When Lyme disease causes a positive test for mononucleosis

False positive serologies for Lyme disease have been previously reported in patients with acute infectious mononucleosis. However, a recent paper describes two cases in which Lyme disease was misdiagnosed as mono based on false positive serologies for the Epstein-Barr virus (EBV).

by Daniel J. Cameron, MD MPH

In the article, published in the journal Clinical Infectious Diseases, Pavletic, from the National Institute of Mental Health, reports “two cases of false positive Epstein-Barr virus (EBV) serologies in early-disseminated Lyme disease.”

In the first case, a 16-year-old male from Virginia developed fatigue, myalgias and three brief episodes of fevers over an 18-day period. He was diagnosed with acute infectious mononucleosis based on a positive viral capsid antigen (VCA) IgM and negative VCA IgG.

It was not until 17 days later with the onset of multiple erythematous rashes and right-sided peripheral facial nerve palsy that doctors diagnosed the young man with Lyme disease. Laboratory evaluation revealed a positive C6 peptide ELISA index of 6.02 and a positive IgM immunoblot. He was prescribed a 4-week course of doxycycline and recovered.

“Repeat VCA IgG, VCA IgM and EBNA were negative, indicating that the initial VCA IgM was falsely positive,” according to Pavletic.

In the second case, an avid biker from Maryland presented with a six-day history of fatigue, fever, myalgias and headache. Lyme disease was diagnosed the next day based on multiple erythematous rashes. Lyme serologies were positive by ELISA, IgG and IgM immunoblots.

Twelve days into her illness she tested positive for mononucleosis with a positive VCA IgM, VCA IgG, EBV early antigen, EBNA IgG, and positive monospot.

The fever resolved and the rashes faded with a 21-day prescription of doxycycline. The recovery was complicated by a right upper trunk brachial plexopathy. “The pain resolved and the weakness improved over the next six months,” according to Pavletic.

“Three and a half years later, repeat VCA IgG and EBNA were positive, and VCA IgM was negative.”

According to the authors, both cases were initially misdiagnosed. “Here we present two cases where early manifestations of Lyme disease were initially misdiagnosed as acute EBV infection due to positive VCA IgM results.”

The authors touched on the difficulties interpreting acute mononucleosis testing. “While isolated VCA IgM may indicate early acute mononucleosis, the test can be nonspecific, especially when the likelihood of acute EBV infection is low.” Pavletic adds, “Immune activation with other pathogens can also result in a false positive VCA IgM.”

The second case was difficult to interpret given the positive monspot, heterophile and VCA IgM tests. “In this case, we cannot exclude that the positive VCA IgM could be due to subclinical EBV reactivation, which has little clinical relevance in immunocompetent individuals,” states Pavletic, adding, “Heterophile antibody tests are known to have false positives due to acute infections, autoimmune diseases and cancer.”

In practice, Lyme disease and mononucleosis are common conditions that share similar symptoms. The authors’ two cases remind the reader of the need to consider Lyme disease even if initial serologies suggest mono.

 

References:

  1. Pavletic AJ, Marques AR. Clin Infect Dis. 2017 Apr 4. doi: 10.1093/cid/cix298.

124 Replies to "When Lyme disease causes a positive test for mononucleosis"

  • Carolyn Johnson
    11/29/2018 (8:26 pm)
    Reply

    Dr Cameron
    Thank you ever so much for the work you are doing online. You are a Godsend. Your replies to us re Lyme and mono made perfect sense. We continued with Doxi even though the Dr said 2 weeks was enough. It made no sense to us at first but since we live in an area that is rampant with ticks, have 4 shelties that have all been treated for Lyme I am surprised my doctor would not see the possibility of that being the main cause. I also put my husband on a regime that I have had great results with many cancer patients. High Vitamin C the most important ingredient in the drink. His white platelets went from 40 to 221 in less than 2 weeks at next testing. His spleen went back to normal. He says he feels better than he has in months. I am not sure how to approach
    this with our Dr as he is a first year practicing Dr. and we continued the Doxi when he said it was enough at 2 weeks. It was given to my husband at emerg not by him. We have both learned so much from your posts.
    Thank you again for putting this issue out there . We so appreciate it.

  • Brian Johnson
    11/24/2018 (2:07 am)
    Reply

    This site was an amazing find. Starting October 19th, I ran a fever of 103F (39.5C) for 5 days straight with severe chills, constipation and tiredness. On the 2nd day, I went to the ER and was told by the doctor it was the flu and to treat the fever with acetaminophen and ibuprofen, and also that my platelets were slightly low (140). After the fever broke I started feeling better but was still tired, which I assumed was normal after what I went through. On November 3rd, the fever came back at the same temps as did other symptoms. Again I went to the ER on the 2nd day and again was told it was the flu. But on the 4th day, I went to the ER of a different hospital and that doctor decided since it was my 2nd presentation of the same thing to run a battery of tests from everything from Hepatitis A, B and C to West Nile to Lyme to bacterial infections etc. My platelet count was only 60 then. She asked me to come back the next day to get an ultrasound of my organs (liver, kidney, spleen etc) and then to return again in a few hours when an internist was available. The ultrasound showed an enlarged spleen and fatty liver. On that next ER visit, my platelet count was 49 and my wife noticed a rash that seemed to disappear and reappear elsewhere (not a bulls-eye rash). The ER doctor and the internist discussed my case and decided to start me on a 2 week course of doxycycline 100mg. Amazingly, my fever finally broke the next day (6 days into this 2nd stretch), which was now 2 weeks ago, and has not returned. However, I still get tired in the afternoon and sometimes nap (which is not normal).

    About 5 days later, I was called by the ER doctor who told me I tested positive for Lyme.

    Today I just had a follow up with my regular doctor who reviewed ALL the tests, and he told me that though I tested positive for Lyme, I also tested positive for EBV, and that my symptoms were more accurately descriptive of Mono than of Lyme. I had hoped to extend my course of doxycycline but he believes 2 weeks was sufficient and that now my immune system is working on putting the EBV in check. After reading this, I am worried that 2 weeks was not sufficient and that I still need to focus on battling Lyme. Perhaps it is true that my symptoms were from EBV/Mono but after reading all this, this only happened because Lyme compromised my immunity which allowed existing EBV I contracted free reign.

    In your opinion, is 2 weeks of doxycycline 100mg sufficient in my case?

    I will be tested again after Dec 3rd, and I am hoping for a negative result of both Lyme and EBV as well as normal levels for liver function, platelets, etc. In the meantime, I will focus on boosting my immunity with high doses of Vitamin C and other natural methods and hope that can fight off both.

  • Carolyn Johnson
    11/23/2018 (10:15 pm)
    Reply

    My husband (52) came down with a fever of 38 AND 39. I took him to emergency and they supposed it was the flu. Told him to take Tylenol for the fever. The high fever went away but returned a week later. We went back to emerg. same diagnosis and this time Tylenol and Advil again. The fever was less for 3 days ant then back to 39, nite sweats and chills..We went to a different hospital and they took many tests. I noticed a red blotch on his back and then a few more but not the bulls eye and they seem to come and go. His tests showed a swollen spleen, a bit of a fatty liver and very low white platelets- down to 60. They took tests for Lyme and other diseases and we had to wait 5 days for the results. They sent him home with Doxicycline and the next day his fever was down to normal and stayed there during the 2 week course. The tests came back and showed Lyme. WE saw him today re the results and positive for Lyme but also for mono. He said not to take more Doxi and requested lab tests in 2 weeks. He did not have swollen glands or soreness in joints. I think he should take two more weeks of the Doxi as it worked the very next day to take away his fever. The doctor thinks the Doxi has already done its job. Would 2 more weeks hurt along with boosting his immune system with vitamin C in case it is EBV ? How can we cover both bases ? I do not want him to go through what he initially did again. What is the likelihood EPV or LYME or both ? Thank you in advance. I am totally confused on this issue. His platelets are back up to almost normal now after the 2 weeks on Doxi

    • Dr. Daniel Cameron
      11/24/2018 (9:07 am)
      Reply

      I have patients where more than mono and a tick borne illness are both possible. Rocky Mountain Spotted Fever, Ehrlichia and Anaplasmosis should be considered. Both are common conditions. I would have your doctor followed for both conditions. I do not like to cut off treatment for a tick borne illness too early in my patients.

  • Anne ROBERTSON
    10/31/2018 (12:25 am)
    Reply

    Hello Dr. My daughter is pos for cronic bartonella. She is currently in Denver for school and is very sick. swollen glands, face, super cogested, major leg pain, eyes are crusty and goopy. She went to the ER and they said it was either Mono ( which there is no test for) or its viral. My kiddo can eat nor has the energy to do anything. we have tested her for Mono before she was diagnosed with Bart and she was pos for being esposed to it but not currently having it. She never had any signs of mono before till now. I have no idea if she really has mono or a virus. She has been exposed to a close friend at school who just went home with mono. Can the mono test showing she was exposed be wrong? or her bart coudl have casued it to be pos for exposure? and now she currently has it? what test do you suggest we do to figure out if its mono? Are you available to see her? Thanks for this article. Anne

    • Dr. Daniel Cameron
      10/31/2018 (7:26 am)
      Reply

      It is important to look at more than one factor. My latest Lyme disease Science Blog reviews to cases where the child had both conditions. It is not always clear that a positive test e.g. Bartonella is a factor. There are IgG and IgM tests for Epstein Barr and for Cytomegalovirus hat may offer insight into the viral question. I am available. Call my office at 914 666 4665 in New York if you need a tick borne evaluation.

  • Sara Moulton
    10/20/2018 (1:20 am)
    Reply

    I had a tick bite then 10 days later developed very swollen glands. Two weeks later, still swollen glands, IGG and IGM neg for Lyme, but began 100 mg doxy. Two weeks later, no change in swollen glands. Mono test positive. Doctor says no Lyme, stop doxy, mono only. I am concerned that I have both, and that the mono is caused by Lyme reactivating or allowing its development. Is this a likely scenario?

    • Dr. Daniel Cameron
      10/21/2018 (12:55 pm)
      Reply

      Both conditions are common. I would have thought it reasonable to treat for both conditions with followup.

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