What are the treatment options for a 38-year-old male with chronic urticaria (hives) and pruritus (itching) that started after hand, foot, and mouth disease, without signs of anaphylaxis or gastrointestinal symptoms?

Chronic Urticaria Following Hand, Foot, and Mouth Disease: Treatment and Workup

Initial Management Approach

Start with second-generation non-sedating H1-antihistamines at standard doses as first-line therapy, and if symptoms persist after 2-4 weeks, increase the dose up to four times the standard dose before considering additional interventions. 1

First-Line Treatment: Non-Sedating Antihistamines

• Begin with cetirizine 10 mg once daily or loratadine 10 mg once daily, as these are proven effective for chronic spontaneous urticaria 1, 2
• Cetirizine has the shortest time to maximum concentration, which may provide more rapid relief 1
• If inadequate response after 2-4 weeks, increase to up to 4 times the standard dose (e.g., cetirizine 40 mg daily or loratadine 40 mg daily) 1, 3
• Try at least two different non-sedating antihistamines, as individual responses vary significantly 1
• Alternative options include fexofenadine 180 mg, desloratadine 5 mg, or levocetirizine 5 mg 4, 2
• Antihistamines should be used on a regular daily basis, not just when hives occur 5

Important Medication Avoidance

• Avoid NSAIDs (ibuprofen, naproxen), aspirin, and codeine, as these can trigger or worsen urticaria through non-IgE mechanisms 1, 6
• Discontinue ACE inhibitors if the patient is taking them 1

Workup and Red Flags

When to Perform Skin Biopsy

• Obtain a lesional skin biopsy only if individual wheals persist longer than 24 hours, as this suggests urticarial vasculitis rather than chronic spontaneous urticaria 7, 1, 6
• Standard chronic urticaria wheals last 2-24 hours 7
• Biopsy should look for leucocytoclasia, endothelial cell damage, perivascular fibrin deposition, and red cell extravasation 7

Laboratory Testing

• Minimal laboratory workup is needed for typical chronic urticaria without systemic symptoms 6
• If urticarial vasculitis is suspected (wheals >24 hours), obtain serum complement assays (C3, C4) to distinguish normocomplementemic from hypocomplementemic disease 7, 1
• Routine extensive laboratory testing is not recommended for uncomplicated chronic urticaria 6

Second-Line Treatment Options

If High-Dose Antihistamines Fail

• Consider adding H2-antihistamines (such as cimetidine) in combination with H1-antihistamines, though evidence is limited 4
• Short courses of oral corticosteroids (prednisone 40 mg daily or equivalent) can be used for severe flares, tapering over 3-4 weeks 7, 5
• Long-term corticosteroids should be avoided except in very selected cases under specialist supervision 7

Third-Line: Referral and Advanced Therapies

• Refer to allergy/immunology or dermatology if symptoms remain uncontrolled despite high-dose antihistamines (up to 4x standard dose) 6
• Omalizumab 300 mg subcutaneously every 4 weeks is the next step for refractory cases, with up to 6 months allowed for response 7, 1
• Cyclosporine (up to 5 mg/kg body weight) can be considered for severe cases unresponsive to omalizumab, with monitoring of blood pressure and renal function every 6 weeks 7, 1

Adjunctive Measures

Symptom Relief and Trigger Avoidance

• Apply cooling antipruritic lotions such as calamine or 1% menthol in aqueous cream for symptomatic itch relief 1
• Minimize aggravating factors including overheating, stress, and alcohol 7, 1
• Use emollients regularly for any associated dry skin 4

Patient Education

• Explain that chronic urticaria often resolves spontaneously over months to years, though the timeline is unpredictable 1
• Emphasize the importance of daily antihistamine use rather than as-needed dosing 5
• Discuss that up-dosing antihistamines beyond standard doses (up to 4x) is safe, with somnolence being the most common side effect (reported in only 17% of patients) 3

Common Pitfalls to Avoid

• Do not use sedating first-generation antihistamines (diphenhydramine, hydroxyzine) as first-line therapy, as they cause significant sedation and cognitive impairment without superior efficacy 4, 8
• Do not use topical crotamiton cream or capsaicin for chronic urticaria, as evidence does not support their use 4
• Do not pursue extensive allergy testing or food elimination diets unless there is clear temporal relationship between specific exposures and hives 6
• Avoid long-term systemic corticosteroids due to significant side effects 7