What is the diagnosis and appropriate management for a patient, possibly a child or adolescent, presenting with vomiting, tonsillar hypertrophy, headache, fever, and itchy maculopapular rashes?

Diagnosis: Infectious Mononucleosis (Epstein-Barr Virus)

The constellation of vomiting, tonsillar hypertrophy, headache, fever, and itchy maculopapular rash in a child or adolescent is most consistent with infectious mononucleosis caused by Epstein-Barr virus (EBV), which requires supportive care only and avoidance of antibiotics that can trigger or worsen the rash. 1

Clinical Reasoning

Key Diagnostic Features Supporting EBV/Infectious Mononucleosis

• Tonsillar hypertrophy with pharyngitis is a hallmark of EBV infection, distinguishing it from other viral exanthems like roseola that lack significant pharyngeal involvement 1
• Systemic symptoms including generalized fatigue, fever, pharyngitis, lymphadenopathy, and splenomegaly are characteristic of infectious mononucleosis 1
• Follicular conjunctivitis can occur with EBV, typically unilateral with ipsilateral lymphadenopathy 1
• The maculopapular rash in EBV can be pruritic and may appear spontaneously or be triggered by antibiotic administration (particularly ampicillin/amoxicillin) 1

Critical Differential Diagnoses to Exclude

Group A Streptococcal Pharyngitis must be ruled out because it is the only common bacterial pharyngitis requiring antibiotic therapy 1:

• Presents with tonsillopharyngeal erythema, fever, headache, nausea, vomiting, and can have scarlatiniform rash 1
• However, the presence of conjunctivitis, cough, hoarseness, coryza, or viral exanthem strongly suggests viral rather than streptococcal etiology 1
• The itchy maculopapular nature of the rash (rather than scarlatiniform) favors viral etiology 1

Life-Threatening Conditions that must be immediately excluded based on rash characteristics 1, 2, 3:

• Rocky Mountain Spotted Fever (RMSF): Look for petechial/purpuric rash (not simple maculopapular), involvement of palms and soles, thrombocytopenia, elevated hepatic transaminases 1, 2, 3
• Meningococcemia: Look for petechial/purpuric rash, hypotension, altered mental status, respiratory distress 2, 3

Diagnostic Workup

Essential Testing

• Rapid streptococcal antigen detection test (RADT) or throat culture to exclude Group A streptococcus, as this is the only common bacterial pharyngitis requiring antibiotics 1, 4
• Complete blood count with differential: EBV typically shows atypical lymphocytosis (>10% atypical lymphocytes) 1
• Heterophile antibody test (Monospot): Positive in 85-90% of adolescents and adults with EBV infectious mononucleosis by week 2-3 of illness 1
• EBV-specific serology (VCA-IgM, VCA-IgG, EBNA) if heterophile antibody is negative but clinical suspicion remains high 1

Red Flag Assessment

Immediately obtain the following if any red flags present 1, 2, 3:

• CBC with differential, CRP, comprehensive metabolic panel, blood culture
• Acute serology for Rickettsia rickettsii if geographic/seasonal risk or tick exposure possible
• These tests should be obtained before starting antibiotics if bacterial infection suspected

Management Algorithm

If Group A Streptococcus is Identified

• Penicillin is first-line antibiotic therapy 4
• Avoid ampicillin/amoxicillin if infectious mononucleosis is also suspected, as these can trigger severe maculopapular rash in 80-100% of EBV patients 1

If EBV/Infectious Mononucleosis is Diagnosed

Supportive care only 1:

• Antipyretics (acetaminophen or ibuprofen) for fever and discomfort
• Adequate hydration
• Rest during acute phase
• No antibiotics indicated - they are ineffective against EBV and may worsen rash 1

Activity restrictions 1:

• Avoid contact sports for 3-4 weeks due to splenomegaly risk (splenic rupture)
• Gradual return to normal activities as symptoms resolve

If Red Flags for RMSF are Present

Start doxycycline immediately, regardless of age (including children <8 years) if any of the following 1, 2, 3:

• Petechial or purpuric rash pattern
• Rash involving palms and soles
• Thrombocytopenia or elevated hepatic transaminases
• Progressive clinical deterioration
• Geographic/seasonal risk for RMSF

Critical timing: Mortality is 0% if treated by day 5, but increases to 33-50% if treatment delayed to days 6-9 2, 3

Common Pitfalls to Avoid

1. Prescribing ampicillin/amoxicillin without excluding EBV: This triggers severe rash in most EBV patients and does not indicate true penicillin allergy 1

2. Assuming absence of tick bite excludes RMSF: Up to 40% of RMSF patients report no tick bite history 2, 3

3. Waiting for serology results before treating suspected RMSF: Early serology is typically negative in the first week; treatment must be based on clinical suspicion 2, 3

4. Dismissing maculopapular rash as benign without assessing for petechiae/purpura: Rash pattern is critical for risk stratification 1, 2, 3

Disposition

Outpatient management is appropriate if 2, 3, 5:

• Patient appears well with stable vital signs
• No petechiae, purpura, or involvement of palms/soles
• No signs of sepsis or clinical deterioration
• Examination consistent with viral pharyngitis/infectious mononucleosis

Immediate hospitalization required if 2, 3:

• Patient appears toxic or has signs of sepsis
• Petechiae, purpura, or progressive clinical deterioration
• Suspected meningococcemia or RMSF with systemic symptoms
• Severe tonsillar hypertrophy causing airway compromise

Return precautions: Instruct patient/family to return immediately if rash becomes petechial/purpuric, or if altered mental status, hypotension, or respiratory distress develops 2, 3