is currently only FDA approved for the treatment of the following:
-chronic lymphocytic leukemia
-idiopathic thrombocytopenia purpura
-pediatric HIV
-primary immunodeficiencies
-Kawasaki Disease
-CIDP (Chronic Inflammatory Demyelinating Polyneuropathy)
-before and after bone marrow transplants
-certain types of kidney transplants

As of 2008, IVIG was in Phase III FDA research trials for the treatment of Alzheimer's.

IVIG is commonly used "off label" by doctors to treat many autoimmune and neurological conditions.  "Off label" use is legal.  It just means that the doctor is prescribing a drug for a use other than something it has received FDA approval for.  Most medications are prescribed "off label" - doctors were prescribing low dose asprin to patients after heart attacks for years, but it wasn't until recently that the FDA approved that as an "on label" use of the drug.  Like many government agencies, the FDA operates at a glacial pace, and they simply cannot keep up with all of the rapid advances in modern medicine.  The FDA has a clear written policy that allows doctors to prescribe drugs "off label."

IVIG has been used to treat the following conditions "off label":
-Clostridium difficile infections
-Grave's Disease
-Guillan-Barre Syndrome
-Inclusion Body Myositis
-Lambert-Eaton Syndrome
-Lyme Disease
-Multifocal Motor Neuropathy
-Multiple Myeloma
-Multiple Sclerosis
-Muscular Dystrophy
-Myasthenia Gravis
-Myelagic Encephalitis/Chronic Fatigue Syndrome
-Neonatal alloimmune thrombocytopenia
-Neuomyelitis optics
-Opsoclonus Myoclonus
-Parvovirus B19
-Pemiphigus vulgaris
-Post-Polio Syndrome
-Post transfusion purpura
-Reflex Sympathetic Dystrophy (Complex Regional Pain Syndrome)
-Renal transplant rejection
-Recurring spontaneous abortion/miscarriage
-Recurring in vitro fertilization failure
-Sjogren's Syndrome
-Stiff Person Syndrome
-Severe Sepsis and Septic Shock in critically ill adults
-Toxic epidermal necrolysis
-Transverse Myelitis

Scientists don't know precisely how IVIG works for all of these conditions, but the general understanding of it is that IVIG reduces inflammation.  There are several theories of how it does that, and in fact, it may reduce inflammation through several different pathways.  Researchers have found that IVIG activates certain receptors in your immune system that inhibit antibody production.  Less antibodies means less tissue damage and inflammation for people with autoimmune diseases. Additionally, scientists believe IVIG may attach itself to abnormal antibodies, and trigger its removal from the body.  IVIG is also believed to react with T-lymphocytes and B-lymphocytes, which are types of white blood cells that are often involved in triggered autoimmune diseases.  Sjogren's occurs when B-lymphocytes over produce, stick around too long and then invade various tissues throughout the body causing inflammatory damage.  IVIG may prevent B-lyphomcytes from attacking a Sjogren's patients own tissues, thus eliminating the autoimmune reaction.

So how can IVIG help POTS?  As you can see, dysautonomia is on the list of ailments that have been treated with IVIG.  POTS is merely a form of dysautonomia, and in many patients POTS is believe to be caused by an underlying infectious and/or autoimmune trigger.  In some patients, like myself, that underlying autoimmune condition can be determined.  I recently learned that my POTS and autonomic neuropathy occurred as a result of Sjogren's Syndrome, an autoimmune disease that can sometimes attack your autonomic and other nerves (motor, sensory and Central Nervous System).  Even if the underlying autoimmune problem can't be identified in every POTS patient, it is possible that some people with idiopathic POTS (POTS from an unknown cause) may respond well to IVIG therapy.  Researchers are currently looking for antibodies that may be the root cause of the autonomic damage seen in POTS patients.  This is a rapidly developing field of medicine, and it is quite possible that these antibodies could be discovered within our lifetime.

In fact, a POTS friend who was recently seen at Mayo Clinic said her doctors told her they were close to publishing a paper on a new antibody believed to be associated with POTS.  

And just last week a researcher in Norway published a research study in which he treated 45 Chronic Fatigue Syndrome patients with Rituxan, a chemo drug used to treat autoimmune conditions like Sjogren's, Lupus and Rheumatoid Arthritis.  Two thirds of the patients were essentially cured from their debilitating Chronic Fatigue symptoms.  While POTS and CFS are not the same thing, there are many overlaps between these illnesses, and both seem to be most common in young women and teens after a viral infection.  Researchers at Johns Hopkins have published data connecting the two syndromes, as have researchers at Vanderbilt University's Autonomic Dysfunction Center.  Both syndromes involve severe orthostatic hypotension and autonomic dysfunction.  They think the major difference is that POTS patients tend to have high catecholamine (think "adrenaline") levels, and Chronic Fatigue patients tend to have low catecholamine levels.  This explains why Chronic Fatigue patients are exhausted all the time, and POTS patients to feel "wired but tired" all the time.  So perhaps after some additional research on the connection between autoimmune conditions, CFS and POTS, Rituxan will become an available therapy to CFS and POTS patients in the future.

IVIG has been used to treat dysautonomia sucessfully in the US and abroad.  There are case reports and peer reviewed research studies in medical journals on this very topic, such as:

“Acute dysautonomia: complete recovery after two courses of IVIg”
26(8) Brain Dev. 542-544 (2004)

“Idiopathic dysautonomia treated with intraveneous gammaglobulin”
71 East Afr. Med. J. 167-170 (1994)

“Acute dysautonomia secondary to autoimmune diseases: Efficacy of intravenous immunoglobulin and correlation with a stimulation of plasma norepinephrine levels”
17(6) Clinical and Experimental Rheumatology 733-736 (1999)

“Five-year Efficacy of Intravenous Gammaglobulin to treat Dysautonomia in Sjögren’s Syndrome” 106(1) Am. J. Med. 125 (1999)

“Acute idiopathic dysautonomia: Electrophysiology and response to intravenous immunoglobulin”
54(3) Neurology 770-771 (2000)

“Acute Autonomic, Sensory and Motor Neuropathy: Successful Treatment with IVIg”
48(10) Intern. Med. 843-846 (2009)

"The wide spectrum of clinical manifestations in Sjögren's syndrome-associated neuropathy"

Brain (November 2005) 128 (11):2518-2534

IVIG has also been used to treat painful sensory neuropathy, a complication that many POTS and Sjogren's patients have - including me.  Small fiber neuropathy is a form of neuropathy that effects the small fiber sensory nerves.  The small fiber sensory nerves are co-located with small fiber autonomic nerves, and on a biopsy, they are virtually indistinguishable from one and other.  So it is not surprising that many POTS patients have autonomic damage and sensory neuropathy too.  Here are just a few of the MANY journal citations for the use of IVIG in treating painful neuropathy:

"Extreme efficacy of intravenous immunoglobulin therapy for severe burning pain in a patient with small fiber neuropathy associated with primary Sjögren's syndrome"
Mod Rheumatol. 2009;19(4):437-40

“Intravenous immunoglobulin treatment for painful sensory neuropathy associated with Sjögren’s syndrome”
279(1-2) J. Neurol. Sci. 57-61 (2009)

77(8) J. Neurol. Neurosurg. Psychiatry 967-969 (2006)

 “Differential response to intravenous immunoglobulin (IVIg) therapy among multifocal and polyneuropathy types of painful diabetic neuropathy”
17(8) J. Clin. Neurosci. 1003-1008 (2010)

“Intravenous Immunoglobulin for the Treatment of Diabetic Lumbosacral Radiculoplexus Neuropathy” 10(8) Pain Med. 1476-1480 (2009)

“Intravenous immunoglobulin therapy markedly ameliorates muscle weakness and severe pain in proximal diabetic neuropathy”
78(8) J. Neurol. Neurosurg. Psychiatry 899-901 (2007)

There are MANY more journal articles on the use of IVIG for painful sensory neuropathy, and every other form of neuropathy that may have an infectious, autoimmune or inflammatory cause.  All you have to do to find these articles is search for IVIG and neuropathy on PubMed.gov, JSTOR or Google.

There are risks associated with IVIG, just like any drug.  Side effects include bad headaches, hives, hypotension, hives, and sometimes bad reactions like aseptic meningitis (swelling of the lining of the brain and spinal cord) and anaphylactic shock (a SEVERE life threatening allergic reaction). Most patients receive IVIG at an infusion center or as an outpatient at the hospital.

IVIG is very expensive.  It can run between $10,000 to $20,000 per dose.  The market price for IVIG changes, and in 2005 there was even a global shortage of IVIG which drove prices even higher.  There are several different brands, but you're not likely to find a deep discount based on the brand - and some brands are considered safer than others.

Unless you have been diagnosed with one of the conditions IVIG has FDA approval for, it is very difficult to get an insurance company to pay for it.  Since it is so expensive, the insurance companies will do whatever it takes to get out of paying for this drug - everything from questioning the legitimacy of your diagnosis, to claiming IVIG isn't medically necessary, to telling you to try cheaper drugs first (even when the medical literature proves those drugs do not help), to claiming it is experimental and not proven safe or proven to work, to trying to invalidate your policy for some obscure reason.  

Thankfully, there is an organization that helps people with IVIG insurance appeals - Advocacy for Patients With Chronic Illnesses.  They even have IVIG insurance appeal letters and supporting medical journal articles for many of the "off label" uses of IVIG on their website.

I have met several patients with autonomic neuropathy and POTS like symptoms who are currently getting IVIG.  Most of them got it approved by their insurance companies after a long, tough battle - and waiting for that battle to play out is not a good idea, because the sooner you get the IVIG, the more likely it is to work, the more likely it is to stop any further nerve damage.  And all of them think the benefits it has provided them outweigh the side effects and potential risks.  It's nice to know there is another drug out there that can help some POTS patients.  Now we just have to get more patients talking to their doctors about this, because it is definitely not a well known therapy within the POTS patient population.  POTS itself is not well known within the medical profession, and its causes and treatment are even less well known.  

I encourage all POTS patients to visit Mayo Clinic in Minnesota, Cleveland Clinic in Ohio or Vanderbilt University in Baltimore as soon as possible after diagnosis.  They have a wealth of information and experience simply not found at your local doctor's office.

1 comment:

  1. I've thought about this before but my dysautonomia specialist wouldn't even discuss it with me. thank you for sharing. very informative!