What is the workup for a patient presenting with intermittent urticaria (hives) all over the body?

Workup for Intermittent Urticaria

For intermittent urticaria (hives) all over the body, perform a focused clinical evaluation to distinguish acute from chronic urticaria and identify potential triggers, but avoid extensive laboratory testing unless specific systemic disease is suggested by history or physical examination. 1

Initial Clinical Assessment

History Taking - Key Elements

• Duration of symptoms: Determine if urticaria is acute (<6 weeks) or chronic (≥6 weeks), as this fundamentally changes the diagnostic approach 2, 3

• Timing and pattern: Document when wheals appear, how long individual lesions last (typical wheals resolve within 2-24 hours; those lasting >24 hours suggest urticarial vasculitis requiring skin biopsy) 4, 5

• Trigger identification: Systematically inquire about:

  • Recent viral infections (most common cause in acute urticaria) 5
  • Food exposures, particularly peanut, tree nuts, milk, shellfish, and fish 6
  • Medications, especially NSAIDs, aspirin, codeine, and ACE inhibitors 7, 4
  • Physical stimuli (heat, cold, pressure, exercise, water) 7, 5
  • Stress and alcohol consumption 7

• Associated symptoms: Screen for angioedema (occurs in one-third of chronic urticaria cases), respiratory symptoms, gastrointestinal complaints, or signs of anaphylaxis 5, 3

• Impact assessment: Use validated tools like the Urticaria Control Test (UCT) to quantify disease burden and guide treatment decisions 6

Physical Examination Focus

• Lesion characteristics: Confirm presence of transient, raised, erythematous wheals with central pallor and surrounding flare 2

• Distribution pattern: Note if generalized versus localized, which may suggest specific physical urticarias 5

• Provocation testing: Consider bedside challenge tests for suspected physical urticarias (ice cube test for cold urticaria, pressure test, dermographism testing) 5

• Signs of systemic disease: Examine for lymphadenopathy, hepatosplenomegaly, joint inflammation, or other features suggesting underlying collagenopathies, endocrinopathies, or malignancy 5

Laboratory Workup - Selective Approach

Acute Urticaria (<6 weeks)

No routine laboratory testing is indicated for acute urticaria unless specific systemic disease is suspected. 1 The vast majority of acute cases are self-limited and resolve without identifying a specific cause 5.

Chronic Urticaria (≥6 weeks)

Limit laboratory evaluation to a focused panel unless history or examination suggests specific conditions: 1

• First-tier testing (only if chronic urticaria confirmed):

  • Complete blood count with differential (to screen for systemic disease) 1
  • Erythrocyte sedimentation rate or C-reactive protein (if urticarial vasculitis suspected) 1
  • Thyroid function tests (thyroid autoimmunity associated with chronic urticaria) 1

• Additional testing only if clinically indicated:

  • Specific IgE testing or skin prick tests only if clear allergic trigger suspected from history 5
  • Autologous serum skin test if autoimmune urticaria suspected (present in one-third of chronic urticaria cases) 5
  • Skin biopsy only if individual wheals persist >24 hours (to rule out urticarial vasculitis) 4, 5
  • Complement levels (C4, C1 inhibitor) only if isolated angioedema without urticaria suggests hereditary angioedema 3

Critical Pitfalls to Avoid

• Do not perform extensive allergy panels or autoimmune workups routinely: 80-90% of chronic urticaria is idiopathic, and extensive testing rarely changes management 1

• Recognize antihistamine-induced urticaria: Paradoxically, some patients develop worsening urticaria from H1-antihistamines themselves due to cross-reactivity between piperazine and piperidine derivatives 8

• Distinguish urticaria from anaphylaxis: If urticaria occurs with respiratory symptoms, hypotension, or gastrointestinal symptoms after known allergen exposure, treat as anaphylaxis with intramuscular epinephrine first 6

• Avoid NSAIDs in all urticaria patients: These medications can trigger or worsen urticaria through non-IgE mechanisms 7, 4

When to Refer

Consider subspecialty referral for:

• Chronic urticaria unresponsive to high-dose second-generation antihistamines (up to 4× standard dose) 6, 7
• Suspected physical urticarias requiring specialized provocation testing 5
• Isolated angioedema without wheals (may require evaluation for hereditary angioedema) 3
• Wheals persisting >24 hours requiring biopsy 4