What is the best treatment approach for a patient with chronic urticaria and elevated C-Reactive Protein (CRP) levels?

Treatment Approach for Chronic Urticaria with Elevated CRP

For a patient with chronic urticaria and CRP of 14 mg/L, initiate second-generation H1-antihistamines at standard doses, and if inadequate control persists after 2-4 weeks, increase the dose up to 4-fold before advancing to omalizumab 300 mg every 4 weeks. 1

Understanding the Elevated CRP

Your patient's elevated CRP (14 mg/L) suggests a potential autoimmune endotype of chronic spontaneous urticaria (CSU):

• High CRP levels correlate with elevated IgG anti-TPO and may indicate non-histaminergic (autoimmune) CSU, which has distinct treatment implications 2
• Consider measuring total IgE and IgG-anti-TPO levels to calculate their ratio, as a high IgG-anti-TPO to total IgE ratio is the best surrogate marker for autoimmune CSU 3
• Patients with autoimmune CSU are more likely to fail standard antihistamine therapy and may require earlier advancement to omalizumab or cyclosporine 3

Stepwise Treatment Algorithm

Step 1: Second-Generation H1-Antihistamines (First-Line)

• Start with standard-dose second-generation H1-antihistamines (cetirizine, desloratadine, fexofenadine, levocetirizine, or loratadine once daily) 1
• Offer at least two different antihistamine options since individual responses vary 1
• Assess disease control after 2-4 weeks using the Urticaria Control Test (UCT), with a score ≥12 indicating well-controlled disease 1

Step 2: Updose Antihistamines if Needed

• If UCT score remains <12, increase the antihistamine dose up to 4-fold the standard dose 1
• This updosing approach is common practice despite being above manufacturer's licensed recommendations, as benefits outweigh risks 1
• Given your patient's elevated CRP suggesting autoimmune CSU, they may be less likely to respond to antihistamines alone 3

Step 3: Omalizumab (Second-Line)

• If symptoms remain inadequately controlled after 2-4 weeks of updosed antihistamines, advance to omalizumab 300 mg subcutaneously every 4 weeks 1, 4
• Allow up to 6 months for patients to respond to omalizumab before considering it a treatment failure 1
• For insufficient responders, consider updosing omalizumab by shortening intervals and/or increasing dosage, with a maximum recommended dose of 600 mg every 14 days 1
• Omalizumab works independently of autoimmune markers, making it effective regardless of the underlying endotype 1

Step 4: Cyclosporine (Third-Line)

• For patients who fail to respond to high-dose omalizumab, consider cyclosporine up to 5 mg/kg body weight 1, 5
• Cyclosporine may be particularly effective in non-histaminergic (autoimmune) responders like your patient with elevated CRP 3
• Monitor blood pressure and renal function (BUN and creatinine) every 6 weeks during cyclosporine treatment 1
• Be aware of potential adverse effects including hypertension, hirsutism, gum hypertrophy, and renal impairment 1

Disease Monitoring and Step-Down Strategy

• Use the UCT at each visit to guide treatment decisions, aiming for complete disease control (UCT ≥16) 1
• Once complete control is achieved for at least 3 consecutive months, consider stepping down treatment to assess for spontaneous remission 1
• Reduce antihistamine doses by no more than 1 tablet per month during step-down 1
• If breakthrough symptoms occur during dose reduction, return to the last dose that provided complete control 1

Additional Considerations

• Advise patients to avoid nonspecific aggravating factors including overheating, stress, alcohol, aspirin, and NSAIDs 1
• Brief courses of systemic corticosteroids can be used for severe flares only, not for long-term management 5
• More than half of patients with chronic urticaria will experience resolution or improvement within one year 6