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"

  • Joy pehl
    05/22/2019 (2:21 pm)
    Reply

    In 2017 after hiking i noticed a tick on the back of my leg . I pulled on it thinking i got it off . 2 days later my leg still hurt and went to my family doctor. Seeing it was on the back of my leg i never noticed the bullseye rash . The doctor lanced it and removed the head …horribly painful for such a little pin dot . Immediately I was put on doxycycline for 30 days twice a day . It was like i had the flu and very sick to my stomach. The doctor took me off of the med just 2 weeks after starting . The bloodwork he did the first day i went in tested negative .The Symptoms still plague me on and off . He’s been blaming it on the fibromyalgia i have had for 16 years . But this is much different. I went to a walk in clinic about 3 months ago with a swollen gland the size of a golf ball on the back of my head with all the same symptoms except very very exhausted and headache . They tested for Epstein barr and it tested positive . I had mono as a teen so they said it could test false positive . Still feeling sick and was told by my family doctor it could take 6 months to get better . Now my hands hurt alot and my joints and muscles . Almost like it’s my bones . Can’t grasp things as well or open simple things like a bottle . My finger joints are developing bumps and the bottom of one of my feet . All of this on my left side . I don’t know if this could all be connected . Even my left breast became infected since the positive test for Epstein barr . Could it be lyme? Epstein barr? Kinda scared

    • Dr. Daniel Cameron
      05/22/2019 (3:35 pm)
      Reply

      I am reluctant to blame the problem on a old Epstein Barr titer in my practice. The blood test for Lyme disease can be negative when doxycycline is given. I typically look a second time for Lyme disease.

  • Veronica
    05/21/2019 (12:58 am)
    Reply

    I had Lyme disease in 2010 but we caught it on time, I was treated and felt normal again for 5 years, in 2015 I got tired and anxiety attacks went to ER and they found Mono, its been 4 years and still not recovered I have seen so many doctors and I haven’t found any answer or diagnosis for my symptoms, feeling exauhusted all the time and big pressure in my head, that makes it vibrate when I seat, I have to rest all the time if I stand for long, I keep active but I get so exhausted.

    I also got menopause at the same time of Mono which was considered early I was only 45 so everything is so confusing for drs to determine what’s going on.
    What should I do, they have done all kinds of tests and they found that most of my hormones are not normal, and they just prescribed supplements.
    What should I do, I feel like this has to be with Lyme.

    • Dr. Daniel Cameron
      05/21/2019 (1:19 pm)
      Reply

      Even doctors experienced treating Lyme disease differ in their approach. Babesia is a commonly overlooked tick bore infections associated with sweats. You might also benefit from a second look to make sure another illness is not the cause.

  • Dr. Daniel Cameron
    05/21/2019 (12:05 am)
    Reply

    I find other antibiotics helpful for patient in my practice.

  • Brian
    04/16/2019 (7:45 pm)
    Reply

    Please read LAB 257. This was an eye opener for myself and my wife who has late stage Chronic Lymes disease and has suffered terribly. It is very sad to read but will provide the truth behind Lymes, West Nile Virus etc… Keep in mind that Lymes mimics hundreds of other diseases.

    • Cynthia
      05/20/2019 (4:42 pm)
      Reply

      I went from Doctor to Doctor for a year and half trying to find out what was wrong. I had dizzy spells, headaches, Memory loss, Stinging in the head, burning skin, fever occasionally, Joint pain, feeling like something is crawling on me, feeling like something is stinging me. Stinging in both my eyes and tongue. Sometimes stinging on my nose and lips, burning up at night, feeling tired all time and hurts to walk. I was diagnosed with Chronic Lyme disease with Neuropahty. I had 21 day oral antibodies and then two months later had 4 weeks Picc line of Doxy. I felt better while I was on doxy but a few days coming off I am back to were I was at before. The pain is horrible and some days I just want to die. They did a blood test last week and Epstein Barr came back high.

      Did you wife get any better? What helped?

  • daniel
    03/21/2019 (9:43 pm)
    Reply

    thank you for your reply.
    What do you make of the WB results that seem to be positive (or cross reactive with previous positive EBV??) which was then followed by a negative Lyme IgG/IgM ab Result <0.91?

    • Dr. Daniel Cameron
      03/21/2019 (11:43 pm)
      Reply

      You could have a positive band (s) for many reasons. Your doctor would have to use clinical judgment.

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