What additional tests or considerations are warranted for a patient with prolonged respiratory symptoms, cervical lymphadenopathy, fever, cough, and fatigue, beyond CBC (Complete Blood Count) with differential, EBV (Epstein-Barr Virus)/CMV (Cytomegalovirus)/HIV (Human Immunodeficiency Virus) serologies, and chest X-ray?

Additional Diagnostic Considerations for Prolonged Respiratory Symptoms with Cervical Lymphadenopathy

You should add tuberculosis testing (sputum AFB smear/culture and/or IGRA/TST), comprehensive metabolic panel including liver function tests, ESR or CRP, and consider Mycoplasma pneumoniae serology to your initial workup.

Critical Additional Testing

Tuberculosis Evaluation (Highest Priority)

• Obtain sputum for acid-fast bacilli (AFB) smear and culture given the >3-week duration of respiratory symptoms with systemic features—this classic presentation warrants TB exclusion 1
• Consider tuberculin skin test (TST) or interferon-gamma release assay (IGRA) if sputum cannot be obtained 1
• TB should be strongly considered in any patient with persistent cough >2-3 weeks accompanied by fever, night sweats, weight loss, and fatigue 1

Inflammatory Markers

• Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) to assess degree of systemic inflammation and help differentiate bacterial from viral etiologies 2
• These markers are particularly useful for monitoring disease progression and response to treatment 2

Comprehensive Metabolic Panel

• Liver function tests (AST, ALT, alkaline phosphatase) are essential as elevated transaminases can indicate CMV infection, EBV hepatitis, or other systemic infections 2, 3
• Include lactate dehydrogenase (LDH) and creatinine kinase as these may be elevated in atypical infections 2

Atypical Bacterial Pathogens

• Mycoplasma pneumoniae serology and throat PCR should be considered, as this organism causes respiratory symptoms with systemic features and can present with cervical lymphadenopathy 2
• If Mycoplasma serology is positive, obtain CSF PCR if any neurological symptoms develop 2

Additional Considerations Based on Clinical Context

If Immunocompromised Status Suspected

• Toxoplasma gondii serology if HIV test returns positive with low CD4 count 2
• Consider cryptococcal antigen if CD4 count <50 cells/μL 2
• HHV-6/7 and HHV-8 testing may be warranted if HIV-positive with persistent lymphadenopathy 4

Respiratory Virus Panel

• Respiratory virus testing (influenza, parainfluenza, RSV, adenovirus, human metapneumovirus) is indicated for patients with upper respiratory symptoms and cough 2
• This is particularly important as CMV pneumonia, though rare in immunocompetent hosts, can present with prolonged respiratory symptoms and atypical lymphocytosis 3

If Specific Features Present

• Blood cultures if fever persists or patient appears systemically ill 2
• Consider Bartonella antibody testing if there is cat exposure, particularly with seizures or neurological symptoms 2
• Tick-borne disease testing if relevant exposure history 2

Common Pitfalls to Avoid

Don't Dismiss Prolonged Symptoms as Viral

• The 3-week duration with persistent lymphadenopathy and new fever makes simple viral URI unlikely 1, 5
• Viral bronchitis typically resolves within 5-7 days, though cough may persist up to 3 weeks 5
• This patient's worsening course with new fever argues against uncomplicated viral infection

Don't Overlook TB in Low-Risk Populations

• TB can occur in patients without classic risk factors 1
• Diagnostic delay increases transmission risk—maintain high index of suspicion 1
• The combination of >3 weeks of symptoms, cervical lymphadenopathy, and systemic features (fever, fatigue) is classic for TB 1

Recognize Atypical Presentations

• HIV-positive patients may have atypical TB presentations with lower lobe infiltrates rather than upper lobe cavitation 1
• CMV can cause severe pneumonia in immunocompetent hosts with atypical lymphocytosis and elevated transaminases 3

Algorithmic Approach to Interpretation

If WBC Shows Lymphocytosis with Atypical Lymphocytes

• Strongly suggests viral etiology (EBV, CMV) but doesn't rule out bacterial infection 6
• Check for elevated transaminases which support CMV or EBV 3
• Consider CMV PCR if >9% atypical lymphocytes with elevated liver enzymes 3

If WBC Shows Elevated Granulocytes (>10.0 x 10⁹/L)

• Specificity of 84% for bacterial infection at this threshold 6
• At >15.0 x 10⁹/L, specificity increases to 97% for bacterial etiology 6
• However, normal WBC does not exclude bacterial infection (low sensitivity) 6

If Chest X-ray Shows Infiltrate

• Increases likelihood of bacterial pneumonia 5-fold 7
• Upper lobe infiltrates with cavitation suggest TB 1
• Bilateral infiltrates with air bronchograms may indicate atypical pathogens including CMV 3