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Summary Table

Feature	Detail
Risk Factors	Children aged 5-15 years, winter/early spring season, close-contact environments (schools, daycare), immunocompromised states
Etiology	Most commonly viral (adenovirus, EBV, rhinovirus). Among bacterial causes, Group A Streptococcus (GAS) is the most important and most tested organism
Patient Presentation	Acute-onset sore throat, odynophagia (painful swallowing), fever, malaise, referred otalgia
Classic Physical Exam	Erythematous, enlarged tonsils with or without tonsillar exudate, tender anterior cervical lymphadenopathy, fever >38.3C. Absence of cough, rhinorrhea, and conjunctivitis favors bacterial etiology
Key Diagnostic Results	Rapid Antigen Detection Test (RADT) for GAS as best initial test; throat culture as gold standard. Centor/McIsaac scoring guides need for testing
Management	Amoxicillin is first-line for GAS tonsillitis. Penicillin V is an alternative. In penicillin allergy: azithromycin or clindamycin. Supportive care for viral etiologies
Keywords	"Sore throat with tonsillar exudate," "tender anterior cervical lymphadenopathy," "absence of cough," "strawberry tongue," "sandpaper rash" (scarlet fever overlap)

1. Pathophysiology

Acute tonsillitis is an inflammatory process of the palatine tonsils, which are lymphoid tissue masses positioned at the junction of the oral cavity and oropharynx. These tonsils form part of Waldeyer's ring, a circumferential band of lymphoid tissue that serves as a first-line immunologic barrier against inhaled and ingested pathogens.

In viral tonsillitis, the offending organism invades the tonsillar epithelium and triggers a local immune response dominated by lymphocytic infiltration. This produces diffuse pharyngeal erythema, mild tonsillar enlargement, and symptoms that overlap with a typical upper respiratory infection (cough, rhinorrhea, conjunctivitis). The presence of these concurrent symptoms is a key reason why viral etiology does not warrant antibiotic therapy and is a commonly tested concept.

In bacterial tonsillitis caused by GAS (Streptococcus pyogenes), the pathophysiology is driven by bacterial adherence to the tonsillar epithelium via M protein and lipoteichoic acid. The M protein is also the key virulence factor that enables the organism to resist phagocytosis. GAS then releases streptolysin O and S, DNases, and hyaluronidase, which cause direct tissue destruction and a robust neutrophilic inflammatory response. This is why GAS tonsillitis characteristically produces purulent tonsillar exudate and prominent tender anterior cervical lymphadenopathy, unlike most viral causes.

The reason we treat GAS tonsillitis with antibiotics is not primarily to shorten symptom duration (though it does by roughly 1-2 days). The primary goal is to prevent acute rheumatic fever (ARF), a nonsuppurative complication driven by molecular mimicry between the streptococcal M protein and cardiac myosin. This cross-reactivity leads to pancarditis. Antibiotics must be initiated within 9 days of symptom onset to effectively prevent ARF. Notably, antibiotic treatment does not reliably prevent post-streptococcal glomerulonephritis (PSGN), which is mediated by immune complex deposition and follows a different immunologic timeline. This distinction is heavily tested.

2. Classification and Clinical Manifestation

Type	Etiology	Clinical Features	Distinguishing Clues
Viral Tonsillitis	Adenovirus, rhinovirus, influenza, parainfluenza, EBV, Coxsackie	Gradual onset, low-grade fever, concurrent cough/rhinorrhea/conjunctivitis, diffuse pharyngeal erythema without significant exudate	Presence of cough and rhinorrhea strongly suggests viral cause
Bacterial (GAS) Tonsillitis	Streptococcus pyogenes	Abrupt onset, high fever (>38.3C), severe odynophagia, tonsillar exudate, tender anterior cervical lymphadenopathy, headache, abdominal pain (in children), absence of cough	Absence of cough + exudate + anterior LAD + fever = classic GAS
EBV Tonsillitis (Infectious Mononucleosis)	Epstein-Barr Virus	Adolescent/young adult, prolonged fatigue, posterior cervical lymphadenopathy, hepatosplenomegaly, tonsillar enlargement that may be severe, possible palatal petechiae	Maculopapular rash after amoxicillin/ampicillin administration is a classic exam pearl
Herpangina	Coxsackie A virus	Young children, small vesicles/ulcers on the posterior pharynx and soft palate, high fever	Vesicular lesions on posterior pharynx (vs. anterior mouth in hand-foot-mouth)
Diphtheria	Corynebacterium diphtheriae	Grayish-white pseudomembrane that bleeds when removed, "bull neck" lymphadenopathy, unvaccinated child	Pseudomembrane + unvaccinated status

Clinical Scoring: Modified Centor (McIsaac) Criteria

Criterion	Points
Tonsillar exudate or swelling	+1
Tender anterior cervical lymphadenopathy	+1
Fever (history or measured >38C)	+1
Absence of cough	+1
Age 3-14 years	+1
Age 15-44 years	0
Age 45 years or older	-1

Interpretation

Score	Recommendation
0-1	No testing needed, symptomatic treatment only
2-3	Perform RADT; treat if positive
4-5	Empirical antibiotic treatment is reasonable (or test then treat)

3. Diagnostic Workup

Test	Role	Key Details
Rapid Antigen Detection Test (RADT)	Best Initial Test	High specificity (>95%), moderate sensitivity (70-90%). A positive result confirms GAS and treatment can begin immediately
Throat Culture	Gold Standard / Most Accurate Test	Sensitivity 90-95%. Required as backup when RADT is negative in children/adolescents. Takes 24-48 hours
Anti-Streptolysin O (ASO) titer	Retrospective confirmation	Not used for acute diagnosis. Used to confirm prior GAS infection when evaluating for ARF or PSGN
Monospot (Heterophile Antibody Test)	Screening for EBV	Order when you suspect infectious mononucleosis (prolonged symptoms, posterior LAD, splenomegaly). May be falsely negative in children <4 years
Complete Blood Count	Supportive	Lymphocytosis with atypical lymphocytes suggests EBV. Leukocytosis with neutrophilia and left shift is more suggestive of bacterial infection

The diagnostic approach begins with clinical assessment using the Modified Centor score. For patients scoring 2-3, proceed with RADT. If the RADT is positive, the diagnosis is confirmed and you initiate antibiotics. If the RADT is negative in a child or adolescent, you must follow up with a throat culture because the sensitivity of RADT is not high enough to rule out GAS in this age group. In adults, a negative RADT alone is generally sufficient to withhold antibiotics, because adults have a lower risk of ARF and lower GAS prevalence.

A common exam scenario presents a child with classic GAS features but a negative RADT. The correct next step is throat culture, not empirical antibiotics. Conversely, if the question gives you a positive RADT, no further testing is needed regardless of age.

ASO titers should never be ordered in the acute setting. They rise 1-3 weeks after infection and peak at 3-5 weeks. Their role is limited to supporting the diagnosis of ARF or PSGN in a patient with a compatible clinical picture weeks after the pharyngitis episode.

If the vignette describes an adolescent with prolonged sore throat, fatigue, posterior cervical lymphadenopathy, and splenomegaly, pivot to ordering a Monospot test. If the patient is under 4 years old with a similar picture, Monospot may be falsely negative, and EBV-VCA IgM serology becomes the preferred test.

4. Management and Treatment

Scenario	Treatment	Dose / Details
GAS Tonsillitis, first-line	Amoxicillin	50 mg/kg/day (max 1000 mg/day) orally once daily or divided BID for 10 days
GAS Tonsillitis, alternative	Penicillin V	Children: 250 mg BID-TID for 10 days. Adults/adolescents: 500 mg BID-TID for 10 days
GAS Tonsillitis, IM option	Benzathine Penicillin G	Single IM dose. Children <27 kg: 600,000 units. Children >27 kg and adults: 1.2 million units. Preferred when adherence is a concern
Penicillin Allergy (non-anaphylactic)	Cephalexin	20 mg/kg/dose BID (max 500 mg/dose) for 10 days
Penicillin Allergy (anaphylactic/severe)	Azithromycin	12 mg/kg/day (max 500 mg) on day 1, then 6 mg/kg/day (max 250 mg) on days 2-5
Penicillin Allergy (anaphylactic/severe), alternative	Clindamycin	7 mg/kg/dose TID (max 300 mg/dose) for 10 days
Viral Tonsillitis	Supportive care only	Analgesics (acetaminophen or ibuprofen), adequate hydration, rest. No antibiotics
EBV Tonsillitis	Supportive care	Analgesics, hydration, avoid contact sports until splenomegaly resolves (risk of splenic rupture). Avoid amoxicillin/ampicillin
Recurrent GAS Tonsillitis	Consider tonsillectomy	Indicated per Paradise criteria: 7 episodes in 1 year, 5 per year for 2 years, or 3 per year for 3 years

Acute stabilization in GAS tonsillitis centers on prompt antibiotic initiation. Amoxicillin is preferred over penicillin V in children because of its better taste and availability as a palatable suspension, with equivalent efficacy. The full 10-day course is mandatory to eradicate the organism from the pharynx and prevent ARF, even if symptoms resolve within 2-3 days. This is a frequently tested point: a vignette may ask about a patient who feels better at day 3 and asks whether to stop antibiotics. The answer is always to complete the full course.

When adherence is questionable (e.g., a vignette describing a patient with a history of medication noncompliance, or a socially unstable situation), single-dose intramuscular Benzathine Penicillin G is the best choice. This guarantees adequate drug levels without relying on the patient to finish an oral course.

For patients with penicillin allergy, the next step depends on the severity of the allergy. A history of mild rash (non-anaphylactic) allows the use of a first-generation cephalosporin like cephalexin, since the cross-reactivity rate between penicillins and first-generation cephalosporins is low (approximately 1-2%). A history of anaphylaxis, angioedema, or urticaria to penicillin mandates avoidance of all beta-lactams, and the correct choice becomes azithromycin or clindamycin.

Corticosteroids (single-dose dexamethasone) may be used as adjunctive therapy for severe odynophagia to reduce pain and allow oral intake, but this is not the primary treatment and is not universally recommended.

For recurrent tonsillitis, the question often tests whether you know the Paradise criteria for tonsillectomy. If a vignette describes a child meeting these frequency thresholds despite adequate antibiotic courses, the next best step is referral for tonsillectomy.

Peritonsillar abscess is the most common suppurative complication. It presents with severe unilateral sore throat, trismus (difficulty opening the mouth), "hot potato" (muffled) voice, and uvular deviation away from the affected side. Management is needle aspiration or incision and drainage plus IV antibiotics (ampicillin-sulbactam or clindamycin). This must not be confused with uncomplicated tonsillitis.

5. Differential Diagnosis and Distractors

Differential Diagnosis	Why It Is Similar	Key Discriminator
Infectious Mononucleosis (EBV)	Sore throat, tonsillar enlargement, exudate, fever, cervical lymphadenopathy	Posterior cervical LAD (vs. anterior in GAS), hepatosplenomegaly, prolonged fatigue, atypical lymphocytes on CBC, maculopapular rash after amoxicillin
Peritonsillar Abscess	Severe sore throat, fever, tonsillar swelling	Unilateral bulging, trismus, "hot potato" voice, uvular deviation. This is a complication, not uncomplicated tonsillitis
Retropharyngeal Abscess	Fever, sore throat, neck stiffness, odynophagia in a young child	Neck hyperextension/stiffness, drooling, refusal to eat, widened prevertebral space on lateral neck X-ray. Usually age <4 years
Epiglottitis	Acute sore throat, fever, dysphagia, drooling	Tripod positioning, inspiratory stridor, toxic appearance, "thumbprint sign" on lateral neck X-ray. No tonsillar findings on oral exam
Diphtheria	Sore throat, pharyngeal membrane, cervical lymphadenopathy	Grayish pseudomembrane that bleeds on removal, "bull neck," unvaccinated patient. Myocarditis and cranial neuropathies are late complications
Viral Pharyngitis (Adenovirus, Rhinovirus)	Sore throat, fever, pharyngeal erythema	Concurrent cough, rhinorrhea, conjunctivitis. No exudate. Gradual onset. Modified Centor score 0-1
Scarlet Fever	GAS pharyngitis features overlap completely	This is GAS tonsillitis with an erythrogenic exotoxin-mediated rash: diffuse "sandpaper" erythematous rash, strawberry tongue, circumoral pallor, Pastia lines. Treatment is identical to GAS tonsillitis
Ludwig Angina	Sore throat, fever, difficulty swallowing	Bilateral submandibular and sublingual space infection, "woody" induration of the floor of the mouth, tongue elevation. Usually follows dental infection, not tonsillar infection

6. Traps and High-Yield Pearls

The most common way students lose points on tonsillitis questions is by failing to distinguish viral from bacterial etiology. A vignette that includes cough, rhinorrhea, or conjunctivitis alongside sore throat is pointing you toward a viral cause, and the correct answer is supportive care only, not antibiotics. The absence of cough is one of the strongest individual predictors of GAS and is almost always included in well-written GAS vignettes as a deliberate signal.

The second major trap involves EBV mononucleosis. When a vignette describes an adolescent with sore throat and the physician prescribes amoxicillin empirically, followed by the development of a diffuse maculopapular rash, the question is testing your knowledge that aminopenicillins trigger this characteristic rash in EBV infection. The rash is not a true penicillin allergy and should not be documented as one.

A third commonly tested concept is the workup sequence after a negative RADT in a child. Many students incorrectly jump to empirical antibiotics. The correct next step is always throat culture in pediatric patients to avoid missing GAS due to the limited sensitivity of RADT.

Finally, never confuse the nonsuppurative complications. Antibiotics prevent ARF but do not prevent PSGN. Both can appear in the same question stem, and the tested concept is knowing which complication is preventable with timely treatment. The core competency here is recognizing the appropriate clinical scenario, applying the Centor criteria correctly, ordering the right test at the right time, and understanding the rationale for a full antibiotic course: prevention of rheumatic heart disease.

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