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Useful signs, symptoms, and hematologic parameters for diagnosing infectious mononucleosis
Clinical Question
What symptoms, physical findings, and laboratory results are most useful in the diagnosis of infectious mononucleosis?
Bottom line
The clinical symptoms that are (minimally) useful in diagnosis IM are headache and sore throat. Moderately useful physical findings include splenomegaly, palatal petechiae, and any lymphadenopathy. Hematologic parameters are most useful for accurately diagnosing IM, including an elevated lymphocyte count and the presence of atypical lymphocytes. See the Synopsis for specifics. 2a
Reference
Study design: Systematic review
Funding: Self-funded or unfunded
Setting: Various (meta-analysis)
Synopsis
These investigators performed an updated systematic review and meta-analysis of the accuracy of the symptoms, clinical signs, and hematologic parameters for the diagnosis of infectious mononucleosis (IM). They performed a thorough search of PubMed without language restrictions, in addition to a manual search of reference lists from pertinent publications. Eligible studies included cohort studies with sufficient information to calculate both the sensitivity and specificity of the findings and case series with sufficient data to calculate the sensitivity. Two individuals independently evaluated potential articles for inclusion criteria and methodologic quality using a standard evaluation tool. Any differences were resolved by consensus discussion with a third reviewer. A total of 17 studies met inclusion criteria, including 3 judged at high risk of bias, 5 at moderate risk of bias, and 9 at low risk of bias. The only clinical symptoms significantly associated with IM (albeit minimally) were headache (positive likelihood ratio [LR+] 1.19; 95% CI 1.01 - 1.45; negative likelihood ratio [LR–] 0.72; 0.50 - 0.98) and sore throat (LR+ 1.12; 1.01 - 1.125; LR– 0.67; 0.41 - 0.99). Useful physical findings included splenomegaly (LR+ 2.39; 1.11-5.51; LR– 0.66; 0.50 - 0.84), palatal petechiae (LR+ 1.32 - 11.4; LR– 0.57 - 0.94), and any lymphadenopathy (LR+ 1.26; 1.05 - 1.65; LR– 0.37; 0.20 - 0.67). Fever was of minimal value. Laboratory results of value included absolute lymphocyte counts greater than 4 x 109/L (LR+ 10.20; 4.79 - 16.0) and the presence of atypical lymphocytes greater than 10% (LR+ 8.97; 3.39 - 19.5) or atypical lymphocytes greater than 40% (LR+ 50.3; 38.6 - 64.1). The combination of lymphocytes greater than 50% and atypical lymphocytes greater than 10% was also highly useful to rule in disease (LR+ 50.40; 8.43 - 162).
Reviewer
David C. Slawson, MD
Professor and Vice Chair of Family Medicine for Education and Scholarship
Atrium Health
Professor of Family Medicine, UNC Chapel Hill
Charlotte, NC
Comments
Mono diagnosis
A bit of a head scratcher. It would have been useful for the reviewer to include some kind of description of what patients were included these studies. Presumably at a sore throat. Bottom line seems to be that clinical findings (both history and exam) are not terribly useful in diagnosing mono with any degree of certainty. Hence if mono is suspected a CBC can be useful early on although one wonders if a rapid strep test might provide better information (and can be done at the point of care). At least this article confirmed my perspective that mono vs strep is difficult to sort on without some kind of testing.
Tonsillar hypertrophy
How on Earth did they not comment whatever on tonsillar hypertrophy. Most of the cases I've seen had this. I agree on the elevated lymphocytes being very suspicious, but what about elevation in LFTs? And no comment about the Monospot, before or after 7 days??
Infectious Mono
See above lab tests.
periorbital swelling
an uncommon but very telling sign has been periorbital swelling.
mono
still around
Infectious mononucleosis
Infectious mononucleosis is caused by the Epstein-Barr Virus (EBV). The recent article "Multiple sclerosis: Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis," by K Bjornevik et al, Science, Volume 375, 21 January 2022, page 296 demonstrates that EBV infection causes multiple sclerosis. (See also the Perspective on page 264 in the same issue by W.H. Robinson and L.Steinman, entitled, "Infection with Epstein-Barr virus is the trigger for the development of multiple sclerosis.") The development of a vaccine against EBV could potentially reduce the incidence of mononucleosis and of multiple sclerosis
sx minimal help and labs more helpful
dx of mono