IVIG Stopped Working for Your Small Fibre Neuropathy. What Comes Next

If IVIG worked and then stopped working, you are not out of options. You are in the group that stem cell transplant was designed for.

Autoimmune small fibre neuropathy is one of the hardest conditions in neurology to get taken seriously. The burning feet, the electric pain that arrives at night, the racing heart on standing, the gut that has stopped behaving, the sweating that is either absent or drenching. Many patients spend years being told their standard nerve tests are normal and therefore nothing is wrong, when the problem is that standard nerve conduction testing does not measure small fibres at all.

When the diagnosis is finally made by skin biopsy or autonomic testing, the treatment path is usually immunoglobulin, steroids, or rituximab. For a meaningful number of patients these work. For others they work for a while and then stop. This article is for that second group, and for people with autoimmune autonomic ganglionopathy, dysautonomia of autoimmune origin, and rare treatment resistant neuropathy who have already been through the standard ladder.

What autoimmune small fibre neuropathy actually is

Small fibre neuropathy is damage to the thinly myelinated A-delta and unmyelinated C fibres. These are the nerves that carry pain and temperature, and they also run the autonomic nervous system: heart rate, blood pressure on standing, sweating, digestion, bladder function.

When the cause is autoimmune, the immune system is producing antibodies and immune cells that attack those fibres. That is a different disease from diabetic or chemotherapy induced small fibre damage, and it responds to different treatment. A 2025 retrospective controlled study in Scientific Reports looked specifically at high dose long term immunoglobulin in autoimmune autonomic and sensory small fibre neuropathy, and found measurable benefit in that population. A report in Neurology Neuroimmunology and Neuroinflammation described a relapsing remitting, immunotherapy responsive form of small fibre neuropathy, which is important because it establishes that this is a treatable immune disease and not simply nerve wear.

The clinical problem is what happens when the immune attack keeps restarting. That is where the conversation changes.

Why immunoglobulin and rituximab stop working

Immunoglobulin, steroids, plasma exchange and rituximab all work by suppressing or diluting an immune system that is already misbehaving. None of them replace it. The autoreactive memory cells that started the attack are still present, and when drug levels fall or the cell population repopulates, the attack resumes.

This is the same mechanism that drives relapse in CIDP, in myasthenia gravis, in NMOSD and in multiple sclerosis. A 2026 systematic review in the Journal of the Peripheral Nervous System examined the whole clinical evidence base for immunoglobulin in small fibre neuropathy and found the picture is genuinely mixed, which matches what patients report: some people respond well, some respond and then lose the response, and some never respond at all.

If you are in the second or third group, escalating the same class of drug is not a strategy.

What stem cell transplant does differently

HSCT does not suppress the immune system. It resets it.

The process runs in four stages. First, your own blood forming stem cells are mobilised and collected. Second, a conditioning regimen clears the autoreactive immune cells, including the memory cells that drug therapy leaves behind. Third, your own cells are reinfused. Fourth, over the following months the immune system rebuilds from those cells, and the rebuilt repertoire does not carry the same autoreactive programming.

Because the cells are your own, there is no donor, no rejection risk and no graft versus host disease. Our full explanation of the stages is on the how it works page, and the condition specific detail is in our HSCT guide for small fibre neuropathy.

What the evidence shows for rare and treatment resistant neuropathy

There is a growing body of transplant experience across autoimmune neurological disease, and specific reports in closely related treatment resistant neuropathies. A large randomised trial in small fibre neuropathy has not been run yet.

A 2023 review of HSCT for autoimmune neurological diseases sets out the current position across the whole field, including the neuropathies. In treatment resistant nodopathy, a group that had failed every standard therapy, there is a published account of successful transplant in anti-Caspr1 antibody nodopathy. In stiff person syndrome, a rare autoimmune neurological condition with a similar treatment resistant profile, there is a documented successful transplant in glycine receptor antibody positive disease. A broader review of HSCT for neurological disease covers the safety and outcome data across conditions.

That body of work says two things. The mechanism is sound, and it has worked in patients with rare treatment resistant autoimmune neuropathy. And the decision is made patient by patient, not by diagnosis label.

Are you a candidate?

Candidacy for rare and treatment resistant neuropathy is assessed individually. The features that point towards transplant being appropriate are:

• A confirmed autoimmune mechanism, ideally with a positive antibody, an abnormal skin biopsy showing reduced intraepidermal nerve fibre density, or abnormal autonomic function testing
• Documented failure or loss of response to at least two standard therapies, typically immunoglobulin plus steroids, rituximab or plasma exchange
• Ongoing disease activity rather than fixed damage from a burnt out process
• Organ function and general fitness sufficient for the conditioning regimen
• Realistic expectations about what stopping the attack means for symptoms that are already established

That last point matters. Transplant is aimed at halting the immune attack. Nerve fibres that are still viable can and do recover, and patients frequently report pain reduction and autonomic improvement over the following year. Fibres that have been destroyed over many years recover more slowly and sometimes incompletely. Getting to treatment earlier gives you more to save.

The most reliable way to find out where you stand is to send us your records. Our team reviews them with the transplant physicians and comes back with a straight answer. You can start that on the eligibility form.

Autoimmune autonomic ganglionopathy and dysautonomia

Autoimmune autonomic ganglionopathy is the most clearly antibody defined condition in this group, usually associated with ganglionic acetylcholine receptor antibodies. Patients present with orthostatic intolerance, gastrointestinal dysmotility, absent sweating, dry eyes and mouth, and bladder dysfunction. Standard care is immunoglobulin, plasma exchange, steroids and rituximab, and the same relapse problem applies.

Autoimmune dysautonomia more broadly, including the autonomic presentations that follow infection, sits on the same spectrum. Where the immune mechanism is demonstrable and standard therapy has failed, the transplant conversation is legitimate. Where it is not, it is not, and we will tell you that.

This is why we build depth in this area rather than a thin page per label. The conditions overlap, the antibodies overlap, and the decision logic is the same across all of them.

Why patients come to HSCT Hospital India

More than 1,500 patients have been treated with HSCT at our partner hospital. The hospital is accredited by JCI USA and holds NABH and NABL accreditation. We use the lower intensity approach, which has the better safety profile, and there is no follow up chemotherapy. Patients stay in deluxe private rooms with triple HEPA filtration through the neutropenic period.

The all inclusive package is 30,000 US dollars for a 30 day stay for the patient and one attendant. That covers the treatment, the room, all doctors’ fees, tests, consultations, medicines and consumables, neuro physiotherapy, food, laundry and airport transfers. The full breakdown is on the treatment package page, and you can compare what other countries charge on our HSCT cost by country comparison. For context, the same treatment in the United States runs from 150,000 to 200,000 dollars.

The waiting list is short, which for a progressive neuropathy is not a convenience issue. More about the facility is on the hospital page and the clinical team is listed on the medical team page.

Patients treated with the same protocol

We treat a wide autoimmune canvas with the same protocol, and patients from across that canvas have written about their outcomes. A patient with small fibre neuropathy has described her recovery after HSCT in India. A patient with stiff person syndrome has described her treatment. More accounts across conditions are collected on our patient stories page.

These are individual outcomes, and they show what the same protocol has done in related treatment resistant autoimmune neurological disease.

What to do next

If immunoglobulin has stopped holding your neuropathy, the useful next step is not another cycle. It is finding out whether your disease is still immunologically active and whether you are a transplant candidate.

Send your neurologist letters, your skin biopsy or autonomic testing results, your antibody panel and a list of what you have already tried, through the eligibility form. You will get a considered answer from people who assess these cases every week.

For the full condition detail, read our small fibre neuropathy guide. To see the whole range of conditions we treat with this protocol, including lupus, scleroderma, Crohn’s disease and myositis, see all our HSCT treatment guides. Patients considering treatment who want to preserve future options should also read our note on fertility preservation before HSCT.