What lab tests and treatment are recommended for a patient with urticaria?

Laboratory Testing and Treatment for Urticaria

Laboratory Testing Recommendations

Acute Urticaria

No routine laboratory testing is required for acute urticaria unless the patient's history suggests a specific underlying cause. 1

• Testing should only be performed when the history suggests an IgE-mediated reaction to environmental allergens (latex, nuts, fish), which can be confirmed by skin-prick testing or CAP fluoroimmunoassay 1
• The diagnosis remains primarily clinical 1

Chronic Spontaneous Urticaria (CSU)

For mild CSU responding to H1 antihistamines, no investigations are required. 1

For moderate to severe CSU not responding to antihistamines, the 2022 international guideline recommends basic testing including: 1

• Differential blood count (to detect eosinophilia from helminth infections or leukopenia from systemic lupus erythematosus) 1
• C-reactive protein level or erythrocyte sedimentation rate (usually normal in CSU but elevated in urticarial vasculitis and autoinflammatory syndromes) 1
• Total IgE level (low or very low levels suggest autoimmune CSU) 1
• IgG anti-thyroid peroxidase (anti-TPO) antibodies (elevated levels suggest autoimmune CSU; thyroid autoimmunity occurs in 14% of CSU patients vs 6% in controls) 1
• Thyroid function tests should be performed, especially if autoimmune etiology is suspected 1

The ratio of IgG anti-TPO to total IgE is currently the best surrogate marker for autoimmune CSU. 1 Patients with autoimmune CSU typically have elevated IgG anti-TPO and low total IgE levels 1

Physical Urticarias

• Diagnosis is confirmed by provocation testing with subsequent trigger threshold assessment 1
• No routine laboratory testing beyond confirmation of the diagnosis 1

Urticarial Vasculitis (When Suspected)

If individual urticarial lesions persist longer than 24 hours, suspect urticarial vasculitis and perform:

• Deep punch biopsy extending to the subcutis (not superficial biopsy, which will miss diagnostic vascular changes) 2
• The biopsy should target the most tender, reddish, or purpuric lesion 2
• Histopathology will show fibrinoid necrosis, leukocytoclasia, endothelial damage, and red cell extravasation 2

Angioedema Without Wheals

• Serum C4 level as initial screening test for hereditary and acquired C1 inhibitor deficiency 1
• If C4 is low (<30% mean normal), confirm with quantitative and functional C1 inhibitor assays 1

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Treatment Algorithm

First-Line Treatment

Second-generation H1 antihistamines at standard doses are the first-line treatment for all forms of urticaria. 1, 3, 4

• These are preferred over first-generation antihistamines due to superior safety and efficacy profile 4
• Examples include cetirizine, loratadine, fexofenadine, desloratadine 3

Second-Line Treatment (If Inadequate Response After 2-4 Weeks)

Increase the dose of second-generation H1 antihistamines up to four times the standard dose. 1, 3, 4

• This is off-label but recommended by international guidelines 4
• Continue for 2-4 weeks or earlier if symptoms are intolerable 4

Third-Line Treatment (If Still Inadequate After Dose Escalation)

Add omalizumab (anti-IgE antibody) to the treatment regimen. 4

• For CSU: 150 or 300 mg subcutaneously every 4 weeks (dosing not dependent on IgE level or body weight) 5
• For asthma-associated urticaria: 75-375 mg SC every 2-4 weeks based on serum IgE and body weight 5
• Continue for up to 6 months; if inadequate response, proceed to fourth-line 4
• Omalizumab has been a remarkable advancement and improves quality of life beyond symptom control 4

Fourth-Line Treatment (Refractory Cases)

Add cyclosporine to second-generation H1 antihistamines. 4

• Reserved for cases refractory to omalizumab 4
• Requires subspecialist referral 3

Adjunctive Therapies

• Short-term systemic corticosteroids may be considered for acute exacerbations and refractory cases, but not for long-term use 4
• H2 antihistamines, leukotriene receptor antagonists can be added as adjunctive treatment, though benefits are not clearly established 3, 6
• Avoidance of nonspecific aggravating factors such as overheating, stress, alcohol, NSAIDs, and ACE inhibitors 1

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Critical Pitfalls to Avoid

• Never dismiss urticaria with anaphylaxis features (bronchospasm, hypotension, throat swelling) without immediate treatment with intramuscular epinephrine 6
• Do not perform superficial punch biopsies when urticarial vasculitis is suspected; they will miss diagnostic vascular changes 2
• Do not abruptly discontinue corticosteroids upon initiating omalizumab therapy 5
• Do not use omalizumab for emergency treatment of allergic reactions or anaphylaxis 5
• Be alert for eosinophilic conditions (vasculitic rash, worsening pulmonary symptoms, cardiac complications, neuropathy) especially when reducing oral corticosteroids 5

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Prognosis

More than one-half of patients with chronic urticaria will have resolution or improvement of symptoms within one year 3, though the average duration is 2-5 years 4. Disease severity correlates with disease duration 4.