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.

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

  • Lon Honzell
    10/09/2018 (8:25 pm)
    Reply

    Years ago I was diagnosed with Mono, severe case. Was hospitalized for three days, getting well? 18-20 Years later was diagnosed with MS, Which I still have. was tested for Lyme disease, not found. Through out this process I kept telling doctors I thought it was something else. No it’s MS, MRI’s shows it? Still having my doubts, what was I to do. Except keep taking that non working MS Medication.
    Until much later, Now. I have been doing some personnel research, coming to the conclusion it is Lyme Disease. ?

    • Dr. Daniel Cameron
      10/10/2018 (1:57 pm)
      Reply

      It can be so difficult to make a diagnosis. In some cases, my patients have more than one condition. It would be reasonable to include a doctor familiar with tick borne illnesses in your evaluation.

  • Mike
    08/31/2018 (8:44 pm)
    Reply

    I was bitten by a tick in April 2018 and developed fatigue, night sweats and joint pain in knees, hands and feet 3 weeks later. I was prescribed 3 weeks of Doxycycline. The night sweats stopped but the fatigue and joint pain have remained. I had bloodwork 2 weeks ago and was told I have acute active EBV. My IgM for 39 and 23 were positive for Lyme, Lyme IgG/IgM is .94 ISR, quant IgM is 2.01 index. I was told I don’t have Lyme, just EBV. Is it possible I have Lyme, could the Epstein-Barr cause the joint pain or is something else going on?

    • Dr. Daniel Cameron
      09/02/2018 (1:17 am)
      Reply

      Lyme and EBV are common Acute active EBV is defined differently by differing doctors. Sometimes the EBV is old. You should included a doctor with experience working with Lyme disease.

  • Vivian Verrier
    08/30/2018 (9:21 pm)
    Reply

    I got a bullseye rash 3 times in 2005. Same spot. Drs. Said noone can get a bugbite on the bra line. 13 years later I FINALLY may get treatment for Lyme. Lots of positive tests. Not ALL . Was told about EBV. Recently. Lyme ruined my life. Destroyed my body and spirit..wonder if 4 weeks of doxycycline will work. So many years later.

    • Dr. Daniel Cameron
      08/31/2018 (6:14 am)
      Reply

      A single antibiotic course of 4 weeks does not always work even when treated earlier. You should include a doctor experienced in treating Lyme disease along with your other doctors.

  • Shelly Willis
    07/27/2018 (7:19 pm)
    Reply

    My 2 yr granddaughter had an engorged tick removed ,followed by rash near bite, high fever ,vomiting diarrhea and swollen lymph nodes in her neck. Started amoxicillin ,4 days after removal of tick and then amox-clav a few days after finishing the amoxicillin.high fever stopped but started complaining of sore hands knees elbows neck and back also complained of tummy pain would wake up in the middle of the night crying due to the neck /back pain and her hands and fingers were hurting.wrnt back to Dr. Asked to be tested for Lyme disease and any other illness that could be causing this. Out now anit 5 weeks at this point Lyme test came back negative ,but positive Rocky Mountain spotted fever numbers very low. Sent to our infectious disease who said the test was iffy reordered a better test at a better Laboratory and said it could also be tularemia. tularemia came back negative Rocky Mountain Spotted Fever positive once again
    One week doxycycline. She is better than she was but symptoms are slowly starting to reoccur went to another specialist who said there’s no way she had Rocky Mountain Spotted Fever do to the timeline she would have died did blood test for what all I’m not sure but now is saying she is positive for mono and still waiting on the rest of the test results to come back. My question is could this be Lyme disease instead of rmsf or mono? No one has actually told us what the numbers were for any of the test so far but I’m just worried with her only being too that we’re not going to get the right course of treatment and what the long lasting effects could be… please any advice on what to do next would be greatly. appreciated

    • Dr. Daniel Cameron
      07/28/2018 (6:36 pm)
      Reply

      Your granddaughter’s illness reflects the difficulties knowing what the cause or causes are when a tick borne illness is part of the concern. The CDC includes up to a 2 week of doxycycline in young children for RMSF without dental problems. RMSF is a serious illness that can be deadly. The fact that your daughter is alive does not rule out RMSF. It is always good to look at other illnesses including Epstein Barr and Cytomegalovirus illness (causes of Mono). Our practice does not work with children your grandaughter’s age. Keep working on it.

  • Rita
    06/16/2018 (10:32 pm)
    Reply

    How does CMV virus compare to Ebv? Could they be mistaken? Also I had shingles, HPV virus, what’s the best way to go about testing for all these issues, my mris ,show pineal cyst ,5.5mmx6.5mmx7.5mm,
    1-along with felt to be in normal limits-signal in mass cell, mild right side mastoiditis, , yet..2 yrs later MRI has expanded compared to original mri-maistoidtis right side,
    2- prominence in surrounding area soft tissue nasopharyngitis, and mild prominence of cystic adrenoid of lymphoid tissue? I know these aren’t Lyme, but with constant sinus issues, and trouble swallowing without choking often lately, I wonder if you think it warrants following up?

    • Dr. Daniel Cameron
      06/17/2018 (11:12 pm)
      Reply

      It is common to find evidence of a range of virus on testing. It can be difficult to sort out ENT issues. Don’t forget to look a second time at the bacteria and Babesia that are in a tick.

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