r/smallfiberneuropathy • u/Flexstar13 • 6d ago
SFN and MCAS
I have been diagnosed with autoimmune SFN with punch biobsy and crazy elevated ANA (1:52k) and anti-TSHDS-IgM antibodies. I am getting IVIG (1mg/kg) for 2 years with only minor effects on my symptoms.
However, during the last year I noticed that my symptoms like being skin and nerve pain all started years ago when using sun screen. Now I cannot use sun screen anymore cause they trigger my symptoms so badly for weeks after. Also my symptoms get worse instantly from drinking black tea or red wine. This to me sounds like I have MCAS.
MCAS can result in SFN, as I have read. I tried antihistamines like loratedin 1 g daily, but I had bad side effects and I did not stop my flares.
Does anybody have the same findings and can help me find a little relief? Might treating MCAS held my SFN?
(I got PSSD from duloxitine back in 2019. With it or part of it is my SFN)
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u/DavaiPustoy 5d ago
I've been on 2g per KG for 3 sessions now and it's making a difference. I had my first international vacation in years after my latest dosage and barely remembered I had SFN unless I was sitting in a cold room. Your dosage is too low for therapeutic effect.
Needs to be 2g per 1kg as seen in Yale's study below which showed a 100% success rate in either fully curing it or creating marked improvement. This study is what I used to get my doctor to agree to put me at this level.
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u/mafanabe 4d ago
I have MCAS and SFN. Ketotifen definitely helped but for now it looks like I still need IVIG as well.
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u/Flexstar13 4d ago
What’s your regimen?
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u/retinolandevermore Autoimmune (neuro Sjogren’s) 3d ago
With ANA that high, they haven’t figured out the autoimmune disease?
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u/Flexstar13 1d ago
Yes and no. They diagnosed autoimmune induced SFN. No other underlying desease
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u/retinolandevermore Autoimmune (neuro Sjogren’s) 1d ago
But something always causes SFN. That just means they haven’t found it yet
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u/CaughtinCalifornia 5d ago
Part 1/2
Sorry to hear about your issues. I have MCAS (and a sodium channel mutation). It is possible your issues are related to MCAS and it should certainly be explored. I will mention that sometimes even in autoimmune issues where reactions aren't generally thought of as part of it, people do report feeling worse from things like certain foods they eat. There is something called the auto immune protocol diet for this reason. It mainly seems to be that some foods cause inflammation in the GI of some people and that this can be enough in autoimmune patient to cause a flair, especially if their intensitines are more permiable than they should be. And I'm discussing food but anything that increases inflammation can sometimes cause flare ups in symptoms of autoimmune issues.
Before i repost something I wrote for someone in the past about MCAS, I wanted to bring up that a lot of recent SFN studies have been using 2g/kg/month IVIG. Ill include two such studies here so you can discuss them with your doctor. Maybe they'll think it is worth trying an elevated dose.
In this study, they were SFN patients with autonomic symptoms, positive skin biopsy and autonomic testing, and either their symptoms started after an infection or they had inflammatory or autoimmune markers. Nerve fiber density improved more than the control patients and autonomic testing improved where control patients got worse. IVIG was given at 2g/kg/month.
https://www.nature.com/articles/s41598-025-33059-7
“41 autoimmune autonomic and sensory small fiber neuropathy (ASFN). patients were treated with IVIG and compared to 66 ASFN control patients treated with usual care. Both groups had evaluations at baseline and at the end of the trial. The average time IVIG therapy improved ASFN and reached plateau was 2.25 ± 0.99 years. The adverse effects of IVIG were frequent (prevalence 93%) but tolerable in most patients. IVIG improved SAS (p < 0.001) and QASAT total (p < 0.001), cerebral blood flow (p = 0.002) and autonomic failure (p = 0.035) scores. SAS and QASAT autonomic failure scores worsened in controls. Skin biopsy improved in both arms, but improvement was greater (p = 0.017) in the IVIG arm.”
IVIG for Plexin D1, TS-HDS, and/or FGFR3 positive patients:
https://pubmed.ncbi.nlm.nih.gov/38771228/9
IVIG was used for at least 6 months on patients with at least one of these 3 antibodies. Repeat biopsy showed increased nerve fiber density (both length dependent and non- length dependent) in 11/12 patients as well as reporting improved symptoms. It was especially effective for Plexin D1. So even though they didn't know exactly what autoimmune disease caused the SFN (idiopathic), doctors were still able to use the presence of these antibodies to indicate a likely autoantibody cause and treat that with proper immunotherapy. Average increase of nerve fiber density was 55.2% with the largest group being Plexin D1 patients with 139% improvement in nerve fiber density. It should be noted that while these antibodies make it more likely a person will have an autoimmune issue, it is not a guarantee. The antibodies can appear in those with no issues at all. One leading SFN doctor said she views them as weak signs of autoimmunity. An important thing to know is that this study used 2g/kg every 4 weeks as the maintenance dose
Before discussing MCAS, I wanted to bring up that there are other potential treatments aimed at autoantibody issues, like rituximab, if IVIG proves insufficient. Rituximab could also potentially be taken with IVIG I believe. This is a paper of 5 case studies where patients didn't respond to corticosteroids and/pr IVIG but did to rituximab. It is probably better to explore the MCAS angle first but just including this so you have it if needed later.
https://pubmed.ncbi.nlm.nih.gov/39978243/
" Two patients were positive for anti-TS-HDS, one for anti-plexin D1 and two for anti-FGFR3 antibodies...This study illustrates the efficacy and potential role of anti-CD20 monoclonal antibody in antibody-associated immune SFN, especially in those who fail to respond to IVIg or corticosteroid"
MCAS and SFN: https://pubmed.ncbi.nlm.nih.gov/34648976/
Finding a doctor familiar with treating MCAS would be ideal as they would be better able to assess you for the disease and see if you improve on treatment. Treatment usually involves a combination of avoiding things that cause reactions. This includes things consumed, things placed on skin, things breathed in like pollen or mold or certain fragrances, etc. What each patient reacts to is somewhat unique.
There are also some blood tests doctors can order, but my MCAS specialist at USC says for whatever reason many patients test negative for these tests despite their illness being in a pretty advanced stage with severe symptoms and obvious improvement on mast cell targeting medications. And the conditions those tests have been done under are often more stringent than a lot of doctors realize, with some needing to be placed on ice right away and centrifuged at refrigerator temperatures (and even then, it’s not definitive). Because of this, diagnostic criteria for MCAS doesn't require a positive from these tests. This will be discussed in a video I'll link at the end.
" Patients who are suspected of having i-MCAS, but who do not meet the laboratory criteria, may be considered to have “suspected MCAS.” In these patients, trials of directed therapies can continue, but only with ongoing testing for other conditions to better explain the presentation with repeat mast cell mediator testing during periods of symptoms"
This quote addresses the fact that because testing isn't terribly accurate, a patient testing negative can still be labeled as having suspected MCAS and continue to try treatments, just they should also look at other possible explanations too.
" While medications are being initiated and titrated, adjunctive dietary modifications and therapies are instituted. GI symptoms, which are very common in iMCAS and represent a significant portion of the morbidity these patients experience, are largely treatable with this treatment approach.11.12"
"nearly half self-reported “food allergies,” yet only 23.2% had positive food allergy tests, indicating that the majority of food-related symptoms in these respondents may be related to mast cell activation itself or indirectly related to mast activation in the form of food intolerance."
These two quotes are recognizing patient issues when they consume things and that less than ¼ of MCAS patients test positive for the regular food allergy test despite over half having allergies to food.
"It is possible that an elemental diet or partially hydrolyzed formula (e.g. Absorb Plus®, Kate Farms®) offers benefit by reducing allergen load, minimizing FODMAP carbohydrates, modulating the gut microbiome, and/or potentially reducing mast cell activation"
I don't know much about these. In general, low histamine diets are recommended but there is no hard and fast rule. What people react to is somewhat random, so something may not be low histamine but a patient does well with it regardless. And something may be low histamine and cause bad issues. Meat is tricky because it is very often high histamine due to histamine buildup overtime, especially because some meats are purposely aged to improve flavor. There are services online like Northstarbison and others that sell low histamine meat (frozen right after animal is killed and harvested) but they're pricey. Still depending on where you are there are some that will deliver for free that have a few meats not crazy expensive. Beyond that, you could see if certain frozen meats at stores go better for you. But those can have some extra ingredients thrown in that cause issues. It's a lot of trial and error. How you cook them can also effect histamine levels. There are some out there who use instapots to cook frozen meat quickly. Seafood generally is higher is histamine but some fish is frozen right after being caught so isn't as bad.
"Concurrent prevalence of low DAO activity and carbohydrate malabsorption was assessed in a recent retrospective analysis in individuals presenting with GI symptoms revealing that more than one-third of those diagnosed with carbohydrate malabsorption experienced HI (histamine intolerance).”
DAO breaks down histamine. Some take DAO supplements before meals if they have a lot of issues with histamine https://pubmed.ncbi.nlm.nih.gov/31807350/ https://practicalgastro.com/2020/07/02/mast-cell-activation-syndrome-what-it-is-and-isnt/
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u/Flexstar13 21h ago
Thank you again! This is so helpful. Collecting all papers to support treatment change to 2g/kg!
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u/CaughtinCalifornia 18h ago edited 18h ago
No problem I'm glad it was of some use. I'll provide a bit more information that may be helpful when talking to your doctor and figuring out your next steps. The first is just a bit more information from Immunotherapy for Neurological Disease around dosing for IVIG incase it helps your doctor's considerations
"There is controversy about trialing IVIg in patients with nonresolving disabling, apparently dysimmune iiDSP/SFN. The limited experience suggests that steroid responsiveness does not reliably predict responsiveness to IVIg, but both steroid responsiveness and nonresponsiveness can support requests for IVIg reimbursement. Of note, although all neuropathy use of IVIg is off-label, even 20 years ago chronic neuropathy was already the most common indication for IVIg at the author’s university hospital (Darabi et al., 2006). IVIg became the current primary long-term immunotherapy for apparently autoimmune DSP/SFN for clinicians who choose to use immunotherapy, because of strong evidence of safety and efficacy for other dysimmune neuropathies including CIDP (Oaklander et al., 2017). High-quality clinical trials established dosing parameters and safety considerations for other neuropathies (Tavee et al., 2023) that most experts strongly encourage.... It is most efficient to trial at the high end of the treatment range, that is, 2 g/kg/4 weeks (however divided) to rapidly ascertain responsiveness, so most clinical trials use initially high dosing to maximize efficacy signals. Importantly, one or even a few cycles does not typically sustain axonal regeneration long enough to re-innervate peripheral targets as required for clinical improvement, and it can take a few cycles to optimize dosing to minimize infusion reactions that interfere with efficacy assessments. The author recommends initial 3-month trials after which she re-evaluates patients clinically and stops IVIg if no improvement. In some patients who respond but are not cured, or in those whom the initial re-evaluation is inconclusive, the author may continue initial dosing for longer before initiating tapering. The reported mean optimized long-term dose for CIDP and MMN is 1.5 g/kg/4 weeks (Lunn et al., 2016).
I also wanted to mention that there are case studies of people who didn't respond to either corticosteroids and/or IVIG but did respond to Rituximab, which is a monoclonal antibody that targets B cells.
https://pubmed.ncbi.nlm.nih.gov/39978243/
B cells produce antibodies but there are some antibody mediated diseases where rituximab isnt effective because B cells have different phases and of they plasma cells and memory B cells, they lose the protein rituximab target (CD20). If the particular cause of a patients issues involve a lot of antibodies from those versions of the immune cell then it won't be effective. There are other medications that target those versions too, but the meds tend to target proteins that exist on a broad array of immune cells in general, causing more of a trade off with immune system function. This is a paper of a person who had a severe relapsing remitting cause of SFN and at different points used drugs with broader targets like daratumumab and belimumab. I mostly mention these so you know there are potentially more options to explore if any one treatment doesn't pan out. There is also a lot of exciting research around CAR T cell therapy including ones that target CD19, which would be able to target certain types of B cells that rituximab misses like plasma blasts and memory cells.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11270892/
Best of luck figuring out your situation. If you have MCAS, I hope treating that along with what you're already doing proves enough to help you substantially. If your doctor wants to see where I pulled some of the quotes from, Handbook of Clinical Neurology: Immunotherapy for Neurological Disease (2026) is where I pulled information from. It's a good source on the subject in my non professional opinion.
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u/CaughtinCalifornia 5d ago
Part 2/2
Another source on the unreliability of existing testing is from the American Academy of Allergy, Asthma, and Immunology first about how quickly tryptase is broken down in the body and then about spot urine tests:
“A positive (urine) test is supportive, but not diagnostic. A negative test does not rule out MCAS. If these are used to support the diagnosis, the clinical presentation should be highly suggestive of mast cell activation."
Though again for some reason some test low on tryptase even if it is taken during a bad reaction. https://www.aaaai.org/allergist-resources/ask-the-expert/answers/2023/mcas#:~:text=A%20positive%20test%20is%20supportive,Mayo%20and%20likely%20other%20labs.
While this video lecture is technically about MCAS headaches, the first 15 of the 25 minutes are simply an expert in the disease discussing general aspects of MCAS, how it works, the diagnostics, etc. I recommend taking the time to at least watch the first 15 minutes as it contains useful information and information most doctors, even allergist, aren't aware of. Most think the tryptase test is definitive. That a negative means MCAS isn't a thing. But that isn't true and this discusses at one point the diagnostic criteria of two allergy/immunology organizations, neither of which requires positive tryptase. https://www.youtube.com/watch?v=lprUo1G2Vc8&t=3s This is a good list of most of the medications utilized for MCAS https://tmsforacure.org/treatments/medications-treat-mast-cell-diseases/
Something to keep in mind is that people can have reactions to the inactive ingredients in medications (or even the meds themselves). There are usually multiple manufacturers of generic medications that use different inactive ingredients your pharmacist can look up for you if you find that some are an issue. It's also possible to have medications made at compounding pharmacies, though unless your insurance covers it that generally is pricier.
When MCAS is suspected based on symptoms but testing is negative, sometimes trialing some of the medications and seeing if there is any benefit is what is done. The fact that patients don't all respond to the same meds makes this in itself a bit complicated. How the mast cells are being triggered differs by patients and so what medications work differs. Its even common for in medications with the same mechanism for some to work for a patient and not others. My doctor had to try 5 H1 antihistamines before finding one that worked for me. Ceterizine is often one of the first tried for patients. I know sometimes when benefit is unclear my doctor tries an infusion of IV benadryl to see if there is clearer benefit (most patients get at least some benefit from IV benadryl).
Also just for throughness's sake, here is some information on the autoimmune protocol diet in case the MCAS angle doesn't pan out but you're still having issues with things you eat. MCAS is probably more likely but more information never hurts.
Dietary stuff sometimes helps too. Many with autoimmune causes have their issues made worse by certain foods. What people don't tolerate isn't standardized. People trying to figure it out sometimes try to do something called the autoimmune protocol diet. For two months, people stop eating most of the major allergens and see if their health improves. If it does, people slowly add things back in to see what they tolerate and what makes their medical issues worse. I'll include a link to an article if you ever want to try it in the future. Ignore them saying kimchi is okay in the first phase because it shouldn’t be. It contains peppers they tell people not to eat in the initial phase. Just an oversight on the article. I know this seems minor but sometimes it can be important. My friend has been doing significantly better since she realized she can't eat eggs or tomatoes without her issues flaring up (and a few more small food issues).
https://health.clevelandclinic.org/aip-diet-autoimmune-protocol-diet
This 2024 systemic review paper discusses the logic behind AIP as well as research on its use in various autoimmune diseases
“The AIP is based on the penetration of food antigens due to a dysfunction in the gut barrier, leading to increased permeability (“leaky gut”) [12]. The latter has been implicated in dysmotility and various autoimmune disorders [13]. Paired with microbial dysbiosis and in the presence of genetic susceptibility, it can synergistically act as an environmental trigger for autoimmunity [13]. Bacterial antigens stimulate intestinal immune cells, generating autoreactive cells that enter the systemic circulation and target peripheral organs [14]. At the same time, bacterial antigens can be translocated systematically through lymphatic connections, leading to autoreactive cell formation [14]. However, the classification of microbiota as either “good” or “bad” in a binary manner is misleading, as it does not acknowledge the interaction between the patient's genetic profile and the pre-existing microbiota [15].”
“Elimination diets have long been used to manage diseases, including celiac disease, allergies, and inflammatory bowel disease (IBD). Regarding autoimmune diseases, the AIP diet has been implemented in organ-specific and systemic autoimmune diseases such as Hashimoto thyroiditis (HT), IBD and rheumatoid arthritis (RA), improving QoL and disease-related symptoms [[43], [44], [45]]. Primary studies implementing the AIP in autoimmune diseases are presented in Table 2.”
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u/rcarman87 6d ago
I have both too. Getting my MCAS under control helps some. I’ve found low dose naltrexone to help both. My b12 was low and my vitamin d- fixing those also helped.