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Sore Throat, Tonsillitis, and Glandular Fever

Distinguishing bacterial from viral pharyngitis, using clinical scoring tools, safe antibiotic prescribing, glandular fever pitfalls, and managing complications.

Clinical Differentiation

Several distinct diagnoses present as sore throat, and distinguishing between them directs management:

  • Viral pharyngitis/tonsillitis: The most common cause of sore throat (approximately 70 to 80% of cases). Caused by rhinovirus, adenovirus, parainfluenza, or other respiratory viruses. Self-limiting; antibiotics are not beneficial.
  • Bacterial tonsillitis: Most commonly caused by Group A beta-haemolytic Streptococcus (Streptococcus pyogenes — GABHS). Features: abrupt onset, high fever (>38°C), bright red tonsillar erythema with or without exudate, anterior cervical lymphadenopathy, absence of cough. Responds to penicillin.
  • Glandular fever (infectious mononucleosis): Caused by Epstein-Barr virus (EBV). Features: exudative tonsillitis, generalised lymphadenopathy (including posterior cervical), splenomegaly, hepatomegaly, fatigue, and a characteristic petechial rash on the soft palate. Classically affects young adults (the "kissing disease"). Critical management point: do NOT prescribe amoxicillin or ampicillin.
  • Peritonsillar cellulitis: Unilateral peritonsillar erythema and swelling without a discrete abscess. Trismus absent or mild. Treat as tonsillitis with IV antibiotics.
  • Quinsy (peritonsillar abscess): A collection of pus in the peritonsillar space. Hallmarked by trismus, drooling, uvular deviation, and a muffled "hot potato" voice. Requires drainage — see the quinsy guide.

Clinical Scoring: Centor and FeverPAIN

Centor Score

The Centor score is a validated tool used to estimate the probability of Group A Streptococcal (GABHS) pharyngitis and guide antibiotic prescribing. One point is awarded for each of the following:

  • Tonsillar exudate
  • Tender anterior cervical lymphadenopathy
  • Fever (history of fever or temperature >38°C)
  • Absence of cough

Modified Centor score (McIsaac modification) adds: +1 point for age 3 to 14 years; 0 points for age 15 to 44 years; -1 point for age 45 years or over.

  • Score 0 to 1: very low probability of GABHS (<10%) — no antibiotics, no throat swab
  • Score 2 to 3: intermediate probability — consider delayed prescription or throat swab
  • Score 4 to 5: high probability (~50%) — consider immediate antibiotics

FeverPAIN Score

The FeverPAIN score was developed in the UK (Little et al., 2013) specifically for primary care and is now endorsed by NICE. One point is awarded for each of:

  • Fever in the last 24 hours
  • Purulence (tonsillar exudate or purulent tonsils)
  • Attendance rapidly — within 3 days of symptom onset
  • Inflamed tonsils (severely inflamed tonsils)
  • No cough or coryza
  • Score 0 to 1: 13 to 18% chance of streptococcal infection — no antibiotics
  • Score 2 to 3: 34 to 40% — consider delayed antibiotic prescription
  • Score 4 to 5: 62 to 65% — immediate antibiotic prescription

Tonsillitis: Management

Typical presentation is a sore throat with bright red tonsils, cervical lymphadenopathy (especially level II — jugulodigastric nodes), high fever, and difficulty eating or drinking. The patient may appear clinically dehydrated.

The initial management plan should include:

  • Insert IV cannula and take bloods: FBC (look for lymphocytosis suggesting viral cause, neutrophilia suggesting bacterial), U&Es, LFTs (hepatomegaly in EBV), CRP, glandular fever screen (monospot / Paul-Bunnell test)
  • Benzylpenicillin 1.2 g IV (penicillin is the antibiotic of choice for GABHS tonsillitis)
  • Diclofenac 50 mg orally TDS (NSAIDs provide the most effective analgesia for sore throat — the PR route is available if the patient cannot swallow; warn the patient diplomatically in advance)
  • Codeine phosphate 30 to 60 mg orally QDS
  • Paracetamol 1 g orally or IV QDS
  • Difflam (benzydamine) spray — two sprays every 4 hours for topical oropharyngeal analgesia
  • Fluid replacement with IV normal saline if the patient appears clinically dehydrated (usually 1 litre or more as a starting point)

If after 90 minutes the patient still cannot eat or drink, admit with regular medications as above. However, most patients will feel significantly better after analgesia and can be discharged home with:

  • Phenoxymethylpenicillin (penicillin V) 500 mg four times daily for 7 days
  • Regular paracetamol and ibuprofen
  • Safety netting advice: return if symptoms worsen, develop trismus (difficulty opening mouth), develop difficulty breathing, or develop a quinsy

Admission criterion: Admit only if the patient is unable to eat or drink despite adequate analgesia, or if there are signs of complications.

Do NOT prescribe amoxicillin or ampicillin to any patient with sore throat without first excluding glandular fever. In patients with EBV infection, aminopenicillins (amoxicillin, ampicillin) cause a widespread maculopapular rash in up to 80 to 100% of cases. This is not a true penicillin allergy — it is an immune-mediated reaction specific to the EBV-infected state. Penicillin V and benzylpenicillin are safe in EBV. Use penicillin V for all standard sore throat patients.

Glandular Fever (Infectious Mononucleosis)

Glandular fever is caused by Epstein-Barr virus (EBV), a ubiquitous herpesvirus transmitted via saliva. It has a peak incidence in adolescents and young adults. The incubation period is 4 to 6 weeks.

Clinical Features

  • Exudative tonsillitis (white or grey-green exudate covering the tonsils)
  • Petechiae on the soft palate (a classic but not universal finding)
  • Generalised lymphadenopathy — including posterior cervical lymphadenopathy (unlike GABHS tonsillitis, which mainly causes anterior cervical lymphadenopathy)
  • Splenomegaly (present in up to 50% of cases)
  • Hepatomegaly and elevated liver transaminases (mild hepatitis)
  • Profound fatigue — may persist for weeks to months
  • Maculopapular rash (spontaneously in approximately 5 to 15% of cases; in up to 80 to 100% if given aminopenicillins)

Investigations

  • Monospot test (heterophile antibody test): A rapid bedside latex agglutination test for heterophile antibodies produced by EBV-infected B lymphocytes. Sensitivity is approximately 85% in adults but can be as low as 50 to 60% in children under 4 years and in the first week of illness. A negative monospot does not exclude glandular fever.
  • Paul-Bunnell test: The classical laboratory heterophile antibody test, now largely superseded by the monospot but essentially the same principle. If the monospot is negative and EBV is still suspected, discuss with biochemistry.
  • Blood film: Shows a characteristic lymphocytosis with atypical lymphocytes (sometimes called "Downey cells" — large, irregular lymphocytes with abundant basophilic cytoplasm). The presence of atypical lymphocytes on film is supportive of EBV infection.
  • EBV serology (VCA IgM/IgG, EA, EBNA): Definitive serological diagnosis. VCA (viral capsid antigen) IgM is elevated acutely. EBNA antibodies appear after recovery. Useful when monospot is negative but clinical suspicion remains high.
  • LFTs: Mildly elevated transaminases are common in EBV infection.
  • FBC: Lymphocytosis, sometimes thrombocytopenia.

Management of Glandular Fever

  • Supportive care: rest, adequate hydration, analgesia (paracetamol and NSAIDs)
  • Antibiotics are not indicated for EBV infection — if bacterial superinfection is suspected, use penicillin V (never amoxicillin)
  • Corticosteroids: A short course of oral prednisolone (typically 40 to 50 mg daily for 5 days) is used in severe EBV with significant tonsillar oedema causing airway compromise or difficulty swallowing, or with severe thrombocytopenia or haemolytic anaemia. Routine use in uncomplicated glandular fever is not recommended.
  • Splenomegaly and contact sports: Advise the patient to avoid all contact sports for a minimum of 2 to 3 months due to the risk of splenic rupture. For patients involved in contact or collision sports (rugby, martial arts, etc.), advise that they may return to sport only after an ultrasound confirms resolution of splenomegaly.

Complications of Tonsillitis and Glandular Fever

  • Quinsy (peritonsillar abscess): The most common local complication — see quinsy guide.
  • Parapharyngeal abscess: Deep neck space infection extending into the parapharyngeal space. Can compromise the airway. Requires CT imaging and urgent surgical drainage.
  • Retropharyngeal abscess: More common in children. CT confirms the diagnosis. Urgent drainage in theatre.
  • Airway compromise: Massive tonsillar enlargement, particularly in EBV, can threaten the airway — most common in young children. Systemic steroids and ENT involvement are essential.
  • Splenic rupture: A rare but life-threatening complication of EBV splenomegaly — presents with left upper quadrant pain and haemodynamic instability.
  • Rheumatic fever: Rare in the UK but important — caused by post-streptococcal immune-mediated damage to heart valves, joints, brain, and skin. Prompt treatment of GABHS tonsillitis reduces the risk.
  • Glomerulonephritis: Another post-streptococcal complication — urinalysis at follow-up.
  • Chronic fatigue: A significant proportion of EBV patients develop prolonged fatigue lasting months.

Frequently Asked Questions

How do I use the FeverPAIN and Centor scores in practice?

Both scores estimate the probability of bacterial (Group A Streptococcal) throat infection and guide antibiotic prescribing. NICE recommends using either FeverPAIN or Centor. Practically: if the score is low (FeverPAIN 0 to 1 or Centor 0 to 1), no antibiotics are needed — reassure and advise self-care. If intermediate, consider a delayed prescription (to be filled only if symptoms do not improve in 48 to 72 hours). If high, prescribe immediately. Avoid the reflex antibiotic prescription for all sore throats — approximately 80% are viral and self-limiting.

Why does glandular fever cause a rash when amoxicillin is given?

In EBV infection, B lymphocytes are infected and activated. Aminopenicillins (amoxicillin, ampicillin) trigger an abnormal immune reaction in this B-lymphocyte-activated state, producing a widespread, itchy maculopapular rash in 80 to 100% of patients. This is not a true penicillin allergy — the patient is not at increased risk of allergy to penicillin V or other penicillins in the future (outside of the EBV-infected state). However, many patients are incorrectly labelled as penicillin allergic as a result, which has significant downstream consequences for antibiotic prescribing. It is therefore essential to exclude EBV before prescribing any aminopenicillin for a sore throat.

A monospot test is negative but I still think the patient has glandular fever. What should I do?

A negative monospot does not exclude glandular fever. Sensitivity is only 85% overall, and considerably lower in children under 4 years (up to 50% false negative) and in the first week of illness (before heterophile antibodies reach detectable levels). If clinical suspicion remains high, request: (1) FBC and blood film — atypical lymphocytes (Downey cells) on the film are highly suggestive; (2) EBV serology — VCA IgM elevation confirms acute infection; (3) LFTs — elevated transaminases support the diagnosis. Discuss with your biochemistry or virology department if uncertain.

When should I admit a patient with tonsillitis?

The principal admission criterion is inability to eat or drink despite adequate analgesia — typically because of pain or severe odynophagia (pain on swallowing). Additional indications include: suspicion of quinsy (needs drainage); suspicion of deep neck space infection (parapharyngeal or retropharyngeal abscess); airway compromise or stridor; clinical dehydration requiring IV fluids; very young children or immunocompromised patients; and failure to improve after initial IV antibiotics and analgesia.

What are the indications for tonsillectomy in recurrent tonsillitis?

NICE recommends tonsillectomy should be considered using the Paradise criteria: 7 or more clinically significant episodes in the preceding year, or 5 or more episodes per year in the preceding two years, or 3 or more episodes per year in the preceding three years, with each episode documented as sore throat with fever (>38.3°C), cervical lymphadenopathy, tonsillar exudate, or positive throat culture for GABHS. Tonsillectomy is also indicated after a quinsy (interval/hot procedure). NICE also considers the impact on quality of life, schooling, and work.

How do you manage EBV with airway compromise?

EBV-associated airway compromise, caused by massive tonsillar enlargement, is most common in young children. It is a medical emergency. Immediate steps: (1) sit the patient upright; (2) administer high-flow oxygen; (3) give systemic dexamethasone (0.6 mg/kg IV up to 8 mg) — corticosteroids are indicated for airway-threatening EBV despite not being routinely recommended for uncomplicated cases; (4) call ENT and anaesthetics urgently; (5) if the airway is critically compromised, the patient may need intubation in theatre or emergency tracheostomy. Do not examine the throat aggressively or cause agitation — this can worsen obstruction.

What antibiotic do you prescribe for bacterial tonsillitis and for how long?

The antibiotic of choice for Group A Streptococcal (GABHS) tonsillitis is penicillin. In the acute hospital setting: benzylpenicillin 1.2 g IV QDS. For outpatient/discharge: phenoxymethylpenicillin (penicillin V) 500 mg four times daily for 7 to 10 days (NICE recommends 5 to 10 days). For patients with a genuine penicillin allergy: clarithromycin 500 mg twice daily for 5 to 10 days. Never prescribe amoxicillin or ampicillin for an unclarified sore throat — the EBV rash risk is significant.

How would you distinguish quinsy from tonsillitis in an ST3 viva?

The key differentiating feature is trismus (inability to open the mouth fully), which is almost universal in quinsy and absent in uncomplicated tonsillitis. Other quinsy hallmarks: unilateral peritonsillar swelling (not the tonsil itself) displacing the uvula to the contralateral side; a muffled "hot potato" voice; drooling (unable to swallow saliva); and severe unilateral throat pain. Examination reveals a smooth, tense, erythematous bulge in the peritonsillar space, typically superior and lateral to the affected tonsil. Management requires drainage (aspiration or incision and drainage) in addition to antibiotics — antibiotics alone are insufficient for an established abscess.

What are the risks of splenic rupture in glandular fever and how should patients be counselled?

Splenic rupture is a rare but potentially fatal complication of EBV-associated splenomegaly, occurring in approximately 0.1 to 0.5% of EBV cases. Splenomegaly is present in up to 50% of patients at some point during illness. Rupture can occur with minimal or no trauma — even straining or coughing. All patients diagnosed with EBV should be advised to avoid contact and collision sports for a minimum of 2 to 3 months. For athletes wishing to return to sport, an abdominal ultrasound confirming resolution of splenomegaly should be obtained. Patients should be warned to seek emergency care for sudden severe left upper quadrant pain or haemodynamic instability.

References

  1. NICE. Sore throat (acute): antimicrobial prescribing (NG84). National Institute for Health and Care Excellence; 2018.
  2. Centor RM, Witherspoon JM, Dalton HP, Brody CE, Link K. The diagnosis of strep throat in adults in the emergency room. Med Decis Making. 1981;1(3):239–246.
  3. Little P, Hobbs FD, Moore M, et al. Antibiotic prescription strategies for acute sore throat: a prospective observational cohort study. Lancet Infect Dis. 2014;14(3):213–219. [FeverPAIN score validation]
  4. McIsaac WJ, White D, Tannenbaum D, Low DE. A clinical score to reduce unnecessary antibiotic use in patients with sore throat. CMAJ. 1998;158(1):75–83.
  5. Candy B, Hotopf M. Steroids for symptom control in infectious mononucleosis. Cochrane Database Syst Rev. 2006;(3):CD004402.
  6. Ebell MH. Epstein-Barr virus infectious mononucleosis. Am Fam Physician. 2004;70(7):1279–1287.
  7. Sidell D, Shapiro NL, Bhattacharyya N. Obesity and the risk of obstructive sleep apnea in children with tonsil hypertrophy. Laryngoscope. 2012;122(5):1130–1133.