In a healthy adult or adolescent who recently had a sore throat (likely viral pharyngitis) and now presents with a new itchy, blanchable urticarial rash, what is the most likely etiology and how should it be evaluated and managed?

Urticarial Rash Following Sore Throat

This presentation most likely represents acute viral urticaria triggered by the preceding pharyngitis, and should be managed with second-generation H1-antihistamines as first-line therapy, with consideration for streptococcal infection screening if the urticaria is severe or persistent. 1, 2

Most Likely Etiology

Viral infections are the predominant cause of acute urticaria following respiratory tract infections in this clinical scenario. 2, 3

• In pediatric studies of acute urticaria associated with infectious illness, 90.9% had symptoms of respiratory tract infection, with analytic findings suggestive of viral infection in 79.5% of cases 3
• Specific viral pathogens identified include enterovirus (most common), parvovirus B19, Epstein-Barr virus, influenza, and cytomegalovirus 3
• Enterovirus infection shows significant association with acute urticaria during infectious disease (p = 0.0054) 3

Important Consideration: Streptococcal Pharyngitis

Beta-hemolytic streptococcal infection may be causative in many cases of acute urticaria following sore throat, even when the infection is not clinically apparent. 4

• In one study, 13 of 32 cases (40.6%) of acute urticaria had evidence of streptococcal infection via positive throat culture or significant streptococcal exoenzyme antibodies 4
• The streptococcal infection may not always be clinically obvious at presentation 4

Evaluation Approach

The diagnosis of urticaria is primarily clinical and extensive investigation is not required for most cases of acute urticaria. 1

History Should Focus On:

• Duration of individual wheals (typically 2-24 hours in ordinary urticaria) 1
• Presence of angioedema 1
• Recent medication use, particularly antibiotics, NSAIDs, or ACE inhibitors 1, 2
• Physical triggers (heat, cold, pressure, exercise) 1
• Known allergen exposures 1

Recommended Investigations:

For mild acute urticaria responding to antihistamines: No investigations are required. 1

For severe or persistent cases, consider:

• Throat culture and streptococcal enzyme levels (Streptozyme test) to evaluate for streptococcal pharyngitis 4
• Full blood count with differential if systemic features present 1
• Erythrocyte sedimentation rate if wheals persist beyond 24-48 hours (to evaluate for urticarial vasculitis) 1

Critical Pitfall: Antibiotic Attribution

Antibiotics are frequently blamed for urticaria developing during infectious illness, but this is often incorrect. 3

• In one study, 47.7% of children with infection-associated urticaria had received antibiotics before developing the rash 3
• When these patients were subsequently challenged with the same antibiotic, no adverse reactions occurred, indicating the infection itself—not the antibiotic—was the likely trigger 3
• Do not automatically discontinue appropriate antibiotic therapy for documented streptococcal infection when urticaria develops 4

Management Algorithm

First-Line Treatment:

Second-generation, non-sedating H1-antihistamines are the mainstay of therapy. 1, 5

• Examples include cetirizine, loratadine, fexofenadine, or desloratadine 5
• Over 40% of patients show good response to antihistamines 1
• Doses above manufacturer's licensed recommendations may be used when benefits outweigh risks 1

For Inadequate Response:

Combination therapy should be considered before escalating to corticosteroids. 1

• Add H2-antihistamines (e.g., ranitidine, famotidine) 1
• Add sedating antihistamines at night (e.g., hydroxyzine, diphenhydramine) 1
• Consider antileukotriene agents (e.g., montelukast) for resistant cases 1, 2

Corticosteroids:

Oral corticosteroids should be restricted to short courses for severe acute urticaria or angioedema affecting the mouth. 1

• Reserve for cases not responding to antihistamine therapy 2, 6
• Use the shortest course possible due to adverse effects 6

Adjunctive Measures:

Minimize nonspecific aggravating factors. 1

• Avoid overheating, stress, and alcohol 1
• Avoid aspirin and NSAIDs, which can worsen urticaria through leukotriene formation 1
• Avoid codeine and other direct mast cell degranulators 1, 7
• Apply cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) for symptomatic relief 1

When to Suspect Alternative Diagnoses

If individual wheals persist longer than 24-48 hours, consider urticarial vasculitis and obtain skin biopsy. 1

If angioedema occurs without wheals, screen for C1 esterase inhibitor deficiency with serum C4 level. 1

Prognosis

Most cases of acute urticaria resolve within days to weeks with appropriate treatment. 1

• Patients with wheals alone typically clear by 6 months 1
• Patients with both wheals and angioedema may have active disease for longer periods 1