What are the differential diagnoses and initial work‑up for a patient presenting with cough, fever and vomiting without diarrhea, abdominal pain, or anorexia?

Differential Diagnosis for Cough, Fever, and Vomiting Without Diarrhea or Abdominal Pain

The most critical diagnosis to consider is pertussis (whooping cough), particularly if the vomiting occurs immediately after coughing paroxysms, as this combination has 78% specificity for pertussis and requires immediate macrolide antibiotic therapy to prevent severe complications and transmission. 1, 2

Primary Differential Diagnoses

Pertussis (Whooping Cough)

This is the diagnosis you cannot afford to miss. Post-tussive vomiting (vomiting triggered specifically by coughing episodes) is a hallmark feature that strongly suggests pertussis. 1, 2

Key diagnostic features:

• Paroxysmal cough (prolonged coughing episodes with inability to breathe during spells) lasting ≥2 weeks 1
• Vomiting that occurs immediately after coughing fits, not independently 2, 3
• Inspiratory "whoop" sound following cough paroxysms (though may be absent in vaccinated individuals) 1, 2
• Presence of fever actually argues AGAINST pertussis - absence of fever has 81.8% sensitivity for pertussis 1

Critical action: Start empiric azithromycin or erythromycin immediately upon clinical suspicion without waiting for laboratory confirmation, as early treatment reduces severity and prevents transmission. 2, 3

COVID-19

This is the second most important consideration given the combination of respiratory and gastrointestinal symptoms. 1, 4

Key features:

• Gastrointestinal symptoms (nausea/vomiting) occur in 3.7-25% of COVID-19 cases 1, 4
• GI symptoms can precede respiratory symptoms by several days, making early recognition challenging 1, 4
• Presence of vomiting increases likelihood of positive COVID-19 test by 70% 4
• Fever, cough, and vomiting together during high-prevalence periods warrant COVID-19 testing 4

Obtain nasopharyngeal RT-PCR for SARS-CoV-2 and check liver enzymes (elevated AST/ALT in 15-56% of cases). 1, 4

Influenza

Particularly relevant in children, where influenza frequently presents with vomiting alongside respiratory symptoms. 2

Key features:

• Young children may present primarily with vomiting rather than typical influenza manifestations 2
• Occurs during influenza season with systemic illness appearance 2
• Can mimic bacterial sepsis in infants with high fever and vomiting 2

Pneumonia (Community-Acquired)

Fever, cough, and vomiting can occur together, though vomiting is less specific. 1

Key features:

• Elderly patients may have minimal cough or fever despite pneumonia 1
• Chest radiograph is essential to evaluate for infiltrates 1
• Consider atypical presentations in older adults 1

Acute Bacterial Sinusitis

Less likely given the absence of specific sinus symptoms, but can present with vomiting. 2

Key features:

• Vomiting occurs from gagging on post-nasal drainage, not post-tussive 2
• Usually accompanied by prolonged cough and irritability 2
• Mechanism differs from pertussis (gagging vs. post-cough paroxysms) 2

Initial Diagnostic Work-Up

Immediate assessment priorities:

1. Characterize the cough and vomiting relationship:

   • Does vomiting occur immediately after coughing fits? (suggests pertussis) 1, 2
   • Is the cough paroxysmal with inability to breathe during episodes? 1
   • Is there an inspiratory whoop? 1

2. Obtain nasopharyngeal specimens:

   • COVID-19 RT-PCR (mandatory during high-prevalence periods) 1, 4
   • Pertussis culture or PCR from nasopharyngeal aspirate/swab 3
   • Influenza testing if seasonal 2

3. Laboratory studies:

   • Complete metabolic panel including liver enzymes (AST/ALT) 1, 4
   • Complete blood count 1

4. Chest radiograph:

   • Essential to evaluate for pneumonia, tuberculosis, or other pulmonary pathology 1, 3

Age-Specific Considerations

For infants (<12 months):

• Hospitalize immediately if pertussis suspected due to high risk of apnea, bradycardia, and death 3
• Continuous cardiorespiratory monitoring required 3
• Infants may present with apneic spells and minimal cough initially 3

For children:

• Post-tussive vomiting has 60% sensitivity and 66% specificity for pertussis (less helpful than in adults) 1
• Consider influenza, which frequently causes vomiting in pediatric populations 2
• Assess for dehydration and electrolyte disturbances requiring aggressive fluid replacement 2, 4

For elderly patients:

• Higher mortality risk with COVID-19 requiring hospital admission 4
• Atypical presentations of pneumonia and tuberculosis are common 1
• May have minimal fever despite serious infection 1

Critical Pitfalls to Avoid

• Do not dismiss pertussis because fever is present - while absence of fever supports the diagnosis, fever does not completely exclude it, especially early in the illness 1
• Do not attribute vomiting solely to gastroenteritis when respiratory symptoms are present - this combination demands consideration of pertussis, influenza, and COVID-19 2, 4
• Do not delay empiric macrolide therapy while awaiting pertussis confirmation - treatment must begin immediately upon clinical suspicion 2, 3
• Do not assume all vomiting with cough is post-tussive - carefully distinguish vomiting triggered by coughing paroxysms from independent vomiting 2
• Do not overlook COVID-19 when GI symptoms predominate - test even if respiratory symptoms are mild 1, 4

Immediate Management Based on Most Likely Diagnosis

If pertussis suspected (post-tussive vomiting + paroxysmal cough):

• Start azithromycin immediately 2, 3
• Isolate patient for 5 days after antibiotic initiation 3
• Identify and treat close contacts with macrolide prophylaxis 3

If COVID-19 suspected:

• Isolate and test 4
• Supportive care with aggressive hydration and electrolyte monitoring 4
• Monitor liver enzymes and QTc if using anti-emetics 4

If influenza suspected during season:

• Consider oseltamivir if within 48 hours of symptom onset 2
• Supportive care and hydration 2