How should I evaluate and treat a 13‑year‑old with urticaria, and what are the key differential diagnoses?

Management and Differential Diagnosis of Urticaria in a 13-Year-Old

Second-generation H1 antihistamines at standard pediatric doses are the first-line treatment for urticaria in a 13-year-old, and the diagnosis is primarily clinical—routine laboratory testing is unnecessary unless the history suggests a specific trigger or the urticaria persists beyond 6 weeks. 1, 2

Initial Clinical Assessment

Determine the duration and pattern of individual wheals:

• Wheals lasting 2–24 hours that resolve without scarring indicate ordinary urticaria 1, 2
• Wheals persisting beyond 24 hours strongly suggest urticarial vasculitis and require skin biopsy 1, 2
• Contact urticaria resolves within 2 hours of exposure 2
• Physical urticarias (except delayed-pressure type) resolve within 1 hour 2

Identify the temporal pattern:

• Acute urticaria (≤6 weeks) is most common in adolescents and typically triggered by viral infections, foods, drugs, or insect stings 3, 4
• Chronic urticaria (>6 weeks) requires a different diagnostic and therapeutic approach 3, 5

Screen for red flags that suggest alternative diagnoses:

• Painful or burning lesions (rather than purely itchy) indicate urticarial vasculitis 2
• Residual hyperpigmentation, ecchymosis, or purpura after wheals resolve signals vascular damage 2
• Angioedema without wheals lasting up to 3 days suggests C1-inhibitor deficiency 2
• Systemic symptoms (fever, joint pain, fatigue) warrant evaluation for vasculitis or autoinflammatory syndromes 1, 6

Diagnostic Approach

For acute or episodic urticaria:

• No investigations are required unless the history points to a specific allergen 1, 2
• When environmental allergens (latex, nuts, fish) are suspected, confirm IgE-mediated reactions with skin-prick testing or specific IgE fluoroimmunoassay 1, 2
• Interpret allergy test results only in clinical context—positive tests without clinical correlation do not establish causation 1

For chronic urticaria (>6 weeks) with severe disease or poor antihistamine response:

• Obtain complete blood count with differential to detect eosinophilia (parasitic infections) or leukopenia (systemic lupus erythematosus) 1, 2
• Measure erythrocyte sedimentation rate or C-reactive protein—normal in ordinary chronic urticaria but elevated in urticarial vasculitis and autoinflammatory syndromes 1, 2
• Check thyroid autoantibodies (anti-TPO) and thyroid function tests, especially when autoimmune etiology is suspected 1, 2
• Consider total IgE and IgG-anti-TPO ratio as the best surrogate marker for autoimmune chronic spontaneous urticaria 2

For suspected urticarial vasculitis:

• Perform lesional skin biopsy to confirm small-vessel vasculitis (leukocytoclasia, endothelial damage, perivascular fibrin deposition, red cell extravasation) 1, 2
• Measure serum complement (C3, C4) to distinguish normocomplementemic from hypocomplementemic disease—the latter carries worse prognosis 1, 2
• Refer to rheumatology for systemic lupus erythematosus overlap evaluation 2

For angioedema without wheals:

• Screen with serum C4 level—sensitivity >95% for C1-inhibitor deficiency when C4 is <30% of normal 1, 2
• If C4 is low, confirm with quantitative and functional C1-inhibitor assays 1, 2
• Type I hereditary angioedema shows low immunochemical and functional C1-inhibitor; Type II shows normal antigen but reduced functional activity 1, 2

Key Differential Diagnoses

Chronic spontaneous urticaria:

• Most common chronic form in children; approximately one-third have circulating autoantibodies against high-affinity IgE receptor or IgE itself 7
• Autologous serum skin test offers reasonably sensitive and specific screening in experienced centers 1

Chronic inducible urticaria (physical urticarias):

• Accounts for 5–10% of chronic urticaria in children 7
• Specific triggers include pressure, cold, heat, exercise, dermographism 2
• Cholinergic urticaria is triggered by stimuli that induce sweating (raised core temperature, exercise, emotional stress) rather than overheating per se 8
• Diagnosis requires specific provocation testing 1, 2

Urticarial vasculitis:

• Distinguished by painful wheals persisting days with residual bruising 2
• Requires skin biopsy and full vasculitis workup 1, 2

Hereditary angioedema:

• Approximately half of patients experience first episode before age 10, with worsening around puberty 2
• Non-pruritic, non-pitting angioedema progressing over ~24 hours, resolving in 48–72 hours 2
• Minor trauma (venipuncture) can trigger attacks 2
• Critical pitfall: Antihistamines, corticosteroids, and epinephrine are ineffective because edema is bradykinin-mediated, not histamine-mediated 2

Autoinflammatory syndromes and systemic diseases:

• Consider cryopyrinopathies, hyper-IgD syndrome, PFAPA, TRAPS, Schnitzler syndrome when systemic symptoms accompany urticaria 6
• Rule out systemic-onset juvenile idiopathic arthritis, collagenopathies, endocrinopathies 3, 7

Mastocytosis:

• Must be differentiated from chronic urticaria because treatment differs 3

First-Line Treatment

Pharmacologic therapy:

• Second-generation H1 antihistamines at standard pediatric doses are the cornerstone of treatment 2, 4
• Approximately 40% of children achieve adequate control with antihistamine monotherapy 2
• For children ≥12 years, no licensed H1 antihistamine is contraindicated; for younger children, verify age-specific product labeling 2

Short-course oral corticosteroids:

• Use lower than adult regimens (adult dose: 50 mg daily for 3 days) to shorten severe acute episodes 2
• Limit to brief courses; avoid long-term use except in selected severe cases under specialist supervision 2

Adjunctive measures:

• Apply topical cooling agents (calamine lotion or 1% menthol in aqueous cream) for symptomatic itch relief 1, 2
• Avoid aggravating factors: overheating, emotional stress, alcohol 1, 2
• Avoid aspirin and NSAIDs—they trigger mast-cell degranulation and worsen urticaria 1, 2
• Use ACE inhibitors with caution if angioedema is present 1

Emergency Management

For laryngeal angioedema or anaphylaxis:

• Administer intramuscular epinephrine immediately 2
• For a 13-year-old (typical weight 40–60 kg), use standard adult 300 µg epinephrine autoinjector 2
• Give second dose if no significant improvement after first 2
• Parenteral hydrocortisone may be added for severe laryngeal edema, recognizing delayed therapeutic effect 2
• Prescribe epinephrine autoinjector for home use when history indicates risk of recurrent life-threatening attacks 2

For hereditary angioedema attacks:

• First-line therapies: plasma-derived C1-inhibitor concentrate (20 U/kg), icatibant (bradykinin-B2 receptor antagonist), or ecallantide (plasma kallikrein inhibitor) 2
• Prepare for possible endotracheal intubation if airway involvement 2

Chronic Urticaria Management

Step-up approach for inadequate response to standard-dose antihistamines:

• Consider adding H2 antihistamine, though evidence for benefit is limited and mainly for associated dyspepsia 1, 2
• Antileukotrienes may benefit a small subgroup 7
• For refractory chronic urticaria, omalizumab and cyclosporine are effective 5
• Tacrolimus has been used successfully in resistant cases 7

Common Pitfalls to Avoid

• Do not perform extensive laboratory workups for typical acute urticaria—they add no clinical value 2
• Do not use antihistamines, corticosteroids, or epinephrine for hereditary angioedema—these are ineffective for bradykinin-mediated edema 2
• Do not overlook urticarial vasculitis—any wheal persisting >24 hours requires biopsy 1, 2
• Do not prescribe long-term corticosteroids—reserve only for selected severe cases under specialist care 2
• Do not miss C1-inhibitor deficiency—screen with C4 when angioedema occurs without wheals 1, 2

Specialist Referral Indications

• Suspected hereditary angioedema: refer to allergist/immunologist for definitive diagnosis, treatment planning, and family screening 2
• Urticarial vasculitis: refer to rheumatology for systemic lupus erythematosus evaluation 2
• Paraneoplastic syndrome consideration: consult hematology-oncology 2
• Chronic urticaria refractory to antihistamines: refer to dermatology or allergy for advanced therapies 5