IVIG for autoimmune small-fiber neuropathy

My experience with Intravenous Immunoglobulins (IVIG)

Hi everyone, good to see you back here! 🌺

Many people have asked me if I had tried IVIG (intravenous immunoglobulins) or SCIG (subcutaneous immunoglobulins) to treat my autoimmune small-fiber neuropathy. 

Yes, I had IVIG and SCIG for quite some time 

It worked very well for my neuropathy, but it was quite a ride 

Around February 2019, my autoimmune small-fiber neuropathy had been in remission for 3 months, after my second acute onset episode had been broughtunder control. Both prior episodes started after a viral upper respiratory tract infection, and both went into remission with high-dose oral prednisone. 

However, to control my second episode, I had to take prednisone for almost a year (vs 3 months for episode 1) and taper it very slowly. Symptoms had come back several times when I tried to reduce it faster (I'll write about this another time). So here I was, happy that this resistant episode of SFN was finally controlled. 

But once again, I caught a respiratory tract infection, and 10 days later the exact same neuropathy symptoms started abruptly. I had a few viral infections in between as well, which didn't cause any symptoms, so I don't know what was different about this one. I must react to some specific virus, but I don't know which one it is. First, i developed pain and erythromelalgia in my feet and couldn't tolerate shoes, and within a day my hands got sore too and my nose started to itch. 

Obviously, I was very disheartened by this set-back. I still had prednisone at home and immediately took 50mg to stop my syptoms from getting worse. However,  I knew that taking prednisone for months and months again was not an option without harming my body. 

I needed a treatment that was not predisone and that would not destroy my body long-term

When episode 2 started, I got treated by Prof. Maryanne Walker in Boston (not her real name) where I was living at the time. Back then, she prescribed prednisone, but she also told me that if my small-fiber neuropathy came back she recommends getting IVIG. She also advised me to get in touch with Prof. Wexler in Switzerland (not his real name). He is THE NEUROLOGIST for small-fiber neuropathy in the German speaking part of Switzerland. Apparently, I had to go all the way to Boston to find out about that......

So I got in touch with Prof. Wexler's clinic....

...and was told, that the next available appointment was in 4 months. Exactly what you want to hear when you are in a desperate medical situation. So, I got in contact with Dr. Soland, my local neurologist who is an excellent neurologist and who had seen me through my prior two episodes of SFN. He knew Prof. Wexler and referred me urgently, but we both expected a long wait. 

Much to my surprise, I got a phone call from Prof. Wexler's clinic the next day. Apparently, someone had cancelled their appointment and they asked if I was able to come in the next day. Of course, I dropped everything to make this appointment happen. 

I went to Lucerne and met Prof. Wexler 

I also brought my discharge letters by Prof. Maryanne Walker, whom he knew from different research meetings, in which she wrote that she recommends IVIG if my neuropathy ever needed longer-term treatment.  

Prof. Wexler agreed that IVIG was the best treatment choice

However, he warned me that many health insurances refused to pay this treatment for patients with small-fiber neuroapthy, because obviously it is not very well researched, like everything other possible treatment for SFN. 

The difference between prednisone and IVIG is just that you can get a month worth of prednisoen for around 20 Swiss Francs (20 USD), whereas IVIG treatment costs around 40'000 Swiss Francs or more (approx 40'000 USD) per year in Switzerland. 

IVIG are immunoglobulins (aka antibodies), extracted from donated blood

They have originally been used to boost the immune system of people with antibody deficiencies. Over the years, it has become apparent, that high doses of immunoglobulins can control antibody-mediated autoimmune diseases. The way how IVIG works in autoimmune diseases is not fully understood. 

It is assumed that if you infuse heaps of healthy antibodies into the blood stream, they sort of outcrowd the bad ones (i.e. the auto-antibodies), which also speeds up their excretion. But other mechanisms of action are discussed as well.  

Prof. Wexler wrote a letter to my health insurance to apply for IVIG treatment, and we both prepared for a long back and forth fighting my health insurance. Much to our surprise though, they didn't argue at all. They aproved my treatment within a matter of days. I know, I got very lucky there!

I started IVIG treatment about a week after my symptoms started

Everyone assured me that IVIG caused basically no side effect

...and I believed them. I had to go in three days in a row to get a total loading dose of 1.5g/kg body weight of Privigen®. I was still on 50mg prednisone, which had already controlled most symptoms, and which I was going to take for another week after starting IVIG. 

So I sat in the infusion room of the neurology ward hooked up to a needle and an infusion stand for several hours per day. The staff was very nice, and it was also kind of 'nice' to see other people in a similar situation (although of course I don't wish this on anyone). The infusions went smoothly and I left the clinic optimistically on day 3. I was symptom-free, though I didn't know if this was due to prednisone or if IVIG was already doing anything. I did however notice that my feet started to be more tinlgy in the evening after the second infusion. 

In the evening after the third infusion, I developed a very bad headache...

I had been told that IVIG could cause headaches, but I thought that a little headache would be be nothing to worry about if the treatment helped. And sure enough, noone told me how bad such a headache could get. So I figured I'd just sleep it off, and went to bed hoping I would wake up fresh again in the morning. 

But the headache got worse and worse by the hour....

Sleep was 100% not an option, and by midnight I had a 9/10 headache. I was in pain all the way down my neck and spine right to my tail bone. I couldn't move and could only lie in one sideways position. On top of that I was super nausious. I took all the pain and nausea medication I could find in my well-stocked drug cabinet (I am a pharmacist after all), but even touched the pain. 

Towards the morning the pain easeed up a bit and I finally fell asleep

When I woke up a few hours later, the headache was almost gone. Now that I was functional again, I started to do some online research and found that these types of delayed headaches were actually quite common with IVIG. It also appears that they seem to be more common in patients with autoimmune problems. It is assumed that IVIG triggers some sort of mast cell attack on the meninges, i.e. an aspeptic (non-infectious) meningitis. That made a lot of sense to me, because what I had was definitely not just a headache....

I got in touch with Prof. Wexler and told him about my horrific headache experience. He agreed that I likely had a 'mild' meningitis. If this was mild, I don't want to find out how severe meningitis feels like.... He said that they will reduce infusion speed the next time, which should make it better. Also, I was only going to get 1g/kg per month from now on. Lower doses should also cause less headache. So I was optimistic that we would be able to control this. 

One week later, I tapered prednisone and the neuropathy remained in remission

I was very happy that IVIG seemed to do a great job. My next infusion was planned for 4 weeks after the last infusion. 

However, 3 weeks after the last IVIG infusion, my small-fiber symptoms come back from one day to the next

I told Prof. Wexler about this when I went in for my next infusion and he said to see what happens after this infusion. He said that I likely experience so called 'end of cycle symptoms', where symptoms come back as the effect of IVIG wears off. 

And sure enough, symptoms did disappear again within 2 days after the next infusion. 

But the headache came back as well.🤯 Thanks to the lower dose and the slower infusion speed the headache was a bit less intense, but still intense enough to make me absolutely miserable. And worst of all, this time the pain lasted for almost 2 weeks.

On top of that, I developed an allergic whole body rash, which lasted about 10 days and was super itchy. But in light of the severe headache, the rash seemed like a very minor nuisance. 

So here I was, neuropathy-free but with a headache that was probably worse than having neuropathy. It felt like chosing between Sodom and Gomorrah. And as the headache eased up, the 'end of cycle neuropathy symptoms' started over. 

Initially, we had hoped that 1 or 2 IVIG infusions may put my small-fiber neuropathy into remission for good. But that was obviously not the case, and it seemed that I needed long-term treatment.

However, we were far away from a good treatment plan

Prof. Wexler was also surprised about the severity of my headaches, which made me pretty much non-functional in daily life. So with each round of infusions, we further reduced the dose, the interval between infusions, and the infusion speed. This did make my headaches less intense, but unfortunately, even less intense headaches were still severe enough to make me miserable.

We reduced the dose as much as possible

At some point, I sat in the infusion room for 8 hours straight every week to be infused with a small dose (15g or so) of IVIG. Nonetheless, I still had a 24/7 headache accompanied by nausea that didn't allow me to enjoy my life. 

Antihistamines helped to take the edge off the pain

Because it's assumed that this headache is due to a mast cell reaction towards the meninges, regular painkillers don't work, but antihistamines can help to reduce the pain. Interestingly, the newer antihistamines, which do not make you tired didn't work for me at all. I tried levocetirizine and fexofenadine and had absolutely no improvement. 

The antihistamine that worked for me was diphenhydramine. It's an old type of antihistamine, which makes you very tired, because it crosses the blood brain barrier. Given that the headache stems from an inflammation of the meninges, it makes sense to me that a drug that crosses the blood brain barrier works better. That is just my hypothesis though. 

In the US, diphenhydramine is frequently used as an anti-allergy drug and is sold under the brand name Bedadryl. However, in Switzerland, it is only sold as a sleeping pill under the brand name Benocten. At first, I felt pretty stupid going into the pharmacy and asking for sleeping pills several times. And of course, when I told them what I needed it for, they just looked at me with big eyes...I started to worry they would put a note into my patient profile about potential drug abuse. But Prof. Wexler gave me a prescription for it, which took care of this. 

But you can imagine, it's not ideal to take 'sleeping pills' during the day all the time. You might have an improved headache, but you also just have to go and take a nap. You do get used to them a bit, and after a while you don't get so tired from them, but nontheless, this was not an ideal long-term plan, as the headache was far from gone anyway. 

After 3 months of this torture we decided that IVIG wasn't for me...

...and applied to switch to subcutaneous immunoglobulins (SCIG)

SCIG is essentially the exact same thing as IVIG, you just administer it yourself at home and it goes under your skin instead of into your blood. And because you don't give it directly into your blood stream, it arrives in your body much slower and causes much less side effects, including headaches. 

The problem was just, that SCIG had only recently been licensed in Switzerland, and of course not for autoimmune small-fiber neuropathy. We didn't know if insurance would approve it, although the cost to them are pretty much the same or maybe even a bit less because they don't have to pay for hospital staff doing the infusion. 

Thankfully, health insurance agreed to this change and I was able to start SCIG. I will write a separate post about my SCIG journey next time.  

So all in all, yes IVIG worked very well to control my autoimmune small-fiber neuropathy. Symptoms were in complete remission for 3 weeks after each infusion. But IVIG wreaked havoc on my body. 

I think doctors just don't really worry about side effects that are not directly dangerous, i.e. that can't kill you. Even if that means you can't live your life. When I started my immunosuppression, doctors discussed the risk of infection with me over and over. However, this risk of infection has affected my life so much less than the torture I was inflicted on by IVIG. 

This is totally not to discourage anyone to try IVIG!!

I'm still glad I tried it, and I would do it again, because it led me to a treatment that worked and that I tolerated better. Also, almost everyone else I know, who tried or is getting IVIG tolerates it much better than me. I just got unlucky there. However, I feel like it's important to share this experience, becuase noone had warned me sufficiently of these potential side effects. 

If you plan to get IVIG, it might be better to start with a small dose at a very slow speed and see how you go. It also make sense to take a lot of antihistamines before and after the infusion and if you don't tolerate IVIG well maybe even some steroids (usually dexamethasone). 

This is a very helpful paper, which discusses exactly this problem, and which provides a raodmap on how to best start IVIG inpatients with autoimmune small-fiber neuropathy. They do also write, that in their experience, this type of headache is more common in young patients with autoimmune SFN. Make sure you bring this to your pre-IVIG meeting with your neurologist and make sure they have read it. Prof. Wexler totally agreed with this paper, and we adjusted my treatment according to it, which was successful in the end.

I will tell you more about my journey with SCIG (Hizentra (R)) in my next post. And until then I wish you a good weekend!

Thank you for your continued interest in my blog and for your support. 

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Categories: IVIG, treatment