SFN without pain?

[Castorp]

Hello,

I have recently received a diagnosis of apparently autoimmune SFN based on the results of a corneal confocal microscopy and a sudoscan test. (I live in Spain, and here it is impossible to get a reliable skin biopsy). I also have elevated FGFR3 antibodies, which seems to be associated with autoimmune SFN.

Nevertheless, I feel like something is still being missed. In particular, I am concerned with this diagnosis because I have no pain and, to the best of my knowledge, this is the main symptom in SFN. Accordingly, I would like to know if it is possible to have SFN without experiencing pain.

I have several autonomic issues compatible with POTS (e.g. tachycardia when standing or temperature regulation problems) which, according to my neurologist, are caused by SFN. However, my worst symptom is a non-stop profound malaise 24/7. I have experienced this unrelenting malaise since the beginning of my illness in March 2020 every single day. I try to describe it to my doctors as feeling like I have constantly a severe flu (without any respiratory symptoms) which never goes away. This malaise is really incapacitating and I am unable to leave my house and spend most of the day in bed.

I wonder if this daily malaise is actually a SFN symptom. Does anyone else with SFN experience a similar feeling?

Thanks in advance for your help.

 

[kangaSue]

Elevated FGFR3 antibodies are found in neuropathies other than paifil sensory neuropathies such as SFN so having SFN without pain could also be diagnosed as autonomic neuropathy (AN), and quite common for AN to also affect your body temperature regulation.

It's also quite common to have AN with a number of autoimmune conditions, including any of the connective tissue disorders or Ehlers Danloss Syndrome and some of these could also account for your malaise. POTS can go with these things as well.

 

[Pyrrhus]

Nevertheless, I feel like something is still being missed. In particular, I am concerned with this diagnosis because I have no pain and, to the best of my knowledge, this is the main symptom in SFN.

Small Fiber Neuropathy (SFN) can happen in any part of your body and the symptoms of the SFN will vary dramatically depending upon where in your body the SFN is found. Pain is not "the main symptom" of SFN.

I have several autonomic issues compatible with POTS (e.g. tachycardia when standing or temperature regulation problems) which, according to my neurologist, are caused by SFN.

Dysautonomia is caused by neuropathy, but there are many different types of neuropathy, not just SFN. So you generally can not assume that your dysautonomia is caused by SFN.

I try to describe it to my doctors as feeling like I have constantly a severe flu

This malaise is really incapacitating

I wonder if this daily malaise is actually a SFN symptom.

I have never heard of "flu-like symptoms" being caused by SFN.

I hope this helps.

 

[Shanti1]

@Castorp I had the same question you had and I'm glad you posted it. I found this interesting paper:
Small Fiber Neuropathy: Disease Classification Beyond Pain and Burning
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5912271/

Even within diseases that affect purely small fibers, we now understand that this can present as purely sensory disruption such as pain, purely autonomic dysfunction, or in some patients a combination of both sensory and autonomic.

So small fiber neuropathy can be categorized as sensory neuropathy, autonomic neuropathy, or both.

Coincidently, I just happened to be listening to a live-stream on SFN from a doc at Oregon Health Sciences University Comprehensive Pain Clinic this morning. She felt strongly about the role of SFN in dysautonomia, basically saying that blood vessels in muscles are controlled by nerves and SFN causes a loss of control of the muscle blood supply.

She talked about a mechanism brought up in other threads, which is how SFN causes blood to cross from your arterial vessels to your venous system before it reaches the capillary bed, leading to poor oxygenation. This is her slide:

She also talked about diagnosis, here is her list, they are tests that could be performed by a doctor, but I'm guessing someone would have better luck with a neurologist or specialist in ME/CFS, SFN, or Fibro:

• Sensory testing (pinprick test/ sensation test/ reaction time to temperature like ice water)
• QSART test- this is basically a test measuring your ability to sweat, which is an indication of the autonomic function of the nerves in the skin. https://my.clevelandclinic.org/heal...quantitative-sudomotor-axon-reflex-test-qsart
• Tilt table test
• 

Biopsy (which is the gold standard) and autoantibody tests can also be used, but she said she usually doesn't need them. She said the antibody panels for SFN are really expensive and she usually only runs them if she is trying to build a case for insurance for IGIV therapy.

I'm not sure about SFN and malaise, but maybe a connection if your cells/tissues aren't getting oxygen due to the dysautonomia from SFN.

 

[JadeD]

It depends what small nerve fibres are affected as there are several different types. For example your sympathetic nerve fibres could be affected but maybe the noiceptive (c-fibres) are not hence why you do not have pain but you have dysautonomia.

I had a specialist nerve test called microneurography recently which confirmed that my sympathetic nerve fibres, my c fibres and my sudomotor fibres are all affected indicating small fibre neuropathy. This makes sense as I have widespread body pain, sweating and PoTS which are symptoms of all three types of nerve fibres not functioning properly.

SFN can definitely cause malaise probably through a few different mechanisms which they’re still trying to work out.

 

[Shanti1]

Diagnosing small fiber neuropathy in clinical practice: a deep phenotyping study
Nadine Egenolf*, Caren Meyer zu Altenschildesche*, Luisa Kreß, ...
First Published March 23, 2021
https://journals.sagepub.com/doi/full/10.1177/17562864211004318

 

[Inara]

Accordingly, I would like to know if it is possible to have SFN without experiencing pain.

I have SFN, confirmed by QST and skin biopsy of upper and lower leg. I have no pain. I have dysautonomia, presenting, amongst others, as hyperadrenergic and neuropathic POTS. I have Raynaud's, too, and I have problems with temperature regulation. The sweat test was normal. At a clinic, a "finger test" was performed (it was part of a trial), which is better known from cardiology: I don't know its official name. Some apparature was put over my index finger tip, and a suction was produced. Then, the reaction of the small vessels was measured. In my case, these vessels didn't react as they should.

 

[minimus]

There seem to be two schools of thought about small fiber neuropathy among neurologists -- the mainstream view is that the hallmark symptom is pain, sometimes severe, tingling, and/or loss of sensation in the skin, often starting in the feet and hands. The second, newer school, led by Anne Oaklander at Harvard Medical School, is that small fiber neuropathy can cause a wide array of symptoms, not just pain, because the loss of small fiber nerves causes autonomic dysfunction, e.g. impaired gastric motility leading to digestive problems and (possibly) malaise, venous insufficiency resulting in muscle fatigue, muscle pain, brain fog, etc. A number of her lectures are available on YouTube.

I have small fiber neuropathy diagnosed by skin biopsy sent to Oaklander's lab as part of a workup by David Systrom in 2018. Systrom's invasive CPET showed I have severe cardiac preload failure and poor oxygen extraction in the skeletal muscle, which he thought might be attributable in part to SFN. However, after seeing Systrom I went to two neurologists at teaching hospitals in New York, who don't buy into Oaklander's view. When they see SFN, they think painful and tingling skin, possibly some digestive issues, but not much beyond that. Not surprisingly, they see someone like me with moderate/severe ME/CFS as a medical mystery, not as someone whose primary problem is SFN.

I think there's a third school of thought that poorly understood chronic illnesses like ME/CFS, post-treatment Lyme, and fibromyalgia result over time in SFN through some unknown mechanism -- possibly, chronic infection or blood sugar disturbances caused by insulin resistance. In this school of thought, SFN is a co-traveler that arises in chronic illness, but is not the main cause of our symptoms. In other words, SFN is correlated with but not causative of certain chronic illnesses.

My only suggestion would be to consider trying IVIG to see if it helps with malaise, regardless of whether SFN is the root cause of your symptoms. Though some people can't tolerate IVIG, the side effects can be made more tolerable by an extremely slow infusion rate and pretreatment with IV saline, antihistamines like benadryl, and even IV steroids like solumedrol. Side effects can also be mitigated by experimenting with the brand of IVIG used. In my case, for example, I suffered from severe headaches after infusions of Gammagard, but had no side effects from Gamunex-C. Unfortunately, IVIG didn't do that much to help me, but it certainly didn't make me worse and it might be helpful for you.

 

[Pyrrhus]

Systrom's invasive CPET showed I have severe cardiac preload failure and poor oxygen extraction in the skeletal muscle, which he thought might be attributable in part to SFN.

You may be interested in this discussion, which discussed whether Systrom's work could differentiate between SFN caused by dysautonomia and SFN causing dysautonomia:
https://forums.phoenixrising.me/thr...s-joseph-et-al-2021.82907/page-2#post-2374191

Side effects can also be mitigated by experimenting with the brand of IVIG used. In my case, for example, I suffered from severe headaches after infusions of Gammagard

Severe headaches after certain IVIG infusions seems to be a common occurrence in ME.
I wonder whether it might warrant a poll...

 

[Inara]

My only suggestion would be to consider trying IVIG to see if it helps with malaise, regardless of whether SFN is the root cause of your symptoms.

I got SCIG, it didn't help with symptoms like exhaustion and fatiguability or muscle problems. It worsened POTS for 2-3 days substantially. I had severe headaches (took prednisolone for it). But SCIG is not IVIG.

The neurologist that diagnosed SFN only recommended IVIG for autoimmune SFN. Even then, there's no guarantee it helps (see studies).

 

[Castorp]

Thank you very much for your replies. I find all them very helpful. In particular, the paper mentioned by @Shanti1 shows that there is a type of SFN patients who have autonomic dysfunction (e.g. POTS) as their predominant complaint rather than pain. This is consistent with the work of Oaklander and seems to mean that it is possible to have SFN without experiencing pain.

In my case I have been tested for different treatable causes of SFN (e.g. diabetes, Lyme, celiac disease, B12 deficiency, Sjogren,...), with negative results. Nevertheless, I have elevated titers of several adrenergic receptor autoantibodies, which tends to be common in POTS and ME/CFS patients. Interestingly, I also have positive levels of autoantibodies to FGFR3, a highly specific SFN-associated autoantibodies. In view of this, my neurologist thinks that I have apparently autoimmune SFN and that this SFN is causing all my symptoms, including my unrlenting malaise.

Following the recommendations in the literature, I have attempted corticosteroids, IVIG and plasmapheresis, but unfortunately I have not experienced any change in my symptoms. This is really disheartening because, according to the findings by Oaklander, most people with autoimmune SFN improve significantly with IVIG and corticosteriods.

Having reached this point, my neurologist is considering to use immunosuppressant drugs such as Rituximab or Azathriopine (Imuran). Nevertheless, taking into account the null results of my previous treatments (especially IVIG and plasmapheresis), I have serious doubts that this strategy may be useful in my case and I wonder to what extent the autoantibodies themselves are causing my symptoms (i.e. are these autoantibodies pathogenic?)

 

[Shanti1]

@Castorp
While there is no doubt that SFN is associated with dysautonomia, POTS can occur in the absence of SFN. In a post above, Pyrrus linked to a discussion debating if altered blood flow/vascular dysautonomia causes SFN or if SFN causes altered blood flow/vascular dysautonomia. Maybe it is a bit of both.

While many with ME/CFS have SFN, others, such as myself, do not (but I do get PEM, brain fog, and other symptoms). I can understand your misgivings on your doctor's strategy. There is clearly so much more involved in ME/CFS than SFN and, although there may be cases where it is indicated, this study showed no benefit for Rituximab in ME/CFS. Maybe others can chime in who have experience with it.

I think of malaise as being related to immune dysfunction and altered cytokine signling (inflammatory cytokines can cause malaise) or to vegas nerve/brain inflammation signaling "sickness behavior", causing us to feel ill (Dr. Michael VanElzakker's work). Maybe also related to mitochondrial dysfunction secondary to intracellular/intramitochondrial infections or toxins.

 

[Haru]

Hello,

I have recently received a diagnosis of apparently autoimmune SFN based on the results of a corneal confocal microscopy and a sudoscan test. (I live in Spain, and here it is impossible to get a reliable skin biopsy). I also have elevated FGFR3 antibodies, which seems to be associated with autoimmune SFN.

Nevertheless, I feel like something is still being missed. In particular, I am concerned with this diagnosis because I have no pain and, to the best of my knowledge, this is the main symptom in SFN. Accordingly, I would like to know if it is possible to have SFN without experiencing pain.

I have several autonomic issues compatible with POTS (e.g. tachycardia when standing or temperature regulation problems) which, according to my neurologist, are caused by SFN. However, my worst symptom is a non-stop profound malaise 24/7. I have experienced this unrelenting malaise since the beginning of my illness in March 2020 every single day. I try to describe it to my doctors as feeling like I have constantly a severe flu (without any respiratory symptoms) which never goes away. This malaise is really incapacitating and I am unable to leave my house and spend most of the day in bed.

I wonder if this daily malaise is actually a SFN symptom. Does anyone else with SFN experience a similar feeling?

Thanks in advance for your help.

Autoantibodies can be pathogenic as in the case of many autoimmune diseases. Immunosuppressants like Rituximab blocks the productions of these antibodies. Ivig and plasmapheresis have a different mode of action.

 

[kelly8]

I just got this diagnosis as well. My Dr is going to try diavasc as a medication. His thoughts are to improve blood flow to help with SFN and raynauds. I guess some other practitioners were trying this out. I'm already on gammaguard ivig so hopefully this will help make things a little better. Anyone else have experience with trying this drug?

 

[kangaSue]

I just got this diagnosis as well. My Dr is going to try diavasc as a medication. His thoughts are to improve blood flow to help with SFN and raynauds.

Just a point of note here. Diavasc is a calcium channel channel blocker med but nerve and vascular blood flow can sometimes be better improved from using a potassium channel activator med or a nitrodilator (which activate potassium channels after being enzymatically converted to nitric oxide) rather than a calcium channel blocker as these meds can have more efect on the resistance vessels involved in regulating microvascular blood flow.
https://www.cvpharmacology.com/vasodilator/nitro
https://www.cvpharmacology.com/vasodilator/K-openers

 

[Dan_USAAZ]

Nevertheless, I feel like something is still being missed. In particular, I am concerned with this diagnosis because I have no pain and, to the best of my knowledge, this is the main symptom in SFN. Accordingly, I would like to know if it is possible to have SFN without experiencing pain.

I had skin punch biopsies done about three months ago, to be used in a few tests. One of the tests was for SFN. The neurologist was surprised when the results came back as positive for SFN, as SFN was not the primary reason for getting the biopsies. She followed up with an autoimmune blood panel, which was negative and some autonomic testing, which did not show any substantial abnormalities.
Similar to you and some of the others here, I do not believe I experience the type of pain that would normally be associated with SFN.

 

[Shanti1]

Similar to you and some of the others here, I do not believe I experience the type of pain that would normally be associated with SFN.

Thank you for sharing the results of your biopsy. Do you have other symptoms that could be attributed to SFN, such as POTS, alterations in blood flow, or inability to sweat/ excessive sweating?

 

[Dan_USAAZ]

Thank you for sharing the results of your biopsy. Do you have other symptoms that could be attributed to SFN, such as POTS, alterations in blood flow, or inability to sweat/ excessive sweating?

I am not extremely familiar with all the SFN symptoms, but those that I am familiar with and which which you mention I am negative for.

The following are my results for some of what you mention.

The following are the results from the bloodwork. The lab referred to this as their Neuromuscular Antibody Report.

 

[Shanti1]

@Dan_USAAZ Thanks for sharing your results. There have been discussions on if SFN leads to altered capillary blood flow or the other way around and on the spectrum of symptoms that SFN can cause. I am learning myself, which is why I asked.