In a 54‑year‑old woman with a two‑week history of sore throat, hoarseness, odynophagia, productive white‑gel cough, a dull headache, a 15‑minute episode of loss of consciousness with brief hand stiffening, epigastric acidic sensation, left tonsillar white spot, no cervical lymphadenopathy, normal neurologic exam, and a past medical history of gout treated with allopurinol, what are the most likely diagnoses and the recommended next steps in management?

Differential Diagnosis and Management

This patient requires urgent evaluation for allopurinol hypersensitivity syndrome (AHS) given her constellation of symptoms—including white tonsillar spots, headache, brief loss of consciousness with hand stiffening, and systemic symptoms—occurring while on allopurinol for gout. 1

Most Likely Diagnoses

Primary Concern: Allopurinol Hypersensitivity Syndrome

• AHS presents with erythematous rash, fever, hepatitis, eosinophilia, and worsening renal function, with a 25% mortality rate 1
• This patient's white tonsillar spots may represent mucosal involvement of a severe cutaneous adverse reaction (SCAR), which includes Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) 2
• The brief loss of consciousness with hand stiffening could represent seizure activity associated with severe systemic hypersensitivity 1
• AHS typically occurs within the first few weeks of allopurinol therapy, particularly in patients with renal impairment 1

Secondary Considerations

• Acute viral pharyngitis/laryngitis (possibly COVID-19 Omicron variant, which presents with acute odynophagia, severe sore throat, and white pharyngeal changes in young to middle-aged adults) 3
• Infectious mononucleosis or other viral pharyngitis with secondary bacterial superinfection 4
• Gastroesophageal reflux disease (GERD) contributing to odynophagia and epigastric symptoms 5

Immediate Next Steps

Urgent Laboratory Evaluation

Stop allopurinol immediately and obtain:

• Complete blood count with differential (looking specifically for eosinophilia >20% and leukocytosis) 1
• Comprehensive metabolic panel including liver function tests (AST, ALT, bilirubin) and renal function (creatinine, BUN) 1
• Serum uric acid level 6
• COVID-19 PCR testing 3
• Throat culture and rapid streptococcal antigen test 4

Critical Physical Examination Findings to Document

• Examine for any skin rash, particularly maculopapular exanthema, which may be subtle initially 1
• Assess for hepatomegaly or right upper quadrant tenderness 1
• Document extent of pharyngeal involvement and any airway compromise 3
• Repeat neurological examination with attention to mental status changes 1

Airway Assessment

• If severe odynophagia with concern for upper airway edema, perform flexible laryngoscopy to exclude epiglottitis or laryngeal edema 3
• This is particularly important given the acute odynophagia and history of brief loss of consciousness 3

Management Algorithm

If AHS is Confirmed (eosinophilia, elevated liver enzymes, worsening renal function):

1. Immediate hospitalization for supportive care 1
2. Start systemic corticosteroids (prednisolone 1 mg/kg/day) 1
3. Monitor for progression to multi-organ failure 1
4. Never rechallenge with allopurinol or oxipurinol (40% cross-reactivity) 7
5. Future gout management: consider febuxostat (non-purine xanthine oxidase inhibitor with less cross-reactivity) or uricosuric agents like probenecid if renal function is normal 8, 6

If Viral Pharyngitis/Laryngitis is Primary Diagnosis:

1. Supportive care with adequate hydration and analgesia 3
2. Consider short course of systemic corticosteroids for severe laryngeal inflammation 3
3. Monitor for secondary bacterial infection requiring antibiotics 3
4. Still discontinue allopurinol given unclear contribution to symptoms 9

Regarding Gout Management Going Forward:

• If allopurinol must be discontinued, alternatives include febuxostat (40-120 mg daily) or uricosuric agents (probenecid, sulphinpyrazone) if renal function is normal 8, 6
• Benzbromarone can be used in mild-to-moderate renal impairment but carries hepatotoxicity risk 7, 6
• Allopurinol desensitization should only be attempted if mild hypersensitivity and all other alternatives have failed—never in severe reactions or AHS 7

Critical Pitfalls to Avoid

• Do not dismiss white tonsillar spots as simple pharyngitis without considering drug reaction, especially in patients on allopurinol 1, 4
• Do not continue allopurinol pending workup if AHS is suspected—the mortality rate is 25% 1
• Do not assume the brief loss of consciousness was vasovagal without ruling out seizure or severe systemic reaction 1
• Do not restart allopurinol without confirming the diagnosis and considering HLA-B*58:01 testing if available, particularly given potential renal impairment 1, 2