When is a workup for chronic spontaneous urticaria (CSU) indicated in children?

Workup for Chronic Spontaneous Urticaria in Children

In children with chronic spontaneous urticaria (CSU), extensive routine laboratory workup is not indicated; limit initial testing to a thorough history, physical examination, basic tests (differential blood count, C-reactive protein/ESR, total IgE, and IgG-anti-TPO), and patient-reported outcome measures. 1

Initial Diagnostic Approach

The diagnostic workup in pediatric CSU should follow the "7 Cs" framework to guide when and what testing is appropriate 1:

Mandatory Initial Assessment

• History and physical examination including review of patient photo documentation of wheals/angioedema 1
• Basic laboratory tests only 1:
  • Differential blood count
  • C-reactive protein level or erythrocyte sedimentation rate
  • Total IgE level
  • IgG-anti-thyroid peroxidase (anti-TPO) level
• Patient-reported outcome measures: Urticaria Control Test (UCT) for disease control assessment 1

When to Pursue Extended Workup

Additional testing is indicated only when the history or physical examination suggests specific underlying conditions 1. The guidelines explicitly recommend against routine extensive testing 1.

Specific Clinical Scenarios Requiring Further Investigation:

1. Suspected Autoimmune CSU 1

• Low or very low total IgE levels combined with elevated IgG-anti-TPO suggests autoimmune CSU 1
• High ratio of IgG-anti-TPO to total IgE is the best surrogate marker 1
• Consider CU index testing in patients not responsive to H1-antihistamines to detect antibodies against IgE, FcεRI, or FcεRII 1

2. Angioedema Without Wheals 1

• Measure C4 and C1-inhibitor levels (quantitative and functional) 1
• If acquired angioedema suspected, check for C1q antibodies 1
• If tests unremarkable but history suggests hereditary angioedema, perform gene mutation analysis 1

3. Suspected Urticarial Vasculitis 1

• Individual wheals lasting >24 hours (versus typical 2-24 hours in ordinary urticaria) 1
• Skin biopsy showing small vessel vasculitis with fibrinoid deposits 1

4. Suspected Autoinflammatory Syndromes 1

• Recurrent fever with urticaria
• Systemic symptoms (joint pain, malaise)
• Consider: systemic-onset juvenile idiopathic arthritis, cryopyrin-associated periodic syndromes (CAPS), Muckle-Wells syndrome, or neonatal-onset multisystem inflammatory disease 1

5. Suspected Chronic Inducible Urticaria 1

• Ask: "Can you make your wheals appear? Can you bring out your wheals?" 1
• If history suggests inducible urticaria, perform standardized provocation testing 1

Key Differences in Pediatric CSU

Pediatric CSU differs significantly from adult disease, making extensive workup even less necessary 2:

• Lower frequency of angioedema (19.1% vs 59.8% in adults) 2
• Shorter disease duration (5 months vs 12 months in adults) 2
• Lower anti-TPO positivity (9% vs 24.7% in adults) 2
• Lower elevated CRP rates (11.1% vs 46.5% in adults) 2
• Better response to antihistamines with less need for omalizumab (7% vs 20.8% in adults) 2

Common Pitfalls to Avoid

Do not order allergy testing routinely - CSU is not an allergic condition, though skin prick test positivity may be more common in adults (39.3%) than children (28.8%) 2. This represents comorbid atopy, not causation.

Do not pursue extensive autoimmune workups without clinical indicators - While total IgE levels correlate with disease duration in children (r=0.262, p=0.021), this does not justify routine extensive testing 3.

Recognize that most pediatric CSU is self-limited - Remission rates at 1,2,3, and 4 years are 43.7%, 56.2%, 68.7%, and 75.0% respectively in children with CSU 3, supporting a conservative diagnostic approach.

Monitoring Disease Activity

Use validated tools rather than pursuing laboratory investigations 1:

• 7-Day Urticaria Activity Score (UAS7) for disease activity (maximum score 42) 1
• UCT score for disease control (cutoff for well-controlled disease: ≥12 points) 1
• Angioedema Control Test (AECT) if angioedema present (cutoff: ≥10 points) 1