Tonsillitis

Epidemiology and Etiology

Epidemiology

• Viral tonsillitis: children < 5 years and young adults
• Streptococcal tonsillitis: 
  • Children aged 5–15 years (not seen in children < 3 years of age)
  • In adults: often before the age of 40 years
  • More frequent in winter and spring

Etiology

• Viral (most common): 
  • Epstein-Barr virus (EBV): causes 90% of infectious mononucleosis
  • Adenovirus
  • Coxsackie
  • Cytomegalovirus (CMV)
  • Influenza A and B
  • Parainfluenza viruses
  • Respiratory syncytial virus
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
  • Human immunodeficiency virus (HIV)
• Bacterial:
  • Group A Streptococcus (GAS): most common bacterial cause
  • Mycoplasma pneumonia
  • Corynebacterium diphtheria
  • Neisseria gonorrhoeae
  • Fusobacterium 
• Fungal: Candida (seen in denture wearers, asthma patients using corticosteroid inhalers, immunocompromised patients)

Clinical Presentation

Viral infection

• Mild tonsillar exudates
• Conjunctivitis
• Cough (upper respiratory tract infection)
• Rhinorrhea
• Infectious mononucleosis: fatigue, palpable spleen/splenomegaly, or axillary adenopathy

Bacterial infection

• GAS tonsillitis: 
  • Febrile (> 38°C (100.4°F))
  • Sore throat (may be severe), malaise
  • Pharyngotonsillar erythema and exudate
  • Tender and swollen anterior cervical adenopathy
  • Palatal petechiae
  • Strawberry tongue
  • Scarlatiniform rash
• C. diphtheria tonsillitis: 
  • Presents with sore throat and fever 
  • Commonly seen in unvaccinated individuals 
  • Patient with a gray tonsillar pseudomembrane (hallmark of the disease)
• N. gonorrhea tonsillitis: 
  • Sore throat and fever seen in sexually active people
  • Along with a sore throat, it is common to have symptoms related to genital tract infection.

Fungal infection

• Thrush (oropharyngeal candidiasis): white plaques in the oropharynx
• Many patients are asymptomatic; some with cottony feeling in the mouth and oral pain when eating

Diagnosis

The diagnosis is clinical, as it is based on history and examination findings.

Initial assessment

• Age of the patient
• Accompanying symptoms: Common viral illnesses have other symptoms, such as cough, conjunctivitis, and rhinorrhea.
• Risk factors (school exposure, immunocompromised state, vaccination status, sexual and illicit drug history, season)

Tests

Group A Streptococcus infection:

• Tests for GAS:
  • Rapid streptococcal antigen test or rapid antigen detection test (RADT): preferred for initial testing
  • Throat culture
  • Molecular assays
• Use of Centor criteria in GAS tonsillitis:
  • 4 findings given 1 point each
  • Modified to include patient age
  • The likelihood of GAS rises as the total points increase.
  • The features of Centor criteria:
    • Absence of Cough
    • Exudate
    • Cervical Nodes
    • Temperature (fever)
    • Young OR old modifier: age 3–14 years: + 1, age 15–44 years: 0, age ≥ 45 years: – 1
  • Scoring: 
    • < 2 unlikely GAS tonsillitis
    •  2–3: test for GAS
    • > 3: test for GAS; in rare cases, empiric treatment if testing is unavailable
• Risk assessment and clinical judgment for testing still recommended as:
  • Streptococcal infection presents similarly to other etiologies.
  • Examination findings alone can lead to overtreatment with antibiotics.
• In adults: 
  • Positive RADT: treatment is given
  • Negative RADT: no antibiotics; generally, culture is not needed (low incidence of complications such as rheumatic fever)
• In children and adolescents:
  • Rule out viral symptoms.
  • Initial test with RADT
  • If RADT is negative, follow-up throat culture is recommended (as RADT can miss up to 30%). 
  • If RADT is positive: Treat the infection.
  • Important to determine GAS infection as age group is at risk for rheumatic fever, glomerulonephritis, and suppurative complications

Work-up for other etiologies:

• Infectious mononucleosis:
  • Monospot (heterophile antibody test): positive in infection due to EBV
  • Complete blood count would show lymphocytosis.
• If indicated by history and risk factors:
  • HIV test
  • Nucleic acid amplification test or culture for N. gonorrhea 
  • Potassium hydroxide (KOH) preparation on oral lesion scrapings: budding yeasts +/- hyphae in candidal infection

Management

Ancillary treatment

• Analgesics (acetaminophen) and nonsteroidal anti-inflammatory drugs (NSAIDs) 
• Corticosteroids (in cases of severe swelling of tonsils)
• Hydration and gargling with saltwater

Viral infection

• Supportive management
• Viral illness with specific treatment available:
  • Influenza (for specific indications): oseltamivir, zanamivir, baloxavir, peramivir
  • HIV: initiate antiretroviral therapy

Group A Streptococcus infection

• Penicillin V or amoxicillin; 1st-generation cephalosporin an alternative
• Clindamycin/clarithromycin/azithromycin, if penicillin-allergic
• Ampicillin should be avoided if mononucleosis is suspected (induces a generalized rash).
• Prophylaxis (tonsillectomy) for recurrent streptococcal tonsillitis:
  • Indicated for patients age 1–18 years (Paradise criteria):
    • 3 episodes yearly for 3 or more years
    • 5 episodes yearly for 2 years
    • 7 episodes in 1 year
  •  Episodes of tonsillitis should have documentation of ≥ 1 of the following:  
    • Temperature 38.3°C (101°F)
    • Cervical adenopathy
    • Tonsillar exudate
    • Positive test for GAS

Other bacterial infections

• Diphtheria: erythromycin or penicillin G/V 
• Gonorrhea tonsillitis: ceftriaxone and azithromycin

Candidal infection (oropharyngeal thrush)

• Topical agents: clotrimazole troche, miconazole buccal tablet, nystatin oral suspension
• Systemic agents: fluconazole

Clinical Relevance

The following are the complications associated with bacterial tonsillitis/pharyngitis:

• Acute otitis media: a painful type of ear infection that occurs when the middle ear becomes inflamed and infected. This condition can occur from pharyngitis via travel along the eustachian tube.
• Retropharyngeal abscess: a collection of pus inside the retropharyngeal space, extending from local infections or coming from trauma such as dental procedures. If present, it can spread rapidly, cause airway obstruction, and lead to death. Immediate diagnosis and treatment are essential.
• Sepsis/bacteremia: fever, tachycardia, tachypnea, hypotension, and/or altered mentation leading to systemic organ dysfunction. Sepsis results from bacteria entering the bloodstream from a previously localized infection.
• Cervical adenitis: inflammation and infection in the lymph nodes in the cervical chain along the neck. The condition can occur via translocation of bacteria from the infected pharynx.
• Peritonsillar abscess: also called quinsy, a purulent collection between the capsule of the palatine tonsil and the pharyngeal muscles. The condition presents with fever, sore throat, and odynophagia, and, on examination, a bulging is seen around (mostly superior) the pharyngeal tonsils.
• Scarlet fever: fever, sore throat, strawberry tongue, and generalized sandpaper rash due to hypersensitivity reaction to exotoxin produced by GAS. Early recognition of GAS pharyngitis and subsequent antibiotic treatment can prevent this complication.
• Acute rheumatic fever: myocarditis, valvulitis (mitral regurgitation), and valvular heart disease (mitral +/- aortic regurgitation/stenosis) due to antibody cross-reactivity from a GAS infection. Early recognition of GAS pharyngitis and subsequent antibiotic treatment can prevent this complication.
• Post-streptococcal glomerulonephritis (PSGN): a type 3 hypersensitivity reaction that can occur 1–3 weeks following initial GAS infection. Clinical presentation includes microscopic/gross hematuria, edema, and hypertension. Diagnosis is via elevated antibody titers to strep antigens and low C3 levels. 

The following conditions are differential diagnoses of tonsillitis:

• Epiglottitis: also presents with fever, sore throat, and odynophagia; however, the presence of lymphadenopathy and exudate around the tonsils distinguishes tonsillitis from epiglottitis.
• Croup: also called laryngotracheobronchitis. Croup is caused by a viral infection or, rarely, by a bacterial infection that results in swelling inside the trachea. The infection interferes with normal breathing. Patients develop a characteristic barking cough and stridor, but can also have acute enlargement of the tonsils.
• Lemierre’s syndrome: jugular vein suppurative thrombophlebitis, often caused by Fusobacterium necrophorum. Symptoms include high fever, unilateral neck swelling (which can be similar to lymphadenopathy), and pain with respiratory symptoms. This condition affects healthy adolescents and adults.