Tonsillitis and Pharyngitis

Viral (70–80% of cases, the default cause)

• Respiratory viruses: rhinovirus, coronavirus, adenovirus (pharyngoconjunctival fever in swimming-pool outbreaks), influenza, parainfluenza — direct epithelial infection with cytokine-driven mucosal edema; cough, rhinorrhea, hoarseness, and conjunctivitis are the mechanistic fingerprint of diffuse airway involvement
• EBV: infects B cells via CD21, driving a reactive CD8 T-cell expansion — exudative tonsillitis, posterior cervical adenopathy, splenomegaly, and atypical lymphocytosis with a positive heterophile antibody
• CMV: infects monocytes/macrophages and epithelial/endothelial cells, producing a heterophile-negative mononucleosis syndrome in which fever and malaise dominate and pharyngitis and adenopathy are comparatively mild
• Acute retroviral syndrome (HIV): nonexudative pharyngitis with mucocutaneous ulcers, rash, and adenopathy weeks after exposure; the CDC recommends HIV RNA plus antigen/antibody testing because antibody may still be negative
• Enteroviruses: coxsackie A causes herpangina (posterior palatal vesicles) and hand-foot-and-mouth disease; HSV causes anterior gingivostomatitis

Bacterial

• Group A Streptococcus: the pathogen that changes management, since IDSA guidance targets antibiotics at GAS to prevent rheumatic fever
• Fusobacterium necrophorum: an anaerobe of the tonsillar crypts, disproportionately in adolescents/young adults, and the organism behind Lemierre syndrome
• Groups C and G Streptococcus, Arcanobacterium haemolyticum (scarlatiniform rash in a teenager with a negative strep test), Mycoplasma pneumoniae
• Sexually transmitted: Neisseria gonorrhoeae (exudative pharyngitis after receptive oral sex), secondary syphilis
• Corynebacterium diphtheriae: exotoxin-mediated necrosis producing an adherent gray pseudomembrane that bleeds when scraped — a stem cue for the unvaccinated or foreign-born patient

• Viral invasion and local inflammation: Viral pathogens (rhinovirus, adenovirus, EBV, influenza, parainfluenza, coronavirus) infect respiratory epithelium, triggering local production of inflammatory cytokines (IL-6, TNF-α, IL-1) and recruitment of neutrophils and lymphocytes, resulting in mucosal edema, erythema, and exudate formation

• Bacterial adhesion and immune evasion: Group A Streptococcus uses M protein and other virulence factors to evade opsonophagocytosis, adhere to epithelial cells via hyaluronic acid mimicry (molecular mimicry), and trigger intense suppurative inflammation with neutrophil infiltration; other bacterial pathogens (S. aureus, H. influenzae, N. gonorrhoeae) similarly express adhesins and produce proteases

• Tonsillar structure and bacterial colonization: Palatine tonsils contain crypts with lymphoid tissue that create anaerobic microbial niches; bacterial pathogens colonize these crypts and breach epithelial barriers, leading to abscess formation and potential dissemination

• Post-streptococcal sequelae mechanisms: In susceptible hosts, molecular mimicry between GAS M protein and human myosin, tropomyosin, and other cardiac proteins triggers cross-reactive antibody and T-cell responses, leading to acute rheumatic fever (ARF) and post-streptococcal glomerulonephritis (PSGN); these occur in 0.3-3% of untreated GAS infections

• Viral pharyngitis: Gradual onset over 1-2 days with mild to moderate sore throat, low-grade fever, rhinorrhea, cough, hoarseness, and conjunctivitis; absence of purulent exudate is common; symptoms peak at 3-4 days and resolve within 7 days; systemic symptoms are mild

• Bacterial (GAS) pharyngitis: Abrupt onset with severe sore throat, high fever (often >38.5°C), dysphagia, and exudative tonsils (yellow or white patches); enlarged, erythematous tonsils with enlarged anterior cervical lymphadenopathy (tender, unilateral or bilateral); absence of cough and rhinorrhea help distinguish from viral causes; symptoms develop rapidly over 12-24 hours

• Scarlet fever variant of GAS: Presents with classic pharyngitis plus a sandpaper-textured rash on trunk and extremities sparing palms/soles, with strawberry tongue (white coating with red papillae initially, then red and denuded); rash typically appears 24-48 hours after fever onset and fades by 3-4 days

• Infectious mononucleosis (EBV): Severe pharyngitis with thick, adherent pseudomembrane, marked lymphadenopathy, splenomegaly, atypical lymphocytosis, and prominent systemic symptoms; may include hepatitis and risk of airway obstruction; heterophile antibody test (Monospot) or EBV serologies confirm diagnosis

• Epiglottitis and retropharyngeal abscess (red flags): Severe dysphagia, drooling, stridor, tripod positioning, and respiratory distress indicate potentially life-threatening complications; these require immediate imaging and airway management

• Peritonsillar abscess: Unilateral throat pain, fever, trismus, hot potato voice, asymmetric tonsillar enlargement with uvular deviation away from affected side, and difficulty swallowing liquids

• Clinical scoring systems (Centor/Modified Centor Criteria): The Modified Centor Score (1 point each for fever ≥38°C, no cough, swollen/exudative tonsils, tender anterior cervical lymphadenopathy; subtract 1 point for age ≥45 years) helps stratify risk: score ≥3 has ~50% probability of GAS, score 0-1 has ~10% probability; a score ≥4 or score 3 with positive rapid antigen test warrants antibiotics

• Rapid antigen detection test (RADT) and throat culture: RADT has 85-95% sensitivity and 95-99% specificity for GAS; negative RADT in patients with high pretest probability (Centor score ≥3) should be confirmed with throat culture, which remains gold standard but takes 24-48 hours; culture also identifies non-GAS pathogens

• Complete blood count and differential: Viral infections show lymphocytic predominance; GAS typically shows neutrophilic predominance with left shift; EBV shows atypical lymphocytes (>10%) and mononucleosis can present with marked lymphocytosis and thrombocytopenia

• Imaging and further workup: Lateral neck radiograph (soft tissue technique) or CT/MRI if peritonsillar or retropharyngeal abscess suspected (asymmetric swelling, unilateral symptoms); intraoral ultrasound can assess for collection; imaging unnecessary for uncomplicated pharyngitis

• EBV and other serologies: Monospot (heterophile antibody test) is rapid for acute EBV infection; EBV-specific serology (IgM and IgG antibodies to VCA, EBNA) confirms diagnosis; consider testing for other viral pathogens only in severe or prolonged cases

• Viral pharyngitis (supportive care): NSAIDs (ibuprofen 400-600 mg Q6-8H or naproxen 220-500 mg BID) or acetaminophen (650-1000 mg Q4-6H) for fever and pain; throat lozenges, salt water gargles, and hydration; antibiotics are contraindicated and ineffective; most symptoms resolve within 3-7 days

• Group A Streptococcal pharyngitis first-line antibiotics:
• Penicillin V orally (40,000 units/kg/day divided QID for 10 days; standard adult dose 250-500 mg QID) remains first-line due to excellent efficacy and lack of resistance; beta-lactam allergy low risk (cross-reactivity <1% with cephalosporins)
• Amoxicillin (50 mg/kg/day once daily or divided, up to 1000 mg daily; typical 500 mg once or twice daily) is acceptable alternative with better palatability in children
• Cephalexin 500 mg QID for 10 days for penicillin-allergic patients (cephalosporin cross-reactivity is rare; use cautiously only if no history of Type I hypersensitivity)

• Group A Streptococcal pharyngitis second-line and special situations:
• Macrolide antibiotics (azithromycin 12 mg/kg on day 1, then 6 mg/kg/day for 4 days; erythromycin 500 mg QID for 10 days) if true penicillin allergy; clarithromycin 250 mg BID for 10 days as alternative; rising macrolide resistance noted in some regions
• Clindamycin 300 mg TID for 10 days for severe infections or poor compliance (longer-acting); excellent for anaerobic coverage if abscess present
• Fluoroquinolones (moxifloxacin or levofloxacin) reserved for immunocompromised patients or treatment failures; not routine due to side effects and resistance concerns

• Symptomatic management:

Suppurative (local spread from tonsillar crypts)

• **Peritonsillar abscess (quinsy)**: pus collects between the tonsillar capsule and superior constrictor; hot potato voice, trismus, and uvular deviation away from the affected side. Needle aspiration or incision and drainage plus antibiotics covering strep and oral anaerobes — urgent, and an airway emergency if respiratory compromise develops
• Retropharyngeal abscess: spread to retropharyngeal nodes in children under ~5; neck stiffness, drooling, and widened prevertebral (retropharyngeal) soft tissue on a lateral neck film — classically more than about 7 mm at C2 or 14 mm at C6 in children, on a properly extended inspiratory film. Contrast-enhanced CT of the neck is the confirmatory study. Emergency — risk of airway obstruction and descending mediastinitis
• Lemierre syndrome: Fusobacterium septic thrombophlebitis of the internal jugular vein with septic pulmonary emboli; persistent fever and unilateral neck pain after "improving" pharyngitis, cavitary lung nodules on CT. Emergency
• Contiguous spread: otitis media, sinusitis, suppurative cervical adenitis
• Streptococcal toxic shock syndrome / necrotizing fasciitis: superantigen-driven; hypotension with a diffuse rash. Emergency

Non-suppurative (immune-mediated)

• Acute rheumatic fever: molecular mimicry; carditis, migratory polyarthritis, chorea per the AHA 2015 revised Jones criteria. Prompt antibiotics prevent it — the entire rationale for treating GAS
• Post-streptococcal glomerulonephritis: immune-complex deposition, cola-colored urine, edema, hypertension, low C3. Antibiotics do not prevent it — a favorite distractor

Treatment-related

• Aminopenicillin rash in EBV: a characteristic, frequently cited morbilliform eruption after amoxicillin/ampicillin (older case series reported very high rates; modern prospective estimates are closer to one-third); it is not a true IgE-mediated penicillin allergy and should not be recorded as one
• IgE-mediated anaphylaxis to penicillin (epinephrine 0.3 mg IM); cephalosporin cross-reactivity is low — on the order of a few percent — and tracks shared R1 side chains, not the beta-lactam ring
• Clindamycin: C. difficile colitis. Macrolides and fluoroquinolones: QT prolongation; fluoroquinolones carry FDA boxed warnings for tendinitis/tendon rupture and peripheral neuropathy
• Post-tonsillectomy hemorrhage: primary within 24 hours, secondary around days 5–10 as eschar sloughs — emergency

• Cough and rhinorrhea argue against strep: the single most useful discriminator in a stem. Conjunctivitis, hoarseness, oral ulcers, or diarrhea point to a virus, and IDSA advises against testing patients with these features at all — testing them only uncovers chronic carriers
• Best next step for suspected GAS is a rapid antigen test, not empiric antibiotics: per IDSA, a negative RADT in a child requires backup throat culture (high stakes for rheumatic fever), whereas in adults backup culture is not routinely needed because ARF incidence is very low
• Antibiotics prevent acute rheumatic fever but not post-streptococcal glomerulonephritis: the classic distractor. ARF follows pharyngitis only; PSGN can follow pharyngitis or impetigo
• Ampicillin/amoxicillin rash in mononucleosis: a teenager with exudative pharyngitis, posterior cervical adenopathy, and splenomegaly who develops a diffuse morbilliform rash after amoxicillin has EBV — do not label them penicillin-allergic
• **Uvula deviates away from a peritonsillar abscess**, with trismus and muffled voice; the next step is drainage plus antibiotics, not CT in a classic unilateral presentation. Drooling, stridor, and tripoding instead mean the airway comes first
• Persistent fever, unilateral neck tenderness, and cavitary lung nodules after pharyngitis = Lemierre syndrome (Fusobacterium necrophorum) — the one association examiners love in young adults
• No test of cure and no routine treatment of carriers: asymptomatic carriage with a positive test plus a viral syndrome is the trap that generates unnecessary antibiotic answers
• Recurrent tonsillitis is a frequency question: AAO-HNS uses documented episode counts over 1–3 years (Paradise criteria) to justify tonsillectomy; a single severe episode does not
• A unilaterally enlarged, firm tonsil that does not resolve in an adult is oropharyngeal carcinoma (often HPV-related) until proven otherwise — not tonsillitis