What is the work-up for a patient presenting with recurrent intermittent urticaria?

Work-up for Recurrent Intermittent Urticaria

For patients with recurrent intermittent urticaria, the work-up should be guided by a detailed clinical history focusing on wheal duration, triggers, and associated symptoms, with laboratory testing reserved only when specific red flags suggest underlying systemic disease. 1

Initial Clinical Assessment

The cornerstone of evaluation is a focused history and physical examination targeting specific diagnostic clues:

Key Historical Elements

• Wheal duration: Ask specifically "For how long does each individual wheal last?" Wheals lasting 2-24 hours suggest ordinary urticaria, while those persisting >24 hours indicate possible urticarial vasculitis requiring skin biopsy. 1

• Trigger identification: Ask "Can you make your wheals appear? Can you bring out your wheals?" to identify physical urticarias (cold, pressure, heat, vibration, dermographism). 1

• Medication review: Specifically inquire about ACE inhibitors, angiotensin II receptor blockers, gliptins, and neprilysin inhibitors, as these can cause angioedema that may present intermittently. 1

• Associated symptoms requiring immediate attention:

  • Recurrent unexplained fever, joint/bone pain, or malaise suggest autoinflammatory disease 1
  • Abdominal pain may indicate hereditary or acquired angioedema 1

Disease Activity Documentation

• Implement the 7-Day Urticaria Activity Score (UAS7) prospectively, having patients score both wheal count (0-3 points) and pruritus intensity (0-3 points) daily for 7 consecutive days, yielding a total score of 0-42 points. 1

Laboratory Testing: A Selective Approach

Routine extensive laboratory testing is not recommended for recurrent intermittent urticaria unless specific clinical features suggest underlying disease. 1, 2

Limited Testing for Uncomplicated Cases

For patients with typical intermittent urticaria without red flags, minimal or no laboratory testing is appropriate, as chronic urticaria is idiopathic in 80-90% of cases. 2

Targeted Testing When Red Flags Present

Only pursue laboratory evaluation when specific clinical features warrant investigation:

• If wheals persist >24 hours: Skin biopsy of lesional skin to evaluate for urticarial vasculitis (look for small vessel damage in papillary/reticular dermis and fibrinoid deposits). 1

• If fever, joint pain, or malaise present:

  • C-reactive protein and erythrocyte sedimentation rate 1
  • Test for paraproteinemia in adults 1
  • Consider skin biopsy for neutrophil-rich infiltrates 1
  • Gene mutation analysis for hereditary periodic fever syndromes if strongly suspected 1

• If prominent angioedema without wheals:

  • Complement C4, C1-INH levels and function 1
  • C1q and C1-INH antibodies if acquired angioedema suspected 1
  • Gene mutation analysis if above tests unremarkable but history suggests hereditary angioedema 1

Provocation Testing for Physical Urticarias

When history suggests inducible urticaria, perform standardized provocation testing to confirm diagnosis and identify specific triggers, allowing for targeted trigger avoidance strategies. 1, 3

Critical Pitfalls to Avoid

• Do not order extensive allergy panels or food testing for chronic/recurrent urticaria, as these are rarely helpful and food allergy is an uncommon cause in this population. 4, 5

• Do not perform retrospective symptom assessment - the UAS7 must be completed prospectively for 7 consecutive days, as recall bias significantly reduces accuracy. 6

• Do not assume all urticaria is benign - some physical urticarias (particularly cold urticaria) can progress to anaphylaxis in severe cases, requiring patient education and emergency action planning. 1, 3

• Do not continue ACE inhibitors if angioedema is present - remission should occur within days to 6 months of discontinuation. 1

Classification Determines Next Steps

The clinical pattern guides management:

• Episodic/intermittent ordinary urticaria: Focus on trigger identification through detailed history and patient diary; most cases remain idiopathic. 1

• Physical urticaria confirmed by provocation: Emphasize trigger avoidance and physical desensitization strategies. 3

• Suspected autoinflammatory syndrome: Refer for specialized evaluation, as treatment requires IL-1 inhibitors rather than standard antihistamine therapy. 7