BB0172, a Borrelia burgdorferi Outer Membrane Protein That Binds ...
Positive Borrelia burgdorferi serology secondary to intravenous immunoglobulin therapy
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LETTER TO THE EDITOR Positive Borrelia burgdorferi serology secondary to intravenous immunoglobulin therapy KEYWORDS Intravenous immunoglobulin; Lyme disease; Neuroborreliosis; False-positive serology 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 days 3 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 0163-4453/$36 ª 2011 The British Infection Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2011.10.004 www.elsevierhealth.com/journals/jinf Journal of Infection (2012) 64, 117e118
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Transcript of Positive Borrelia burgdorferi serology secondary to intravenous immunoglobulin therapy
Journal of Infection (2012) 64, 117e118
www.elsevierhealth.com/journals/jinf
LETTER TO THE EDITOR
Positive Borrelia burgdorferi serology secondaryto intravenous immunoglobulin therapy
01do
KEYWORDSIntravenous
immunoglobulin;Lyme disease;Neuroborreliosis;False-positive serology63-4453/$36 ª 2011 The British Infei:10.1016/j.jinf.2011.10.004
False-positive results of serological tests for Borreliaburgdorferi antibodies are recognised in a number ofinfections, such as syphilis, parvovirus and Epstein Barrvirus, and in various other inflammatory conditions.1 We de-scribe a case where misleading positive Borrelia burgdorferiantibodies were caused by the administration of intrave-nous immunoglobulin.
A 78-year-old man presented with bilateral ptosis, nearcomplete ophthalmoplegia, bilateral facial weakness, are-flexia and gait ataxia. Initial investigations revealed subtlecranial nerve enhancement on MRI and mediastinal lymph-adenopathy on CT chest. He had normal acetyl cholinereceptor antibody and anti GQ1b antibody titres, makingthe diagnoses of myasthenia gravis and Miller Fishersyndrome respectively unlikely.
The diagnosis was unclear but neurosarcoidosis wassuspected and he was treated empirically with high dosesteroids 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 whichtime his clinical condition had evolved to include a painfulpolyradiculopathy. Therefore blood was taken for Borreliaburgdorferi antibodies and was strongly positive by Westernblot (nine specific bands), despite no history of tick exposureor rash consistent with erythema migrans. The patient wastreated with intravenous ceftriaxone for possible neuro-borreliosis. However, we were suspicious the positive resultmight be attributable to his IVIg treatment and managed totrack down a serum sample taken just prior to his IVIgtreatment but after his neurology symptoms had been
ction Association. Published by E
present for over two months. This pre IVIg sample wasnegative for Borrelia burgdorferi antibodies on westernblot. His cerebrospinal fluid was acellular, which makesneuroborreliosis less likely, and Borrelia burgdorferi DNAwas not detected by PCR. Given the gentleman had been bedbound between the two samples with no opportunity for tickexposurewe concluded the positive result was a confoundingeffect due to receiving pooled donor IVIg. A repeat sampletaken twoweeks after the positive sample remainedwesternblot positive but with fewer bands (eight positive bands) andnoticeable reduction in intensity, in keeping with decay oftransfused antibody. The patient continued to deteriorateneurologically and no firm diagnosis was made in life despiteextensive investigation. The final autopsy diagnosis wasencephalomyelitis of presumed paraneoplastic origin basedon the pathological appearances although no tumour wasidentifiable. There was no evidence of sarcoid or infection.
Intravenous immunoglobulin is an important treatmentfor a diverse range of conditions, particularly in the fields ofneurology and haematology.2 It is prepared by extractingIgG from large pools of plasma donations (>1000 donors/pool) under strict regulations as laid out by the WorldHealth Organisation (WHO) and Food and Drug Administra-tion (FDA). Its safety relies on donor selection, screeningof 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 andpooled 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
lsevier Ltd. All rights reserved.
118 Positive Borrelia burgdorferi serology secondary to intravenous immunoglobulin therapy
sourced from USA, Germany, Austria, Czech Republic, Swe-den and Switzerland. Lyme disease is endemic in all ofthese countries, with significant background seropreva-lence to Borrelia burgdorferi in the population. All thishas potential implications when interpreting serologicaltests in IVIg recipients. There are case reports describingmisleading positive results for infections such as syphilisand Toxoplasma following passive transfer of antibodiesvia pooled human IgG.4e7 We found a single case report inthe literature of positive Borrelia antibodies caused by in-travenous immunoglobulin.8 A number of clinical presenta-tions which may mimic neuroborreliosis are treated withIVIg. A misleading positive antibody result may expose a pa-tient to unnecessary and potentially harmful treatment anddelay the correct diagnosis being made. We found no men-tion of this potential adverse effect of intravenous immuno-globulins in the Department of Health ‘Clinical Guidelinesfor Immunoglobulin use’ or the Association of British Neu-rologists ‘Guidelines for the use of Intravenous Immuno-globulin in Neurological Diseases’.2,9 Clinicians need to beaware of possible confounding effects of IVIg on subsequentserology tests, and communicate with the laboratory iftheir patient has recently received intravenous immuno-globulin. Futhermore, we recommend that where IVIg is be-ing used without a firm diagnosis, serum should be storedbefore administration of IVIg to provide a baseline samplewhich enables retrospective testing, should this berequired.
Funding
None declared.
Conflict of interest
None declared.
Acknowledgements
This article was reviewed by Prof Robert Will, Edinburgh. DrDarrel Ho-Yen, National Lyme Borreliosis Testing Laboratoryfor Scotland, performed serological tests on our case andassisted with their interpretation.
References
1. The epidemiology, prevention, investigation and treatment ofLyme borreliosis in United Kingdom patients: a position state-ment by the British Infection Association. J Infect 2011;62:329e38.
2. Department of Health. Clinical guidelines for immunoglobulinuse. 2nd ed., www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_085235; 2008.
3. Lichtiger B. Laboratory serological problems associated with ad-ministration of intravenous IgG. Curr Iss Transfus Med 1994;3:1e7.
4. Lichtiger B, Rogge K. Spurious serological test results in patientsreceiving infusions of intravenous immune gammaglobulin. ArchPathol Lab Med 1991;115:467e9.
5. Constable SA, Parry CM, Enevoldson TP, Bradley M. Positive se-rological tests for syphilis and administration of intravenous im-munoglobulin. Sex Transm Infect 2007;83:57e8.
6. Rossi KQ, Nickel JR, Wissel ME, O’Shaughnessy RW. Pas-sively acquired treponemal antibody from intravenous im-munoglobulin therapy in a pregnant patient. Arch PatholLab Med 2002;126:1237e8.
7. Pelloux H, Fricker-Hidalgo H, Brocher G, Goullier-Fleuret A,Ambroise-Thomas P. Intravenous immunoglobulin therapy: con-founding effects on serological screening for toxoplasmosisduring pregnancy. J Clin Microbiol 1999;37:3423e4.
8. Luyasu V, Mullier S, Bauraind O, Dupuis M. An unusual case ofanti-Borrelia burgdorferi immunoglobulin G seroconversioncaused by administration of intravenous immunoglobulins. ClinMicrobiol Infect 2001;7:697e9.
9. Association of British Neurologists.Guidelines for the use of Intra-venous Immunoglobulin inneurological diseases, abn.org.uk/abn/userfiles/file/IVIg-guidelines-final-July05.pdf; July 2005.
Katherine Murray*Department of Clinical Neurosciences,
Western General Hospital, Crewe Road,Edinburgh EH4 2XU, UK
E-mail address: [email protected]
Kristjan O. HelgasonDepartment of Microbiology,
Royal Infirmary, Edinburgh, UK
Accepted 17 October 2011Available online 21 October 2011
* Corresponding author. Tel.: þ44 131 537 1000; fax: þ44 131 5371137.
