Acute Tonsillitis

Acute inflammation of the palatine tonsils, usually part of a wider pharyngitis, and one of the most frequent reasons for antibiotic prescription in primary care despite the majority of cases being viral.

Anatomy relevant to the disease and its complications

The palatine tonsils sit in the tonsillar fossa between the palatoglossal and palatopharyngeal arches, bounded laterally by the superior constrictor and the pharyngobasilar fascia. Deep to this lies the parapharyngeal space, which is why untreated peritonsillar infection tracks into the neck. The tonsil has 10 to 30 deep crypts lined by specialised reticulated epithelium, which increases antigen contact and also traps debris, permitting the formation of tonsilloliths and providing a reservoir for organisms.

Blood supply arises from the tonsillar branch of the facial artery, the ascending pharyngeal, the lingual, the descending palatine and the ascending palatine arteries, with the main pedicle at the inferior pole. The internal carotid artery lies approximately 2 to 2.5 cm posterolateral to the tonsil, and closer in children and where the vessel is tortuous, which is the anatomical basis for catastrophic haemorrhage during dissection.

Innervation is from the glossopharyngeal nerve and the lesser palatine branches of the maxillary nerve. The glossopharyngeal nerve also supplies the tympanic branch, that is Jacobson nerve, which explains referred otalgia.

Microbiology

• Viral in 70 to 85 percent of adults and 60 to 75 percent of children: rhinovirus, coronavirus, adenovirus, influenza, parainfluenza, respiratory syncytial virus, Epstein Barr virus, cytomegalovirus, herpes simplex, enterovirus and, in acute retroviral syndrome, HIV.
• Group A beta haemolytic Streptococcus, that is Streptococcus pyogenes, in 15 to 30 percent of children and 5 to 15 percent of adults. This is the organism whose treatment prevents rheumatic fever.
• Groups C and G streptococci, Fusobacterium necrophorum which is the agent of Lemierre syndrome and is disproportionately represented in adolescents and young adults, Arcanobacterium haemolyticum which produces a scarlatiniform rash in adolescents, Haemophilus influenzae, Staphylococcus aureus and anaerobes.
• Neisseria gonorrhoeae in pharyngitis with a sexual history, which is often asymptomatic.
• Corynebacterium diphtheriae where vaccination coverage is poor, producing an adherent grey pseudomembrane that bleeds on removal, with cervical oedema and systemic toxicity.

Why identifying group A streptococcus matters

Untreated streptococcal tonsillitis carries a risk of acute rheumatic fever, which remains a substantial cause of acquired heart disease in sub Saharan Africa, South Asia and Oceania. Antibiotic treatment started within 9 days of symptom onset prevents rheumatic fever. It does not prevent post streptococcal glomerulonephritis. In high incidence settings the threshold for treating and for taking throat swabs is appropriately lower than in low incidence settings, and this is a genuine and important geographical difference in practice.

• Sore throat of rapid onset, with odynophagia and dysphagia.
• Referred otalgia through the glossopharyngeal nerve, with a normal ear examination.
• Fever, malaise, headache and myalgia.
• Halitosis.
• Reduced oral intake, which is the main driver of admission in children.
• Abdominal pain and vomiting in children, which is common with streptococcal infection.

Findings favouring bacterial over viral aetiology

• Tonsillar exudate, though this occurs in adenovirus and infectious mononucleosis too and is not by itself discriminating.
• Tender anterior cervical lymphadenopathy.
• Fever above 38 degrees Celsius.
• Absence of cough, coryza, conjunctivitis, hoarseness and oral ulceration, which are viral features.
• Palatal petechiae and a scarlatiniform sandpaper rash with circumoral pallor and a strawberry tongue, which indicate scarlet fever.

Examination

• Enlarged erythematous tonsils with exudate or follicular pus.
• Uvula midline. Uvular deviation with trismus and a muffled voice indicates peritonsillar abscess.
• Cervical lymphadenopathy, with the pattern noted: anterior in streptococcal disease, generalised and posterior in infectious mononucleosis.
• Assess hydration, particularly in children.
• Examine for splenomegaly and hepatomegaly, and for a generalised rash.

Red flags requiring urgent assessment

• Trismus, drooling, muffled hot potato voice and unilateral swelling, indicating peritonsillar abscess.
• Stridor, respiratory distress, inability to lie flat and a tripod posture, indicating airway compromise from epiglottitis or a deep neck space infection.
• Neck stiffness, torticollis and neck swelling, indicating retropharyngeal or parapharyngeal abscess.
• Rigors with unilateral neck pain and swelling along sternocleidomastoid in an adolescent, indicating Lemierre syndrome with internal jugular vein thrombophlebitis and septic pulmonary emboli. This has a high mortality if missed and is the reason Fusobacterium coverage matters in this age group.
• Grey adherent membrane with bull neck and systemic toxicity, indicating diphtheria.
• Unilateral persistent tonsillar enlargement with ulceration, induration, or a neck mass in an adult, indicating malignancy.
• Persistent symptoms with pallor and bruising, indicating leukaemia.

Clinical scoring identifies the group in whom testing or treatment is worthwhile.

Centor criteria, modified by McIsaac: one point each for tonsillar exudate, tender anterior cervical adenopathy, fever by history, and absence of cough; plus one point for age 3 to 14 years, zero for 15 to 44 years, and minus one for 45 years and above.

• Score 0 to 1: streptococcal probability under 10 percent. No testing, no antibiotics.
• Score 2 to 3: probability 15 to 35 percent. Rapid antigen test or culture, treat if positive.
• Score 4 to 5: probability 50 to 60 percent. Test and treat, or in high rheumatic fever incidence settings treat empirically.

FeverPAIN score: one point each for fever in the past 24 hours, purulence, attendance within 3 days of onset, severely inflamed tonsils, and no cough or coryza. Scores of 4 to 5 give a 62 to 65 percent streptococcal probability.

Investigations

• Rapid antigen detection test for group A streptococcus, with a specificity above 95 percent and a sensitivity of 70 to 90 percent. A positive result confirms; a negative result in a child in a high incidence setting should be backed up by culture.
• Throat swab culture, which remains the reference standard and takes 24 to 48 hours.
• Full blood count where infectious mononucleosis, leukaemia or agranulocytosis is suspected. Lymphocytosis with atypical lymphocytes suggests mononucleosis; neutropenia raises the possibility of agranulocytosis, which is an emergency and requires immediate withdrawal of any causative drug such as carbimazole, clozapine or methotrexate.
• Monospot or heterophile antibody test, which is insensitive in the first week and in young children. Epstein Barr virus specific serology with viral capsid antigen immunoglobulin M is more reliable.
• Liver function tests in mononucleosis, which are abnormal in the majority.
• HIV testing where the presentation fits acute retroviral syndrome, that is fever, pharyngitis, rash, lymphadenopathy and mucosal ulceration. Note that HIV antibody testing may be negative in seroconversion, so request HIV RNA or a fourth generation antigen antibody assay.
• Blood cultures in a septic patient.
• Contrast enhanced computed tomography of the neck for suspected deep neck space infection, and with venous phase imaging where Lemierre syndrome is suspected, looking for internal jugular thrombus, together with chest imaging for septic emboli.
• Anti streptolysin O and anti DNase B titres have no role in acute diagnosis, since they rise late. They are used retrospectively when rheumatic fever or glomerulonephritis is being investigated.

Differential diagnosis

• Infectious mononucleosis: adolescent or young adult, prolonged malaise, generalised and posterior cervical lymphadenopathy, splenomegaly, palatal petechiae, marked tonsillar hypertrophy sometimes with airway compromise, atypical lymphocytosis.
• Peritonsillar abscess.
• Epiglottitis and supraglottitis: severe odynophagia disproportionate to a relatively normal oropharynx, muffled voice, drooling, and a rapidly progressive course. This is the diagnosis to consider when the throat looks less impressive than the patient.
• Herpangina and hand foot and mouth disease from coxsackievirus, with vesicles and ulcers on the soft palate and tonsillar pillars.
• Primary herpetic gingivostomatitis, with anterior oral vesicles and gingivitis.
• Agranulocytosis and acute leukaemia.
• Tonsillar malignancy: squamous cell carcinoma, and lymphoma with unilateral rapid enlargement.
• Kawasaki disease in a child with prolonged fever, conjunctivitis, mucosal changes, rash and desquamation.
• PFAPA syndrome, that is periodic fever with aphthous stomatitis, pharyngitis and cervical adenitis, occurring in young children with strikingly regular episodes every 3 to 6 weeks, complete wellness between episodes, and dramatic response to a single dose of corticosteroid.

Symptomatic treatment, which is the mainstay in all cases

• Paracetamol 1 g every 6 hours in adults, maximum 4 g in 24 hours; 15 mg/kg every 6 hours in children, maximum 60 mg/kg in 24 hours.
• Ibuprofen 400 mg every 8 hours in adults, maximum 2.4 g in 24 hours; 10 mg/kg every 8 hours in children, maximum 40 mg/kg in 24 hours. Ensure adequate hydration before prescribing, and avoid in dehydration and renal impairment.
• Combining paracetamol and ibuprofen provides better analgesia than either alone in severe odynophagia.
• Adequate fluid intake, which frequently requires explicit instruction and encouragement, particularly in children where poor intake precipitates admission.
• Benzydamine hydrochloride 0.15 percent spray or mouthwash for topical analgesia.
• Salt water gargles.
• Avoid aspirin in children under 16 years, given Reye syndrome.

Corticosteroid

A single dose of dexamethasone 10 mg orally or intravenously in adults, or 0.6 mg/kg to a maximum of 10 mg in children, provides significant additional pain relief and faster resolution in severe cases. It is appropriate for severe odynophagia, poor oral intake, and airway concern in infectious mononucleosis. It should not be given routinely for mild disease.

Antibiotics

Indications:

• Positive rapid antigen test or culture for group A streptococcus.
• FeverPAIN score 4 to 5 or Centor score 3 to 4 with high clinical suspicion.
• Systemic illness, sepsis, or signs of complication.
• Immunocompromise, including diabetes and asplenia.
• High rheumatic fever incidence setting, where the threshold is lower.
• Scarlet fever.

Regimens:

• Phenoxymethylpenicillin 500 mg orally four times daily, or 1 g twice daily, for 10 days in adults. Children: 250 mg four times daily under 12 years, or 12.5 mg/kg four times daily. The 10 day course is required for rheumatic fever prevention and eradication, and shorter courses are not equivalent for that purpose, though 5 to 7 days is adequate for symptom control alone in low incidence settings.
• Amoxicillin 500 mg three times daily, or 50 mg/kg per day in children, is an acceptable alternative with better palatability, but must be avoided if infectious mononucleosis is possible, since it produces a florid maculopapular rash in the great majority of such patients. This rash is not a penicillin allergy and mislabelling it as such follows the patient for life.
• Benzathine benzylpenicillin 1.2 million units intramuscularly as a single dose in adults, or 600000 units in children under 27 kg, where adherence to a 10 day oral course is doubtful. This is the preferred option in high rheumatic fever incidence settings with poor follow up.
• Penicillin allergy: clarithromycin 500 mg twice daily for 5 days in adults, or azithromycin 500 mg daily for 3 days. Note rising macrolide resistance in Streptococcus pyogenes in many regions.
• Clindamycin 300 mg four times daily for severe penicillin allergy, and for recurrent disease where beta lactamase producing organisms in the tonsillar crypts inactivate penicillin.
• Co amoxiclav 625 mg three times daily for recurrent disease, treatment failure and suspected anaerobic involvement.
• Avoid tetracyclines and trimethoprim, which have poor streptococcal activity.
• Metronidazole added where Fusobacterium or anaerobic infection is suspected, particularly in an adolescent with severe unilateral symptoms.

Delayed prescribing

Providing a prescription to be used if symptoms fail to improve within 3 to 5 days, or worsen, reduces antibiotic use substantially without increasing complications. It is appropriate for intermediate scores in low incidence settings.

Indications for admission

• Inability to maintain oral intake, with dehydration.
• Airway concern: stridor, drooling, inability to lie flat.
• Sepsis.
• Suspected deep neck space infection or Lemierre syndrome.
• Immunocompromise, neutropenia, or diabetes with poor control.
• Failure of oral therapy.
• Massive tonsillar hypertrophy in mononucleosis with obstruction.

Inpatient management

• Intravenous fluids: 0.9 percent sodium chloride, with maintenance and replacement of deficit.
• Intravenous benzylpenicillin 1.2 g every 6 hours in adults, or 25 mg/kg every 6 hours in children; or co amoxiclav 1.2 g every 8 hours where anaerobic cover is needed; with clindamycin 600 mg every 6 hours in penicillin allergy.
• Add metronidazole where Fusobacterium is a concern.
• Regular intravenous paracetamol and, where tolerated, a nonsteroidal anti inflammatory drug.
• Dexamethasone for severe odynophagia and airway oedema.
• Airway monitoring, with anaesthetic and intensive care involvement where obstruction is developing. In severe mononucleosis with airway compromise, corticosteroid, nasopharyngeal airway and, rarely, intubation or tracheostomy are required.

Complications and their management

• Peritonsillar abscess, retropharyngeal and parapharyngeal abscess, managed as detailed under those conditions.
• Lemierre syndrome: intravenous antibiotics with anaerobic cover, typically piperacillin with tazobactam 4.5 g every 6 to 8 hours or a carbapenem plus metronidazole, for 4 to 6 weeks; imaging for internal jugular thrombus and septic pulmonary emboli; drainage of metastatic abscesses; and a case by case decision on anticoagulation. Suspect it in any young patient with tonsillitis followed by rigors, unilateral neck pain and pulmonary symptoms.
• Acute rheumatic fever, presenting 2 to 4 weeks after streptococcal pharyngitis with carditis, polyarthritis, chorea, erythema marginatum and subcutaneous nodules, and diagnosed by the Jones criteria. Requires long term secondary prophylaxis with benzathine benzylpenicillin 1.2 million units intramuscularly every 3 to 4 weeks, continued for a minimum of 10 years or until age 21 in the absence of carditis, and longer with established valve disease.
• Post streptococcal glomerulonephritis, which is not prevented by antibiotic treatment.
• Scarlet fever.
• Streptococcal toxic shock syndrome and necrotising infection.
• Airway obstruction from massive tonsillar hypertrophy.
• PFAPA syndrome: a single dose of prednisolone 1 to 2 mg/kg at the onset of an episode aborts it dramatically, which is diagnostically useful. Tonsillectomy is curative in the majority.

Advice on discharge

Return immediately for difficulty breathing, inability to swallow saliva, drooling, trismus, neck swelling, rigors or a rash. Explain the natural course, that symptoms typically last 5 to 7 days, and give clear analgesia instructions with the emphasis on regular rather than as required dosing.