Does This Patient Have Infectious Mononucleosis?: The Rational Clinical Examination Systematic Review

JAMA. 2016 Apr 12;315(14):1502-9. doi: 10.1001/jama.2016.2111.


Importance: Early, accurate diagnosis of infectious mononucleosis can help clinicians target treatment, avoid antibiotics, and provide an accurate prognosis.

Objective: To systematically review the literature regarding the value of the clinical examination and white blood cell count for the diagnosis of mononucleosis.

Data sources: The databases of PubMed (from 1966-2016) and EMBASE (from 1947-2015) were searched and a total of 670 articles and abstracts were reviewed for eligibility.

Study selection: Eleven studies were included that reported data sufficient to calculate sensitivity, specificity, or both for clinical examination findings and white blood cell count parameters compared with a valid reference standard.

Data extraction and synthesis: Data were abstracted from each article by at least 2 reviewers, with discrepancies reconciled by consensus. Clinical findings evaluated in only 1 study are reported with sensitivity, specificity, likelihood ratio (LR), and 95% confidence interval, which were calculated from the available data. Findings evaluated in only 2 studies were summarized with their range, findings evaluated in 3 studies were summarized with a univariate random-effects summary, and findings evaluated in 4 or more studies were summarized with a bivariate random-effects meta-analysis.

Main outcomes and measures: Sensitivity, specificity, and LRs for the diagnosis of mononucleosis.

Results: Mononucleosis is most commonly present among patients aged 5 to 25 years (especially those aged 16-20 years, among whom approximately 1 in 13 patients presenting with sore throat has mononucleosis). The likelihood of mononucleosis is reduced with the absence of any lymphadenopathy (summary sensitivity, 0.91; positive LR range, 0.23-0.44), whereas the likelihood increases with the presence of posterior cervical adenopathy (summary specificity, 0.87; positive LR, 3.1 [95% CI, 1.6-5.9]), inguinal or axillary adenopathy (specificity range, 0.82-0.91; positive LR range, 3.0-3.1), palatine petechiae (specificity, 0.95; positive LR, 5.3 [95% CI, 2.1-13]), and splenomegaly (specificity range, 0.71-0.99; positive LR range, 1.9-6.6). Symptoms are of limited value for the diagnosis of mononucleosis; sore throat and fatigue are sensitive (range, 0.81-0.83) but nonspecific. The presence of atypical lymphocytosis significantly increases the likelihood of mononucleosis (summary LR, 11.4 [95% CI, 2.7-35] for atypical lymphocytes ≥10%, 26 [95% CI, 9.6-68] for those with 20%, and 50 [95% CI, 38-64] for those with 40%). The combination of a patient having greater than 50% lymphocytes and greater than 10% atypical lymphocytes also is useful (specificity, 0.99; positive LR, 54 [95% CI, 8.4-189]).

Conclusions and relevance: In adolescent and adult patients presenting with sore throat, the presence of posterior cervical, inguinal or axillary adenopathy, palatine petechiae, splenomegaly, or atypical lymphocytosis is associated with an increased likelihood of mononucleosis.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Axilla
  • Fatigue / diagnosis
  • Humans
  • Infectious Mononucleosis / diagnosis*
  • Leukocyte Count*
  • Lymphatic Diseases / diagnosis
  • Lymphocyte Count
  • Neck
  • Pharyngitis / diagnosis
  • Physical Examination*
  • Purpura / diagnosis
  • Sensitivity and Specificity
  • Splenomegaly / diagnosis
  • Symptom Assessment
  • Young Adult