What is the diagnosis and next step in management for a 23-year-old female with a history of asthma and alleged allergy to chicken, presenting with severe itchiness (pruritus) on the palms and soles, fever, and nonproductive cough after swimming in cold weather, who has tried cetirizine (hydroxyzine) with some relief but significant drowsiness?

Diagnosis: Likely Acute Viral Respiratory Infection with Secondary Urticaria, Possibly Complicated by Cetirizine Hypersensitivity

The most critical next step is to immediately discontinue cetirizine, as the patient may be experiencing paradoxical worsening of urticaria due to antihistamine hypersensitivity, and switch to a non-sedating second-generation antihistamine from a different chemical class, such as loratadine or fexofenadine. 1, 2

Clinical Reasoning and Differential Diagnosis

The clinical presentation suggests a viral upper respiratory infection (fever, nonproductive cough after cold water exposure) that triggered a secondary urticarial reaction. However, the severe palmoplantar pruritus with minimal relief from cetirizine raises concern for:

• Cetirizine hypersensitivity: The FDA label explicitly warns that allergic reactions to cetirizine can occur, and patients should stop use immediately if this develops 1. Although rare, cetirizine-induced urticaria and hypersensitivity reactions are well-documented, with cetirizine being the most commonly reported oral antihistamine causing paradoxical allergic reactions 2.

• Viral exanthem with palmoplantar involvement: While Rocky Mountain spotted fever classically presents with palmoplantar rash, this patient lacks the typical petechial progression and has a different exposure history 3. The timing (5 days post-swimming) and fever/cough pattern favor a viral etiology.

• Acute urticaria secondary to viral infection: Common in young adults with atopic history (asthma) 3.

Immediate Management Algorithm

Step 1: Discontinue Current Antihistamine

• Stop cetirizine immediately due to possible hypersensitivity reaction causing paradoxical worsening 1, 2
• Cetirizine and hydroxyzine (which the patient may have cross-reactivity to given her chicken allergy history) are piperazine derivatives that can cause cutaneous drug eruptions 4

Step 2: Switch Antihistamine Class

• Initiate loratadine 10 mg daily or fexofenadine 180 mg daily as these are structurally distinct from cetirizine (piperazine class) and less likely to cause sedation 5
• These second-generation antihistamines are first-line for mild allergic symptoms and urticaria 5, 6
• Avoid hydroxyzine entirely given structural similarity to cetirizine and documented cross-reactivity 4, 2

Step 3: Add Adjunctive Therapy for Severe Pruritus

• Consider adding a short course (3-5 days) of oral corticosteroids (prednisone 40-60 mg daily) given the severity of symptoms (8/10 pruritus) and inadequate response to antihistamines alone 3
• This is particularly important given her asthma history, as poorly controlled allergic symptoms can worsen asthma control 3

Step 4: Assess and Manage Respiratory Component

• Evaluate asthma control: Check for wheezing, chest tightness, or increased cough beyond the initial viral symptoms 3
• Given her asthma history, ensure she has a short-acting beta-agonist (SABA) available and consider stepping up asthma therapy if symptoms worsen 3
• Patients with asthma and allergic rhinitis benefit from treating both conditions concurrently 3

Step 5: Monitor for Anaphylaxis Warning Signs

• Educate patient on anaphylaxis symptoms: difficulty breathing, throat swelling, dizziness, or rapid progression of symptoms 3
• Given possible antihistamine hypersensitivity, she should be monitored closely for 20-30 minutes after any new medication trial 3

Key Clinical Pitfalls to Avoid

• Do not assume antihistamines are always safe: Hypersensitivity to antihistamines, while rare, presents most commonly as urticaria/angioedema, which can be mistaken for inadequate treatment of the underlying condition 2
• Do not continue ineffective therapy: If symptoms persist or worsen despite appropriate antihistamine therapy for 72 hours, reassess the diagnosis 7
• Do not ignore the asthma history: Patients with asthma are at higher risk for severe systemic reactions and require closer monitoring 3
• Do not overlook alternative diagnoses: If palmoplantar pruritus persists beyond 7-10 days or develops petechiae, consider tickborne illness (though less likely given exposure history) or other systemic causes 3

Follow-Up Plan

• Reassess in 48-72 hours: Symptoms should improve significantly with appropriate antihistamine therapy 5, 7
• If no improvement: Consider oral challenge testing with alternative antihistamines under medical supervision to identify tolerated preparations 2
• If symptoms resolve: Document cetirizine as a drug allergy and recommend avoidance of all piperazine derivatives (cetirizine, hydroxyzine, levocetirizine) 6, 4, 2
• Long-term: Once acute symptoms resolve, evaluate for persistent allergic rhinitis and consider allergen testing and environmental control measures 3, 5