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:
- Pavletic AJ, Marques AR. Clin Infect Dis. 2017 Apr 4. doi: 10.1093/cid/cix298.
teri k
09/28/2021 (6:03 pm)
It’s great to find this site I’m happy to be able to leave a comment and hopefully get some answers.
10-10-2001 I was bit by a deer tick. At the time I lived in the middle of the woods in Connecticut about 10 miles away from Lyme Connecticut so the area was ground zero for Lyme disease.
within three days I couldn’t move my joints my whole body hurt I had nodules growing on the hands of my fingers. The sunlight bothers my eyes. I was in so much pain. It would literally take me 10 minutes just to get out of bed in the morning because my body felt like it had rigor mortis. I kept going to my general practitioner literally crying every time I went and I was told I did not have Lyme disease. A dog that lived in our home died of Lyme disease. A woman that lived in our home at the time got Alzheimer’s disease and her early 40s. The person that I was living with at the time got lLyme disease. I finally found an infectious disease Doctor Who was willing to treat me without a positive Lyme disease test. I was on doxycycline for almost a year I swear that is what saved my life. For a few years afterwards I would get a refill of doxycycline when my symptoms would start to appear that took care of it.
Recently my doctor my current doctor tested me for Epstein-Barr virus positive. All of the tests were positive. I do not have Epstein-Barr. I have Lyme disease. When I first got Lyme disease I never had a positive test result ever not one of them were positive but I know it’s what I have because I remember the day I was bit by the tick because it was my birthday. So I guess my question is now what do I do about this. Can I get some doxycycline from someone as I feel that this Lyme disease has completely ravaged my body. My Epstein-Barr virus levels were through the roof on my test.
I live in florida now- any recommendations?
Dr. Daniel Cameron
09/28/2021 (7:55 pm)
I am glad you improved for a while. You will need to be evaluated again by a doctor who is experienced in treating Lyme disease to see if there are any treatment options. There are other treatments than doxycycline. You should also rule out other illnesses. You should check out lists to include The Global Lyme Alliance, ILADS and the Lyme disease association.
Brandi Powell
07/09/2021 (7:08 am)
Hi, I hope you still check comments here, doctor. I have had chronic EBV for a while on tests not many symptoms of it. I did have other symptoms that mimicked MS. I had a full workup done and did not have MS. I had been fine for the last three years, and then in March, I got my covid-19 vaccine. All the symptoms I had four years ago have come back and strong. I went to the doctor again. I made my way to a hematologist who took 21 vials of blood. My liver enzymes are always elevated, my sed rate is always higher than normal, and I have high immunoglobulin IG. I tested for Lyme, but only bands 41 and 39 iGG came back positive. My doctor still said, since I have no answers and some positive, let’s treat you for Lyme. I’ve been on doxycycline for two weeks. I’m Bout to do two more weeks. When I take the antibiotics, I feel better. My symptoms are well when not in antibiotics, numb patches on my head, wrist, and back of the leg. Tingling in my face scalp and lip. Constantly. Hair loss always liver enzyme issues etc. Just looking for some answers, do you think I’m doing the right course of treatment? Also, can EBV and Lyme be working together?
Thanks.
Dr. Daniel Cameron
07/09/2021 (7:28 am)
Thanks for sharing your story including a flare-up. I have Lyme disease patients who have done well with the vaccine and some had had a flare-up.
It sounds as if doxycycline is helping. It is still unclear as to how much EBV plays a role. I advise my patients to a second time at a infection.
Oath Hawa
10/10/2021 (5:43 pm)
Same exact experience.
Some IgM lyme tests came positive in Feb 2021.
Symptoms of Fatigue and brain Fog became severe after Covid vaccination during March 2021.
Doctor prescribed doxycycline in May 2021 as trial therapy for 4 weeks. Felt much better during the antibiotics therapy. Symptoms returned after antibiotics stopped. I have history of Mono 20 years.
I suspect that Mono has been reactivated by undiagnosed Covid.
Maybe.
Dr. Daniel Cameron
10/10/2021 (6:17 pm)
And maybe the tick borne illness has not resolved.
Matt
07/29/2020 (8:13 am)
Hello,
Can I please get some advise? Would deeply appreciate.
I’m a man who was diagnosed with mono at age 21. I was really sick but recovered from the initial symptoms in a month or two.
However, severe neurological symptoms remained till this day 5 years later.
My skin on my legs and arms are constantly burning and I have severe head pressure. Can’t stand up for long.
I have been tested for many things and they always come back negative/normal. In my country, chronic lime does not exist. Patients with those symptoms arr classified as “mentally ill”. So no lime doctor around.
Would it still be an idea for me to try some weeks of doxycycline? Reading about this gave me some hope.
Dr. Daniel Cameron
07/29/2020 (7:20 pm)
I advise individuals with similar symptoms to consider treatment starting with doxycycline if I cannot find another cause. It will depend on the clinical judgement of your doctor.
Matt
08/06/2020 (6:06 am)
Thank you very much dr.
I have now been prescribed doxycycline. My doctor is not sure about doses and duration though as he is not knowledgable about Lyme or EBV.
Could you please tell me what you advise your patients regarding dose and how and when to take doxycycline?
Deeply appreciate it.
Matt
Dr. Daniel Cameron
08/06/2020 (11:44 pm)
Doctors are divided. Some prescribe 10 to 14 days for their patients. I typically prescribe 4 weeks and have them return for evaluation.
Matthew Rudolph
06/26/2022 (7:43 pm)
Doc, I have had multiple ebv tests over the years.
Always the same..
igm neg
vca IGG pos- 600>
ea IGG neg
ebna IGG neg
probably close to 20 years it’s been like this. My 18 yr old is testing the same. I have always had muscle problems and fatigue since I was 18. Now I’m 43. My GP does not know what to make of it. Similar reactions by other GPs over the years. Had two diagnose me for CFS saying that eating right and exercise is the best thing. I work for UPS as a driver… lots of exercise. lol. I always feel tired and wiped out. Everyday every joint hurts and aches. Pain goes away if I drink lots of coffee… lol.
Dr. Daniel Cameron
06/27/2022 (8:11 pm)
EBV can stay positive even in healthy patients in my practice. I find that looking again for another illness including a tick borne illness might be helpful.
Nichole
06/23/2020 (5:06 pm)
I believe my husband has Lyme and possibly anaplasmosis, we are still waiting for bloodwork results. He has a positive monospot for sure. If his mono is a result of Lyme how contagious is it, if at all?
Dr. Daniel Cameron
06/24/2020 (9:58 am)
I have not heard that Lyme disease makes Mono more contagious.
Bobbie ann williams
08/09/2019 (12:48 am)
My daughter has lyme and coinfections, came off all meds for lyme in april. Few weeks later had a sinus infection and was treated. About 3 weeks later wound up in hospital running a 104 fever. After almost 2 weeks in one hospital was transferred to another hospital. Was given an Ivig treatment and fever finally was gone. Long story short, she had a very severe case of ebv and mono. She also had many other issues happen caused from the ebv. Is PCR testing better than testing for the antibodies of ebv? Having a conflict between our llmd and hematologist/oncologist who treated my daughter in hospital. Llmd wants her to take 1gram of valtrex a day where as hematologist doesnt want her too.
Dr. Daniel Cameron
08/09/2019 (11:18 pm)
I am not familiar with the reliability of the PCR test for EBV. I cannot tell from the request whether antibiotics were prescribed.
Amanda
01/09/2020 (8:37 pm)
Hi Bobbie – My story is very similar to your daughters. Although, not nearly as severe! I am so sorry you had to go through that. However, I was diagnosed with lymes 5 months ago and went through treatment. A few weeks later I developed a sinus infection, which was my first one ever. Then two weeks after that I was diagnosed with mono. I am still experiencing horrible fatigue and nausea even 5 weeks after the diagnosis. I know something is still not right and I continue to feel pressure and pain on the left side of my chest and arm. Did you happen to find something that worked for your daughter? Is she better? I really would appreciate any update or insight you could give me as I try to navigate my way through this!
Dr. Daniel Cameron
01/10/2020 (9:12 am)
I find it difficult to determine when Lyme disease has resolved in my patients. Lyme disease can lead to head pressure that mimics head pressure. Lyme disease and “mono” can look alike.