What is the diagnosis and management for a 33-year-old male with a 5-year history of recurrent urticaria, who responds well to Fexofenadine (Fexofenadine), and recently developed lip swelling with weals, living in a damp environment, and follows a vegetarian diet that includes milk and milk products?

Chronic Spontaneous Urticaria with Angioedema

This patient has chronic spontaneous urticaria (CSU) with recent progression to angioedema, and should continue fexofenadine but escalate to 180 mg once daily (or up to 4-fold standard dosing if needed), while investigating for potential environmental triggers related to the damp home environment and considering food protein sensitivities despite the vegetarian diet. 1, 2, 3

Diagnosis

Chronic Spontaneous Urticaria (CSU) with Angioedema

The 5-year history of recurrent urticaria classifies this as chronic (>6 weeks duration), and the recent development of lip swelling indicates progression to angioedema. 1, 3

Key Diagnostic Features:

• Wheals lasting 2-24 hours distinguish ordinary urticaria from physical urticaria (which typically lasts <1 hour, except delayed pressure urticaria). 1
• Lip swelling with wheals represents angioedema, which occurs in approximately 50% of chronic urticaria patients and indicates a poorer prognosis—over 50% of patients with combined wheals and angioedema have active disease after 5 years, compared to 50% clearance by 6 months in those with wheals alone. 1
• Good response to fexofenadine confirms histamine-mediated disease and rules out non-histaminergic causes. 4, 5

Critical Differential to Exclude:

Rule out hereditary or acquired C1 inhibitor deficiency if angioedema occurs without wheals or if angioedema persists >24 hours, as this requires completely different management with C1 inhibitor concentrate rather than antihistamines. 1

Environmental and Dietary Triggers

Damp Home Environment:

• Mold exposure from damp housing can trigger or exacerbate chronic urticaria through both IgE-mediated and non-IgE mechanisms. 1
• Dust mite proliferation increases in damp environments and represents a potential chronic allergen exposure. 1

Vegetarian Diet Considerations:

• Milk and milk products are among the most common food triggers for urticaria, particularly in adults with chronic urticaria. 1, 6
• Food protein sensitivities can manifest as chronic urticaria even without classic IgE-mediated immediate reactions. 1
• Consider a 2-4 week elimination trial of dairy products to assess for improvement, as food triggers in chronic urticaria often cause delayed rather than immediate reactions. 1

Management Algorithm

Step 1: Optimize Antihistamine Therapy

Increase fexofenadine to 180 mg once daily as the initial dose escalation. 2, 4, 5

• Fexofenadine 180 mg once daily is specifically studied and effective for chronic idiopathic urticaria. 4, 5, 7
• If inadequate control after 2-4 weeks, escalate up to 4-fold standard dosing (240 mg twice daily has been studied and proven safe). 1, 8, 5
• Current guidelines explicitly support increasing antihistamine doses beyond manufacturer recommendations when benefits outweigh risks, which is now common clinical practice. 1, 8

Why fexofenadine over alternatives:

• Completely non-sedating at all doses, including doses up to 240 mg twice daily. 2, 4
• Rapid onset of action (≤2 hours) with long duration suitable for once-daily dosing. 4
• No cardiac toxicity even when combined with erythromycin or ketoconazole. 4

Step 2: Add Adjunctive Therapy if Monotherapy Insufficient

After 2-4 weeks at maximum fexofenadine dosing, if control remains inadequate:

• Add H2 antihistamine (e.g., cimetidine) in combination with fexofenadine, as H1 and H2 antagonist combinations may provide better urticaria control than H1 antihistamines alone. 1, 8
• Consider adding montelukast 10 mg daily, which equals the efficacy of doubled antihistamine doses but with significantly less sedation. 8

Step 3: Environmental Modification

Address damp home environment immediately:

• Reduce indoor humidity to <50% using dehumidifiers to minimize mold and dust mite proliferation. 1
• Inspect for visible mold and remediate professionally if present. 1
• Use allergen-impermeable mattress and pillow covers to reduce dust mite exposure. 1

Step 4: Dietary Trial

Consider 2-4 week dairy elimination trial:

• Eliminate all milk and milk products for 2-4 weeks while maintaining adequate calcium and vitamin B12 supplementation. 1
• Reintroduce systematically after the trial period to assess for symptom recurrence. 1

Step 5: Referral for Refractory Cases

If symptoms persist despite 4-fold antihistamine dosing plus adjunctive therapy:

• Refer to allergy/immunology specialist for consideration of omalizumab 300 mg subcutaneously every 4 weeks, which is second-line therapy for chronic spontaneous urticaria. 8, 3

Critical Pitfalls to Avoid

• Do NOT use NSAIDs or aspirin, as they can trigger or worsen urticaria through cyclooxygenase inhibition and should be avoided in all urticaria patients. 8, 6, 3
• Do NOT assume all second-generation antihistamines are equally non-sedating—cetirizine may cause sedation (13.7% vs 6.3% placebo), while fexofenadine does not cause sedation even at high doses. 2, 8
• Do NOT perform extensive laboratory workup unless individual wheals persist >24 hours (requiring biopsy to rule out urticarial vasculitis) or there are systemic symptoms suggesting underlying disease. 1, 6
• Do NOT use oral corticosteroids for maintenance therapy—restrict to short courses only for severe acute exacerbations. 1

Monitoring and Follow-up

• Assess response at 2-4 week intervals when escalating antihistamine doses. 8
• Use Urticaria Control Test (UCT) to quantify disease burden—patients with UCT score ≤16 require dose escalation. 8, 6
• Once complete control achieved for 3 consecutive months, consider gradual dose reduction by no more than 1 tablet per month. 8
• If breakthrough symptoms occur, return to the last dose that provided complete control. 8

Prognosis

More than 50% of patients with chronic urticaria will have resolution or improvement within one year, though the presence of angioedema suggests a longer disease course with over 50% still having active disease after 5 years. 1, 3