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False positive Lyme tests secondary to IVIg


P_Mom

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No trying to "open a can of worms." However, I do think this is important to consider.

 

Philamom.....MAY be involved in your daughters recent positive IGG Lyme tests given the IVIg she recieves. Just something to look into...if so desired.

 

 

 

False-positive results of serological tests for Borrelia burgdorferi antibodies are recognised in a number of infections, such as syphilis, parvovirus and Epstein Barr virus, and in various other inflammatory conditions.1 We de- scribe a case where misleading positive Borrelia burgdorferi antibodies were caused by the administration of intrave- nous immunoglobulin.

A 78-year-old man presented with bilateral ptosis, near complete ophthalmoplegia, bilateral facial weakness, are- flexia and gait ataxia. Initial investigations revealed subtle cranial nerve enhancement on MRI and mediastinal lymph- adenopathy on CT chest. He had normal acetyl choline receptor antibody and anti GQ1b antibody titres, making the diagnoses of myasthenia gravis and Miller Fisher syndrome respectively unlikely.

The diagnosis was unclear but neurosarcoidosis was suspected and he was treated empirically with high dose steroids with no benefit. He then received an empirical five- day course of intravenous human normal immunoglobulin (IVIg) (Kiovig, total dose 2 g/kg) with apparent improvement. This was repeated approximately four weeks later, by which time his clinical condition had evolved to include a painful polyradiculopathy. Therefore blood was taken for Borrelia burgdorferi antibodies and was strongly positive by Western blot (nine specific bands), despite no history of tick exposure or rash consistent with erythema migrans. The patient was treated with intravenous ceftriaxone for possible neuro- borreliosis. However, we were suspicious the positive result might be attributable to his IVIg treatment and managed to track down a serum sample taken just prior to his IVIg treatment but after his neurology symptoms had been

present for over two months. This pre IVIg sample was negative for Borrelia burgdorferi antibodies on western blot. His cerebrospinal fluid was acellular, which makes neuroborreliosis less likely, and Borrelia burgdorferi DNA was not detected by PCR. Given the gentleman had been bed bound between the two samples with no opportunity for tick exposure we concluded the positive result was a confounding effect due to receiving pooled donor IVIg. A repeat sample taken two weeks after the positive sample remained western blot positive but with fewer bands (eight positive bands) and noticeable reduction in intensity, in keeping with decay of transfused antibody. The patient continued to deteriorate neurologically and no firm diagnosis was made in life despite extensive investigation. The final autopsy diagnosis was encephalomyelitis of presumed paraneoplastic origin based on the pathological appearances although no tumour was identifiable. There was no evidence of sarcoid or infection.

Intravenous immunoglobulin is an important treatment for a diverse range of conditions, particularly in the fields of neurology and haematology.2 It is prepared by extracting IgG from large pools of plasma donations (>1000 donors/ pool) under strict regulations as laid out by the World Health Organisation (WHO) and Food and Drug Administra- tion (FDA). Its safety relies on donor selection, screening of each plasma donation for blood borne viruses, plus addi- tional virus inactivation procedures.3 Intravenous immuno- globulin has a half-life of approximately 22 days3 and pooled IgG contains antibodies to numerous microorgan- isms, which the donor population has been exposed to, in- cluding measles, hepatitis A, B and C, varicella and tetanus. The human plasma used to manufacture IVIg in our case is

sourced from USA, Germany, Austria, Czech Republic, Swe- den and Switzerland. Lyme disease is endemic in all of these countries, with significant background seropreva- lence to Borrelia burgdorferi in the population. All this has potential implications when interpreting serological tests in IVIg recipients. There are case reports describing misleading positive results for infections such as syphilis and Toxoplasma following passive transfer of antibodies

via pooled human IgG.We found a single case report in literature of false positive BB test secondary to intravenouous immunoglobulin. A number of clinical presentations which may mimic neuroborreliosis are treated with IVIg. A misleading positive antibody result may expose a patient to unnecessary and potentially harmful treatment and delay the correct diagnosis being made. We found no mention of this potential adverse effect of intravenous immunoglobulins in the Department of Health ‘Clinical Guidelines for Immunoglobulin use’ or the Association of British Neurologists ‘Guidelines for the use of Intravenous Immuno- globulin in Neurological Diseases’.2,9 Clinicians need to be aware of possible confounding effects of IVIg on subsequent serology tests, and communicate with the laboratory if their patient has recently received intravenous immuno- globulin. Futhermore, we recommend that where IVIg is being used without a firm diagnosis, serum should be stored before administration of IVIg to provide a baseline sample which enables retrospective testing, should this be required.

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I do think this study raises an important point - one that the forum has been aware of for awhile. This man's positive western blot was done shortly after his second IVIG, with a half life of donor antibodies being 3 weeks. A follow-up WB two weeks later showed a slight decrease in positive bands. We've always advised parents to wait as long as possible - 8 weeks? 10 weeks? before doing a WB if they've done IVIG.

 

I don't think any of us want to treat our kids for a disease they don't have. Had the forum been as lyme-aware when I was at this point, I would've been happier to know about Igenex before we did IVIG instead of having to wait 3 months afterward. I think it's one reason I'd recommend it to someone who had outlier symptoms or non-strep triggers before they did IVIG.

 

There is also a new lyme test that Philamom has posted about on the lyme forum that does not look for antibodies but instead is able to culture spirochetes from the blood sample. Similar to a strep culture. If you see a spirochete growing in a petri dish of your blood, not much question about whether you have lyme. And it wouldn't matter whether you'd had IVIG or not.

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Quoting, and questions...

 

"False-positive results of serological tests for Borrelia burgdorferi antibodies are recognised in a number of infections, such as syphilis, parvovirus and Epstein Barr virus, and in various other inflammatory conditions.1 We de- scribe a case where misleading positive Borrelia burgdorferi antibodies were caused by the administration of intrave- nous immunoglobulin."

 

Really curious about the "Inflammatory conditions" that can cause a false positive on Lyme tests. Anyone know? seeing as so many pandas kids are turning up with Lyme......is it REALLY Lyme? When you think about it, there are people treating their kids for Lyme bases on Igenex's test, with only a handful of positive bands. Maybe it's the bands reacting because of the inflammatory disease (ie., PANDAS)? Just thinking aloud here...

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I think you end up having to test for other "signs" - e.g. we tested C3a and C4a immune complexes, which are suggestive of lyme. You can also do PCR, as they did in the study, plus the new tests I mentioned. Still, I think it comes down to doing what works. If you treat for lyme with say, combo abx, and your kid gets better, do I care whether it was lyme or bartonella or myco p.? If I treat for Pandas and my kid doesn't get better, is it helpful to test for additional PANS infectious triggers? To look at methylation with genetic testing? To look for pyroluria? In my case, yes, it was worth doing these additional tests because it brought us missing pieces. But it's not everyone's answer.

 

With the exception of the new test, the testing stinks. Just as it stinks to have no definitive test for Pandas. My kids both have elevated Cunningham numbers but one never had strep. Where we are with the science behind all of these diseases is so archaic that it comes down to pursing a treatment that brings results.

 

Not arguing here. I think there are unfortunately way too many unanswered questions and way too many sick kids.

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LLM....I was unaware of this. There may be many that are aware of this finding, (was it ever posted?? If so...I missed it) however, I do think it is a broad statement to say "the forum" has been aware of this for awhile. So, posted for those of us still in the dark about it.

 

It is also helpful for "newbies" to be aware. (maybe get a pre IVIg blood sample as suggested.....good suggestion I think)

 

For me...I do want to know what my child has/had. It helps for research purposes (for PANDAS recognition, acceptance and treatment) and I want my kids to know, too. I don't want them wondering what the heck was wrong with them. I want them to be aware for future generations also. I don't want them to have to scramble with it like we did if, God forbid, their kid/s come down with it.

 

Not arguing here either. I think it is a very valid, reasonable article to put out there. One that shouldn't be argued down...just taken as is and the info. tucked away if not acted upon. To each his own and everyone's interpretation....his own. If I were treating my child for Lyme and co (and getting IVIg)...I would want to be made aware.

 

Yes, the new Lyme test that is hopefully coming out soon....soon isn't soon enough! So many will be helped by it!

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LLM....I was unaware of this. There may be many that are aware of this finding, (was it ever posted?? If so...I missed it) however, I do think it is a broad statement to say "the forum" has been aware of this for awhile. So, posted for those of us still in the dark about it.

 

It is also helpful for "newbies" to be aware. (maybe get a pre IVIg blood sample as suggested.....good suggestion I think)

 

For me...I do want to know what my child has/had. It helps for research purposes (for PANDAS recognition, acceptance and treatment) and I want my kids to know, too. I don't want them wondering what the heck was wrong with them. I want them to be aware for future generations also. I don't want them to have to scramble with it like we did if, God forbid, their kid/s come down with it.

 

Not arguing here either. I think it is a very valid, reasonable article to put out there. One that shouldn't be argued down...just taken as is and the info. tucked away if not acted upon. To each his own and everyone's interpretation....his own. If I were treating my child for Lyme and co (and getting IVIg)...I would want to be made aware.

 

Yes, the new Lyme test that is hopefully coming out soon....soon isn't soon enough! So many will be helped by it!

We had this NEW test done. My daughter's culture is positive.

Edited by philamom
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P.Mom---what new Lyme test is coming out soon?

 

The new lyme test is a blood culture, not an antibody test. So there is no false positive. If they culture the spirochetes from your blood then you have it. However, there are still false negatives. :wacko: My LLMD told me in a known positive sample they are able to culture borellia 80% of the time. And even if you have lyme there's no guarantee that they will catch it in your blood sample. They suggest going off antibiotics for a minimum of 4 weeks, and then doing the blood draw in the afternoon. Apparently that's when lyme is most likely to be in the blood stream.

 

http://www.advanced-lab.com/news/borrelia_culture_update.php

 

P. Mom, thank you for posting the study! No arguments here! I was not aware that IVIG could cause a false positive on a lyme test. It makes perfect sense, but I never thought about it. With all the PANDAS kids that are testing positive for lyme this is definitely good information to have.

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I think most treating Dr.'s (the ones that have to sign the Igenex test, perhaps the same one that signed for the IVIG)

I would think (hope) would know any antibody testing after IVIG needs to be done at least 6 weeks after

(and we waited a full 3 months after)

because it takes at least 4-6 weeks for all the IVIG antibodies to leave the body.

 

I wish to God I would have had Lyme testing before we had our IVIG's.

We had to pay cash for them. We did not have immune deficiencies.

We were also high on CamK test.

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Quoting, and questions...

 

"False-positive results of serological tests for Borrelia burgdorferi antibodies are recognised in a number of infections, such as syphilis, parvovirus and Epstein Barr virus, and in various other inflammatory conditions.1 We de- scribe a case where misleading positive Borrelia burgdorferi antibodies were caused by the administration of intrave- nous immunoglobulin."

 

Really curious about the "Inflammatory conditions" that can cause a false positive on Lyme tests. Anyone know? seeing as so many pandas kids are turning up with Lyme......is it REALLY Lyme? When you think about it, there are people treating their kids for Lyme bases on Igenex's test, with only a handful of positive bands. Maybe it's the bands reacting because of the inflammatory disease (ie., PANDAS)? Just thinking aloud here...

 

 

Really sounds like they're just talking out of their ###### there regarding "inflammatory conditions".

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A previous lurker... but this interested me enough to look further.

 

The above posted information is from a "letter to the editor" in Journal of Infection. It is not a study, and is based on the observation of one patient's case. Near as I can tell, the doctors are basing the assumption (that IVIG caused false positive) from the fact that the pre-IVIG blood sample turned up false for borrelia, while the post IVIG sample was positive. As is well known, false negatives are highly possible with borrelia -- so there is no way to say that wasn't the case with the original pre-ivig blood draw. And perhaps the IVIG procedure provoked a positive test. There is simply no way to know.

 

I'm not saying that IVIG will never cause false postive. I honestly do not know if there is any authoritative medical research out there that has stated this. But this letter of one case observation should not be relied upon as evidence of such.

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Hi BluYorkie. Welcome to the forum and thanks for the heads up. I would still recommend tucking this info away because there are so many unknowns. I am looking forward to hearing more about you and your family. I imagine you have an affected family member that caused you to lurk and now join . Do you have a PANDAS child?

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