What are the next steps for a patient with acute onset tender cervical and inguinal lymphadenopathy, fatigue, and no pharyngitis?

Management of Acute Onset Tender Cervical and Inguinal Lymphadenopathy with Fatigue

Laboratory testing for infectious mononucleosis should be the highest priority in a patient with acute onset tender cervical and inguinal lymphadenopathy, fatigue, and no pharyngitis, with complete blood count and monospot testing being the initial diagnostic tests.

Initial Diagnostic Approach

Primary Testing (First Line)

1. Complete Blood Count (CBC)

   • Look for lymphocytosis with atypical lymphocytes (>10%), which is characteristic of infectious mononucleosis 1, 2
   • Assess for relative lymphocytosis and monocytosis which can help distinguish between viral and bacterial causes 3

2. Heterophil Antibody Test (Monospot)

   • Rapid screening test for infectious mononucleosis
   • Positive in 85-90% of adolescents and adults with EBV infection 1
   • May be negative early in the course of illness (first 1-2 weeks)

Secondary Testing (If Initial Tests Inconclusive)

1. EBV-Specific Serology

   • IgM antibody to EBV viral capsid antigen (VCA) - most valuable for diagnosing acute primary EBV infection 1
   • EBV nuclear antigen (EBNA) antibodies - absence suggests acute infection 4

2. Other Infectious Workup

   • Consider testing for other common infectious causes:
     • CMV serology (IgM and IgG) - may show dual positivity with EBV in some cases 4
     • Toxoplasmosis serology (indirect fluorescent antibody test) 3
     • Streptococcal testing if any pharyngeal symptoms develop

Diagnostic Reasoning

The clinical presentation strongly suggests infectious mononucleosis, which is characterized by:

• Cervical lymphadenopathy (classic finding)
• Fatigue (cardinal symptom)
• Absence of pharyngitis (can occur in some cases)
• Possible inguinal lymphadenopathy (part of generalized lymphadenopathy pattern)

While pharyngitis is part of the classic triad of infectious mononucleosis (fever, pharyngitis, and cervical lymphadenopathy), not all patients present with all three features 2. The prospective study by Rea et al. found that fatigue and cervical lymphadenopathy were more consistent findings than fever or splenomegaly in contemporary practice 2.

Differential Diagnosis

1. Infectious Mononucleosis (EBV)

   • Most likely diagnosis given the constellation of symptoms
   • Primarily affects young adults 15-35 years of age 1
   • Can present with significant lymphadenopathy and fatigue even without pharyngitis 2

2. Other Viral Infections

   • CMV - can cause a mononucleosis-like syndrome
   • HIV - consider in appropriate risk groups
   • Other respiratory viruses

3. Bacterial Infections

   • Streptococcal or staphylococcal infection (though these typically cause unilateral rather than bilateral cervical lymphadenitis) 5
   • Tuberculosis (subacute/chronic presentation)
   • Atypical mycobacterial infection 6

4. Other Causes

   • Cat-scratch disease (Bartonella henselae)
   • Toxoplasmosis
   • Kawasaki disease (in children) 6
   • Lymphoma or other malignancy (if lymphadenopathy persists)

Management Considerations

1. Supportive Care

   • Rest and adequate hydration
   • Analgesics/antipyretics for symptom relief

2. Monitoring

   • Follow-up in 2-4 weeks to ensure resolution of symptoms
   • Most symptoms and laboratory abnormalities resolve within 1 month, though fatigue and lymphadenopathy may persist longer 2

3. Precautions

   • Avoid contact sports for at least 3-4 weeks due to risk of splenic rupture (the most common potentially fatal complication) 1
   • Monitor for rare complications involving pulmonary, neurologic, and hematologic systems

Important Caveats

• Persistent lymphadenopathy (>4-6 weeks) or progressive symptoms warrant further investigation, including possible lymph node biopsy
• Significant liver injury can be an initial manifestation of infectious mononucleosis and should prompt liver function testing 4
• Dual positive IgM antibodies to both EBV and CMV can occur, making initial diagnosis challenging 4
• In patients with generalized lymphadenopathy, consider broader differential including malignancies and collagen vascular diseases if infectious workup is negative 5

Remember that while infectious mononucleosis is typically self-limited, proper diagnosis is important to rule out more serious conditions and to provide appropriate guidance regarding activity restrictions and expected course of illness.