What is glandular fever, also known as infectious mononucleosis, in adolescents and young adults?

What is Glandular Fever (Infectious Mononucleosis)?

Glandular fever, also known as infectious mononucleosis, is a clinical syndrome caused primarily by Epstein-Barr virus (EBV) that characteristically presents with the triad of fever, tonsillar pharyngitis, and cervical lymphadenopathy, most commonly affecting adolescents and young adults aged 15-24 years. 1, 2

Causative Agent and Transmission

• EBV is the primary pathogen responsible for infectious mononucleosis, though cytomegalovirus (CMV), Toxoplasma gondii, and acute HIV infection can produce similar mononucleosis syndromes 3, 4
• The virus is transmitted primarily through saliva via intimate oral contact among teenagers and young adults, earning it the colloquial name "kissing disease" 5, 6
• At least 90% of adults worldwide are seropositive for EBV, with 40-90% seroprevalence by adolescence depending on socioeconomic status 3, 6

Clinical Presentation

Classic Features

• The characteristic triad consists of:
  • Fever (often mild)
  • Tonsillar pharyngitis with sore throat
  • Cervical lymph node enlargement 5, 2

Additional Common Manifestations

• Profound fatigue that typically resolves within three months but may persist longer 2
• Periorbital and/or palpebral edema (typically bilateral) occurs in approximately one-third of patients 2
• Splenomegaly develops in approximately 50% of cases 2, 7
• Hepatomegaly occurs in approximately 10% of cases 2
• Skin rash (usually widely scattered, erythematous, and maculopapular) appears in 10-45% of cases 2

Age-Related Differences

• Primary EBV infection in children under 10 years is usually asymptomatic or shows nonspecific courses, while symptomatic disease predominantly affects those older than 10 years, adolescents, and young adults 6, 7
• The incubation period extends up to seven weeks before symptoms appear 6

Laboratory Findings

Hematologic Changes

• Peripheral blood leukocytosis with lymphocytes comprising at least 50% of the white blood cell differential count 1, 2
• Atypical lymphocytes constituting more than 10% of the total lymphocyte count support the diagnosis 1, 2

Diagnostic Testing

• The heterophile antibody test (Monospot) is the most widely used initial test, usually becoming positive between the sixth and tenth day after symptom onset with sensitivity of 87% and specificity of 91% 1
• False-negative heterophile results are common in children younger than 10 years and early in infection, with an approximate 10% false-negative rate overall 1
• When clinical suspicion remains high despite negative heterophile testing, EBV serologic testing should include IgM antibodies to viral capsid antigen (VCA), IgG antibodies to VCA, and antibodies to Epstein-Barr nuclear antigen (EBNA) 1
• The presence of VCA IgM antibodies in the absence of EBNA antibodies indicates recent primary EBV infection, while EBNA antibodies indicate infection more than 6 weeks prior 1, 7

Clinical Course and Prognosis

• Infectious mononucleosis is generally a benign and self-limited disease with most patients experiencing uneventful recovery 2
• Symptoms usually subside after a few weeks, though protracted courses can occur 6
• Infectious mononucleosis is a risk factor for chronic fatigue syndrome 2

Serious Complications

Splenic Rupture

• Spontaneous splenic rupture occurs in 0.1-0.5% of patients and is potentially life-threatening, representing the most feared complication 2, 7

Other Complications

• Life-threatening manifestations can involve the pulmonary, ophthalmologic, neurologic, and hematologic systems 2, 7
• In immunocompromised patients, there is increased risk of lymphoproliferative disorders and hemophagocytic syndrome 1

Management Approach

Supportive Care

• Treatment is mainly supportive as no generally effective specific therapy exists 1, 6
• Reduction of activity and bed rest as tolerated are recommended 2
• Patients should be advised to avoid contact sports or strenuous exercise for 8 weeks or while splenomegaly is still present to prevent splenic rupture 2

Medications

• Aciclovir therapy does not ameliorate the course of infectious mononucleosis in otherwise healthy individuals 1
• Corticosteroids should be reserved for specific complications 1
• Antiviral agents such as aciclovir, ganciclovir, and foscarnet have no proven role in established disease in immunocompetent patients 1

Special Populations

• In immunocompromised patients with suspected primary EBV infection, immunomodulator therapy should be reduced or discontinued if possible 1
• In severe primary EBV infection, antiviral therapy with ganciclovir or foscarnet may be considered despite lack of supporting evidence 1
• Primary EBV infection poses particular threat in patients on thiopurines, with reports of fatal infectious mononucleosis-associated lymphoproliferative disorders 1

Important Caveats

• False-positive heterophile antibody results may occur in patients with leukemia, pancreatic carcinoma, viral hepatitis, and CMV infection 1
• Over 90% of normal adults have IgG antibodies to VCA and EBNA antigens reflecting past infection, which can complicate interpretation 1
• When heterophile and EBV testing are negative, consider testing for other causes of mononucleosis-like illness including CMV infection, HIV infection, Toxoplasma gondii infection, adenovirus infection, and streptococcal pharyngitis 8, 1