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A 19-year-old male college student presents to the outpatient department with a 10-day history of high-grade fever, severe sore throat with odynophagia, marked fatigue and generalised aching. He was started on amoxicillin 500 mg three times daily by a local practitioner 3 days ago for "strep throat". On day 2 of amoxicillin he developed a diffuse, non-pruritic, maculopapular rash over the trunk and limbs.
On examination: temperature 38.7 degrees C, pulse 96/min, BP 118/76 mmHg. There is exudative tonsillitis with grey-white membrane, palatal petechiae, tender posterior cervical lymphadenopathy (nodes up to 2 cm), epitrochlear nodes, palpable splenomegaly (3 cm below the costal margin) and mild hepatomegaly. There is periorbital oedema. The rash is diffuse, blanching, maculopapular, non-confluent.
Investigations: Hb 13.4 g/dL, WBC 14.2 x 10^9/L (lymphocytes 62%, with 18% atypical lymphocytes), platelets 130 x 10^9/L. ALT 110 U/L, AST 95 U/L, bilirubin 28 micromol/L. Monospot (heterophile) positive.
Questions
a) What is the diagnosis, and what is the significance of the rash? (2 marks)
Infectious mononucleosis due to primary Epstein-Barr virus (EBV, HHV-4) infection. The classic triad (fever, exudative tonsillar pharyngitis, posterior cervical lymphadenopathy) plus splenomegaly, palatal petechiae, periorbital oedema (Hoagland sign), atypical lymphocytes and a positive Monospot confirm the diagnosis. The diffuse maculopapular rash after amoxicillin is the EBV ampicillin/amoxicillin rash — it occurs in 80-100% of IM patients given these drugs, is NOT a true IgE-mediated penicillin allergy, and is caused by EBV-driven polyclonal B-cell activation. Stop the amoxicillin; the patient will likely tolerate penicillins normally in future.
b) List four characteristic clinical features and the atypical cells on the blood film. (2 marks)
- Fever + exudative tonsillar pharyngitis + palatal petechiae
- Tender posterior cervical (and epitrochlear) lymphadenopathy
- Splenomegaly (with hepatomegaly and mild hepatitis)
- Periorbital oedema (Hoagland sign) and prolonged fatigue
- Blood film: lymphocytosis with atypical lymphocytes over 10% — these are reactive CD8+ cytotoxic T cells (Downey cells) responding to EBV-infected B cells, not leukaemic blasts.
c) Outline the definitive management and the FOUR specific things to AVOID. (3 marks)
Management is supportive: rest (as tolerated), adequate hydration, paracetamol 1 g every 6 hours (max 4 g/day) or ibuprofen 400 mg every 8 hours for fever/pain, salt-water gargles, throat lozenges.
AVOID:
- Ampicillin/amoxicillin (and cefprozil) — the rash. If streptococcal co-infection is proven, use phenoxymethylpenicillin or cephalexin.
- Alcohol during the hepatitis phase.
- Contact sport / strenuous exercise / heavy lifting for a minimum of 3-4 weeks until asymptomatic with the spleen normal on ultrasound (splenic rupture risk peaks weeks 2-3).
- Routine corticosteroids and antivirals — not beneficial in uncomplicated IM (Cochrane 2015); reserve steroids for impending airway obstruction, severe thrombocytopenia/haemolysis, or neurology.
Counsel the patient on the disease course (acute illness 1-2 weeks; fatigue may persist weeks-months) and warning signs (left-upper-quadrant or shoulder-tip pain, dyspnoea, bleeding, severe headache, weakness).
d) Describe two serious complications and their immediate management. (2 marks)
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Splenic rupture (around 0.1-0.5%; peaks weeks 2-3; LUQ pain, Kehr sign — shoulder-tip referral, falling Hb, signs of shock). Management: ABC, two large-bore IV cannulae, crossmatch, IV fluid resuscitation for haemorrhagic shock, urgent focused ultrasound (FAST) or CT abdomen, and urgent surgical referral — stable ruptures managed non-operatively; unstable or continuing bleed → splenectomy or splenic artery embolisation.
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Impending airway obstruction from massive tonsillar/adenoidal hypertrophy (muffled "hot-potato" voice, drooling, stridor). Management: sit upright, humidified oxygen, nebulised adrenaline, IV dexamethasone (0.6 mg/kg, max 10 mg), urgent ENT and anaesthetic review to secure the airway (nasopharyngeal airway, expert intubation, rarely tracheostomy).
(Other acceptable: autoimmune haemolytic anaemia — transfuse ± steroids; EBV-HLH in immunocompromised/XLP — HLH-2004 protocol, rituximab, specialist referral.)
e) Name two EBV-associated malignancies. (1 mark)
- Endemic (African) Burkitt lymphoma — t(8;14) c-myc translocation; jaw mass in children.
- Nasopharyngeal carcinoma (almost 100% EBV; South Chinese / Cantonese predisposition).
Also accept: Hodgkin lymphoma (mixed-cellularity), EBV-positive gastric carcinoma, extranodal NK/T-cell lymphoma, post-transplant lymphoproliferative disease (PTLD), oral hairy leukoplakia (HIV). EBV is also the strongest known risk factor for multiple sclerosis.