What are the differential diagnoses for a patient presenting with sore throat, fever, swollen lymph node, cough, and headache?

Differential Diagnosis for Sore Throat, Fever, Swollen Lymph Node, Cough, and Headache

The presence of cough strongly suggests a viral upper respiratory tract infection rather than bacterial pharyngitis, and testing or antibiotics are not indicated unless specific features suggest Group A Streptococcus or other serious bacterial infection. 1, 2

Primary Consideration: Viral Upper Respiratory Infection

The constellation of symptoms—particularly the presence of cough alongside sore throat, fever, headache, and lymphadenopathy—points overwhelmingly toward viral etiology:

• Viral URI is the most likely diagnosis when cough accompanies pharyngitis symptoms, as cough is highly suggestive of viral origin and uncommon in bacterial pharyngitis 1, 2
• Common viral causes include rhinovirus, coronavirus, adenovirus, influenza virus, parainfluenza virus, respiratory syncytial virus, Epstein-Barr virus, and enteroviruses 1
• The presence of cough, along with other respiratory symptoms, strongly suggests viral rather than streptococcal etiology 1, 2

Key Bacterial Consideration: Group A Streptococcus (GAS)

While less likely given the cough, GAS pharyngitis must be considered in specific circumstances:

• GAS pharyngitis typically presents WITHOUT cough—the absence of cough is actually part of the modified Centor criteria used to assess likelihood of streptococcal infection 1
• Suspicious features for GAS include: sudden-onset severe sore throat, tonsillopharyngeal exudates, tender anterior cervical adenopathy, fever, scarlatiniform rash, palatal petechiae, and swollen tonsils 1
• Testing for GAS should NOT be performed when clinical features strongly suggest viral etiology (presence of cough, rhinorrhea, conjunctivitis, hoarseness, or diarrhea) 1
• GAS is primarily a disease of children 5-15 years of age and occurs most commonly in winter and early spring 1

Other Important Differential Diagnoses

Influenza

• Commonly presents with fever, headache, myalgias, and constitutional symptoms accompanied by respiratory symptoms including cough 1, 2
• Nausea and vomiting as presenting symptoms are common, particularly with influenza 2

Infectious Mononucleosis (Epstein-Barr Virus)

• Presents with pharyngitis, fever, and generalized lymphadenopathy (not just cervical) 1, 3
• Often accompanied by splenomegaly and prolonged fatigue 3
• More common in adolescents and young adults 3

Other Bacterial Causes (Less Common)

• Groups C and G β-hemolytic streptococci: Can cause pharyngitis but no specific treatment guidelines exist 1
• Mycoplasma pneumoniae or Chlamydia pneumoniae: Consider when associated with atypical pneumonia 1, 3
• Arcanobacterium haemolyticum: Rare in the United States; associated with scarlet fever-like rash in teenagers and young adults 1, 3
• Neisseria gonorrhoeae: Consider in sexually active individuals with pharyngitis 1

COVID-19

• Presents with fever, cough, headache, sore throat, and malaise 1
• May include nasal congestion, runny nose, and systemic symptoms 1
• Consider based on epidemiological exposure and community prevalence 1

Clinical Decision Algorithm

Step 1: Assess for viral features (any present = likely viral)

• Cough present? 1, 2
• Nasal congestion or rhinorrhea? 1, 2
• Conjunctivitis? 1
• Hoarseness? 1
• Diarrhea? 1

If YES to any above: Viral URI is the diagnosis—no testing or antibiotics needed 1, 2

Step 2: If NO viral features, apply Modified Centor Criteria for GAS

• Fever by history (1 point)
• Tonsillar exudates (1 point)
• Tender anterior cervical adenopathy (1 point)
• Absence of cough (1 point) 1

If <3 criteria: No testing needed 1 If ≥3 criteria: Perform rapid antigen detection test or throat culture 1

Critical Pitfalls to Avoid

• Do not test for GAS when cough is present—this identifies carriers rather than acute infections and leads to unnecessary antibiotic use 1, 4
• Do not prescribe antibiotics for viral pharyngitis—they provide no benefit and increase adverse events 1, 2
• Do not assume purulent appearance requires antibiotics—viral infections commonly cause tonsillar exudates 1, 2
• Watch for red flags suggesting serious conditions: difficulty swallowing, drooling, neck swelling, or severe toxicity may indicate peritonsillar abscess, epiglottitis, or Lemierre syndrome requiring urgent evaluation 1

Management Based on Diagnosis

For Viral URI (most likely in this case):

• No antibiotics indicated 1, 2
• Symptomatic treatment with analgesics, antipyretics, and supportive care 1, 2
• Expected duration 5-7 days, may persist up to 10 days 2
• Reassess if symptoms persist beyond 10 days, worsen after initial improvement, or severe symptoms develop 2

For Confirmed GAS (only if tested and positive):

• Penicillin or amoxicillin is first-line treatment 1, 4
• Treatment duration: 10 days to prevent rheumatic fever 1, 3