Would you consider using IVIG for POTS in the absence of any clear autoimmune condition or abnormal antibodies?

I completely agree with the answer above. It would be a pretty rare consideration, overall.

Recent placebo-controlled and blinded studies examining the efficacy of IVIG for idiopathic or antibody-associated (FGFR, TSHDS) small fiber neuropathy found no benefit of the treatment in terms of small fiber density on follow-up biopsy or symptom scores, compared to placebo (Gibbons et al., PMID 36367813 and Geerts et al., PMID 33766992).

The question presumes that an autoimmune neuropathy is involved in the pathophysiology of POTS. Neuropathic POTS, as confirmed with a skin biopsy, is actually rather rare. For what it's worth, I've seen one patient with biopsy evidence of small fiber neuropathy in the last year and this patient had an asymptomatic ...

IVIG use for POTS patients is off-label and not FDA approved regardless of autoimmunity. The use of IVIG has been reported to be beneficial in a subgroup of POTS patients with suspicion of an autoimmune cause such as having positive relevant antibodies, in the setting of a known autoimmune disease or in some cases of post-infectious onset. If the patients do not have a history suggestive of autoimmunity as the cause and no relevant positive lab testing or not having a known autoimmune disease, I do not recommend IVIG infusions and would stick with symptomatic treatment.

Do I use IVIG in POTS in the absence of any CLEAR autoimmune condition or antibodies? The keyword here is CLEAR and my short answer is NO.

However, there are several shortcomings in my answer.

1. What is a clear autoimmune condition? We do not have criteria to define it yet.
2. What antibodies are we talking about? The list keeps growing. Does the absence of detectable antibodies today rule out an autoimmune condition? Probably not.

So what do I do? I defer IVIG, don't just exclude it. I keep looking for an antibody especially if there is no improvement with symptomatic treatments or worsening. Sometimes an antibody shows up later down the road. If I clinically suspect an autoimmune etiology and don't find that famous antibody, I repeat the et...

I just wanted to add this recent publication to update the discussion of this question:

Vernino et al., PMID 38311655

It is only a small trial and I think more data are needed. However, it does provide evidence to show that IVIG does not seem to be a beneficial treatment option for POTS.